Revisioning Psychiatry: Cultural Phenomenology, Critical Neuroscience, and Global Mental Health

The concept of mental illness in the West is largely shaped by the DSM diagnostic model. The DSM categorization of psychiatric disorders has been useful in driving research, and psychiatric neuroscience has made enormous strides in identifying some of the brain-based factors that contribute to mental disorders such as autism, schizophrenia, and bipolar disorder, as well as suggesting possible drug therapies. Continue reading

What are the Key Questions the Kavli Neuroscience Prize Winners Would Now Like to Address?

See full interviews with Cornelia Bargmann, Winfried Denk, and Ann Graybiel in Nature Reviews Neuroscience (October 2012). 

Cornelia Bargmann (Rockefeller University)

We’re asking whether there might be a logic underlying the incredible diversity of animal behaviours, perhaps at the level of genes and circuits. For example, are there conserved biological systems that organize higher-order behaviours, by analogy to the biological conservation that applies to molecular and cellular processes? Do internal states or emotions like hunger, fear or arousal have a straightforward biological basis in neuroanatomy and neurochemistry, or are they the result of ad hoc assemblies of multiple components? How do new behaviours evolve? Are there certain genes and mechanisms that are predisposed to generate new behavioural variations and, if so, how do they work?

Winfried Denk (Max Planck Institute for Medical Research)

Again, my interest lies in the development of tools that I perceive as being useful for a whole range of questions in neurobiology. Knowing the wiring diagram is ultimately necessary, although not necessarily sufficient, for all of systems (circuit?) neuroscience. More specifically, there are things to finish in the retina, and my laboratory is currently working to finish an inner-plexiform connectome. Then it’s on towards developing a whole-mouse-brain microtome.

Ann Graybiel (MIT)

Thanks to the ingenuity of people inventing new methods for working on the brain, we are in the midst of a revolution in which we have the chance to discover functional circuits in the brain and how they relate to behaviour, and to examine the dynamics of neural signalling at different time scales and in different frequency domains. In the field of basal ganglia research, we are just at the beginning of this adventure; for us, understanding the interactions of these deep-forebrain systems with the neocortex and with other functional systems is a primary goal. There are also many questions about the relationship between neural signalling and behaviour, not the least being the state changes that somehow occur between our doing things with conscious intent and doing things nearly automatically. Of course, in our specific workspace, we would like to understand the compartmental architecture of the striatum in functional terms. We have been guessing for a long time!

 

3×5: Culture, Neuroscience, and Psychiatry Schizophrenia Roundup

Many thanks (seriously) to Nev Jones for sending so many great suggestions my way.

Culture/Environment
1. Variation – among individuals, geographically,  and across cultures – in the incidence, precedence, and course of schizophrenia is more complex than previously suggested by three WHO studies (on a putatively better outcome in “developing” vs. “developed” countries). For example, regional data from the Worldwide-Schizophrenia Outpatient Health Outcomes or W-SOHO study suggest a better clinical outcome but a worse functional outcome in regions other than “North Europe” (See, e.g., Haro et al’s “Cross-national clinical and functional remission rates.”)

Studies also continue to support variation within geographical region, e.g., Kirkbride et al’s PLOS One systematic review, “Incidence of schizophrenia and other psychoses in England, 1950–2009,” which describes, in particular, higher rates among “migrants and their descendants of black Caribbean and black African origin” and among those of “mixed ethnicity,” which the authors suggest may be a possible marker of “third-generation descendants.” Urban birth/upbringing also remains a significant risk factor, “independent of differences in the age, sex and ethnic population structure of different geographical areas, and correlated to a number of socio-environmental factors including ethnic density, social cohesion, social fragmentation, deprivation, and inequality.”

2. Early Adversity: A 3/29/12 meta-analysis published online by Jim van Os et al. supports the link between childhood adversity and risk of psychosis.  “Childhood adversities increase the risk of psychosis: A meta-analysis of patient-control, prospective- and cross-sectional cohort studies.” The addition of cannabis use appears to increase risk even further (Konings et al., 2012). But see also Susser and Widom’s July 2012 critique of such studies, “Still searching for lost truths about the bitter sorrows of childhood.

3. Diagnosis and Social Abandonment: In “Psychosis and the fog of reality,” Vaughan Bell of Mind Hacks has provided pdfs of two articles by journalist Rachel Aviv: “God knows where I am: What should happen when patients reject their diagnosis?” in the 5/30/11 New Yorker and “Which way madness lies: Can psychosis be prevented?” in the 12/10 issue of Harper’s. See also David Dobbs’s post, “What’s it like to be schizophrenic” and Jocelyn Marrow and Tanya Luhrmann’s recent paper for Culture, Medicine, and Psychiatry (CMP) on social abandonment in India and the US. And finally, Schomerus et al’s (2012) bleak conclusion of their meta-analysis that “Increasing public understanding of the biological correlates of mental illness seems not to result in better social acceptance of persons with mental illness.”

4. Cognition/Anthropology of Neuroscience: Elizabeth Bromley, Gail Fox Adams, and John Brekke’s “A video ethnography approach for linking naturalistic behaviors to research constructs of neurocognition in schizophrenia” in The Journal of Neuropsychiatry and Clinical Neuroscience (3/1/12). See also Bromley’s exploration of researchers’ understanding of the concept of “cognition” as it applies to schizophrenia in “The Texture of the Real” (CMP, 2012).

5. First-person Experience: The blog Ruminations on Madness, provides, as always, some much-need insight on philosophy, psychiatry, and first-person experience. In “Excerpts from the journals of E” the author provides us with the fragments of a brilliant philosophy student’s trajectory following his first episode of  psychosis.

The blog itself testifies to the more complex view that “schizophrenia” covers a range of conditions, capacities, and behaviors, that outcomes are as diverse as the people to whom the label is attached, and that living with the disorder offers in itself an important research perspective. The blog is an opportunity for significant advocacy, in regard to which, addressing anthropologists, psychiatrists, psychologists, and others in the mental health field in Berlin last year, Arthur Kleinman said,

We have all failed in a way that our brothers and sisters and cousins in the AIDS community have not failed. If you went back twenty years, you would see that everything I’ve said about the chronically mentally ill you could say about AIDS patients. And in twenty years the situation for AIDS patients has radically changed. There has been enormous efficacy from advocacy in the AIDS field. We have failed in the area of advocacy. And what I want to suggest is that in the future those of who who build your careers here: Advocacy will be part of your careers. Rather than seeing advocacy as a threat to academic life, you’re going to come to see advocacy as central to the new academy in the future.”

Neuroscience

See also Ford & Mathalon’s (2012) review, “Neurobiology of schizophrenia: Search for the elusive correlation with symptoms” in Frontiers.

1. Epigenetics: Steven Hyman, “Target practice: HDAC inhibitors for schizophrenia,” in News and Views / Nature Neuroscience published online 8/28/12 re Kurita et al. on targeting epigenetic changes that occur with the use of antipsychotics.

2. Vulnerability: Jim van Os and Richard Linscott’s introduction to a special issue of Schizophrenia Bulletin,The extended psychosis phenotype – Relationship with schizophrenia and with ultrahigh risk status for psychosis.

3. More Gene x Environment: Book review of The Origins of Schizophrenia, edited by Alan Brown and Paul Patterson. (Reviewed by Michael Owen, MRC Centre for Neuropsychiatric Genetics and Genomics, and Neuroscience and Mental Health Research Institute, Cardiff University.)

4. Schizophrenia and Autism: Kong et al’s 8/23/11 Nature paper, “Rate of de novo mutations and the importance of father’s age to disease risk.

5. Auditory Hallucinations: A series of related papers featured in July 2012 Schizophrenia Bulletin prepared by members of the International Consortium on Hallucination Research [InCoHR] working groups.

Psychiatry/DSM-5

1. DSM-5: Randy Tanon and William Carpenter’s, DSM-5 Status of Psychotic Disorders: 1 Year Prepublication” dd. 4/13/12 in Schizophrenia Bulletin provides a “snapshot of current status of potential changes” in DSM-5 regarding psychotic disorders. The proposed revisions include a “schizophrenia spectrum concept (which would include the attenuated psychosis syndrome listed in Section III – see [4] below). Also, the subtypes of SZ will be dropped in favor of eight or nine possible “dimensional ratings of different psychopathology domains,” including hallucinations, delusions, disorganized speech, abnormal psychomotor behavior, negative symptoms, impaired cognition, depression, and mana. (NB: “Catatonia, formerly a subtype, will now be listed as a “specifier for psychotic disorders, mood disorders, and general medical disorders.”) The authors note that “the issue of how many dimensions are useful, reliably assessed, necessary, and practical remains an open question.”

2. Diagnostic labels: Ruminations on Madness (“In defense of the schizophrenia construct (?)” ) argues that labels can obscure differences between persons and kinds of experiences, but is

less sure … that the advantages of more dimensional or non-label-based approaches outweigh the potential benefits—benefits, specifically, in the domain of identity. Like most sociopolitical minority group labels (Latino or Autistic, for example), “schizophrenic” cuts an arguably over-wide swathe and yet clearly marks something that, for cultural, historical and individual reasons, is shared between individuals and provides a (potentially vital) sense of collective ‘being’ and cohesion. [To make this a little more personal, and to repeat something that I believe I’ve said many times in earlier posts,  I do not think I would be alive today were it not for the deep and sustaining sense of recognition and belonging I found early on in Louis Sass’ brilliant work on schizophrenia.]

3.  Attenuated Psychosis Syndrome (Proposed for Section III of the DSM-5) (Revised April 27, 2012): Because of reliability issues (according to Tanon and Carpenter validity is “fairly established), “this condition is being recommended for further study in Section III, which is the section of the DSM-5 text in which conditions that require further research will be included.”

4. A good prior discussion/debate by Carpenter and Jim van Os, “Should attenuated psychosis syndrome be a DSM-5 diagnosis?” in  Am J Psychiatry 2011, and also a recent review, “A Rose is a Rose is a Rose,” But At-Risk Criteria Differ” by Schultze-Lutter et al. of University Hospital of Child and Adolescence Psychiatry (Bern) and Department of Psychiatry and Psychotherapy (Cologne).

5. William Carpenter’s “The future of schizophrenia pharmacotherapeutics: Not so bleak” in response to Chattaranjan Andrade, Rajiv Radhakrishnan, and Praveen Fernandes, “Psychopharmacology of schizophrenia: The future looks bleak,” in Mens Sana (2012). One question he raises is how reconceptualization of schizophrenia as a multi-dimensional construct will affect drug development?

See also the following (non-psychosis specific):

3×5: Culture, Neuroscience, and Psychiatry Weekly Roundup: Empathy (August 6)

UPDATE: New links from Lori Hogenkamp via Facebook at end of post.

Brief note: I’ve come to realize that empathy (and its putative component processes – mirror neuron networks, affect sharing, mentalizing) brings out almost everything that’s problematic in social neuroscience research: problems of a conceptually vague cover term, problems with extrapolating from animal models (e.g., monkeys don’t imitate); problems with fMRI/ROI, problems with science writing for the public (e.g., this publisher blurb for Marco Iacoboni’s Mirroring People: “From imitation to morality, from learning to addiction, from political affiliations to consumer choices, mirror neurons seem to have properties that are relevant to all these aspects of social cognition”), problems with a too-powerful metaphor (err, the mirror) that’s hard to repack in the box after that last quote :( problems with extrapolating in other ways (see Emily Willingham’s post on what she describes as the “no empathy in autism meme” – as Ian Hacking said, “The history of late 20th century medicine will … also [be] a history of advocacy groups”), etc., etc.

On second thought, there are many positive implications that hover over all this work – for theory of mind, radical embodied cognition, network science approaches to the brain’s structural and functional connectivity  . . .

Many thanks to the Neuroanthropology Interest Group on Facebook for suggestions and Center for Building a Culture of Empathy and Compassion for inspiration! 

Culture

1. “Empathy as cultural process: Insights from the cultural neuroscience of empathy” by Bobby Cheon, Vani Mathur, and Joan Chiao (WCPRR, 2010).

2. Via Eugene Raikhel (Neuroanthropology Interest Group): See the just-published special issue of “Science in Context” on “The Varieties of Empathy in Science, Art, and History.” It includes an article by Shaun Gallagher (“Empathy, Simulation, and Narrative“), one by Allan Young (“The Social Brain and the Myth of Empathy“) and a number of others.

3. Roundup on “Anthropology, Teaching, and Empathy” in early 2012 by Jason Antrosio of Anthropology Report and a related post by Rex on Savage Minds, “Empathy, or, seeing from within.”

4. Hollan, D. C., & Throop, C. J. (2011). The anthropology of empathy: Experiencing the lives of others in Pacific societies. New York: Berghahn.

5. Blog post by Emily Willingham (Dec 2011): “Autistic people: Insensitive to social reputation, sure, but what about empathy?” on the website Autism and Empathy.

Neuroscience

1. Bernhardt, B. C., & Singer, T. (2012). The neural basis of empathy. Annual Review of Neuroscience, 35, 1–23.

2. Decety, J. Norman, G. J., Berntson, G. G., & Cacioppo, J. T. (2012). A neurobehavioral evolutionary perspective on the mechanisms underlying empathy. Progress in Neurobiology, 98(1), 38–48. See also, Decety, J. (2011b). The neuroevolution of empathyAnnals of the New York Academy of Sciences, 1231, 35–45.

3. Zaki, J., & Ochsner, K. N. (2012). The neuroscience of empathy: Progress, pitfalls and promiseNature Neuroscience: Focus on Social Neuroscience [Perspective], 15(5), 675–680.

4. Decety, J. (2011a). Dissecting the neural mechanisms mediating empathy. Emotion Review, 3,92–108. See also, Decety, J. (2010). To what extent is the experience of empathy mediated by shared neural circuits? Emotion Review, 2(3), 204–207.

5. “Empathy and pro-social behavior in rats” Inbal Ben-Ami Bartal, Jean Decety, and Peggy Mason. See also 2011 Science paper by same group.

 

Psychiatry

1. Cheng, Y., Hung, A., & Decety, J. (2012). Dissociation between affective sharing and emotion understanding in juvenile psychopathsDevelopment and Psychopathology, 24, 623–636.

[From Abstract]. . . youth with HCU [high callous-unemotional traits] exhibit atypical neural dynamics of pain empathy processing in the early stage of affective arousal, which is coupled with their relative insensitivity to actual pain. Their capacity to understand intentionality, however, was not affected. Such uncoupling between affective arousal and emotion understanding may contribute to instigating aggressive behaviors in juvenile psychopaths.

[From the paper] It is  important that the affective arousal deficit . . . cannot be explained by a lack of sensorimotor resonance [i.e., mirror neurons], as measured by mu wave suppression [this was an ERP study], which was present in a ll participants. This finding indicates that affective arousal is not mediated by the mirror neuron system.

2. “Empathy and alterity in cultural psychiatry” by Laurence Kirmayer (Ethos, 2008).

3. “Empathy and otherness: Humanistic and phenomenological approaches to psychotherapy of severe mental illness” by Elizabeth Pienkos and Louis Sass (Pragmatic Case Studies in Psychotherapy, 2012).

4. Empathy in mental illness edited by Tom Farrow and Peter Woodruff (CUP, 2007).

5. “Zero degrees of empathy” by Simon Baron-Cohen, covering disorders of empathy (borderline personality disorder, psychopathy, narcissism) and genetic, endocrine, and social influences.

UPDATE:

3×5: Culture, Neuroscience, and Psychiatry Weekly Roundup (July 30)

Culture

1. Ginger Campbell (Brain Science Podcast) interviews UC Berkeley biological anthropologist Terrence Deacon about his book Incomplete Nature: How Mind Emerged from Matterwhich was reviewed by Raymond Tallis is WSJ last November. But see also “Stolen Ideas? Or Great Minds Thinking Alike?” by Tom Bartlett in the Chronicle of Higher Education, which discusses the book’s overlap with works by Alicia Juarrero (Dynamics in Action) and (our favorite) Evan Thompson (Mind in Life). (The FPR interviewed Evan Thompson last year.)

2. Neuroanthropology’s Daniel Lende’s post “Inside the Minds of Mass Killers” is a must-read.

3. Another terrific post on Aurora, which Daniel’s links to, is philosopher Evan Selinger’s “The Philosophy of the Technology of the Gun,” which appeared in the Atlantic.

I think Daniel and Evan throw some much-need light on the social, political, and material environment (including cultural scripts and how technology, to use a thread-bare metaphor, “gets under the skin”) from which acts of violence emerge and, in addition,  the importance of not “lightly equat[ing] mental illness and violence.”

But a commentator (“N” – and I’m assuming “N” is the same author whose brilliant work is featured in a post by David Dobbs) questioned “the divide” Daniel seemed to be drawing “between the cultural & sociopolitical and ‘mental illness,’” as well as that between violence and certain forms of psychosis. A thoughtful back-and-forth with “N” and other commentators followed. I highly recommend reading the whole thing!

4. Speaking of Daniel, Neuroanthropology’s Facebook page is a lot of fun!

5. Somatosphere has a great summary by Dörte Bemme and Nicole D’Souza of a recent global mental health workshop and conference hosted by Laurence Kirmayer and McGill’s Division of Transcultural Psychiatry.

There seems to be a shift among this new generation of researchers (including the post’s authors) to move beyond “static dichotomies (north, south, west, HIC, LMIC, global, local)” and top-down or bottom-up approaches but I’m not sure to what, precisely, apart from recognizing “interesting frictions”?

One advance that has gotten less press is DSM-5′s recognition that mental health, like physical health, is a developmental process and exquisitely sensitive to the timing as well as the intensity of experiences and events. Another comes from recognition of the need for a developmentally oriented network of primary care at the community level that address biological, social, and environmental risk factors for mental as well as medical illnesses – infectious diseases, poverty, stress, migration. (See, e.g., Sunday’s NYT magazine article, “What Can Mississippi Learn from Iran?” re primary health care reform.)

[Dr. Aaron] Shirley [creator of HealthConnect, a model inspired by Iran's primary health care systems] says he believes that the problems of the American poor — living conditions, deficient education, harmful behaviors and the lack of family support and access to healthful lifestyles — demand house calls. This approach was used by groups in Atlantic City and Camden, N.J., profiled by Atul Gawande in The New Yorker last year, which identified the worst offenders of emergency-room readmission and deployed social workers and nurses to figure out the myriad sources of ill health. What was clear above all else from Gawande’s account is that what these people needed was constant attention. Because one stumble — an unpaid electricity bill, for example — can lead to cascading health setbacks.

Neuroscience

1. Great Book, Great Interview: Ginger Campbell interviews Olaf Sporns about Networks of the Brain (MIT, 2011).

2. John Hawks linked to a fascinating paper on his blog, “Evolutionary History and Adaptation from High-Coverge Whole-Genome Sequences of Diverse African Hunter Gatherers” by Lachance et al. in Cell., which points out high levels of genetic diversity within African hunter-gatherer populations.

To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at >60× coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation. We found evidence of archaic introgression in all three populations, and the distribution of time to most recent common ancestors from these regions is similar to that observed for introgressed regions in Europeans. Additionally, we identify numerous loci that harbor signatures of local adaptation, including genes involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing. Within the Pygmy population, we identify multiple highly differentiated loci that play a role in growth and anterior pituitary function and are associated with height.

3. Russell Fernald’s “Social Control of the Brain,” in latest Ann Rev of Neurosci using a fish model.

4. Latest SCAN: “The Association Between Financial Hardship and Amygdala and Hippocampal Volumes: Results from the PATH Through Life Project.

5. Finally, here is a link to the pdfof the 2012 Human Brain Project report because I’m obsessed with this image:

And, in my simple minded way, if we can do this, our collective experts can come up with a solution for Mississippi.

Psychiatry

1. Rutgers press release dd. 7/19/12: Anxiety Disorders in Poor Mothers More Likely to be the Result of Poverty, not Mental Illness.

2. In the July 2012 issue of BJPsych, Psychotic symptoms in young people without psychotic illness: mechanisms and meaning by Graham Murray and Peter Jones.

Psychotic symptoms are common in the general population. There is evidence for common mechanisms underlying such symptoms in health and illness (such as the functional role of mesocorticostriatal circuitry in error-dependent learning) and differentiating factors (relating to non-psychotic features of psychotic illness and to social and emotional aspects of psychotic symptoms). Clinicians should be aware that psychotic symptoms in young people are more often associated with common mental disorders such as depression and anxiety than with severe psychotic illness.

3. Also in the same issue,, psychiatric neuroscientist Mary Phillips has an editorial on “Neuroimaging in Psychiatry: Bringing Neuroscience into Clinical Practice.”

4. Freedman et al’s “Treating a physician patient with psychosis,” Asian Journal of Psychiatry, June 2012 via @JonesNev

5. Also via Nev Jones (@JonesNev): “Voice Hearing and Pseudoseizures in a Maori Teenager: An Example of Mate Maori and Maori Traditional Healing” in Australas Psychiatry, 19 July 2012. See also “Maori Healers’ Views on Wellbeing: The Importance of Mind, Body, Spirit, Family and Land” in Social Science & Medicine (June 2010).

Abstract

Objective: The aim of this paper is to describe a Māori traditional healing approach to assessment and treatment of distressing psychiatric symptoms in a young man.Method:We describe the case of a 17 year old Māori male with voice hearing and pseudoseizures and the assessment and intervention by one of the authors (WN). We report on the young man’s and his family’s experience of this treatment. We outline concepts from a Māori world view that illuminate an indigenous rationale for this approach. Results: A single session traditional Māori healing intervention was associated with immediate resolution of this young man’s psychiatric symptoms and restoration of his sense of wellbeing, despite cessation of antipsychotic treatment. He and his family felt satisfied with the cultural explanation about the origin of his distress, which was congruent with their world view. He remained well at follow-up one year later. Conclusions: Collaboration between psychiatrists and traditional Māori healing practitioners can enhance the mental health care of Māori whaiora (service users) and their families. Indigenous research is required to further evaluate the acceptability and effectiveness of such joint approaches.

Psychiatric Neuroscience, Stigma and the Aging Brain: Dispatch from the Annual Meeting of One Mind for Research

A few weeks ago I attended the first annual meeting of the One Mind for Research Campaign: Curing Brain Disease. (The group’s new CEO is Ret. General Peter Chiarelli, the commanding officer of the 1st Cavalry Division during the Iraq War, and you could practically taste the battle dust in your mouth at the end of the 3-day offensive to eliminate brain disease and its stigma within 10 years.) The meeting, which included NIMH director Thomas Insel, former NIMH director Steven Hyman, and American Psychiatric Association newly elected president John Oldham, featured sessions on the latest psychiatric neuroscience, stigma, and the aging brain. Here are some highlights:

Heterogeneity

One non-surprising take-home message is that psychiatric disorders are not only heterogeneous but many (most?) may eventually be best characterized at the level of circuits/systems. Regarding heterogeneity, the consensus among several speakers was that patients classified as having one illness or another should be further “stratified” as much as possible in order to treat with different neurodeficit-specific compounds  (which is interestingly contrary to some of the proposed changes to DSM-5, such as lumping Asperger’s and Autism, or eliminating subtypes of schizophrenia). UPDATE (8/24/12) This statement requires clarification. The elimination of subtypes in schizophrenia (paranoid, disorganized, catatonic, undifferentiated, etc.) is due to the belief that the disorder’s clinical heterogeneity may be best understood by using a single diagnosis with distinct symptom “dimensions” of psychopathology – hallucinations, delusions, disorganized speech, abnormal psychomotor behavior, negative symptoms (restricted emotional expression or avolition), impaired cognition, depression, mania – each of which, it is proposed, would be measured on a 4-point severity scale. But it’s important to note that these dimensions, or “domains,”  will “cross diagnostic boundaries” introducing a new set of challenges, especially for drug development (Carpenter, 2012).

Here’s an example of why categories can be confounding. Rene Hen gave a fascinating talk on a hippocampus-related process – pattern separation, the way in which our brains are able to reduce “the average overlap between two representations, thus making similar representations more distinct or orthogonalized in order to afford rapid learning without inducing interference and retrieval errors,” which is balanced by pattern completion. Pattern separation is impaired in PTSD as well as schizophrenia.

Connectivity

But I noticed that interest in the intermediate phenotype concept prevalent in psychiatric neuroscience literature during the last decade is now accompanied by an interest in big science, e.g., fresh efforts (reminiscent of Galen’s rete mirabile) to understand structural and functional connections within and across regions of the brain that are, also, exquisitely sensitive to environmental interactions. And this has significant treatment implications. As Emory fear scientist Kerry Ressler remarked, “we have to change how we think about therapy, the brain is not a bag of molecules that can be treated by a drug.”

MIT computational neuroscientist and TED pundit Sebastian Seung (“I am my connectome”) has received a lot of attention in the popular press recently for his work on the connectivity of individual neurons. (According to Seung, the dynamic or functional connectivity of neurons and the white-matter structural “connectome” interact in much the same way water rushing down a mountainside and the terrain over which it flows do.) But one of the most exciting sessions at the conference featured the work of Olaf Sporns and colleagues, who are focusing on structural and functional connectivity at the macro-scale, based on the concept of brain networks. These investigations rely on diffusion imaging (for structural connectivity) and resting state fMRI (for functional connectivity). In his talk, Sporns likened these anatomical connections to complex social or other kinds of networks that exist in the world. (“A common language is emerging,” said Sporns, one that is able to link network interactions within and across multiple levels of organization, which he referred to as “network science.”) Focusing on these interactions seems a little more doable than trying to link objective biomarkers to subjective experience (which Vaughan Bell of Mind Hacks likened to counting commas in a poem).

In the same session, William Seeley gave a fascinating talk on the connectional architecture of neurodegeneration in brain disorders, including Alzheimer’s, each of which has a distinct pattern. His group found, for example, that resting-state connectivity patterns of healthy brains related to episodic memory using fMRI mirrored the atrophy patterns in Alzheimer’s as the disease progressed from the medial temporal lobe to the neocortex. (The more radical idea (that may be reappearing in the science), another speaker said, is that these disorders are connectopathic and initially triggered by rogue proteins.) Here’s a link to the relevant Neuron 2012 paper.

 Stigma

In the session on stigma, Elyn Saks (USC), author of The Center Cannot Hold, discussed the “positive, negative, and cognitive” dimensions of schizophrenia, in regard to the latter dimensions specifically referring to short-term memory, visuo-spatial abilities, etc. She discussed how she was able to balance borderline impairment in some areas of cognition, e.g., short-term memory, by leveraging her strengths and “passed” for many years in academia as “normal.” During the talk I was struck by Dr. Saks’s certainty that psychotherapy is the reason for her lack of negative symptoms, which made me wonder, just how correlated are these symptoms with a person’s level of social disconnection? (The social neuroscience in this area by Naomi Eisenberger – who just published a review in Nature – and others relating social disconnection to some of the same pathways as physical pain is really interesting in this regard.)

Unfortunately, stigma is “alive and well,” according to sociologist Bernice Pescosolido, who spoke eloquently around the depressing fact that despite huge leaps in scientists’ neurobiological understanding of mental illness, despite the disappearance by the rest of us into what Mary-Jo DelVecchio Good calls the “biotechnical embrace” re matters of the mind, there has been virtually no change in Americans’ level of prejudice regarding persons whom NYU anthropologist Emily  Martin refers to as living under the description of a mental disorder. We just don’t believe it’s a disease like any other, and if you or your family have the rotten luck to be on the receiving end, this adds astronomically to the confusion, anxiety, and fear about which neuroanthropologist Greg Downey has so eloquently written ( “Slipping into Psychosis”).

Alzheimer’s and the Fountain of Youth

But I don’t want to end this post on such a depressing note. Stanford researcherTony Wyss-Coray discussed the importance of not seeing the brain as an isolated organ. His group is studying the effects of stress, inflammation, and other environmental insults on brain function. In one experiment, the investigators infused the blood of young mice into old mice, and there were many positive effects in terms of neurogenesis, increased synaptic activity, increased spine density, reduced neuroinflammation, and improved spatial memory. (This announcement initiated a small wave of mouse jokes.) A brilliant neuroscientist sittling behind me said in a vaguely accented English (seriously) that it would be a difficult and expensive process to determine which substances within the blood to focus on; in the meantime, why not just transfuse old people with young people’s plasma? This is precisely what John Huston, playing a Joseph Kennedy-esque character, does in the movie Winter Kills (“I get it from the kids up at Amherst”). As the general concluded, “What I’ve learned among other things is that, THIS IS A GOOD TIME TO BE A MOUSE.”

Can the “connectome” save psychiatry?

An individual’s “connectome” (Sporns, Tonino, & Klötter, 2005; Hagmann, 2005) is in essence a mathematical object that describes all the neural connections in a nervous system. The word was coined by Olaf Sporns et al. in their 2005 paper and independently by Patric Hagmann in his doctoral dissertation. Sporns describes the 2005 paper as a “manifesto” outlining an ambitious research program in support of a model linking structure and function that the authors felt would have a profound impact on how we understand the brain. (The following excerpts are from Sporns’ 2010 talk at the Allen institute; the full video is embedded in references.)

We had no information until just a few years ago about similar data [about brain networks]  from the human brain. That was a big gap in our understanding of the human brain because we had no good structural model for it. We had a lot of imaging data . . . But it’s very difficult to interpret imaging data if you have no structural model by which it is generated. (Allen Institute, 2010)

Since 2005, data-driven research on the connectome (some of which is under the auspices of the NIH Human Connectome Project) is now being conducted at multiple scales: micro (“single neurons and synapses”), meso (“brain regions and pathways”), and macro (“neuronal populations and their interconnecting circuitry”) using different imaging technologies.

Implications for Psychiatry

What is particularly attractive about the concept of a connectome vis-a-vis psychiatry is that it “naturally fits within a larger theoretical framework and thus links neuroscience to modern developments in network science and complex systems” (Sporns, 2011). In other words, it grounds a longstanding intuition that the brain in general and psychiatric disorders in particular reflect continuous interactions of biological and sociocultural systems (Kirmayer, 2012).

In the network science field, in other contexts – internet, social networks, epidemiology  – perturbations of networks are very important to study because people want to know what happens when we lesion the network, what happens when we disrupt its functionality in terms of the global outcomes that result. I think we have a similar question on the horizon here for these neurological, psychiatric conditions. What is it about the brain that has changed in terms of its network architecture that brings about – or is involved or at least associated with – the function that is being perturbed. (Allen Institute, 2010)

A second factor is its ability to account for plasticity (and individual differences). This is because while, on the one hand, the connectome constrains neural activity – Sebastian Seung (2012) likens it to a streambed that organizes the flow of water [1]  (and Sporns calls it a “structural skeleton”), on the other neural activity (thoughts, feelings, and perceptions) over time can change the connectome.

If we have a structural model of the human brain we can actually damage it in the computer. And we can ask questions about how impactful are certain lesions that we make inside this computational model. We make these lesions by deleting a number of nodes and their connections. And we then observe how the dynamics – in a forward computing sense – of the human brain changes as a result of making these lesions.  We can then compare  our empirical data to data that is obtained from people with stroke and we can ask questions about recovery. What is it about the metrics of global brain connectivity, functional interactions that changes in a good outcome scenario and is there anything we can do on an interventional level with therapeutic or other interventional means that can guide brain repair and recovery in a good direction. The brain really is a complex network. If we make a lesion in our model in any particular spot, it’s not just that that spot is lost, and the rest of the brain just goes on doing what it’s doing, all relationships across all other nodes in the brain change, and that’s because the brain responds as a whole. This is something that becomes very plastic and very graspable if you do computational modeling and it really opens up new horizons . . . for understanding the functional impact of lesions and perhaps other disease states as well. (Allen Institute, 2010)

Notes

[1] Computational neuroscientist Sebastion Seung (MIT), who is studying the connectome from the neuron’s eye view, gave an exuberant talk on the connectome at one of the Ted conferences, and now he’s written an exuberant book on the subject that is, seriously, a page turner that concludes with a section on cryonics and “the ultimate cyber-fantasy” of uploading your brain and “living happily ever after as a computer simluation” (2012, xxi).

 References

Hagmann, P. (2005) From diffusion MRI to brain connectomics (Doctoral dissertation). École Polytechnique Fédérale de Lausanne (EPFL), Lausanne.

Seung, S. (2012). The connectome: How the brain’s wiring makes us who we are. New York: Houghton Mifflin Harcourt.

Allen Institute (2010). Olaf Sporns: 2010  Allen Institute for Brain Science Symposium. Retrieved 21 February 2012 from http://www.youtube.com/watch?v=oikjPdV7LbU

Sporns, O. (2011). The human connectome: A complex network. Annals of the New York Academy of Sciences, 1224, 109–125.

Sporns, O., Tononi, G., & Kötter, R. (2005). The human connectome: A structural description of the human brain. PLoS Computational Biology, 1(4), e42. doi:10.1371/journal.pcbi.0010042