She Blinded Me With Science!

I was blinded by an Intellectual Blogging Award bestowed by the blog with that name, not the retro 80's song by Thomas Dolby...


The Golden Age of Wireless

I'm not really big on those meme thingys on teh intarwub, but thanks, Melinda, for the flattering recognition.

This Is Your Brain on Additional Critiques

Still undecided, swing readers?


Photos of Hillary Clinton elicited increased activity in the anterior cingulate cortex, a part of the brain that processes conflicting impulses, in swing voters who reported having an unfavorable opinion of her.

Icons by Jennifer Daniel, New York Times

By now, anyone remotely connected to neuroimaging research knows about the new outlet for your latest sensationalistic findings: a New York Times Op-Ed piece.

But the reality is that we actually don't know what the swing voters in this experiment were thinking, and the attribution of conflicting impulses based on activity in the anterior cingulate cortex is an example of...

the logical fallacy known as "reverse inference" - inferring the participants' emotional state from the observed pattern of brain activity (Aguirre, 2003; Poldrack, 2006).

Several new critiques of the Iacoboni et al. study have appeared in these blogs:

Brain Ethics, by Thomas Ramsøy

Neuroethics & Law Blog, by Martha Farah

Omni Brain, by Steve Higgins

Mind Hacks, by Vaughan Bell

Wired Science, by Brandon Keim

Slate, by Daniel Engber

But the highlight is this Letter to the Editor of the New York Times, signed by 17 experts in neuroimaging:

Politics and the Brain

Published: November 14, 2007

To the Editor:

“This Is Your Brain on Politics” (Op-Ed, Nov. 11) used the results of a brain imaging study to draw conclusions about the current state of the American electorate. The article claimed that it is possible to directly read the minds of potential voters by looking at their brain activity while they viewed presidential candidates.

For example, activity in the amygdala in response to viewing one candidate was argued to reflect “anxiety” about the candidate, whereas activity in other areas was argued to indicate “feeling connected.” While such reasoning appears compelling on its face, it is scientifically unfounded.

As cognitive neuroscientists who use the same brain imaging technology, we know that it is not possible to definitively determine whether a person is anxious or feeling connected simply by looking at activity in a particular brain region. This is so because brain regions are typically engaged by many mental states, and thus a one-to-one mapping between a brain region and a mental state is not possible.

. . .

As cognitive neuroscientists, we are very excited about the potential use of brain imaging techniques to better understand the psychology of political decisions. But we are distressed by the publication of research in the press that has not undergone peer review, and that uses flawed reasoning to draw unfounded conclusions about topics as important as the presidential election.

Adam Aron, Ph.D., University of California, San Diego
David Badre, Ph.D., Brown University
Matthew Brett, M.D., University of Cambridge
John Cacioppo, Ph.D., University of Chicago
Chris Chambers, Ph.D., University College London
Roshan Cools, Ph.D., Radboud University, Netherlands
Steve Engel, Ph.D., University of Minnesota
Mark D’Esposito, M.D., University of California, Berkeley
Chris Frith, Ph.D., University College London
Eddie Harmon-Jones, Ph.D., Texas A&M University
John Jonides, Ph.D., University of Michigan
Brian Knutson, Ph.D., Stanford University
Liz Phelps, Ph.D., New York University
Russell Poldrack, Ph.D., University of California, Los Angeles
Tor Wager, Ph.D., Columbia University
Anthony Wagner, Ph.D., Stanford University
Piotr Winkielman, Ph.D., University of California, San Diego

References

Aguirre GK (2003). Functional Imaging in Behavioral Neurology and Cognitive Neuropsychology. In: T.E. Feinberg & M.J. Farah (Eds.), Behavioral Neurology and Cognitive Neuropsychology. New York: McGraw Hill.

Poldrack RA (2006). Can cognitive processes be inferred from neuroimaging data? Trends in Cognitive Sciences 10: 59-63.

This Is Your Brain on Bad fMRI Studies

Or at least, this will be my brain on bad fMRI studies, if you put me in the scanner while I'm reading the NYT article below, and that's what you'll see.

What happens when you publish your research findings as a New York Times Op-Ed piece before vetting by peer review? Brought to you by some of the same authors of the infamous[ly bad] "Super Bowl Brain Scans" (that stunt was apparently repeated in 2007).

Op-Ed Contributors
This Is Your Brain on Politics

Published: November 11, 2007

This article was written by Marco Iacoboni, Joshua Freedman and Jonas Kaplan of the University of California, Los Angeles, Semel Institute for Neuroscience; Kathleen Hall Jamieson of the Annenberg Public Policy Center at the University of Pennsylvania; and Tom Freedman, Bill Knapp and Kathryn Fitzgerald of FKF Applied Research.

IN anticipation of the 2008 presidential election, we used functional magnetic resonance imaging to watch the brains of a group of swing voters as they responded to the leading presidential candidates. Our results reveal some voter impressions on which this election may well turn.

Our 20 subjects — registered voters who stated that they were open to choosing a candidate from either party next November — included 10 men and 10 women. In late summer, we asked them to answer a list of questions about their political preferences, then observed their brain activity...

The participants viewed photographs of the candidates and video clips of speeches. They also filled out questionnaires before and after the scans to rate their impressions of the candidates. What were the results?

1. Voters sense both peril and promise in party brands. When we showed subjects the words “Democrat,” “Republican” and “independent,” they exhibited high levels of activity in the part of the brain called the amygdala, indicating anxiety. The two areas in the brain associated with anxiety and disgust — the amygdala and the insula — were especially active when men viewed “Republican.” But all three labels also elicited some activity in the brain area associated with reward, the ventral striatum, as well as other regions related to desire and feeling connected. There was only one exception: men showed little response, positive or negative, when viewing “independent.”

So there we have it: anxiety, disgust, reward, desire, and connectedness, all at the same time! What else?

2. Emotions about Hillary Clinton are mixed. [NOTE: really? you don't say]. Voters who rated Mrs. Clinton unfavorably on their questionnaire appeared not entirely comfortable with their assessment. When viewing images of her, these voters exhibited significant activity in the anterior cingulate cortex, an emotional center of the brain that is aroused when a person feels compelled to act in two different ways but must choose one. It looked as if they were battling unacknowledged impulses to like Mrs. Clinton. [NOTE: um, this sounds a little like palm reading to me...do we actually know what the subjects were thinking while they looked at her photo?]

Subjects who rated her more favorably, in contrast, showed very little activity in this brain area when they viewed pictures of her.

This phenomenon, not found for any other candidate, suggests that Mrs. Clinton may be able to gather support from some swing voters who oppose her if she manages to soften their negative responses to her. But she may be vulnerable to attacks that seek to reinforce those negative associations.

Did we really need fMRI to tell us that Mrs. Clinton should try to soften the negative responses of swing voters?

Read more, if you dare (also see Kaplan et al., 2007 for a published fMRI study on viewing pictures of the 2004 presidential candidates).

Reference

Kaplan JT, Freedman J, Iacoboni M. (2007). Us versus them: Political attitudes and party affiliation influence neural response to faces of presidential candidates. Neuropsychologia 45:55-64.

We investigated how political party affiliation and political attitudes modulate neural activity while viewing faces of presidential candidates. Ten registered Democrats and 10 registered Republicans were scanned in an event-related functional MRI paradigm while viewing pictures of the faces of George Bush, John Kerry, and Ralph Nader during the 2004 United States presidential campaign. We found that compared with viewing one's own candidate, viewing the candidate from the opposing political party produced signal changes in cognitive control circuitry in the dorsolateral prefrontal cortex and anterior cingulate, as well as in emotional regions such as the insula and anterior temporal poles. BOLD signal in these regions correlated with subjects' self-reported ratings of how they felt emotionally about the candidates. These data suggest that brain activity when viewing a politician's face is affected by the political allegiance of the viewer and that people regulate their emotional reactions to opposing candidates by activating cognitive control networks.

Cell and its Ads

Do Cell Press journals really need Google Ads?

Copyright © 2007 Cell Press. All rights reserved.
Cell, Vol 131, 391-404, 19 October 2007

Article

Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions

Vaishnav Krishnan et al.

Summary

While stressful life events are an important cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The molecular mechanisms underlying such resilience are poorly understood. Here, we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations that differ along several behavioral and physiological domains. By a combination of molecular and electrophysiological techniques, we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability or insusceptibility. We show that molecular recapitulations of three prototypical adaptations associated with the unsusceptible phenotype are each sufficient to promote resistant behavior. Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance, and illustrate the importance of plasticity within the brain's reward circuits in actively maintaining an emotional homeostasis.

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Cerebro Muerto

The Brain Dead Collective are a group of like minded Goths and Metallers determined to run decent, fun and friendly events in the Birmingham (UK) area.

On a tangentially related note, it's the Day of the Dead tomorrow. According to The Museum of New Mexico Foundation:

El Dia de los Muertos, held on November 2nd is an important religous holiday in Mexico. Also called All Souls Day, it is an occasion marked by festive celebrations to honor the dead. Cemetaries are cleaned and decorated, special food and candies cooked, and home altars are designed in homage to ones ancestors. It is a day of joyous remembrance, not of sadness. The special songs, poems, foods and Day of the Dead art created for El Dia de los Muertos reflect this outlook.

Sugar skulls. Image from HEAVY LITTLE OBJECTS.

Sugar skulls are among the ofrendas placed at the graves of dead loved ones, and at altars commemorating them.

Image credit

License: this photograph copyright ©2005. Terms of use

Will You Digg This PNAS Article On Digg?

Digg

Probably not. And even if you did, the collective Digg audience will forget about it in 69 minutes.

To study the dynamics of collective attention and its relation to novel inputs in a natural setting, we analyzed the behavioral patterns of 1 million people interacting with a news web site whose content is solely determined by its own users. Because people using this web site assign each news story an explicit measure of popularity, we were able to determine the growth and decay of attention for thousands of news stories and to validate a theoretical model that predicts both the dynamics and the statistical distribution of story lifetimes.

The authors (Wu & Huberman, 2007) go on to describe a model of decay culminating in this equation:

Reference

Wu F, Huberman BA. (2007). Novelty and collective attention. Proc Natl Acad Sci. Oct 25; [Epub ahead of print].

The subject of collective attention is central to an information age where millions of people are inundated with daily messages. It is thus of interest to understand how attention to novel items propagates and eventually fades among large populations. We have analyzed the dynamics of collective attention among 1 million users of an interactive web site, digg.com, devoted to thousands of novel news stories. The observations can be described by a dynamical model characterized by a single novelty factor. Our measurements indicate that novelty within groups decays with a stretched-exponential law, suggesting the existence of a natural time scale over which attention fades.

...But My Subgenual Cingulate Is Sad

In the previous post, The Neurocritic discussed an article in Nature in which greater activity in the rostral anterior cingulate cortex (rACC) was associated with optimism¹ (Sharot et al., 2007). "But wait!" you might say, "what about the sad cingulate?" Neuroimaging studies have shown that the sad subgenual cingulate (Brodmann area 25), located beneath the genu of the corpus callosum, is overly active in depression (Mayberg et al., 2000; see also Greicius et al., 2007). This excessive activity is dampened in those who respond to six weeks of fluoxetine treatment (Prozac, an SSRI antidepressant), but remains elevated in those who don't. Is this the same brain region in the two experiments? Let's take a look.


On the left is Fig. 2a of Mayberg et al. (2000), showing a decrease in area 25 (Cg25) activity in fluoxetine responders, as measured by PET. On the right is Fig. 2b of Sharot et al. (2007), showing the optimistic rACC region. At first glance, the two "hot spots" appear to be in quite similar locations. However, there are differences in the precise centers of mass, as indicated by the respective x y z coordinates (according to Talairach and Tournoux, a standard 3D atlas of the human brain), and in the designated Brodmann areas (numbered cortical regions based on cytoarchitecture).

	x, y, z	BA
Mayberg	10,22,-14	25
Sharot	-11, 42, -1	32

The x coordinate indicates right or left hemisphere, y is anterior/posterior, and z is dorsal/ventral. Although activations in medial structures generally aren't discussed in terms of left/right hemisphere, because the margin of error is often greater than the distance from the midline (x = 0), here they're centered 10 mm right and 11 mm left of midline, respectively. Furthermore, the Sharot activation is 20 mm in front of the Mayberg activation. Finally, the activations are indicated by different Brodmann areas. Hmm, not the same.

More recently, Mayberg's group demonstrated that deep brain stimulation (DBS) in area 25 was effective in treating severe intractable depression in a small group of patients (Mayberg et al., 2005).

Each [of the six patients] met stringent criteria for treatment resistance defined as failure to response to a minimum of four different antidepressant treatments, including medications, evidence-based psychotherapy, or electroconvulsive therapy, administered at adequate doses and duration during the current episode.

In this procedure, a stimulating electrode is stereotaxically implanted in the targeted region. Dr. Helen Mayberg and her colleagues at Emory University are still recruiting patients with treatment resistant depression to participate in a clinical trial using chronic, high frequency stimulation of the subgenual cingulate white matter. To determine the anatomical connectivity of the sad cingulate region, a new study performed tractography (using diffusion-weighted magnetic resonance imaging) to trace the pathways mediating treatment response with DBS (Johansen-Berg et al., 2007). The authors compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow), which appears to be the optimistic rACC region of Sharot and colleagues.


Figure 3 (Johansen-Berg et al., 2007). Connectivity-based parcellation of ACC and location of electrode contacts. (A, B) Population probability maps of connectivity-defined sACC and pACC. Color scales represent the population probability of a voxel belonging to sACC (from 50% [dark blue] to 80% [light blue] probability) or pACC (from 50% [red] to 80% [yellow] probability). Also shown are the locations of effective electrode contacts from 9 patients overlaid in black. Effective electrode locations are mainly localized within the sACC subregion.

Can we directly link the "optimistic rACC" (pACC) to depression, as stated in the Nature paper? Or more specifically, to DBS efficacy [and Prozac efficacy], as indicated by the work of Mayberg and colleagues? Not really. The effective electrode contacts were in sACC. The critical comparison of sACC vs. pACC connectivity is illustrated below. Is the latter highly interconnected with the amygdala? Doesn't seem to be.


From Figure 4 (Johansen-Berg et al., 2007). Tracts from sACC and pACC regions. (A–F) Population maps of results of probabilistic tractography from the pACC and sACC subregions. Color scales represent the population probability of a voxel belonging to a pathway from pACC (A, B, red to yellow) or sACC (C–F, dark blue to light blue). Abbreviated labels indicate gray matter regions that are connected with sACC or pACC via these pathways. (A, B): Pathways from pACC connect with the anterior midcingulate cortex, AMCC (A); frontal pole, FP (A); nucleus accumbens, NAC (A); hypothalamus (A); and fornix (B). (C, D, E, F): Pathways from the sACC connect with the orbitofrontal cortex, OFC (C, F); NAC (C, D); hypothalamus (C, D); AMCC (C); fornix (C); and amygdala (E, F).

How do we account for these discrepancies in the Nature paper? The tractography article was published after the former went to press, but earlier work by Mayberg et al. was neglected. However, other results were cited (Drevets et al., 1997). These investigators found resting metabolic activity in ventral ACC to be reduced in both unipolar and bipolar depression, contrary to sad cingulate hyperactivity. What's up with that? Here's what Mayberg et al. (2005) suggest:

The baseline pattern of subgenual cingulate hyperactivity in combination with frontal hypoactivity described here in this TRD patient group is a finding that is in contrast to the hypoactivity reported in a more rostral region of subgenual medial prefrontal cortex in familial bipolar and unipolar depressed patients (Drevets et al., 1997). This distinction suggests important differences across subtypes of depression that are potentially relevant to the pathophysiology of major depressive disorders and perhaps their treatment.

What have we learned? Location matters. It's helpful to read the literature. So it goes...

Footnote

¹ Positive correlation with optimism was for the contrast imagine future events (positive) versus imagine future events (negative).

References

Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386:824-7.

Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF. (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 62:429-37

Johansen-Berg H, Gutman DA, Behrens TE, Matthews PM, Rushworth MF, Katz E, Lozano AM, Mayberg HS. (2007). Anatomical Connectivity of the Subgenual Cingulate Region Targeted with Deep Brain Stimulation for Treatment-Resistant Depression. Cereb Cortex. Oct 10; [Epub ahead of print]. free PDF

Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.

Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA. (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48:830-43.

Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45:651-60.

Sharot T, Riccardi AM, Raio CM, Phelps EA. (2007). Neural mechanisms mediating optimism bias. Nature. Oct 24; [Epub ahead of print].