Saturday, September 14, 2013

George Dvorsky - Does Consciousness Arise from Quantum Processes in the Brain?

Stuart Hameroff pretty much lost ALL credibility with anyone in the science world when he was featured so prominently in the horrible pseudo-documentary, What the Bleep Do We Know!? (my original review of the film and a brief comment on the "extended director's cut").

Here is a critique of that film (including, indirectly, refutation of Hameroff's [lack of] understanding of physics) from the Rational Wiki:
One of the key misrepresentations of quantum theory in the film is the line "quantum theory is the science of possibility", directly implying that the discovery and development of quantum mechanics somehow allows anything to happen, such as walking on water. More accurately, quantum theory is the science of probability; although the distinction is subtle to some, it is very important. Quantum phenomena, at least in the Copenhagen Interpretation, are all about the probability that a sub-atomic particle will be found at a particular position - crucially, this is only applicable in reality at the sub-atomic level.

The basic facts of neurology and quantum mechanics presented in the film are correct. Facts such as the uncertainty principle, where an object cannot have its exact position and momentum measured simultaneously (sometimes explained as the quantum effect that observing something fundamentally changes what is observed) is also real with real implications. However, the main mistake in the film is that it attempts to extrapolate these effects, which are only observed with atoms and electrons, to the macroscopic world. Thus, when the main character turns away from a basketball, the film depicts that it is now impossible to know its position because you're not observing it, such as in the Schrodinger's cat thought experiment. Of course, in reality, the ground is observing the ball every time it collides with it (there's nothing special about human eyes when it comes to observation in this sense), and the sound waves generated also let a person with their back turned know fairly precisely where it is (although the main character is deaf...).

Such extrapolations of very real quantum phenomena into unrealistic conclusions are often the cornerstone of the modern New Age movement which seeks to prove itself with science. These effects are certainly not observed in the macroscopic world. Other points raised in the film and presented as fact include that water molecules are influenced by thought, or that the brain cannot distinguish between fantasy and reality. All these points are either based on very unsound or fraudulent evidence, or distortions of real research.[3]
Anyway . . . I share all of this to inform you that what you are about to read should held lightly and with considerable skepticism.

It's not clear as of now whether Hameroff and Penrose are on to something, since there is no way at this time to test their hypotheses. However, it is clear that Hameroff engages in some seriously muddled thinking and does so under the authority of his degree and position at the University of Arizona.

[How fitting that this shows up the same day I receive the announcement for the 2014 Toward a Science of Consciousness Conference, which Hameroff co-founder and co-organizes each year.]

Does consciousness arise from quantum processes in the brain?

George Dvorsky

Stuart Hameroff is a Professor of Anesthesiology and Psychology at the University of Arizona — but he's a pariah as far as most neuroscientists are concerned. The reason? Consciousness, he dares say, is far more than just a computational process — it's actually quantum.

Along with the esteemed mathematician Sir Roger Penrose, Hameroff is the co-author of the highly controversial Orch OR model of consciousness (Orchestrated Objective Reduction) — the suggestion that quantum phenomenon, rather than classical mechanics, can explain conscious awareness.

The theory presents a new kind of wave function collapse that occurs in isolation, called objective reduction. This wave function collapse, they argue, is the only possible non-physical thing that can account for a non-computable process, namely consciousness. They speculate that this could happen inside the brain's microtubules.

Recently, Nikola Danaylov of the Singularity 1 on 1 podcast caught up with Hameroff to learn more. The result is a fascinating one hour interview in which the two discuss a number of topics, including various theories of mind, how anesthesia can inform the debate, the Orch OR model, and why the vast majority of scientists are disdainful of it.

In addition, they get into some weird territory and discuss quantum souls, the afterlife, reincarnation, and Hinduism and Buddhism. They even hit some futurist topics like the Singularity, cryonics, and chemical brain preservation, and also discuss Hameroff's upcoming paper (together with Roger Penrose) where they will review and present new evidence in support of their theory. 


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Image: Sebastian Kaulitzki/Shutterstock.

Toward a Science of Consciousness Conference - Tucson, April 21-26, 2014 (20th Anniversary)


Looks like an excellent conference this year - with some seriously cool plenary speakers. Among the names announced so far: John Searle, Daniel Dennett, David Eagleman, Christof Koch, Ned Block, Susan Blackmore, and Rebecca Goldstein (among others).

I hope to attend as much of it this year as my hectic schedule allows.

Toward a Science of Consciousness

The Tucson Conference - 20th Anniversary

April 21-26, 2014

It was 20 years ago today......

Plenary Speakers TSC 2014 bios / photos including:

  • Susan Blackmore
  • Karl Deisseroth
  • Rebecca Goldstein
  • Henry Markram
  • Petra Stoerig
  • Ned Block
  • Daniel Dennett
  • Stuart Hameroff
  • George Mashour
  • Giulio Tononi
  • David Chalmers
  • David Eagleman
  • Christof Koch
  • John Searle
  • and many more....

Toward a Science of Consciousness - 20th Anniversary
The Tucson Conference - April 21-26 2014

Scientists, philosophers, researchers, scholars, artists and humanists are invited to the 20th Anniversary of the first Tucson conference “Toward a Science of Consciousness” held in 1994. The 2014 conference will reflect on 20 years of progress, present understanding and future directions in the science of consciousness.

On-Line Registration - NOW OPEN ! | click here

Submit your Abstracts
Submission Deadline: December 15

Please review the taxonomy and general abstract guidelines

You do not have to make payment in order to open a registration record and to submit an abstract for consideration

Workshops - Pre-Conference Workshop Proposals
Please review the workshop proposal guidelines

email to:

Workshop Proposal Deadline: September 15 | Notifications by Oct 1

Additional Conference Information:

Friday, September 13, 2013

The "Richard Lewis Model" Explains Every Culture In The World

Someone on Facebook linked to this article, but I have forgotten who - sorry. From Business Insider, Gus Lubin offers a brief profile of British linguist Richard Lewis and his model of cultures. Lewis has plotted out the world's cultures on three qualities: Linear-actives (people who pursue goals in a linear, step-by-step manner), Multi-actives (multi-taskers who operate less by schedules or more by importance), and Reactives (groups who prioritize courtesy and respect).

Here is a brief description of his book (When Cultures Collide, 3rd Edition: Leading Across Cultures) from Amazon:
In this thoroughly updated and expanded 3rd edition of the groundbreaking book, When Cultures Collide: Leading Across Cultures, Richard Lewis includes every major region of the world and more than sixty countries! Capturing the rising influence of culture and the seismic changes throughout many regions of the world, cross-cultural expert and international businessman Richard Lewis has significantly broadened the scope of his seminal work on global business and intercultural communication. Included are new chapters on more than a dozen countries. Within each country-specific chapter, Lewis provides invaluable insight into the beliefs, values, behaviors, mannerisms and prejudices of each culture, lending helpful advice on topics to discuss and those to avoid when communicating, guides to interpreting unique terminology, and modes of behavior that will contribute to successful communication and lasting relationships. Lewis advises on overarching guidelines for proper overseas manners, whether in a restaurant, at the home of a colleague or in the boardroom. Using dozens of scientific, yet highly accessible diagrams and building on his Linear-active, Multi-active and Reactive (LMR) culture type model, Lewis gives managers and leaders practical strategies to embrace differences and work successfully across an increasingly diverse business culture.The 3rd Edition of the popular When Cultures Collide grows in size and information. It contains an additional three countries and regions that now 'play significant roles on the world stage' and include coverage of newer EU member states, the Indian subcontinent, the 'Arab Lands,' the Sub-Saharan region and Latin America in more detail. Country chapters in the new edition also include sidebars that provide a quick look at key motivating factors in each country.
- Kate Berardo, DELTA Intercultural Academy contributor 


  • Different Languages, Different Worlds
  • Cultural Conditioning
  • Categorization of Cultures
  • The Use of Time
  • Bridging the Communication Gap
  • Manners (and Mannerisms)
  • Status, Leadership, and Organization
  • Team Building and Horizons
  • Motivating People and Building Trust
  • Meetings of the Minds
  • English-Speaking Countries Western European Countries
  • Central and Eastern European Countries
  • Nordic Countries
  • The Baltic States and Central Asian Countries
  • Middle Eastern Countries
  • Asian (South, Southeast, East) Countries
  • Latin American Countries
  • Sub-Saharan African Countries
Here is the article Lubin:

The Lewis Model Explains Every Culture In The World

Gus Lubin | Sept. 6, 2013

A world traveler who speaks ten languages, British linguist Richard Lewis decided he was qualified to plot the world's cultures on a chart.

He did so while acknowledging the dangers of stereotypes.

"Determining national characteristics is treading a minefield of inaccurate assessment and surprising exception," Lewis wrote. "There is, however, such a thing as a national norm."

Many people think he nailed it, as his book When Cultures Collide, 3rd Edition: Leading Across Cultures, now in its third edition, has sold more than one million copies since it was first published in 1996 and was called "an authoritative roadmap to navigating the world's economy," by the Wall Street Journal.

Lewis plots countries in relation to three categories:
  • Linear-actives — those who plan, schedule, organize, pursue action chains, do one thing at a time. Germans and Swiss are in this group.
  • Multi-actives — those lively, loquacious peoples who do many things at once, planning their priorities not according to a time schedule, but according to the relative thrill or importance that each appointment brings with it. Italians, Latin Americans and Arabs are members of this group.
  • Reactives — those cultures that prioritize courtesy and respect, listening quietly and calmly to their interlocutors and reacting carefully to the other side's proposals. Chinese, Japanese and Finns are in this group.

He says that this categorization of national norms does not change significantly over time:
The behavior of people of different cultures is not something willy-nilly. There exist clear trends, sequences and traditions. Reactions of Americans, Europeans, and Asians alike can be forecasted, usually justified and in the majority of cases managed. Even in countries where political and economic change is currently rapid or sweeping (Russia, China, Hungary, Poland, Korea, Malaysia, etc.) deeply rooted attitudes and beliefs will resist a sudden transformation of values when pressured by reformists, governments or multinational conglomerates.

Here's the chart that explains the world:
richard lewis model
 Richard Lewis Model (
Some more details on the categories:
lewis model
Lewis Model (
The point of all of this analysis is to understand how to interact with people from different cultures, a subject in which Richard Lewis Communications provides coaching and consultation.

"By focusing on the cultural roots of national behavior, both in society and business, we can foresee and calculate with a surprising degree of accuracy how others will react to our plans for them, and we can make certain assumptions as to how they will approach us," Lewis writes.

Arthur Zajonc on Holding Life Consciously (On Being)

Arthur Zajonc is a physicist by training, but he has served as the President of the Dalai Lama's Mind and Life Institute since 2012. In addition, he is co-founder of the Kira Institute, past-president of the Lindisfarne Association, and co-founder of the Fetzer Institute.

He is author of the book: Meditation as Contemplative Inquiry: When Knowing Becomes Love (2008) and Catching the Light: The Entwined History of Light and Mind (1995), co-author of The Quantum Challenge, Second Edition : Modern Research on the Foundations of Quantum Mechanics (2005), and co-editor of Goethe's Way of Science (1995).

This interview comes from NPR's On Being with Krista Tippett (previously aired in June 2010 and November 2011).

Arthur Zajonc on Holding Life Consciously

September 12, 2013
Previous Versions 
What happens when you bring together science and poetry on something like color or light? Arthur Zajonc is a physicist and contemplative. And he says we can all investigate life as vigorously from the inside as from the outside.

Voices on the Radio

Arthur Zajonc  is emeritus professor of physics at Amherst College and president of the Dalai Lama's The Mind and Life Institute. His books include Meditation as Contemplative Inquiry: When Knowing Becomes Love and The Heart of Higher Education: A Call to Renewal



Books + Music
Krista's Journal

Pertinent Posts from the On Being Blog

Bell Sound Meditation  - Our weekend exercise. Try this 10-minute bell sound meditation and then share your experience with us.

The Ceaseless Society  - A video of Jon Kabat-Zinn's presentation at MIT as he reflects on life in a 24/7 networked world.

A Culture of Availability to Everybody But Yourself?  - Being mindful may mean you just can't shoot that next photo or journal that gorgeous sunset. A 3-minute TEDtalk.

Arthur Zajonc: A Twitterscript - Live from the studio, we tweeted the best nuggets of our interview.

Breathe, and Everything Changes  - Our managing producer, a "yoga cliché," finds a way of putting herself in the way of the divine.

Lovingkindness (Metta) Meditation with Sylvia Boorstein  - Somewhat unexpectedly, the Buddhist teacher offered to lead this meditation for 350 folks during our live event. The result? A magical experience. Try it for yourself and let us know if it translates for you.

Production Credits

  • Host/Producer: Krista Tippett 
  • Executive Producer: Kate Moos 
  • Associate Producer: Nancy Rosenbaum 
  • Associate Producer: Susan Leem 
  • Technical Director: Chris Heagle 
  • Senior Editor: Trent Gilliss

IgNobels 2013! And the Winners Are…

"The Stinker", the official mascot of the Ig Nobel Prizes

It's that yearly event that many scientists likely dread - the awarding of the IgNoble prizes for improbable research.
The Ig Nobel Prizes honor achievements that first make people laugh, and then make them think. The prizes are intended to celebrate the unusual, honor the imaginative — and spur people's interest in science, medicine, and technology. Every year, in a gala ceremony in Harvard's Sanders Theatre, 1200 splendidly eccentric spectators watch the winners step forward to accept their Prizes. These are physically handed out by genuinely bemused genuine Nobel laureates.
The 23rd First Annual Ig Nobel Prize ceremony will happen happened on Thursday, September 12, 2013. The ceremony will be was webcast live. TICKETS for the ceremony are sold out. 
And, from The Scicurious Brain at Scientific American, here are the 2013 winners:

IgNobels 2013! And the Winners Are…

TONIGHT, the 2013 IgNobels Prizes were held in Saunders Theatre at Harvard University! Winners traveled at their own expense, and received the prize from the hands of…real Nobel Prize winners. This year the prizes were accompanied by a new Opera, “The Blonsky Device”. 

And the winners are…*drumroll*
“Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells,” Masateru Uchiyama, Xiangyuan Jin, Qi Zhang, Toshihito Hirai, Atsushi Amano, Hisashi Bashuda and Masanori Niimi, Journal of Cardiothoracic Surgery, vol. 7, no. 26, epub. March 23, 2012.
REFERENCE: “‘Beauty Is in the Eye of the Beer Holder’: People Who Think They Are Drunk Also Think They Are Attractive,” Laurent Bègue, Brad J. Bushman, Oulmann Zerhouni, Baptiste Subra, Medhi Ourabah, British Journal of Psychology, epub May 15, 2012.
REFERENCE: “Dung Beetles Use the Milky Way for Orientation,” Marie Dacke, Emily Baird, Marcus Byrne, Clarke H. Scholtz, Eric J. Warrant, Current Biology, epub January 24, 2013. The authors, at Lund University, Sweden, the University of Witwatersrand, South Africa, and the University of Pretoria
The late Gustano Pizzo [USA], for inventing an electro-mechanical system to trap airplane hijackers — the system drops a hijacker through trap doors, seals him into a package, then drops the encapsulated hijacker through the airplane’s specially-installed bomb bay doors, whence he parachutes to earth, where police, having been alerted by radio, await his arrival. 

US Patent #3811643, Gustano A. Pizzo, “anti hijacking system for aircraft”, May 21, 1972.
REFERENCE: “Humans Running in Place on Water at Simulated Reduced Gravity,” Alberto E. Minetti, Yuri P. Ivanenko, Germana Cappellini, Nadia Dominici, Francesco Lacquaniti, PLoS ONE, vol. 7, no. 7, 2012, e37300.
REFERENCE: “Plant Biochemistry: An Onion Enzyme that Makes the Eyes Water,” S. Imai, N. Tsuge, M. Tomotake, Y. Nagatome, H. Sawada, T. Nagata and H. Kumagai, Nature, vol. 419, no. 6908, October 2002, p. 685.
REFERENCE: “Human Digestive Effects on a Micromammalian Skeleton,” Peter W. Stahl and Brian D. Crandall, Journal of Archaeological Science, vol. 22, November 1995, pp. 789–97.
Alexander Lukashenko, president of Belarus, for making it illegal to applaud in public, AND to the Belarus State Police, for arresting a one-armed man for applauding.
REFERENCE: “Are Cows More Likely to Lie Down the Longer They Stand?” Bert J. Tolkamp, Marie J. Haskell, Fritha M. Langford, David J. Roberts, Colin A. Morgan, Applied Animal Behaviour Science, vol. 124, nos. 1-2, 2010, pp. 1–10.
REFERENCE: “Surgical Management of an Epidemic of Penile Amputations in Siam,” by Kasian Bhanganada, Tu Chayavatana, Chumporn Pongnumkul, Anunt Tonmukayakul, Piyasakol Sakolsatayadorn, Krit Komaratal, and Henry Wilde, American Journal of Surgery, 1983, no. 146, pp. 376-382.
In the words of the wonderful Marc Abrahams, master of ceremonies and editor of “Annals of Improbable Research,” “If you didn’t win an Ig Nobel Prize tonight — and especially if you did — better luck next year.”

I will be writing individual posts for all winners over the next few days!! Look forward tomorrow to more from the IgNobel Prizes!!!

About the Author: Scicurious is a PhD in Physiology, and is currently a postdoc in biomedical research. She loves the brain. And so should you. Follow on Twitter @Scicurious.

The views expressed are those of the author and are not necessarily those of Scientific American.

Thursday, September 12, 2013

A Randomized Controlled Trial of Internal Family Systems-based Psychotherapy for Rheumatoid Arthritis

In a first-of-its-kind "Proof-of-Concept" study, a group of therapists (including IFS founder Richard Schwartz) implemented Internal Family Systems therapy with people who have rheumatoid arthritis. Participants (N=39, 40 controls) were assessed every three months for the length of the study (9 months) and then one year later. They were assessed for self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain, and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory).

The results demonstrated post-treatment improvements for the IFS group (more than the control group) in overall pain [mean treatment effects –14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Post-treatment improvements were still present one year later in self-assessed joint pain [–0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [–3.2 (5.0); p =0.01].

These are promising results that demonstrate a psychotherapeutic intervention for auto-immune disorders may be ad effective (or more so) than pharmacological interventions, which tend to have serious and somethings disastrous side effects.

The article is being offered Open Access by the Journal of Rheumatology.

Full Citation:
Shadick, NA, Sowell, NF, Frits, ML, Hoffman, SM, et al. (2013, Aug 15). A Randomized Controlled Trial of an Internal Family Systems-based Psychotherapeutic Intervention on Outcomes in Rheumatoid Arthritis: A Proof-of-Concept Study. Journal of Rheumatology, 40(9), 11 pgs. doi:10.3899/jrheum.121465 Clinical identifier: NCT00869349. 

A Randomized Controlled Trial of an Internal Family Systems-based Psychotherapeutic Intervention on Outcomes in Rheumatoid Arthritis: A Proof-of-Concept Study

Nancy A. Shadick, Nancy F. Sowell, Michelle L. Frits, Suzanne M. Hoffman, Shelley A. Hartz, Fran D. Booth, Martha Sweezy, Patricia R. Rogers, Rina L. Dubin, Joan C. Atkinson, Amy L. Friedman, Fernando Augusto, Christine K. Iannaccone, Anne H. Fossel, Gillian Quinn, Jing Cui, Elena Losina, and Richard C. Schwartz 



To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS)
psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status.


Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end.


Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group  occurred in overall pain [mean treatment effects –14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [–0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [–3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity.


An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted.

Despite effective pharmacotherapy, many individuals with rheumatoid arthritis (RA) suffer ongoing pain and disability. Living with RA can lead to depression, anxiety, isolation, an overall impaired quality of life [1,2], and increased healthcare resource use [3]. Psychotherapeutic interventions that improve disease activity, pain-related symptoms, and psychological function would be helpful to patients living with this disease.
A number of psychobehavioral interventions have been shown to be effective in improving coping efficacy and other outcomes in patients with RA [4-11]. Cognitive behavioral interventions, in particular, have reduced pain, joint inflammation, physical disability, and depression [5,6,9,10]. The improvements are variable according to the type of intervention, tend to be most effective in newly diagnosed patients, and have limited sustainability [6,9]. For example, effect sizes (ES) for pain and disability in 2 metaanalyses of psychological interventions for RA were modest [12,13]. Also, joint inflammation and swelling were reduced by several interventions, but these results were mostly seen in patients with illness of shorter duration [13]. In a Cochrane review assessing the effectiveness of educational programs for RA, there were positive effects on disability, joint counts, patient global assessments, psychological status, and depression, but the improvements were short-lived [14]. A sustainable intervention that affects disease activity in individuals with longer-term illness could improve patients’ lives. 
The Internal Family Systems (IFS) model is a rapidly emerging individual psychotherapeutic modality developed by Schwartz [15] that teaches patients to attend to and interact with their internal experience mindfully. The model actively recruits self-compassion toward an individual’s parts, conceptualized as subpersonalities that are manifested by strong feelings, judgments, or physical sensations. By fostering an internal dialogue with polarized thinking, IFS reduces emotional intensity and dysregulation; elements that have been shown to increase pain perception [16] and disease activity in RA [4,17]. IFS also uses nonjudgmental noticing and active mindfulness.  Mindfulness-based interventions have been helpful in a number of painful conditions including RA [4,7,18]. To date, more than 2200 therapists worldwide have been trained in the IFS modality [19]. This technique is increasingly being used as adjunctive therapy for certain medical conditions, with anecdotal benefit reported in migraines, back pain, and multiple sclerosis. To our knowledge, our study is the first to evaluate the IFS model’s feasibility, acceptability, and potential efficacy in a randomized trial.

Upaya Zen Podcasts - Cheri Maples: Balancing Equanimity and Compassion in Engaged Practice (08-14-2013)

From Upaya Zen Center, this is a nice teaching from Cheri Maples, a dharma teachert ordained by Zen Master Thich Nhat Hanh. Here is a bit from the introduction to this teacher:
Compassion contains elements of patience, receptivity, awareness, forgiveness, and radical honesty, all of which Cheri discusses in her talk. Cheri defines equanimity as the “ability to be equally near all things.” Compassion involves our tender responsiveness to suffering, our open heart, which can burn if not checked by the cool spaciousness of equanimity. Through developing equanimity, we learn to relax in the midst of suffering.
Difficult work - and a very clear teaching that is useful for a lot of us.

Cheri Maples: 08-14-2013: Balancing Equanimity and Compassion in Engaged Practice

Speaker: Cheri Maples
Recorded: Wednesday Aug 14, 2013

Episode Description: In this wide-ranging and personal talk, Cheri discusses the crucial balance we need to cultivate between compassion and equanimity in our work in the world. Compassion is difficult to define because it incorporates so much. Compassion contains elements of patience, receptivity, awareness, forgiveness, and radical honesty, all of which Cheri discusses in her talk. Cheri defines equanimity as the “ability to be equally near all things.” Compassion involves our tender responsiveness to suffering, our open heart, which can burn if not checked by the cool spaciousness of equanimity. Through developing equanimity, we learn to relax in the midst of suffering. We learn to “withdraw our insistence that the present moment be something other than it is.” In the end, through balancing compassion and equanimity, we become exquisitely sensitive to suffering without getting lost or overwhelmed by it. We learn to respond to life from a place of calm openness.

Cheri Maples is a dharma teacher, keynote speaker, and organizational consultant and trainer. In 2008 she was ordained a dharma teacher by Zen Master Thich Nhat Hanh, her long-time spiritual teacher.

For 25 years Cheri worked in the criminal justice system, as an Assistant Attorney General in the Wisconsin Department of Justice, head of Probation and Parole for the Wisconsin Department of Corrections, and as a police officer with the City of Madison Police Department, earning the rank of Captain of Personnel and Training.

Cheri has been an active community organizer, working in neighborhood centers, deferred prosecution programs, and as the first Director of the Wisconsin Coalition Against Domestic Violence. As Past President of the Dane County Timebank, Cheri was instrumental in creating its justice projects – the Youth Court, which is based on a prevention and restorative justice model; and the Prison Project, a prison education and reintegration initiative supported by multiple community groups.

She has incorporated all of these experiences into her mindfulness practice. Cheri’s interest in criminal justice professionals comes from learning that peace in one’s oown heart is a prerequisite to providing true justice and compassion to others. Her initial focus was on translating the language and practice of mindfulness into an understandable framework for criminal justice professionals. Cheri’s work has evolved to include other helping professionals – health-care workers, teachers, and employees of social service agencies – who must also manage the emotional effects of their work, while maintaining an open heart and healthy boundaries.

Cheri holds a J.D. and a M.S.S.W. from University of Wisconsin-Madison and is currently a licensed attorney and licensed clinical social worker in the state of Wisconsin.


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Mindless: The New Neuro-Skeptics by Adam Gopnik

Over at The New Yorker, Adam Gopnik takes on the new crop of neuroskeptics - those who cast doubt on the media's (and science's) frenzy to expound on all things neuroscience with a tone of certainty, as though we know something definitive. Often, at best, we get correlations, not cause and effect.
Writers on the brain and the mind tend to divide into Spocks and Kirks, either embracing the idea that consciousness can be located in a web of brain tissue or debunking it. For the past decade, at least, the Spocks have been running the Enterprise: there are books on your brain and music, books on your brain and storytelling, books that tell you why your brain makes you want to join the Army, and books that explain why you wish that Bar Refaeli were in the barracks with you. The neurological turn has become what the “cultural” turn was a few decades ago: the all-purpose non-explanation explanation of everything.
Good article from a non-science guy.

~ Adam Gopnik has been writing for The New Yorker since 1986. During his tenure at the magazine, he has written fiction and humor pieces, book reviews, Profiles, reporting pieces, and more than a hundred stories for The Talk of the Town and Comment.


The new neuro-skeptics

by Adam Gopnik September 9, 2013
Neuroscience can often answer the obvious questions but rarely the interesting ones. Illustration by Leo Espinosa.
Neuroscience can often answer the obvious questions but rarely the interesting ones. Illustration by Leo Espinosa. 
Good myths turn on simple pairs— God and Lucifer, Sun and Moon, Jerry and George—and so an author who makes a vital duo is rewarded with a long-lived audience. No one in 1900 would have thought it possible that a century later more people would read Conan Doyle’s Holmes and Watson stories than anything of George Meredith’s, but we do. And so Gene Roddenberry’s “Star Trek,” despite the silly plots and the cardboard-seeming sets, persists in its many versions because it captures a deep and abiding divide. Mr. Spock speaks for the rational, analytic self who assumes that the mind is a mechanism and that everything it does is logical, Captain Kirk for the belief that what governs our life is not only irrational but inexplicable, and the better for being so. The division has had new energy in our time: we care most about a person who is like a thinking machine at a moment when we have begun to have machines that think. Captain Kirk, meanwhile, is not only a Romantic, like so many other heroes, but a Romantic on a starship in a vacuum in deep space. When your entire body is every day dissolved, reënergized, and sent down to a new planet, and you still believe in the ineffable human spirit, you have really earned the right to be a soul man.

Writers on the brain and the mind tend to divide into Spocks and Kirks, either embracing the idea that consciousness can be located in a web of brain tissue or debunking it. For the past decade, at least, the Spocks have been running the Enterprise: there are books on your brain and music, books on your brain and storytelling, books that tell you why your brain makes you want to join the Army, and books that explain why you wish that Bar Refaeli were in the barracks with you. The neurological turn has become what the “cultural” turn was a few decades ago: the all-purpose non-explanation explanation of everything. Thirty years ago, you could feel loftily significant by attaching the word “culture” to anything you wanted to inspect: we didn’t live in a violent country, we lived in a “culture of violence”; we didn’t have sharp political differences, we lived in a “culture of complaint”; and so on. In those days, Time, taking up the American pursuit of pleasure, praised Christopher Lasch’s “The Culture of Narcissism”; now Time has a cover story on happiness and asks whether we are “hardwired” to pursue it.

Myths depend on balance, on preserving their eternal twoness, and so we have on our hands a sudden and severe Kirkist backlash. A series of new books all present watch-and-ward arguments designed to show that brain science promises much and delivers little. They include “A Skeptic’s Guide to the Mind” (St. Martin’s), by Robert A. Burton; “Brainwashed: The Seductive Appeal of Mindless Neuro-Science” (Basic), by Sally Satel and Scott O. Lilienfeld; and “Neuro: The New Brain Sciences and the Management of the Mind” (Princeton), by a pair of cognitive scientists, Nikolas Rose and Joelle M. Abi-Rached.

“Bumpology” is what the skeptical wit Sydney Smith, writing in the eighteen-twenties, called phrenology, the belief that the shape of your skull was a map of your mind. His contemporary heirs rehearse, a little mordantly, failed bits of Bumpology that indeed seem more like phrenology than like real psychology. There was the left-right brain split, which insisted on a far neater break within our heads (Spock bits to the left, Kirk bits to the right) than is now believed to exist. The skeptics revisit the literature on “mirror neurons,” which become excited in the frontal lobes of macaque monkeys when the monkeys imitate researchers, and have been used to explain the origins of human empathy and sociability. There’s no proof that social-minded Homo sapiens has mirror neurons, while the monkeys who certainly do are not particularly social. (And, if those neurons are standard issue, then they can’t be very explanatory of what we mean by empathy: Bernie Madoff would have as many as Nelson Mandela.)

It turns out, in any case, that it’s very rare for any mental activity to be situated tidily in one network of neurons, much less one bit of the brain. When you think you’ve located a function in one part of the brain, you will soon find that it has skipped town, like a bail jumper. And all of the neuro-skeptics argue for the plasticity of our neural networks. We learn and shape our neurology as much as we inherit it. Our selves shape our brains at least as much as our brains our selves.

Each author, though, has a polemical project, something to put in place of mere Bumpology. (People who write books on indoor plumbing seldom feel obliged to rival Vitruvius as theorists of architecture, but it seems that no one can write about one neuron without explaining all thought.) “Brainwashed” is nervously libertarian; Satel is a scholar at the American Enterprise Institute, and she and Lilienfeld are worried that neuroscience will shift wrongdoing from the responsible individual to his irresponsible brain, allowing crooks to cite neuroscience in order to get away with crimes. This concern seems overwrought, copping a plea via neuroscience not being a significant social problem. Burton, a retired medical neurologist, seems anxious to prove himself a philosopher, and races through a series of arguments about free will and determinism to conclude that neuroscience doesn’t yet know enough and never will. Minds give us the illusion of existing as fixed, orderly causal devices, when in fact they aren’t. Looking at our minds with our minds is like writing a book about hallucinations while on LSD: you can’t tell the perceptual evidence from your own inner state. “The mind is and will always be a mystery,” Burton insists. Maybe so, and yet we’re perfectly capable of probing flawed equipment with flawed equipment: we know that our eyes have blind spots, even as we look at the evidence with them, and we understand all about the dog whistles we can’t hear. Since in the past twenty-five years alone we’ve learned a tremendous amount about minds, it’s hard to share the extent of his skepticism. Psychology is an imperfect science, but it’s a science.

In “Neuro,” Rose and Abi-Rached see the real problem: neuroscience can often answer the obvious questions but rarely the interesting ones. It can tell us how our minds are made to hear music, and how groups of notes provoke neural connections, but not why Mozart is more profound than Manilow. Courageously, they take on, and dismiss, the famous experiments by Benjamin Libet that seem to undermine the idea of free will. For a muscle movement, Libet showed, the brain begins “firing”—choosing, let’s say, the left joystick rather than the right—milliseconds before the subject knows any choice has been made, so that by the time we think we’re making a choice the brain has already made it. Rose and Abi-Rached are persuasively skeptical that “this tells us anything about the exercise of human will in any of the naturally occurring situations where individuals believe they have made a conscious choice—to take a holiday, choose a restaurant, apply for a job.” What we mean by “free will” in human social practice is just a different thing from what we might mean by it in a narrower neurological sense. We can’t find a disproof of free will in the indifference of our neurons, any more than we can find proof of it in the indeterminacy of the atoms they’re made of.

A core objection is that neuroscientific “explanations” of behavior often simply re-state what’s already obvious. Neuro-enthusiasts are always declaring that an MRI of the brain in action demonstrates that some mental state is not just happening but is really, truly, is-so happening. We’ll be informed, say, that when a teen-age boy leafs through the Sports Illustrated swimsuit issue areas in his brain associated with sexual desire light up. Yet asserting that an emotion is really real because you can somehow see it happening in the brain adds nothing to our understanding. Any thought, from Kiss the baby! to Kill the Jews!, must have some route around the brain. If you couldn’t locate the emotion, or watch it light up in your brain, you’d still be feeling it. Just because you can’t see it doesn’t mean you don’t have it. Satel and Lilienfeld like the term “neuroredundancy” to “denote things we already knew without brain scanning,” mockingly citing a researcher who insists that “brain imaging tells us that post-traumatic stress disorder (PTSD) is a ‘real disorder.’ ” The brain scan, like the word “wired,” adds a false gloss of scientific certainty to what we already thought. As with the old invocation of “culture,” it’s intended simply as an intensifier of the obvious.

Phrenology, the original Bumpology, at least had the virtue of getting people to think about “cortical location,” imagining, for the first time, that the brain might indeed be mapped into areas. Bumpology brought a material order, however factitious, to a metaphysical subject. In the same way, even the neuro-skeptics seem to agree that modern Bumpology remains an important corrective to radical anti-Bumpology: to the kind of thinking that insists that brains don’t count at all and cultures construct everything; that, given the right circumstances, there could be a human group with six or seven distinct genders, each with its own sexuality; that there is a possible human society in which very old people would be regarded as attractive and nubile eighteen-year-olds not; and still another where adolescent children would be noted for their rigorous desire to finish recently commenced tasks. How impressive you find modern pop Bumpology depends in part on whether you believe that there are a lot of people who still think like that.

For all the exasperations of neurotautology, there’s a basic, arresting truth to neo-Bumpology. In a new, belligerently pro-neuro book, “The Anatomy of Violence: The Biological Roots of Crime” (Pantheon), Adrian Raine, a psychology professor at the University of Pennsylvania, discusses a well-studied case in which the stepfather of an adolescent girl, with no history of pedophilia, began to obsess over child pornography and then to molest his stepdaughter. He was arrested, arraigned, and convicted. Then it emerged that he had a tumor, pressing on the piece of the brain associated with social and sexual inhibitions. When it was removed, the wayward desires vanished. Months of normality ensued, until the tumor began to grow back and, with it, the urges.

Now, there probably is no precise connection between the bit of the brain the tumor pressed on and child lust. The same bit of meat-matter pressing on the same bit of brain in some other head might have produced some other transgression—in the head of a Lubavitcher, say, a mad desire to eat prosciutto. But it would still be true that what we think of as traditionally deep matters of guilt and temptation and taboo, the material of Sophocles and Freud, can be flicked on and off just by physical pressure. You have to respect the power of the meat to change the morals so neatly.

In one sense, this is more neuro-redundancy. Charting a path between these two truths is the philosopher Patricia S. Churchland’s project in “Touching a Nerve: The Self as Brain” (Norton), a limited defense of the centrality of neuro. She is rightly contemptuous of the invocation of “scientism” to dismiss the importance of neuroscience to philosophy, seeing that resistance as identical to the Inquisition’s resistance to Galileo, or the seventeenth century’s to Harvey’s discovery of the pumping heart:
This is the familiar strategy of let’s pretend. Let’s believe what we prefer to believe. But like the rejection of the discovery that Earth revolves around the sun, the let’s pretend strategy regarding the heart could not endure very long. . . . Students reading the history of this period may be as dumbfounded regarding our resistance to brain science as we are now regarding the seventeenth-century resistance to the discovery that the heart is a meat pump.
Humanism not only has survived each of these sequential demystifications; they have made it stronger by demonstrating the power of rational inquiry on which humanism depends. Every time the world becomes less mysterious, nature becomes less frightening, and the power of the mind to grasp reality more sure. A constant reduction of mystery to matter, a belief that we can name natural rules we didn’t make—that isn’t scientism. That’s science.

Yet Churchland also makes beautifully clear how complex and contingent the simplest brain business is. She discusses whether the hormone testosterone makes men angry. The answer even to that off-on question is anything but straightforward. Testosterone counts for a lot in making men mad, but so does the “stress” hormone cortisol, along with the “neuromodulator” serotonin, which affects whether the aggression is impulsive or premeditated, and the balance between all these things is affected by “other hormones, other neuromodulators, age and environment.”

So this question, like any other about neurology, turns out to be both simply mechanical and monstrously complex. Yes, a hormone does wash through men’s brains and makes them get mad. But there’s a lot more turning on than just the hormone. For a better analogy to the way your neurons and brain chemistry run your mind, you might think about the way the light switch runs the lights in your living room. It’s true that the light switch in the corner turns the lights on in the living room. Nor is that a trivial observation. How the light switch gets wired to the bulb, how the bulb got engineered to be luminous—all that is an almost miraculously complex consequence of human ingenuity. But at the same time the light switch on the living-room wall is merely the last stage in a long line of complex events that involve waterfalls and hydropower and surge protectors and thousands of miles of cables and power grids. To say the light switch turns on the living-room light is both true—vitally true, if you don’t want to bang your shins on the sofa sneaking home in the middle of the night—and wildly misleading.

It’s perfectly possible, in other words, to have an explanation that is at once trivial and profound, depending on what kind of question you’re asking. The strength of neuroscience, Churchland suggests, lies not so much in what it explains as in the older explanations it dissolves. She gives a lovely example of the panic that we feel in dreams when our legs refuse to move as we flee the monster. This turns out to be a straightforward neurological phenomenon: when we’re asleep, we turn off our motor controls, but when we dream we still send out signals to them. We really are trying to run, and can’t. If you feel this, and also have the not infrequent problem of being unable to distinguish waking and dreaming states, you might think that you have been paralyzed and kidnapped by aliens.

There are no aliens; there is not even a Freudian wave of guilt driving the monster. It’s just those neuromotor neurons, making the earth sticky. The best thing for people who have recurrent nightmares of this kind is to get more REM rest. “Get more sleep,” Churchland remarks. “It works.” Neurology should provide us not with sudden explanatory power but with a sense of relief from either taking too much responsibility for, or being too passive about, what happens to us. Autism is a wiring problem, not a result of “refrigerator mothers.” Schizophrenia isn’t curable yet, but it looks more likely to be cured by getting the brain chemistry right than by finding out what traumatized Gregory Peck in his childhood. Neuroscience can’t rob us of responsibility for our actions, but it can relieve us of guilt for simply being human. We are in better shape in our mental breakdowns if we understand the brain breakdowns that help cause them. This is a point that Satel and Lilienfeld, in their eagerness to support a libertarian view of the self as a free chooser, get wrong. They observe of one “brilliant and tormented” alcoholic that she, not her heavy drinking, was responsible for her problems. But, if we could treat the brain circuitry that processes the heavy drinking, we might very well leave her just as brilliant and tormented as ever, only not a drunk. (A Band-Aid, as every parent knows, is an excellent cure whenever it’s possible to use one.)
The really curious thing about minds and brains is that the truth about them lies not somewhere in the middle but simultaneously on both extremes. We know already that the wet bits of the brain change the moods of the mind: that’s why a lot of champagne gets sold on Valentine’s Day. On the other hand, if the mind were not a high-level symbol-managing device, flower sales would not rise on Valentine’s Day, too. Philosophy may someday dissolve into psychology and psychology into neurology, but since the lesson of neuro is that thoughts change brains as much as brains thoughts, the reduction may not reduce much that matters. As Montaigne wrote, we are always double in ourselves. Or, as they say on the Enterprise, it takes all kinds to run a starship.

Wednesday, September 11, 2013

Which Professions Have The Most Psychopaths? (PsyBlog)

Are you working with a psychopath? Is your occupation more likely or less likely to attract psychopaths? Kevin Dutton, author of Split-Second Persuasion: The Ancient Art and New Science of Changing Minds (2011) and The Wisdom of Psychopaths: What Saints, Spies, and Serial Killers Can Teach Us About Success (2012), is (aside from Robert Hare) one of the better-known authors on psychopathic personalities (in the U.S. we call psychopathy anti-social personality disorder).  

This brief summary of some of the data comes Jeremy Dean, author of PsyBlog.

Which Professions Have The Most Psychopaths?

Are there ‘successful psychopaths’ amongst us?

According to a survey conducted by psychologist Kevin Dutton—called the Great British Psychopath Survey—here are the top 10 professions with the most psychopaths:
  1. CEO
  2. Lawyer
  3. Media (TV/Radio)
  4. Salesperson
  5. Surgeon
  6. Journalist
  7. Police Officer
  8. Clergyperson
  9. Chef
  10. Civil Servant
And here are the professions with the least psychopaths:
  1. Care Aide
  2. Nurse
  3. Therapist (emphasis added by editor)
  4. Craftsperson
  5. Beautician/Stylist
  6. Charity Worker
  7. Teacher
  8. Creative Artist
  9. Doctor
  10. Accountant

Although people tend to think of psychopaths as killers—indeed about 15-25% of people in prison are psychopaths—in fact many people with psychopathic tendencies are not criminals.

Here are some of the traits of psychopaths:
  • Self-confident
  • Cold-hearted
  • Manipulative
  • Fearless
  • Charming
  • Cool under pressure
  • Egocentric
  • Carefree
If you look through the list of professions, then you can see how a few of these traits might be useful.

None of this means that every CEO or lawyer is a psychopath, nor should the suggestion be that having psychopathic tendencies is helpful in any of these jobs (although it may be!).

Rather, there is an overlap between psychopathic personality traits and the types of people who go into those professions.

Successful psychopath?

A few people try to talk up the benefits of psychopathic personality traits, saying that there are such things as ‘successful psychopaths’: people who benefit from being that way.

But many psychologists have questioned whether there really is such a thing as a ‘successful psychopath’.

That’s because research has found that psychopaths generally do worse at the things that are often associated with success: their relationships are worse, they earn less money and do not generally attain high status (research described in Stevens et al., 2012).

Maybe the standard for a ‘successful psychopath’ should be lower. We should simply be amazed that someone with little or no fear response, unlimited confidence and without fellow-feeling can live outside of an institution, let alone become a respected professional.

~ Jeremy Dean is a psychologist and the author of PsyBlog. His latest book is "Making Habits, Breaking Habits: How to Make Changes That Stick". You can follow PsyBlog on Facebook, Twitter and Google+.

Brain Lipids and Mental Health - A Look at Recent Research


The old adage is that we are what we eat. This is nowhere more true than it is in our brains. In essence, the human brain is a 3-pound lump of fat (well, okay, 2 lbs of fat, since only 2/3 of the brain is made of fats).

Here is a little background on how the brain uses lipids (another name for fats) in building its cells (neurons) and cell membranes:
Membranes – the Working Surface of Your Brain is Made from Fatty Acids

The membranes of neurons – the specialized brain cells that communicate with each other – are composed of a thin double-layer of fatty acid molecules. Fatty acids are what dietary fats are composed of. When you digest the fat in your food, it is broken down into fatty acid molecules of various lengths. Your brain then uses these for raw materials to assemble the special types of fat it incorporates into its cell membranes.

Passing through a cell's membrane into its cell's interior are oxygen, glucose (blood sugar), and the micronutrients the cell needs to function. Metabolic waste products must exit, so the cell won't be impaired by its own pollution.

Protective Myelin is 70% Fat

Myelin, the protective sheath that covers communicating neurons, is composed of 30% protein and 70% fat. One of the most common fatty acids in myelin is oleic acid, which is also the most abundant fatty acid in human milk and in our diet.

Monosaturated oleic acid is the main component of olive oil as well as the oils from almonds, pecans, macadamias, peanuts, and avocados.

Myelin fiber

©1998 Dr. Norberto Cysne Coimbra M.Sc., Ph.D., Laboratory of Neuroanatomy and
Neuropsychobiology, Faculty of Medicine of Ribeirão Preto of the University of são Paulo; Neuroscience Art Galleries
Two of the most important fats are Alpha-linolenic acid (ALA), an omega-3 fat, and Linoleic acid (LA), an omega-6 fat.
ALA is the foundation of the "omega-3" family of fatty acids. Food sources of omega-3 ALA include flax seeds, chia seeds, walnuts, sea vegetables, green leafy vegetables, and cold water fish like salmon, sardines, mackerel, and trout.

The second essential fatty acid you need is Linoleic acid (LA). LA is the foundation of the "omega-6" family of fatty acids. Food sources of omega-6 LA include expeller cold-pressed sunflower, safflower, corn, and sesame oils.
Considerable research suggests that an imbalance of omega-3 and omega-6 fatty acids may lead to a variety of mental disorders, including hyperactivity (ADHD), depression, brain allergies, and autism.  A balanced ratio of omega-3 and omega-6 fats is necessary for a healthy brain, which is structurally composed of a 1:1 ratio of omega-6 to omega-3. In the Western diet, however, we are likely to have at least twenty times more omega-6 fats (from factory-farmed meat and dairy) than omega-3 fats–an unhealthy ratio of 20:1. Some estimates suggest the ratio is as bad as 30:1.

If we consume more omega-3-rich fish (and fish oil) and flax seed oil, eat less sugar, and completely avoid trans fatty acids (found in partially-hydrogenated oils, margarine, and shortening, as well as most processed foods), we can begin to correct the imbalance and have a healthier brain.

With all of that as a background, this new study from Frontiers in Cellular Neuroscience examines the current stage of the research regarding the role of lipids in the brain, concluding "there exists realistic evidence to consider that nutritional therapies based on fatty acids can be of benefit to several currently incurable nervous system diseases."

This article has a 4.5 Impact Factor, which is considerable for an Open Access publication - so this article is getting some attention.

Full Citation: 
Hussain G, Schmitt F, Loeffler J-P and Gonzalez de Aguilar J-L. (2013, Sep 9). Fatting the brain: A brief of recent research. Frontiers in Cellular Neuroscience; 7:144. doi: 10.3389/fncel.2013.00144

Fatting the brain: A brief of recent research

Ghulam Hussain [1,2], Florent Schmitt [1,2], Jean-Philippe Loeffler [1,2] and Jose-Luis Gonzalez de Aguilar [1,2]
1. UMR_S 1118, Université de Strasbourg, Strasbourg, France
2. Mécanismes Centraux et Périphériques de la Neurodégénérescence, U1118, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
Fatty acids are of paramount importance to all cells, since they provide energy, function as signaling molecules, and sustain structural integrity of cellular membranes. In the nervous system, where fatty acids are found in huge amounts, they participate in its development and maintenance throughout life. Growing evidence strongly indicates that fatty acids in their own right are also implicated in pathological conditions, including neurodegenerative diseases, mental disorders, stroke, and trauma. In this review, we focus on recent studies that demonstrate the relationships between fatty acids and function and dysfunction of the nervous system. Fatty acids stimulate gene expression and neuronal activity, boost synaptogenesis and neurogenesis, and prevent neuroinflammation and apoptosis. By doing so, they promote brain development, ameliorate cognitive functions, serve as anti-depressants and anti-convulsants, bestow protection against traumatic insults, and enhance repairing processes. On the other hand, unbalance between different fatty acid families or excess of some of them generate deleterious side effects, which limit the translatability of successful results in experimental settings into effective therapeutic strategies for humans. Despite these constraints, there exists realistic evidence to consider that nutritional therapies based on fatty acids can be of benefit to several currently incurable nervous system diseases. 


Fatty acids represent a class of lipids that are crucial components of all mammalian cells. They display a variety of biological functions to maintain vital cellular processes at various levels. Thus, fatty acids provide energy, function as signaling molecules, and sustain structural integrity of cellular membranes. They are of particular importance for the nervous system for two major reasons. First, the nervous system possesses a very high concentration of fatty acids, second only to adipose tissue (Etschmaier et al., 2011). Second, these fatty acids participate actively both in the development of the nervous system during embryonic and early postnatal life, and in its maintenance throughout adulthood and natural aging (Uauy and Dangour, 2006; Rombaldi Bernardi et al., 2012). Along with these actions, currently incurable pathological conditions of the nervous system, including neurodegenerative diseases, mental disorders, stroke, and trauma, involve deregulated contents of fatty acids. It is therefore believed that these changes contribute in their own right by as yet incompletely understood mechanisms to those pathological processes. In consequence, the roles of fatty acids in health and disease of the nervous system have been intensively investigated in the last few decades. In this piece of work, we focus mainly on studies published during the last five years to show the diversity in the fatty acids implicated in function and dysfunction of the nervous system. The detailed mechanisms of action of fatty acids at the molecular level are not treated in this article, since they are the subject of other recently published reviews (Georgiadi and Kersten, 2012; Yamashima, 2012).

Some Aspects of the Biochemistry of Fatty Acids

According to the IUPAC definition, fatty acids are “aliphatic monocarboxylic acids derived from or contained in esterified form in an animal or vegetable fat, oil or wax” (IUPAC, 1997). Naturally occurring fatty acids mostly consist of an unbranched 4–28 carbon chain that is usually composed of an even number of carbon atoms. On the basis of the carbon chain length, fatty acids are classified into short- (less than six carbon atoms), medium- (6–12 carbon atoms), long- (14–22 carbon atoms), and very long chain fatty acids (more than 22 carbon atoms). Fatty acids in which the aliphatic chain is fully composed of single bonds between carbon atoms are named as saturated fatty acids (SFAs), whereas fatty acids with one or more than one carbon–carbon double bond are called unsaturated fatty acids. Based on the number of double bonds, unsaturated fatty acids are further divided into mono-unsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs; Table 1). Long chain SFAs have relatively high melting points that make them to appear solid at room temperature. Therefore, the body possesses a mechanism to introduce double bonds in the carbon chain, which lowers the melting point and permits functioning in a physiological environment. There are four fatty acid desaturases documented in humans that selectively catalyze the introduction of a double bond in different positions of the carbon chain. Δ-9 desaturase, also known as stearoyl-CoA desaturase (SCD), is charged with synthesizing MUFAs, mainly palmitoleic acid (16:1) and oleic acid (18:1), by introducing a double bond between carbon atoms nine and 10 from the carboxylic acid end (Figure 1; Enoch et al., 1976). Δ-4, Δ-5, and Δ-6 desaturases introduce a double bond at carbon positions 4, 5, and 6, respectively, and work cooperatively with elongases, which are responsible for the extension of the aliphatic chain. The combined actions of desaturases and elongases are implicated in the synthesis of PUFAs (Nakamura and Nara, 2004).

FIGURE 1. Biosynthesis of fatty acids. Medium- to long chain SFAs are successively transformed by the action of elongases (E) into palmitic acid (16:0), which is then either elongated to stearic acid (18:0), and other long chain SFAs, or desaturated, together with stearic acid (18:0), by δ9 desaturase to produce de novo MUFAs of the n-7 and n-9 series, such as palmitoleic acid (16:1) and oleic acid (18:1). In the case of PUFAs, δ6 and δ5 desaturases work cooperatively with elongases to introduce double bonds and extend the aliphatic chain in a successive manner, from ALA (18:3 n-3) to EPA (20:5 n-3) in the n-3 series, and from LA (18:2 n-6) to AA (20:4 n-6) in the n-6 series. Afterward, these end products are further elongated, desaturated, and submitted to peroxisomal β-oxidation (all three steps indicated by OX) to yield DHA (22:6 n-3) and docosapentaenoic acid (22:5 n-6), respectively. Finally, AA (20:4 n-6) is the precursor of potent pro-inflammatory eicosanoids. EPA (20:5 n-3) produces less potent (dashed arrow) eicosanoids and, together with DHA (22:6 n-3), gives rise to docosanoids with anti-inflammatory properties (i.e., resolvins and protectins). GLA, γ-linolenic acid; DHGLA, dihomo-γ-linolenic acid.

TABLE 1. Most typical fatty acids.
According to the position of the first double bond from the methyl end of the fatty acid chain, the most important PUFAs for humans can be divided into two families: n-6 and n-3 PUFAs. Linoleic acid (LA, 18:2 n-6) is the parent fatty acid of n-6 PUFAs, which produces principally arachidonic acid (AA, 20:4 n-6), whereas α-linolenic acid (ALA, 18:3 n-3) is the parent fatty acid of n-3 PUFAs, which gives rise mainly to eicosapentaenoic acid (EPA, 20:5 n-3) and subsequently docosahexaenoic acid (DHA, 22:6 n-3; Figure 1). Both LA (18:2 n-6) and ALA (18:3 n-3) cannot be synthesized indigenously by the human body, so that they must be supplied with food, and such fatty acids are termed as essential fatty acids (Ruzickova et al., 2004; Lands, 2012). In spite of the fact that the body is able to metabolize these essential fatty acids, the efficiency of conversion is low. Hence, the availability not only of essential precursors but also of some of their metabolites, such as EPA (20:5 n-3) and DHA (22:6 n-3), greatly depends on dietary support (Brenna et al., 2009). Alternatively, PUFAs can also be made available by enzymatic processing of membrane phospholipids by phospholipases (Lee et al., 2011). Whatever pathway is involved, several PUFAs can be metabolized by cyclo-oxygenases, lipo-oxygenases, or cytochrome P450 mono-oxygenases to produce other compounds with important biological functions. AA (20:4 n-6) and, to a lesser extent, EPA (20:5 n-3) are transformed into potent pro-inflammatory eicosanoids. Additionally, EPA (20:5 n-3) and DHA (22:6 n-3) generate opposing anti-inflammatory docosanoids, including resolvins and protectins such as neuroprotectin-D1 (NPD1; Bazan, 2009; Figure 1).

Evidence of the Importance of Fatty Acids for Health and Disease of the Nervous System

Fatty Acids and Brain Development

Mother’s own resources, via placenta and milk, provide most of the n-3 PUFAs necessary for brain development during fetal and early postnatal life. Due to this high demand of the developing nervous system in the progeny, maternal brain levels of DHA (22:6 n-3) exhaust during pregnancy and lactation period (Chen and Su, 2012). Thus, enhanced provision or adequate supply of n-3 PUFAs at these stages can yield positive effects on offspring brain development. For instance, increased expression of neuron specific enolase, glial fibrillary acidic protein, and myelin basic protein was observed in pups from mice fed on n-3 PUFA enriched diet, administered from two months prior to mouse conception to end of lactation period (Tian et al., 2011). Similarly, postnatal supplementation of ALA (18:3 n-3), the parent precursor of n-3 PUFAs, enhanced cell proliferation and early neuronal differentiation, while its deprivation resulted in increased proportion of apoptosis in the dentate gyrus of unweaned pups. This ameliorating effect was offset by maternal ALA (18:3 n-3) deficiency during gestation period, suggesting that ALA (18:3 n-3) is not only required at postnatal stages but is also essential for fetal brain development (Niculescu et al., 2011). Importantly, such diets given at perinatal stages may have long lasting consequences in the adulthood. Thus, the abundance of n-3 PUFAs in the diet of pregnant females revealed essential for the development of the glutamatergic system and normal behavior performance in the adult offspring (Moreira et al., 2010a). Also, motor coordination was ameliorated in adulthood when rats were fed on DHA (22:6 n-3) and EPA (20:5 n-3) supplementation starting from gestation stage to postnatal age of 90 days (Coluccia et al., 2009). Finally, n-3 PUFA enriched diets also improved reference and working memory in offspring rats when supplied to mother at gestation stage (Chung et al., 2008).

Frequently, the impact of dietary fatty acids depends on a balance between different types. In a study to assess the effects of quality and quantity of several high fat diets, mice were nourished with various concentrations and types of fats mingled with normal chow. It was noticed that these diets not only modified the lipid profile in brain but also altered spatial memory and learning ability of the pups in a different manner (Yu et al., 2010). In another study, when mice were fed on diets supplemented with either SFAs or MUFAs, MUFAs promoted insulin sensitivity and cortical activity while SFAs did not (Sartorius et al., 2012). Lastly, it is noteworthy that the intake of sufficient quantity of MUFAs prevented the age related deletion of mitochondrial DNA in the brain of aged animals (Ochoa et al., 2011).

Fatty Acids and Neurodegenerative Disorders

The altered amounts of different classes of fatty acids in the nervous system may contribute positively or negatively to any given neuropathological process (Table 2). Using APP-C99-transfected COS-7 cells, a cellular model of Alzheimer’s disease-like degeneration, a study was carried out to investigate the class of fatty acids that was thought to influence the production of Aβ peptide, which is a major neuropathological hallmark of disease. It was shown that palmitic acid (16:0), stearic acid (18:0), upstream n-3 PUFAs, and AA (20:4 n-6) triggered higher secretion of Aβ peptide compared to long chain downstream n-3 PUFAs and MUFAs (Amtul et al., 2011a). These findings were corroborated in vivo by using a transgenic mouse model of early-onset Alzheimer’s disease that expresses the double-mutant form of human APP, which is the precursor protein responsible for the synthesis of Aβ peptide. Decreased levels of Aβ peptide and less accumulation in the form of amyloid plaques were observed in the brain of mice nourished with a diet enriched in n-3 PUFAs, mainly DHA (22:6 n-3; Amtul et al., 2011a). Not only extraneously supplied but endogenously synthesized n-3 PUFAs can suppress the synthesis of Aβ peptide and the formation of amyloid plaques. Lebbadi et al. (2011) crossed 3xTg-AD mice, a model of Alzheimer’s disease, with transgenic mice expressing Δ-3 desaturase (Fat-1) from Caenorhabditis elegans, which endogenously converts n-6 PUFAs into n-3 PUFAs. It was observed that the double transgenic 3xTg-AD/Fat-1 mice had increased brain levels of DHA (22:6 n-3) and lower levels of Aβ peptide. Similarly, MUFAs, mainly oleic acid (18:1 n-9), were also shown to inhibit the production of Aβ peptide and amyloid plaques both in vitro and in vivo (Amtul et al., 2011b). In contrast, n-6 PUFAs, such as AA (20:4 n-6), aggravated Alzheimer’s disease neuropathology, by increasing the synthesis of Aβ peptide (Amtul et al., 2012).

TABLE 2. Changes in brain fatty acid composition in pathological conditions.

The results obtained in experimental models of Alzheimer’s disease have been confirmed, at a certain extent, by studies performed on human brain. Thus, decreased levels of PUFAs and MUFAs, particularly DHA (22:6 n-3) and oleic acid (18:1 n-9), respectively, were observed in the brain of Alzheimer’s disease patients (Martïn et al., 2010). However, other studies reported that, although the abundance of DHA (22:6 n-3) varied highly among patients, the mean quantity of this PUFA did not differ significantly when compared to healthy brains (Fraser et al., 2010). This study also showed that levels of stearic acid (18:0) were reduced remarkably in frontal and temporal cortex, while those of oleic acid (18:1 n-9) were increased in both parts; also, levels of palmitic acid (16:0) appeared increased in the parietal cortex (Fraser et al., 2010). These a priori puzzling abnormalities in MUFAs could be a result of alterations in the expression of MUFA synthesizing genes. Thus, levels of MUFAs in hippocampus, frontal cortex and temporal cortex were elevated in Alzheimer’s disease patients, as was the expression of the SCD isomers SCD1, SCD5a, and SCD5b. In addition, the ratio of MUFAs to SFAs, an index of desaturase activity, was reported to be negatively correlated with the degree of cognitive performance (Astarita et al., 2011).

Less is known about the changes of fatty acids in other neurodegenerative conditions. Fabelo et al. (2011) reported that lipid rafts from brain cortices of patients with Parkinson disease displayed significantly decreased levels of n-3 and n-6 PUFAs, particularly DHA (22:6 n-3) and AA (20:4 n-6), respectively, while SFAs, mainly palmitic acid (16:0) and stearic acid (18:0), were noted augmented, as compared to control subjects. In another study, the effects of diets rich in n-3 or n-6 PUFAs were assessed on cuprizone-induced experimental demyelination, an animal model for multiple sclerosis. It was observed that n-3 PUFAs from various sources affected the pathological phenotype differently; for example, a diet containing n-3 PUFAs from salmon ameliorated the behavioral deficits induced by cuprizone, whereas a diet containing n-3 PUFAs from cod affected similarly as n-6 PUFA enriched or control diet did, suggesting that not only the type of PUFA but its origin is also to consider when prescribing a diet based remedy (Torkildsen et al., 2009). Contrasting these findings, other studies did not corroborate the protective effects of n-3 PUFAs against multiple sclerosis and concluded that neither n-3 nor n-6 PUFAs had any effect on disease progression or remedial influence (Wergeland et al., 2012). Moreover, dietary administration of EPA (20:5 n-3) even accelerated disease progression in mice expressing a mutated form of Cu/Zn-superoxide dismutase (SOD1), which is a model of neuromuscular degeneration as caused by amyotrophic lateral sclerosis (Yip et al., 2013).

Fatty Acids and Traumatic Injury to the Nervous System

Several recent studies have provided evidence that n-3 PUFAs can exert protection against neuronal injury triggered by hypoxia or ischemia. In neonates, these fatty acids protected neurons following hypoxia/ischemia by modulating the microglial inflammatory response through inhibition of the nuclear factor-κB (NF-κB) dependent pathway (Zhang et al., 2010). However, it is important to mention that consistent increased intake of n-3 PUFAs can also affect adversely in some cases. In this respect, a diet rich in EPA (20:5 n-3) and DHA (22:6 n-3) enhanced the risk for intracerebral hemorrhagic stroke in rats, and caused oxidative damage to the brain, probably due to the fact that a high PUFA content increased the danger of lipid peroxidation. Alternatively, n-3 PUFA intake was reported to affect blood viscosity, vasoconstriction, platelet aggregation, and blood clotting ultimately leading to hemorrhaging (Park et al., 2009).

There is also evidence that certain fatty acids have the potential to improve the recovery of the injured spinal cord. Hirakawa et al. (2010) reported that trans-2-decenoic acid ethyl ester, a medium-chain fatty acid derivative, increased the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons and at the site of injury in a rat spinal cord injury model. Indeed, the administration of trans-2-decenoic acid ethyl ester ameliorated functional recovery and reduced lesion size in response to injury, by increasing the expression of ERK1/2, brain-derived neurotrophic factor (BDNF), and anti-apoptotic Bcl-2. Similarly, DHA (22:6 n-3) pre-treatment in an acute spinal cord injury model diminished the extent of functional deficits as compared to that observed in the control group, and this protective effect was associated with increased survival of precursor cells, sparing of white matter and axonal preservation (Figueroa et al., 2012; Lim et al., 2013b). In the same way, mice carrying the Fat-1 transgene for boosting endogenous synthesis of n-3 PUFAs showed better outcome after spinal cord injury (Lim et al., 2013a). Finally, in relation to diabetes, it was shown that the augmentation of epoxy-fatty acid resources, as obtained by inhibiting soluble epoxide hydrolase, resulted in a dose dependent anti-allodynic effect on neuropathic pain due to glucose toxicity (Inceoglu et al., 2012).

Fatty Acids and Neurological Disorders

Particular changes in brain fatty acid composition appear to be intimately connected to a series of neurological diseases, as recently reported in several studies. Thus, Conklin et al. (2010) observed a reduction in the quantity of both saturated and unsaturated fatty acids of various types, including n-3 and n-6 PUFAs, in the cingulate cortex of depressive patients. Similar alternations in n-3 PUFAs, including EPA (20:5 n-3) and DHA (22:6 n-3), were also shown by others (Lin et al., 2010). In another study, it was noticed that the altered concentrations of MUFAs and PUFAs were region-specific. In fact, no changes in n-3 and n-6 PUFAs were found in hippocampus and orbitofrontal cortex of patients with depression but concentrations of MUFAs, such as oleic acid (18:1 n-9), and SFAs, such as palmitic acid (16:0), appeared augmented (Hamazaki et al., 2012). A partial confirmation of these findings emerged from another study showing lowered expression of genes involved in PUFA and MUFA synthesis in the frontal cortex of depressed patients (McNamara and Liu, 2011). It is also noteworthy that lifelong n-3 PUFA deficiency perturbed normal endocannabinoid function in prelimbic prefrontal cortex and accumbens, and this effect was related to impaired emotional behavior (Lafourcade et al., 2011). Although less investigated, several studies also detected changes in fatty acids in patients with schizophrenia. A decrease in docosatetraenoic acid (22:4 n-6) was observed in the nuclei of the amygdala of these patients but other PUFAs, including DHA (22:6 n-3) and AA (20:4 n-6), remained unchanged (Hamazaki et al., 2010, 2012). Interestingly, the decrease in total membrane PUFAs found in erythrocytes of young patients with schizophrenia correlated with the degree of demyelination in brain white matter (Peters et al., 2009).

Lastly, several lines of evidence support the anticonvulsant effects of certain fatty acids in animal models of epileptogenesis, and the administration of PUFA enriched diets has been envisaged to treat epileptogenic convulsions. Using the pentylenetetrazol-induced epilepsy rat model, Porta et al. (2009) showed that a PUFA containing diet increased the threshold level for pentylenetetrazol to induce convulsions. A contemporary study confirmed that rats nourished with n-3 PUFAs exhibited greater resistance to pentylenetetrazol-induced seizures (Taha et al., 2009). In the kindling model of epilepsy, intracerebroventricular injection of DHA (22:6 n-3), or its derivative NPD1, limited the progression in the hippocampus of the electrically induced neuronal hyperexcitability characteristic of seizures (Musto et al., 2011). In contrast, other studies did not corroborate these findings, since DHA (22:6 n-3) or EPA (20:5 n-3) showed neither anticonvulsant activity nor protection against pentylenetetrazol-induced seizures (Willis et al., 2009).

Cellular Roles of Fatty Acids in the Nervous System

Actions of Fatty Acids in the Hippocampus

Many recent studies have investigated the implication of fatty acids in learning and memory processes occurring in the hippocampus (Figure 2). In general, n-3 PUFAs were shown to foster neuronal activity and hence counteract memory deficits. It is well known that increased c-Fos expression is an indicator of neuronal activity in response to extracellular signals like growth factors, and it is initiated when neurons fire action potentials. Commonly, the activity of c-Fos decreases as age extends and spatial memory goes off. Provision of n-3 PUFAs restored c-Fos expression in the hippocampus, and enhanced neuronal activity ultimately leading to the amelioration of memory deficits in aged mice (Labrousse et al., 2012). Dietary DHA (22:6 n-3) also enhanced the expression of F-ATPase involved in mitochondrial ATP synthesis in the CA1 region of the hippocampus, whereas its deficiency led to decreased glucose transporter expression and defective glucose transport in the cerebral cortex (Harbeby et al., 2012). The stimulatory action of n-3 PUFAs on gene expression also appears to affect neurotransmission. In fact, recent proteomics studies performed on mouse brain deficient in DHA (22:6 n-3) revealed a loss of synaptic proteins associated with altered synaptic transmission (Sidhu et al., 2011). In contrast, expression of vesicular glutamate transporters 1 and 2, which are implicated in glutamatergic neurotransmission, was increased in response to ALA (18:3 n-3) exposure (Blondeau et al., 2009). Similarly, DHA (22:6 n-3) provision to rats with traumatic brain injury enhanced learning ability, by modulating the expression levels of synapsin-1, cAMP response element-binding protein-1 and calcium/calmodulin-dependent protein kinase-2 in the hippocampus of treated animals (Wu et al., 2008, 2011). DHA (22:6 n-3) also ameliorated spatial memory in rats by increasing the expression of subtypes of endocannabinoid/endovanilloid receptors (Pan et al., 2011). Last, n-3 PUFAs augmented the expression of a series of transcription factors involved in learning and memory, including retinoic acid receptor, retinoic X receptor and peroxisome proliferator-activated receptor (Dyall et al., 2010).

FIGURE 2. Multiple effects of fatty acids in the hippocampus. n-3 and n-6 PUFAs exert a variety of positive actions that promote formation, storage and processing of learning and memory in the hippocampus. In contrast, SFAs display rather negative actions. Green arrows indicate stimulatory effects while orange arrows represent inhibitory effects.
Many positive actions of DHA (22:6 n-3), and likely other n-3 PUFAs, may therefore converge to enhance synaptic transmission, and ameliorate spatial learning and memory (Connor et al., 2012). In a mouse model of systemic lupus erythematosus and Sjögren’s syndrome, which is characterized by behavioral abnormalities, reduced aged hippocampal neurogenesis and loss of long-term potentiation (LTP), the dietary supplementation with n-3 PUFAs corrected LTP at synapses in the medial perforant pathway/dentate gyrus and enhanced the amount of adult-born neurons in the hippocampus (Crupi et al., 2012). Similarly, docosapentaenoic acid (DPA, 22:5 n-3) also ameliorated hippocampal function by attenuating the reduction in LTP in aged brain (Kelly et al., 2011). Finally, in vitro studies showed that treatment of differentiated PC12 cells with EPA (20:5 n-3) resulted in activation of the neuroprotective PI3-kinase/Akt signaling pathway, a mechanism that might account for the increase in LTP observed in vivo following EPA (20:5 n-3) treatment (Wu et al., 2008; Kawashima et al., 2010).

In Alzheimer’s disease, Aβ peptide induces neuronal apoptosis through degradation of the adaptor protein insulin receptor substrate-1 in a c-Jun N-terminal kinase (JNK)-dependent manner. An n-3 PUFA enriched diet prevented the phosphorylation of JNK, and ultimately protected neurons from death in vitro and improved cognitive deficit in vivo (Ma et al., 2009). Also, lower levels of phosphorylated tau protein and improved brain function were observed by crossing 3xTg-AD mice with Fat-1 expressing mice to enhance the endogenous production of n-3 PUFAs (Lebbadi et al., 2011). Nevertheless, it is noteworthy that 12/15-lipo-oxygenase adversely affected Alzheimer’s disease pathology by synthesizing pro-inflammatory and pro-oxidant hydroperoxyacids resulting from the oxidation of PUFAs, so that genetic ablation of this enzyme ameliorated cognitive function (Yang et al., 2010).

Neuroinflammation is one of the distinctive features of aged or diseased brain, as demonstrated by the activation of glial cells and the increase in the expression of a variety of pro-inflammatory factors. In this respect, it was reported that n-3 PUFA provision restored spatial memory loss in aged animals by suppressing pro-inflammatory interleukin-1β and reverting to normal the morphology of microglia and astrocytes in the hippocampus (Labrousse et al., 2012; Park et al., 2012). n-3 PUFAs also yielded protecting effects to neurons by blocking microglia activation in a transgenic mouse model of systemic lupus erythematosus and Sjögren’s syndrome (Crupi et al., 2012). In the same way, DPA (22:5 n-3) inactivated microglia attenuating neuroinflammation and counteracting spatial learning deficit in aged brain (Kelly et al., 2011). Contrary to the protective effects of PUFAs, SFAs stimulated the secretion of pro-inflammatory cytokines and induced apoptosis in astrocytes. Particularly, palmitic acid (16:0), lauric acid (12:0), and stearic acid (18:0) triggered the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 by engaging toll-like receptor-4 (TLR-4). Moreover, palmitic acid (16:0) also activated caspase-3 and modified the Bax/Bcl-2 ratio in these glial cells for apoptotic demise. Interestingly, these pro-inflammatory actions of SFAs could be reverted by n-3 PUFAs like DHA (22:6 n-3; Gupta et al., 2012; Wang et al., 2012).

Another way by which n-3 PUFAs can afford neuroprotection is by preventing apoptosis. The mouse model of infantile neuronal ceroid lipofuscinosis, a neurodegenerative disease caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency, manifests enhanced endoplasmic reticulum- and oxidative stress that lead to apoptotic cell demise. In PPT1-deficient cells from such mice, intervention of n-3 PUFAs attenuated stress and repressed apoptotic death casting a protection to neuronal cells (Kim et al., 2010; Wu et al., 2011). Similarly, differentiated PC12 cells treated with EPA (20:5 n-3) showed lower rates of apoptosis and suppressed activity of the apoptotic effector caspase-3 (Boudrault et al., 2009; Kawashima et al., 2010). Conjugated LA (18:2 n-6) also protected neurons from mitochondrial dysfunction and demise. Treatment of cortical neurons with this fatty acid following excitotoxic glutamate exposure resulted in decreased glutamate-induced loss of mitochondrial function, increased Bcl-2 expression and prolonged neuronal survival (Hunt et al., 2010). In the same manner, administration of fish oil, that is a rich source of n-3 PUFAs, protected hippocampal neurons from diabetic insult by precluding the expression of apoptosis inducing genes in both CA1 region and cultured cells, and by increasing the expression of anti-apoptotic genes, such as Bcl-2 and Bcl-xL (Zhang and Bazan, 2010; Zhao et al., 2012). Together with caspase-3, ceramides, resulting from the hydrolysis of sphingomyelin by sphingomyelinase, are well-known apoptosis inducing factors. Treatment with DPA (22:5 n-3) inactivated sphingomyelinase and caspase-3 in the hippocampus of elderly rats (Kelly et al., 2011). On the other hand, n-3 PUFA withdrawal modulated the phosphorylation of glycogen-synthase kinase-3β and ERK1/2, predisposing more hippocampal neurons to damage in an in vitro oxygen and glucose deprivation model of ischemia (Moreira et al., 2010b). Along with this, a decrease in the release of PUFAs from cell membranes in the rat hippocampus, as a result of reduced phospholipase-A2 activity, caused alterations in membrane fluidity that could account for loss of spatial memory and cognitive impairment in Alzheimer’s disease (Schaeffer et al., 2011). However, the protective effects of n-3 PUFAs under certain conditions seemed to be limited to some of the members of this class of fatty acids. Thus, only DHA (22:6 n-3) offset the expression of AMPA receptors in the membrane of hippocampal neurons and attenuated neurotoxicity leading to improved cognitive function. Other members of the n-3 PUFA family, especially EPA (20:5 n-3), lacked such a protective effect against AMPA-mediated toxicity (Ménard et al., 2009).

Synaptogenesis is one of the mechanisms by which memory process takes place. Hence, the loss of synapses is characteristic of neurodegenerative conditions and aging. For instance, cortical or hippocampal neurons incubated with the neurotoxic prion-derived peptide PrP82–146, and pre-treated with DHA (22:6 n-3) or EPA (20:5 n-3), showed less loss of synaptophysin-1 and reduced accumulation of prion peptide (Bate et al., 2010). ALA (18:3 n-3) also stimulated the expression of genes involved in synaptic function, like VAMP-2, SNAP-25 and synaptophysin-1, that led to improved stability and physiology of synapses (Blondeau et al., 2009). Similarly, the chronic supplementation of n-3 PUFAs yielded anti-depressant effects by increasing the expression of synaptophysin-1 in the hippocampus (Venna et al., 2009). However, another study performed on SH-SY5Y cells reported that DHA (22:6 n-3) did not affect the neurotransmission machinery, as evaluated by the expression of synaptotagmin-1, syntaxin-1A, and synaptobrevin-1, although the release of noradrenaline by these cells was enhanced (Mathieu et al., 2010).

Hippocampal neurogenesis also contributes to learning and memory processes. The mouse model of systemic lupus erythematosus and Sjögren’s syndrome typically exhibits age-dependent reduced hippocampal neurogenesis. Supplementation of diet with n-3 PUFAs to these mice enhanced the density of bromodeoxyuridine (BrdU)- and doublecortin positive cells in the hippocampus, suggesting an ongoing neurogenesis (Crupi et al., 2012). Similar neurogenesis enhancement was also reported in response to ALA (18:3 n-3) treatment (Blondeau et al., 2009). In addition, AA (20:4 n-6) even increased neurogenesis at postnatal stages when administered at gestation period (Maekawa et al., 2009). Several in vitro studies revealed that not only n-3 PUFA precursors, such as EPA (20:5 n-3), but also naturally derived metabolites, including the neurotrophic N-docosahexaenoylethanolamine, stimulated neurogenic differentiation of neural stem cells (Katakura et al., 2013; Rashid et al., 2013). The importance of the stimulatory role of PUFAs for neurogenesis is also illustrated by experiments reporting increased expression of fatty acid binding proteins (FABPs) in the ischemic hippocampus. FABPs are carriers of PUFAs in the cytoplasm, and their expression declines with age in association with reduced synaptic activity and other cellular functions. CA1 and dentate gyrus regions in the hippocampus showed augmented levels of FABP-5 and FABP-7 after ischemia, suggesting elevated transportation of PUFAs in these regions to restore cellular neurophysiology (Liu et al., 2010; Ma et al., 2010). More importantly, at post-ischemic stages, the subgranular zone in the dentate gyrus of the hippocampus, a niche of adult neurogenesis, displayed a concomitant increase in the neuronal expression of FABPs and the fatty acid receptor GPR40, representing compensatory processes of newborn cells (Boneva et al., 2011a,b; Yamashima, 2012). Finally, it is noteworthy that many of the beneficial actions of PUFAs on hippocampal function were associated with an increase in the production of BDNF, which is a member of the neurotrophin family of growth factors involved in supporting growth, differentiation and survival of neurons (Wu et al., 2008, 2011; Blondeau et al., 2009; Venna et al., 2009; Avraham et al., 2011; Vines et al., 2012).

Actions of Fatty Acids in the Hypothalamus

The central regulation of energy balance involves a number of neuronal circuits in the hypothalamus that either exert anorexic actions or stimulate food intake. In this respect, it was recently shown that certain fatty acids could influence the control of energy homeostasis by the hypothalamus. In general, dietary supplementation with fish oil, rich in n-3 PUFAs, normalized several hypothalamic neurochemical systems in food restricted animals (Avraham et al., 2011). However, supplementation of diet with SFAs induced endoplasmic reticulum stress and expression of cytokines via TLR-4 signaling in the hypothalamus, and this effect resulted in resistance to anorexigenic signals (Milanski et al., 2009). At the cellular level, treating hypothalamic mHy-poE-44 cells with palmitic acid (16:0) increased the expression of the orexigenic neuropeptide-Y, suggesting that this fatty acid could enhance food intake (Fick et al., 2011). Moreover, palmitic acid (16:0) faded insulin signaling and enhanced endoplasmic reticulum stress and caspase-3 cleavage in the same cell line, which resulted in apoptosis in a JNK-dependent manner (Mayer and Belsham, 2010). In another study, exposure to palmitic acid (16:0) displayed no effects on insulin resistance and inflammatory process activation but corroborated the stimulation of endoplasmic reticulum stress and apoptosis, along with the activation of mitogen-activated protein kinase (Choi et al., 2010).

Actions of Fatty Acids in the Nigrostriatal Pathway

Growing evidence supports a link between the dietary intake of n-3 PUFAs and the function (or dysfunction) of the nigrostriatal pathway involved in the control of movement (Figure 3). This relationship was particularly investigated in a number of animal models of Parkinson disease, which is a neurodegenerative condition primarily characterized by the loss of dopaminergic neurons connecting the substantia nigra to the striatum. In several recent studies, n-3 PUFAs were shown to be beneficial by reverting disease phenotype. In the MPTP model of Parkinson disease, pre-treatment of mice with n-3 PUFAs bestowed protection by increasing the expression of BDNF and involving its TrkB receptor (Bousquet et al., 2009; Balanzá-Martïnez et al., 2011). In other studies, it was found that exposure to the n-3 PUFA ethyl-eicosapentaenoate derivative lowered the expression of Bax and caspase-3, and enhanced cortical dopamine levels (Bousquet et al., 2008; Meng et al., 2010). Furthermore, n-3 PUFAs also yielded protective influence indirectly, by attenuating inflammation-causing factors. These fatty acids targeted the NFκB signaling pathway in microglia to suppress their over-activated response and hence protect dopaminergic neurons (Boudrault et al., 2009; Zhang et al., 2010; Ji et al., 2012; Zhou et al., 2012).

FIGURE 3. Conflicting effects of n-3 PUFAs in the nigrostriatal pathway. n-3 PUFAs are commonly endowed with a wide range of helpful effects, as illustrated by the protective benefit that these fatty acids offer to dopaminergic neurons in the nigrostriatal tract against apoptotic and pro-inflammatory cues. However, extreme caution should be exercised since these same PUFAs may not provide complete safety to halt degeneration induced by parkinsonian toxins or even trigger adverse effects, which eventually aggravates the extent of the pathological process.
Other findings, however, did not support the beneficial effects of n-3 PUFAs on Parkinson disease. It was reported that treatment with ethyl-eicosapentaenoate, although minimized pro-inflammatory cytokines and yielded positive effects on procedural memory deficit, it was unable to preclude the loss of nigrostriatal dopamine in MPTP mice (Shchepinov et al., 2011; Luchtman et al., 2012). Similarly, the parkinsonian neurotoxin 6-hydroxydopamine caused lesions in the medial forebrain bundle of rats and motor deficits that remained unaffected by fish oil derived n-3 PUFAs (Delattre et al., 2010). A chronic intervention of a DHA (22:6 n-3) containing diet modified neither the number of cortical glial cells nor the expression of α-synuclein, which is typically involved in disease pathogenesis (Muntané et al., 2010). The use of different animal models of Parkinson disease and the different ways of treating these mice to counteract the pathological process may explain the observed discrepancies. In this respect, it is important to mention that some studies indicated even adverse effects of n-3 PUFAs on Parkinson disease pathogenesis. Indeed, the presence of DHA (22:6 n-3) augmented neuritic injury and astrocytosis in mice transgenic for a Parkinson disease causing mutation in human α-synuclein. In addition, DHA (22:6 n-3) triggered oligomerization of α-synuclein, through the activation of retinoic X receptor and peroxisome proliferator-activated receptor-γ2. Interestingly, its withdrawal from diet was found to be beneficial against the deleterious effects caused by it provision (Yakunin et al., 2012). Finally, structural and conformational modifications in α-synuclein leading to pathological aggregation were brought by DHA (22:6 n-3; De Franceschi et al., 2009, 2011; Bousquet et al., 2011).

Actions of Fatty Acids in the Peripheral Nerves

A subset of peripheral sensory neurons expresses transient receptor potential cation channel-A1 (TRPA1), which is involved in pain and neurogenic inflammation. TRPA1 is a target for a variety of noxious and inflammatory irritant substances. In addition, it was found that n-3 PUFAs could act as a ligand for TRPA1 to excite sensory neurons and hence regulate their responses in vivo (Motter and Ahern, 2012). Transient receptor potential vanilloid cation channel-1 (TRPV1), which is another member of the family, is also found mainly in nociceptive neurons of the peripheral nervous system, where they are involved in transmission and modulation of pain. In this respect, it was shown that NPD1, which has anti-inflammatory properties, inhibited TRPV1 currents induced by capsaicin in dorsal root ganglion neurons, and modulated TRPV1/TNF-α-mediated synaptic plasticity in the spinal cord, suggesting a novel analgesic role (Park et al., 2011). The effects of fatty acids on sensory neurons go beyond receptor signaling. Both n-6 and n-3 PUFAs promoted neurite outgrowth in sensory neurons from dorsal root ganglia of embryos but also adult and aged animals (Robson et al., 2010). Enhanced levels of endogenously synthesized n-3 PUFAs also bestowed beneficial effects in various aspects. Thus, dorsal root ganglion neurons from Fat-1 expressing mice exhibited more resistance to hypoxia and mechanical injury as compared to neurons from wild-type littermates. Furthermore, Fat-1 expressing mice showed better functional recovery after sciatic nerve crush. The increased endogenous levels of n-3 PUFAs reduced the expression of the stress sensor activating transcription factor-3 in dorsal root ganglion neurons, and diminished muscle atrophy (Gladman et al., 2012). Similarly, our own studies also reported that the down-regulation of SCD1, which is in charge of the production of MUFAs such as oleic acid (18:1), triggered accelerated motor function recovery after sciatic nerve crush, providing evidence for a new role of this fatty acid desaturase in modulating the restorative potential of the neuromuscular axis (Hussain et al., 2013).

The retina possesses a high concentration of n-3 PUFAs, particularly DHA (22:6 n-3). Many studies have shown that this fatty acid not only has a structural function but also protects visual neurons from trauma and disease. Recently, it was noticed that the retinal dysfunction induced by diabetes could be recovered to some extent by supplementing DHA (22:6 n-3) extraneously. In fact, diabetes resulted in reduced levels of n-3 PUFAs, by affecting n-3 fatty acid desaturase enzymatic activity, so that the provision of a DHA (22:6 n-3) enriched diet prevented dysfunction of rods and ameliorated vision (Yee et al., 2010). Also, n-3 PUFA derived NPD1, together with pigment epithelial-derived growth factor, promoted corneal nerve regeneration in a rat model of surgical injury (Cortina et al., 2010, 2012; Kenchegowda et al., 2013). However, other studies rather obtained contradictory results. Therefore, augmented levels of DHA (22:6 n-3) bestowed no protection against retinal degeneration in mice carrying a disease-causing VPP rhodopsin mutation and expressing Fat-1 (Li et al., 2009, 2010). In the same way, it was also reported that high levels of DHA (22:6 n-3) in the retina could generate oxidative stress, instead of protection, and hence enhance the susceptibility to degeneration (Tanito et al., 2009).


The biological functions of fatty acids have been investigated intensively during these last years, due to their active involvement in the physiology of both central and peripheral nervous system. They promote brain development, ameliorate cognitive functions in normal and diseased conditions, serve as anti-depressants and anti-convulsants, bestow protection against traumatic insults, and elevate repairing processes. At the cellular level, fatty acids stimulate gene expression and neuronal activity, and boost synaptogenesis and neurogenesis while preventing from neuroinflammatory toxicity and apoptosis (Figure 2). Although the demand for fatty acids in a healthy body applies to any of them, it can be said that, in general, excess of SFAs and, to some extent, n-6 PUFAs brings about negative consequences, whereas MUFAs and n-3 PUFAs are endowed with rather beneficial properties. In this respect, the ratio of n-6 to n-3 PUFAs is of special interest. It has been postulated that a relatively constant n-6:n-3 ratio of about 1:1 constituted a major breakthrough in the expansion of gray matter in the cerebral cortex of modern human beings (Bradbury, 2011). In the brain, the preservation of an optimal n-6:n-3 ratio is crucial to the maintenance of the variety of the cellular processes in which PUFAs participate (Luchtman and Song, 2013). During the last century, however, the n-6:n-3 ratio has dramatically increased up to 20–25:1, particularly in Western societies, because of a high consumption of n-6 PUFAs to the detriment of n-3 PUFA intake (Simopoulos, 2011). Once the equilibrium is broken, an excessively high n-6:n-3 ratio would impair normal brain function and, importantly, predispose to disease (Palacios-Pelaez et al., 2010). According to what we have exposed herein, a huge amount of studies have shown the good and the bad side of different fatty acids in many experimental models of trauma and disease. Nevertheless, the diversity in modeling any given physiopathological condition, together with differences in time, dose and type of fatty acid used to counteract the insult, certainly account for a number of conflicting results concerning the nature of the observed effects. In addition, it must be taken into consideration that particular fatty acids are assumed to foster neuroprotection but engender indeed a series of collateral deleterious actions, such as increasing oxidative stress susceptibility or favoring neurodegenerative protein aggregation, which may preclude the use of these fatty acids under certain (pathological) conditions (Figure 3). Finally, it is also noteworthy that, frequently, studies used nutritional approaches consisting in giving a specific fatty acid or its precursor mixed with others and forming part of foods relatively more complex than desired, since they also contain other substances with potential, uncontrolled positive or negative effects. Taken together, these drawbacks limit the translatability of successful results in terms of neuroprotection obtained in animal experiments into effective therapeutic interventions in humans. Numerous epidemiological studies have put fatty acids forward as key factors contributing to neuropathology but, in some cases, discrepant concentrations of fatty acids were reported in the corresponding diseased brain regions (Table 2). Despite these constraints, on the basis of these epidemiological studies and supported by experimental research, there is quite realistic evidence to envisage that nutritional therapies based on fatty acids can be of benefit to several neurodegenerative and neurological diseases, such as age-related macular degeneration, cognitive decline, depression, and some related behavioral disorders (Prior and Galduróz, 2012; Schleicher et al., 2013). More research is needed now for arriving at the final and conclusive result concerning the type of fatty acid, number of double bonds, origin, particular stage and proper concentration to achieve beneficial therapeutic potential against otherwise incurable diseases.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This work was supported by funds from European Community’s Health Seventh Framework Programme under grant agreement No. 259867, and Thierry Latran Foundation to Jean-Philippe Loeffler; and “Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone” to Jose-Luis Gonzalez de Aguilar. Ghulam Hussain is supported by the Higher Education Commission of the Pakistani government and “Association pour la Recherche et le Développement de Moyens de Lutte contre les Maladies Neurodégénératives” (AREMANE). Florent Schmitt is granted by “Association Française contre les Myopathies” and AREMANE. Jose-Luis Gonzalez de Aguilar is recipient of a “Chaire d’Exellence INSERM/Université de Strasbourg.”

References are available at the Frontiers site.