Wednesday, May 26, 2010

Short Cuts

There is way too much to blog about these days. I can't decide among these 3 new papers:

Sometimes, Categorical Statements about Prefrontal Neurons Are Just Wrong

(1) Earl K. Miller (2007) in The Prefrontal Cortex: Categories, Concepts, and Cognitive Control (PDF):
There was virtually no category effect across the ITC [inferior temporal cortex] population and no examples of neurons whose activity showed the sharp across-distinction/within-category generalization that is the behavioral signature of categorization. Rather, ITC neurons were sensitive to the physical appearance of the individual stimuli; its neurons did not “throw away” information about individuals in favor of the category groupings, like PFC [prefrontal cortex] neurons did. This finding suggests that learned visual categories are abstracted at the level of the PFC, not in visual cortex.
No, not really. Monkeys were able to easily learn visual categories when their lateral prefrontal cortices were ablated bilaterally, IF they were tested using an incentive value task (Minamimoto et al., 2010. Earlier single-unit recording studies (reviewed in the Miller 2007 chapter) required maintenance of a set of two stimulus-response mappings. Thus PFC might be necessary for rule-based response selection, but not for visual categorization.

Minamimoto T, Saunders RC, Richmond BJ (2010). Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex. Neuron 66:501-507.

Categorization is a basic mental process that helps individuals distinguish among groups of negative and positive objects, e.g., poisons and nutrients, or predators and prey. Monkey experiments have suggested that lateral prefrontal cortex (LPFC) participates in learning and processing visual categories. However, in humans category specific visual agnosia follows inferior temporal cortex but not LPFC damage. Here, we use a new behavioral approach to show that both normal monkeys and those with bilateral removal of LPFC learn and generalize perceptual categories of related visual stimuli rapidly without explicit instruction. These results strongly indicate that visual categorization occurs at some earlier stage of feed-forward processing, presumably in temporal cortex, without top-down information from LPFC.

Minamimoto et al.'s incentive value task is shown below.

Figure 1 (A) Sequence of events during a trial of the reward-delay task. A visual cue (Cue) indicates size and delay interval for the reward after successful behavioral reaction (bar release within 200–3000 ms after green target appears).

You Are What You Eat, or Don't Eat

(2) Empathy and Diet? Are vegetarians too sensitive, or more empathetic? And those vegans, they're out of control!

Filippi M, Riccitelli G, Falini A, Di Salle F, Vuilleumier P, Comi G, Rocca MA (2010). The Brain Functional Networks Associated to Human and Animal Suffering Differ among Omnivores, Vegetarians and Vegans. PLoS ONE 5(5): e10847.

Empathy and affective appraisals for conspecifics are among the hallmarks of social interaction. Using functional MRI, we hypothesized that vegetarians and vegans, who made their feeding choice for ethical reasons, might show brain responses to conditions of suffering involving humans or animals different from omnivores. We recruited 20 omnivore subjects, 19 vegetarians, and 21 vegans. The groups were matched for sex and age. Brain activation was investigated using fMRI and an event-related design during observation of negative affective pictures of human beings and animals (showing mutilations, murdered people, human/animal threat, tortures, wounds, etc.). Participants saw negative-valence scenes related to humans and animals, alternating with natural landscapes. During human negative valence scenes, compared with omnivores, vegetarians and vegans had an increased recruitment of the anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG). More critically, during animal negative valence scenes, they had decreased amygdala activation and increased activation of the lingual gyri, the left cuneus, the posterior cingulate cortex and several areas mainly located in the frontal lobes, including the ACC, the IFG and the middle frontal gyrus. Nonetheless, also substantial differences between vegetarians and vegans have been found responding to negative scenes. Vegetarians showed a selective recruitment of the right inferior parietal lobule during human negative scenes, and a prevailing activation of the ACC during animal negative scenes. Conversely, during animal negative scenes an increased activation of the inferior prefrontal cortex was observed in vegans. These results suggest that empathy toward non conspecifics has different neural representation among individuals with different feeding habits, perhaps reflecting different motivational factors and beliefs.

How did the authors get the idea for this experiment??

How Dare You! I Feel So Guilty! This Is an Outrage!

(3) Oh no! The neural correlates of "moral sentiments"? Smells like phrenology to me...

Green S, Ralph MA, Moll J, Stamatakis EA, Grafman J, Zahn R. Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation. Neuroimage 2010 May 19. [Epub ahead of print].

It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. "critical" and "faultfinding"). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals.

Official Short Cuts Theatrical Trailer

Well, it looks like there was a winner after all, at least for tonight...

Minamimoto T, Saunders RC, Richmond BJ (2010). Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex Neuron, 66 (4), 501-507 : 10.1016/j.neuron.2010.04.010

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Friday, May 21, 2010

Attentional bias and "gaydar"

Global or Local? Gay or Eurotrash? Navon figure flanked by two game pieces from Gay or EUROtrash? the ultimate gaydar game!

Believe it or not, there's an article in the new journal Frontiers in Cognition1 entitled "Sexual orientation biases attentional control: a possible gaydar mechanism" (Colzato et al., 2010). What is "gaydar"? And why on earth would one think of studying the allocation of attention to global and local visual perceptual features in relation to gaydar? Here's why:
Individuals with a homosexual orientation are often believed to have a “telepathic sixth sense” (Reuter, 2002) for recognizing each other, an ability that is often referred to as gaydar (Shelp, 2002) – a portmanteau of gay and radar. Even though perceivable differences between homosexuals and heterosexuals may not be salient to everyone, some studies revealed subtle but distinctive features that homosexuals tend to share, such as coiffure (Rule et al., 2008), body-movement and gesturing style (Ambady et al., 1999), speech patterns (Linville, 1998), and penile size (Bogaert and Hershberger, 1999).2 Hence, there is a rich perceptual basis for people to develop a reliable gaydar, and homosexuals are apparently better trained in making use of it.
To test the possible perceptual basis of gaydar, the authors made use of Navon figures (1977), which are comprised of small letters that form a larger letter. The characters can be the same or different, as shown below.

Navon (1977) demonstrated that global visual features take precedence over the local ones ("forest before trees"). When in conflict, the large letter (global) interferes with the ability to identify the smaller letters (local), but local features do not hinder the ability to identify global features. Colzato et al. (2010) reasoned that gay individuals might need to focus on specific and local perceptual cues in order to correctly identify others with the same (or different) sexual orientation. Hence, the global precedence effect was predicted to be smaller in gay people than in straight people.

To test this hypothesis, 42 Dutch participants (25 male and 17 female) were recruited for the study. On a multidimensional Kinsey-like scale (with seven variables each scored from 1-7), half were self-identified as straight (1.0) and the other half as gay (6.5). The stimuli were composed of large and small rectangles and/or triangles. Participants made button press responses to stimulus shape, based on the stimulus dimension (global or local) that was cued on each trial. The results demonstrated that the gay group did indeed show a smaller global precedence effect than the straight folk (see below).

Figure 1 (Colzato et al., 2010). Mean global precedence effect for homosexuals and heterosexuals. Vertical capped lines atop bars indicate standard error of the mean.

Heterosexuals were 68 msec faster to respond to global than to local features, but homosexuals were only 40 msec faster. The groups differed for this main effect of global/local dimension... but we don't know about the interaction with congruity. Nor do we know anything about potential male/female differences, because those weren't reported either. Nonetheless, results are consistent with the interpretation that gay men and women might have a relative bias towards detail-oriented processing when compared to heterosexuals.

Now sexual orientation can join the other studies of group identity and attention to global vs. local features. These same authors previously showed that Dutch Calvinists (who have an independent view of the self) show a smaller global precedence effect than Dutch atheists (Colzato et al., 2008). Other research has demonstrated that participants raised in collectivist Asian cultures tend to be more globally-oriented than individualistic North American participants (Masuda & Nisbett, 2001). What might all this mean?
From a more general perspective, our findings add to previous observations that being a member of a particular social group seems to shape cognitive-control operations in specific ways – whether this group is defined by shared culture, religious practice or, as the present study suggests, shared sexual orientation.


1 The bar for article titles in this journal has been set pretty high, since the other two papers are DOOM'd to switch: superior cognitive flexibility in players of first person shooter games and Games with(out) Frontiers: toward an integrated science of human cognition.

2 Yes, the mean size is larger in gay men. On all five measures of penile length and circumference from Kinsey's original protocol (Bogaert & Hershberger, 1999).


Colzato LS, van den Wildenberg WP, Hommel B. (2008). Losing the big picture: how religion may control visual attention. PLoS One 3:e3679.

Colzato, L., van Hooidonk, L., van den Wildenberg, W., Harinck, F., & Hommel, B. (2010). Sexual orientation biases attentional control: a possible gaydar mechanism. Frontiers in Psychology DOI: 10.3389/fpsyg.2010.00013

Masuda T, Nisbett RE. (2001). Attending holistically vs. analytically: Comparing the context sensitivity of Japanese and Americans. J Pers Soc Psychol. 81:922–934. PDF

Navon D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psych. 9:353–383.

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Wednesday, May 19, 2010

Towards a Focal Consensus in Cognitive Neuroscience: Databases and Meta-Analyses

Moving right along with our timely, fast-paced, cutting edge blog coverage from the CNS 2010 Annual Meeting [held last month], the first symposium urged the field to advance beyond the current piecemeal single-study approach to neuroimaging by moving Towards a cumulative science of human brain function.1 Building comprehensive, structured, and searchable databases (Van Essen, 2009) and using meta-analytic tools (Wager et al., 2009) were proposed to be key methods aimed at achieving this goal.

In his talk, prolific neuroanatomist Dr. David Van Essen (of primate visual cortex wiring diagram fame)2 discussed SumsDB (Surface Management System Database), "a repository of brain-mapping data (surfaces & volumes; structural & functional data) from many laboratories."

Talk 2: Lost in Localization – But Found with Foci!

David Van Essen; Washington University in St. Louis

More than 50,000 studies related to functional imaging of the human brain have been published in recent decades. Of these, more than 10,000 report key experimental data (centers of fMRI activation foci, etc.) in tables of stereotaxic coordinates (‘foci’) in one or another standardized atlas space. To aid in mining this extensive literature, we developed the SumsDB database, which supports storage, visualization, and searching of many types of neuroimaging data. SumsDB includes a Foci Library that currently contains >40,000 foci from ~1,400 published studies. This includes comprehensive coverage of five major journals and almost 15% of the relevant literature. Foci searches can be based on many criteria (e.g., cortical area or region, spatial coordinates, functional criteria, or disease condition). Search results can be viewed online (WebCaret) or downloaded for offline visualization and analysis using Caret sofware. As the Foci Library continues to expand, through contributions from curators and volunteers alike, it will become increasingly valuable as a way to efficiently access the burgeoning neuroimaging literature.

Van Essen emphasized the importance of maintaining a central repository of neuroimaging foci, the 3D localization of peak activations in x, y, z coordinates (Fox et al., 1985). He and his lab have established SumsDB, which currently contains 50,000 foci from 1,700 studies, a relatively small fraction of the literature (see figure below).

Fig. 1 (Derrfuss & Mar, 2009). Total number of published fMRI studies reporting coordinates by year and number of studies included in current coordinate databases.

One impediment to having more complete coverage of the literature is how labor intensive it is to add new articles to the database (30-60 min per paper after 5-10 hr training), as lamented by Derrfuss and Mar (2009) in their Comments and Controversies article in NeuroImage. Because of the effort involved, many in the neuroimaging community haven't been particularly motivated to participate in the project. In in his reply (2009) to Derrfuss and Mar, Van Essen listed the benefits of voluntary data entry duties:
  • submitting foci from publications of your own lab will increase their visibility, through data mining initiated in SumsDB or NIF [Neuroscience Information Framework];

  • submitting relevant studies from your research subfield will facilitate cross-study comparisons and promote broader awareness of research in that area;

  • individual contributors are recognized by ‘provenance’ assignments for each study (or version) entered into SumsDB.

  • SumsDB libraries can also be used to store foci and study collections for ongoing projects that are not yet published. (Data in these libraries are not made public until requested by the submitter and then vetted by a curator in the Van Essen lab to insure conformance to basic metadata description standards.)
And what a great classroom project for graduate students and highly motivated undergraduates! (suggested Van Essen, 2009). Greater participation is essential, however. But who wants to do all that work for free?
An attractive and feasible model is for one or two individuals (students, postdocs, or knowledgeable technicians) from each of many laboratories to enter data published by their own laboratory plus selected topics related to that lab's research interests. For example, if 50 volunteers each added ~20 studies per year (15–30 h per volunteer, including training), the current rate of submission would approximately double, and about half of the relevant literature would be covered in ~5 years.
But even more appealing, a semi-automated data entry system for SumsDB is under development...

What does one do with all that data? In the next talk, Dr. Tor Wager discussed meta-analysis, a statistical technique for summarizing quantitative research. Why is it important to combine results across multiple studies (Wager et al. 2007)?
Meta-analysis is an increasingly popular and valuable tool for summarizing results across many neuroimaging studies. It can be used to establish consensus on the locations of functional regions, test hypotheses developed from patient and animal studies and develop new hypotheses on structure–function correspondence. It is particularly valuable in neuroimaging because most studies do not adequately correct for multiple comparisons; based on statistical thresholds used, we estimate that roughly 10–20% of reported activations in published studies are false positives.
The 'Quick-Search' function in SumsDB can be used to retrieve foci of interest from all papers in the database. For example, one can search by anatomical area (Fig. 1B) or by research topic (Fig. 1C). Searches can also be performed by task, function, disorder, etc.

Adapted from Fig. 1 (Van Essen, 2009). (B) 493 foci localized to area MT+, displayed on the PALS-B12 right hemisphere [Population-Average, Landmark- and Surface-based atlas]. (C) 627 foci associated with studies containing the term ‘music’ in the abstract, keywords, or other metadata.

BrainMap is another major online database. It was developed at the Research Imaging Institute of the University of Texas Health Science Center San Antonio (Fox et al., 2005) and currently contains 1,928 papers (and a more user-friendly interface than SumsDB). The GingerALE program can perform coordinate-based meta-analyses of the neuroimaging literature (on chosen topics or brain areas) using the activation likelihood estimation (ALE) method (see this PDF).

The example below is a figure I generated from entering the x, y, z coordinates from a specific right insular focus [related to low $ offers in a Trust Game by King-Casas et al., 2008] into the Sleuth program (available at, which searched the available database of papers for matches [see Who Can You Trust?]. The resulting list of coordinates and experiments was then imported into the GingerALE program, which performed the ALE meta-analysis. The figure illustrates that this exact same region of the right insula was activated during tasks that assessed speech, language, explicit memory, working memory, reasoning, pain, and listening to emotional music (i.e., not only during social norm violations in the Trust Game).

Other Neurocritic-generated examples include ALE meta-analyses for physical pain (Hypnosis and Pain Control), the left head of the caudate nucleus (Sie Ist Gefundene Steuerung Über Two Languages: Part 2), the right dorsolateral prefrontal cortex (Crime, Punishment, and Jerry Springer), and an update on physical pain (Bleed It Out).

Tor Wager has developed his own meta-analysis software (Multilevel Kernel Density Analysis), a set of Matlab scripts and functions freely available from his website. In addition, he has a nifty collection of meta-analysis data and image files that can be downloaded as well. The documentation for MKDA (PDF) notes some problems with other meta-analysis procedures:
Prior meta-analyses have divided the brain into voxels and plotted peak coordinates. Then count how many peaks within each voxel (the observed frequency count). Compare this to the number expected by chance if peaks were distributed randomly throughout the brain (the expected frequency count). Have to establish threshold (using Monte Carlo method).

Problems with this method: This is a fixed effect procedure which ignores the fact that points are not independent of one another (as they are nested within contrasts within studies). An important consequence is that any single study that has a large number of peaks (due to differences in reporting, voxel size, thresholding) can overly influence the analyses.
MKDA offers a number of different options for dealing with these issues (Wager et al., 2009).

In his talk, Wager discussed four major uses of meta-analysis:
  1. Formulating a priori hypotheses
  2. Testing existing theories
  3. Developing new theories
  4. Making inferences about psychological states
Talk 3: Consensus-building and brain-based taxonomies using meta-analysis

Tor Wager; University of Colorado at Boulder

Much of cognitive and affective neuroscience has centered on identifying particular brain regions or circuits with categories of psychological processes. Properly synthesized, the accumulation of knowledge can aid in this goal. However, without synthesis, more information is not necessarily better, as it may be difficult to separate truly activated brain regions from spurious or idiosyncratic findings. Meta-analysis of neuroimaging data provides a potential solution to this problem. I will present methods and findings from meta-analyses of both cognitive control and emotion. Meta-analyses of cognitive control reveal a consensus on the prefrontal cortical networks involved in cognitive control processes, and a complexity-dependent posterior-anterior hierarchy of prefrontal activity that complements recent findings on prefrontal organization. Conversely, meta-analyses of emotion argue against several long-standing principles of organization of the emotional brain, paving the way for the development of new models. These findings illustrate the utility of meta-analysis in developing taxonomies of psychological processes based on the patterns of brain activity they elicit rather than folk psychological categorization schemes. I will close the talk by presenting a brain-based classification of psychological tasks that suggests that different quadrants of the brain respect different organizational schemes.

The talk used some examples from fMRI studies of emotion. For instance, "The insula is a marker of disgust." In a test of this existing theory, meta-analytic results demonstrated there isn't much specificity in the insula for disgust (as also shown above). Test of another theory ("the amygdala is specific for fear") revealed results consistent with that notion, but the amygdala was just as active for disgust as for fear. Another region important for experiencing emotions emerged from the meta-analysis: the periaqueductal gray (PAG), better known for its involvement in pain and defensive behavior.

A final note is the importance of identifying networks of brain regions involved in a particular function. This can be accomplished by identifying consistent patterns of co-activation in a given meta-analysis (Wager et al., 2009). It's time to stop the madness of the “one tiny brain area controls complex behavior” approach!


1 For more information about the symposium and the first talk in the series, see Coordinates, Consensus, Cooperation: Towards a Cumulative Science of Human Brain Function and Motivating a Cumulative Cognitive Neuroscience, plus this helpful list of links and slides compiled by the symposium organizer.

2 Classic 1991 Felleman and Van Essen paper ("Distributed hierarchical processing in the primate cerebral cortex") is freely available as a 47 page PDF.


Derrfuss J, Mar RA. (2009). Lost in localization: the need for a universal coordinate database. Neuroimage 48:1-7.

Fox PT, Laird AR, Fox SP, Fox PM, Uecker AM, Crank M, Koenig SF, Lancaster JL. (2005). BrainMap taxonomy of experimental design: description and evaluation. Hum Brain Mapp. 25:185-98.

Fox PT, Perlmutter JS, Raichle ME. (1985). A stereotactic method of anatomical localization for positron emission tomography. J Comput Assist Tomogr. 9:141-53.

Van Essen, D. (2009). Lost in localization — But found with foci?! NeuroImage, 48 (1), 14-17. DOI: 10.1016/j.neuroimage.2009.05.050

Wager TD, Lindquist M, Kaplan L. (2007). Meta-analysis of functional neuroimaging data: current and future directions. Soc Cogn Affect Neurosci. 2:150-8.

Wager, T., Lindquist, M., Nichols, T., Kober, H., & Van Snellenberg, J. (2009). Evaluating the consistency and specificity of neuroimaging data using meta-analysis. NeuroImage, 45 (1) DOI: 10.1016/j.neuroimage.2008.10.061

Figure 4 (Felleman & Van Essen, 1991). Hierarchy of visual areas. This hierarchy shows 32 visual cortical areas. ... These areas are connected by 187 linkages, most of which have been demonstrated to be reciprocal pathways.

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Wednesday, May 12, 2010


"Head-wound Hank", from Geek Orthodox.

The 19th century archive of The Lancet1 is filled with simply delightful case reports. Who can resist the allure of early plastic surgery failures, such as RHINOPLASTIC OPERATION, PERFORMED BY M. LISFRANC, FOLLOWED BY DEATH? Or how about a Case of Local Tubercular Deposit on the Surface of the Brain, presented by Robert Dunn, Esq.? Finally, the tragic History of a Case of Hydrophobia, treated at the Hotel Dieu at Paris, by an injection of water into the veins did not end well (through no fault of R. Magendie, of course):2
It results from the history of this case, that a disease, which exhibited all the characters of hydrophobia, ceased by the introduction of a pint* of warm water into the veins; that the patient survived this introduction eight days: that no accident appeared to follow from it; and that the death of the patient appears to have been caused by a local disease, which was wholly unconnected with the hydrophobia, and the new mode of treatment.

* The pint of Paris contains 48 cubic inches. -ED.
In 1828, Dr. Sewall (Professor of Anatomy in the Colombian College, D.C.) reported on two of his cases. They are not for the faint of heart. A warning for political incorrectness is also warranted here.
CASE 1. In February 1827, W. Brown, a coloured man, aged fifty years, in encountering with another individual, received a severe blow on the right side of the head with a sharp spade. When Dr. Sewall arrived, which was only a few minutes after the accident, he found him bleeding profusely, and much exhausted from the loss of blood. Though not insensible, he had lost his reason, and did not know how he came by the injury. There was a deep wound dividing the integuments, the whole of the temporal muscle, penetrating the cavity of the cranium, and extending horizontally, from an inch above the external angular process of the frontal bone, through the parietal bone just above the squamous suture, forming a fissure of three inches in length. The lower portion of bone was considerably depressed, and the two edges separated about half an inch.

Two branches of the temporal artery were taken up; when, on a more critical examination, it was ascertained that the dura mater was divided for an inch in extent...
OK, so the patient really did have a 3 inch crack in his skull with brain matter oozing out. Mr. Brown was treated by Dr. Sewall ("dressings were applied"). When pus was coming from the gaping wound, there was swelling followed by sloughing (apparently). Then bits of brain were scooped away with a spatula. Lovely.

Although he suffered from severe headaches, Mr. Brown was declared none the worse for the wear:
For about ten days after the accident, the patient complained of constant, and sometimes of severe, pain in the head; and on one occasion was affected with a slight spasm of the muscles of the face, neck, and extremities. The wound healed, and in six weeks the patient was quite well. He subsequently followed his occupation, that of scavenger, and did not manifest any deviation in the functions either of body or mind from their ordinary healthy condition.
The bar was probably set pretty low for what was considered an "ordinary healthy condition" for a "coloured" man who worked as a scavenger in 1827...

The second case was of a five year old boy who was kicked in the head by a horse. No race was specified, so we'll assume he was white. More oozing and scooping of brain:
CASE 2. September 18th, 1827, Lewis Poole, aged five years, while playing in the street, was kicked by a horse, and taken up in a state of insensibility. Dr. Sewall arrived a quarter of an hour after the accident, and found a semicircular wound in the integuments of the head, and, corresponding with this, a large fissure in the frontal and parietal bones, about three inches above the external angle of the right eye. Through this fissure a portion of brain protruded, somewhat larger than a walnut, and was composed both of cortical [gray] and medullary [white] matter, which were easily distinguished. This was so far separated from the parts beneath, as to be removed without any violence.

Once again we're informed of the patient's full recovery, but only after much unpleasantness. He was bled to the point of unconsciousness initially and then given a powerful and toxic emetic for two weeks straight:
Particular circumstances prevented the subsequent use of the lancet; but he was purged actively and daily for two weeks, and the pulse kept down by nauseating doses of the tartate of antimony. Extensive suppuration came on, with a copious discharge of pus; the wound gradually healed, and in about five weeks the child was quite well. He has since remained in perfect health.
I wonder for how long that lasted, since Antimony Potassium Tartate is considered a dangerous good (.doc). Inhalation can cause irritation, sore throat, coughing, and shortness of breath. Eye or skin contact causes irritation, redness, and pain. Ironically, the recommended treatment after swallowing this compound is to induce vomiting immediately. The long-term consequences of antimony poisoning are not likely to be conducive to perfect health. Neurosurgical care has certainly come a long way since 1827.


1 Now on Facebook and Twitter! Keeping up with the 21st century.

2 It probably wasn't his fault if the patient was really infected with the rabies virus (aka hydrophobia).


Dr. Sewall (1828). CASES OF INJURY OF THE HEAD, ACCOMPANIED BY LOSS OF BRAIN. The Lancet, 10 (265) DOI: 10.1016/S0140-6736(02)98130-4

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Saturday, May 08, 2010

Motivating a Cumulative Cognitive Neuroscience

Why are large-scale structured databases and meta-analyses important to advance the field of human brain mapping? One reason is that individual functional magnetic resonance imaging (fMRI) studies can be notoriously unreliable and underpowered (Bennett & Miller, 2010; Fliessbach et al., 2010; Kriegeskorte et al., 2009; Vul et al., 2009). At the recent CNS 2010 Annual Meeting, symposium organizer Dr. Tal Yarkoni gave the first talk in a session on the value of a cumulative cognitive neuroscience.

Symposium Session 1
Sunday, April 18, 10:00 am - 12:00 pm, Westmount et al Ballroom

Towards a cumulative science of human brain function

. . .

Talk 1: Motivating a cumulative cognitive neuroscience

Tal Yarkoni; Columbia University and University of Colorado at Boulder

Thousands of functional neuroimaging studies are published every year. Only a small fraction of these studies explicitly attempt a formal synthesis of previous findings. In this talk, I argue for an increased emphasis on cumulative approaches to the study of brain function that aim to synthesize and distill the results of previous studies. Three different motives for such an approach are discussed, including (a) the need to distinguish real findings from false alarms; (b) the desire to organize both cognitive tasks and brain activations into coherent ontologies; and (c) the high likelihood that many fMRI studies are underpowered and consequently produce distorted results. I focus primarily on the last of these points, using simulations and empirical analyses to demonstrate that the results of many individual fMRI studies are likely to appear considerably stronger and more selective than they actually are. I conclude by arguing that these limitations are difficult or impossible to overcome in individual studies, necessitating a stronger focus on consensus building at the disciplinary level.

What are the motivations for consensus building? Here are four major reasons:
The value of a cumulative science
  • Make the literature manageable
  • Distinguish true positives from false positives
  • Develop overarching frameworks
  • Minimize the effects of low power
Yarkoni's talk focused on the last point. The problem with most individual fMRI studies is a lack of statistical power. Yarkoni (2009) argued that:
the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions [from their notorious 2009 paper], the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest.

Fig. 2 (Yarkoni, 2009). Inflation of significant r values as a function of sample size (x axis) and population effect size (lines). Each point represents the result of 10,000 simulated correlation tests, each conducted at a threshold of p < .001, reflecting the most commonly used whole-brain threshold. Dashed lines represent the true correlation size; solid lines represent the mean observed correlation in the sample for only those tests that produce significant results.

Simply put, small n's result in massively inflated brain-behavior correlations. What can be done about this problem? Include more participants in your studies! And make use of the tools that were described by the subsequent speakers (Van Essen, Wager, Poldrack) for synthesis of mega-databases.

For more information, the slides from Tal's talk are available online (PDF).


Bennett CM, Miller MB. (2010). How reliable are the results from functional magnetic resonance imaging? Ann NY Acad Sci. 1191:133-55.

Fliessbach K, Rohe T, Linder NS, Trautner P, Elger CE, Weber B. (2010). Retest reliability of reward-related BOLD signals. Neuroimage 50:1168-76.

Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. (2009). Circular analysis in systems neuroscience: the dangers of double dipping. Nat Neurosci. 12:535-40.

Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. Perspectives on Psychological Science 4:274-290.

Yarkoni, T. (2009). Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009). Perspectives on Psychological Science, 4 (3), 294-298. DOI: 10.1111/j.1745-6924.2009.01127.x

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Wednesday, May 05, 2010

Mindscape explains life, mind, consciousness and happiness

Conflict of interest: ABN, NJS and DRS are scientific co-founders of Mindscape Diagnostics, Inc.

Special review article!

What are mind, consciousness and happiness, in the fundamental context of life? We propose a convergent perspective (coupling evolutionary biology, genomics, neurobiology and clinical medicine) that could help us better understand what life, mind, consciousness and happiness are, as well as provides empirically testable practical implications.
Well. So a speculative, flaky, and pretentious journal article1 (Niculesc et al., 2010) proposed a grandiose theoretical framework for understanding "life" et cetera, et cetera. I was amused.
We propose that the mind can be viewed as a composite of mechanisms that have evolved to achieve GuU [genes (G), proximal umbrella (u), general umbrella (U)] objectives. The latest genetic, neurobiological and clinical evidence suggest that normal mental functioning and psychiatric disorders can be classified in three broad and overlapping domains: the anxiety domain, the mood domain and the cognitive domain (Niculescu, 2006), somewhat paralleling the archaic Freudian constructs of id, ego and super-ego.
Each section of the paper (n=8) is introduced by a scientific quote or aphorism, such as...
“It is always advisable to perceive clearly our ignorance”.

-Charles Darwin

“For a scientist, it is a unique experience to live through a period in which his field of endeavour comes to bloom — to be witness to those rare moments when the dawn of understanding finally descends upon what appeared to be confusion only a while ago — to listen to the sound of darkness crumbling.”

- George E. Palade

Here are the main bullet points, followed by a Venn diagram lacking in explanatory value:
  • Anxiety is about reactivity in the face of uncertainty and potential danger
  • Mood is about trophicity
  • Cognition is about connectivity and congruence—within the organism, and with the environment
  • Consciousness is about monitoring the environment through the mind (anxiety, mood and cognition)
  • Happiness is about achieving GuU objectives

Fig. 1 (Niculesc et al., 2010). Overlap and interdependence: Venn diagram.

In my view this general framework is comparable to horoscopes and fortune telling: so vague that almost anything could fit. However, the authors do get more specific when they speculate on the testable therapeutic implications of "whole organism effects" (see Table 1 below, in the Appendix). Some are radical (anti-cancer medications to treat mood disorders; mood meds to treat cancer); others are mundane (anti-hypertensive medication to treat anxiety [yeah, beta blockers, how novel]; anti-anxiety meds to treat hypertension).

But it gets better!
The above ideas and paradigms can be modeled using a three-dimensional spatial representation of the life landscape–Lifescape, and of the mental landscape–Mindscape. The three dimensions for the Lifescape are G, u, U. The three dimensions for the Mindscape are mood, cognition and anxiety. The axes are not orthogonal, to reflect the interdependence of the three domains. Thus, changes in one dimension translate into changes in the other two dimensions.

Fig. 2 (Niculesc et al., 2010). Mindscape 3D modelling of anxiety, mood and cognition. At each moment in time, an individual is represented by a point with (x, y, and z) coordinates in this tri-dimensional space. The sum of points over time is distributed as a cloud, unique to each individual.

What a coincidence that the name of the authors' company is Mindscape Diagnostics! Hence we have Mindscape psychiatry, Mindscape therapeutics, Mindscape addictions, et cetera, et cetera. Looks like they're really on cloud 9...


1 No, the article was not in Medical Hypotheses. Presumably the Journal of Affective Disorders requires some sort of peer review for special review articles.


Niculescu AB 3rd (2006). Polypharmacy in oligopopulations: what psychiatric genetics can teach biological psychiatry. Psychiatr Genet. 16:241-4.

Niculescu AB 3rd, Schork N, Salomon D. (2010). Mindscape: A convergent perspective on life, mind, consciousness and happiness. Journal of Affective Disorders, 123 (1-3), 1-8 DOI: 10.1016/j.jad.2009.06.022

Appendix (click on image for larger view)

Table 1 (Niculesc et al., 2010). Mind disorders, whole-organism co-morbidities and testable potential therapeutic implications.

From Bacteria to Society: Mind, Consciousness, and Happiness Explained
We propose that mind, consciousness and happiness, readily recognizable at a human organism level as functions of the brain, may hold true in a more rudimentary form at an organ and cellular level. As such, we postulate that they are not restricted to humans or primates, but exist in some form starting with unicellular organisms, and evolve in complexity along with the organism...

...this systems-level view can also be extended to the macro realm of social sciences, by looking at efforts to achieve GuU at a family level, societal level and national level.

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Monday, May 03, 2010

Artistic Renditions of the Science of the Impossible

The Bureau of Subliminal Images [from The London Institute of ’Pataphysics]

A subliminal image is an image that is inadvertently concealed within a natural feature or manufactured object. It can be revealed only by an act of imagination on the part of the observer. Once found, its existence can be demonstrated to another: it can be solved. An imaginary solution par excellence (and an imagery solution as well!). Subliminal images constitute a sort of rational hallucination, and Alfred Jarry was fond of this quotation from Leibniz: “Perception is only a hallucination that is true.” (Days and Nights)

Such a definition implies various exclusions. Deliberately manufactured visual puzzles, illusions and the familiar “duck/rabbit” tests employed by psychologists do not qualify as subliminal images. Likewise, innumerable devotees of belief systems - religious enthusiasts, conspiracy theorists - are capable of, indeed they often cannot avoid, perceiving evidence of their monomanias in the most unlikely corners of external reality (the arrangement of pips inside vegetables, the products of mass-advertising). Too often, unfortunately, these images are only perceptible to their fellow zealots, which disqualifies them as objects for our investigation.

'Pataphysics is a faux science dreamed up by the turn-of-the-20th century absurdist writer, eccentric, and bicycle enthusiast Alfred Jarry.
'Pataphysics is a pseudophilosophy dedicated to studying what lies beyond the realm of metaphysics. It is a parody of the theory and methods of modern science and is often expressed in nonsensical language. The term was coined and the concept created by French writer Alfred Jarry (1873–1907), who defined 'pataphysics as "the science of imaginary solutions, which symbolically attributes the properties of objects, described by their virtuality, to their lineaments".

Jarry provides inspiration for More Often Than Always, Less Often Than Never, a present day art exhibition curated by Noxious Sector,
an ongoing collaborative endeavor by Canadian artists Ted Hiebert, Doug Jarvis and Jackson 2Bears, dedicated to the exploration of alternative cognitive function, the paranormal and the absurd. Conceived as a formalized forum for informal inquiry, Noxious Sector projects take the form of performances, curatorial initiatives and artistic collaborations.
The show will be held at the Richmond Art Gallery [BC, Canada] later this year (Nov 26, 2010 - Jan 23, 2011).

MORE OFTEN THAN ALWAYS, LESS OFTEN THAN NEVER invites artists from around the world to engage with notions of impossibility, uncertainty and the imaginary. Situated on the impossible side of probability, the project invites renderings of improbability, of disregarded possibilities, phantom conjectures, plausible insanities of one sort or another, all of which challenge standardized formulations of what is allowed, acceptable, logical or feasible. This is a call for imaginary solutions to real questions, however artists define the respective places of the imagination and reality for themselves. The curatorial process for the exhibition will also engage these themes, mobilizing UNRESOLVED METHODOLOGIES to problematize its own conceptual framework...

See these guidelines for more information. And don't forget the 2010 World Telekinesis Competition (DEADLINE EXTENDED until MAY 16, 2010)!

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Sunday, May 02, 2010

Coordinates, Consensus, Cooperation: Towards a Cumulative Science of Human Brain Function

The first symposium at Cognitive Neuroscience Society 2010 Annual Meeting two weeks ago was an important and ambitious one, a call for the neuroimaging community to advance beyond the current piecemeal single-study approach to produce comprehensive, structured, and searchable databases. The session was chaired by University of Colorado Boulder post-doc Dr. Tal Yarkoni, author of the excellent blog, [citation needed].

Symposium Session 1
Sunday, April 18, 10:00 am - 12:00 pm, Westmount et al Ballroom

Towards a cumulative science of human brain function

Chair: Tal Yarkoni, Columbia University, University of Colorado at Boulder

This symposium is designed to promote development of a cumulative science of human brain function that advances knowledge through formal synthesis of the rapidly growing functional neuroimaging literature. The first speaker (Tal Yarkoni) will motivate the need for a cumulative approach by highlighting several limitations of individual studies that can only be overcome by synthesizing the results of multiple studies. The second speaker (David Van Essen) will discuss the basic tools required in order to support formal synthesis of multiple studies, focusing particular attention on SumsDB, a massive database of functional neuroimaging data that can support sophisticated search and visualization queries. The third and fourth speakers will discuss two different approaches to combining and filtering results from multiple studies. Tor Wager will review state-of-the-art approaches to meta-analysis of fMRI data, providing empirical examples of the power of meta-analysis to both validate and disconfirm widely held views of brain organization. Russell Poldrack will discuss a novel taxonomic approach that uses collaboratively annotated meta-data to develop formal ontologies of brain function. Collectively, these four complementary talks will familiarize the audience with (a) the importance of adopting cumulative approaches to functional neuroimaging data; (b) currently available tools for accessing and retrieving information from multiple studies; and (c) state-of-the-art techniques for synthesizing the results of different functional neuroimaging studies into an integrated whole.

Tal has compiled this helpful list of links and slides from the CNS symposium.

In future posts, I'll try to summarize the major points of each speaker.

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