Sunday, August 31, 2008

Who Can You Trust?

As a sequel to the "Trust Your Insula" theme from last time (i.e., Borderline … feels like I'm goin' to lose my mind), The Neurocritic has consulted the BrainMap database, which revealed that the anterior insula is activated in a wide variety of cognitive, perceptual, and motor tasks. But first, a recap.

In their recent Science paper entitled The Rupture and Repair of Cooperation in Borderline Personality Disorder, King-Casas et al. (2008) examined how well individuals with borderline personality disorder trusted others in an economic exchange game (called, conveniently enough, the Trust Game). In this game, one player (the Investor) gives a sum of money to the other player (the Trustee). The investment triples, and the Trustee decides how much to give back to the Investor. Relative to the control group, the BPD group was more likely to make a small repayment after receiving a small investment. This reflected a lack of cooperation (or "coaxing" behavior) designed to induce the Investors to trust their partners.

For the fMRI portion of the study, the authors bypassed more general analyses comparing BPD and control brains during the point of investment and the point of repayment. Instead, the major neuroimaging result contrasted the receipt of low investment offers vs. high investment offers, as illustrated below. Control brains showed a nearly perfect linear correlation between $ offer and activity in the anterior insula (expressed here as a negative correlation, because low $ offers correlated with high insula activity). Such a relationship was not observed in BPD brains. In fact, no brain region in the BPD group showed a difference between high and low offers.

Fig. 3 (King-Casas et al., 2008). Response of 38 healthy trustee brains and 55 BPD trustee brains to level of cooperation. (Top). Results of within-group GLM [general linear model] analyses identified cortical regions with greater response to small investments (less than or equal to $5) relative to large investments (greater than $10). (Bottom). Percent change in hemodynamic signal was averaged from the 115 most significant voxels identified in the group-level GLM during the 4- to 8-s period following the revelation of investment. The means + SE of the resulting signal are plotted in $4 bins.1 Responses in bilateral anterior insula in healthy trustees scale strongly and negatively with the size of investment (r = –0.97; bottom left). In contrast, similar analyses in individuals with BPD showed no such relation.

The authors linked the insular activation to the detection of social norm violations in interpersonal contexts, concluding that individuals with BPD are deficient in this regard.2 But what are the participants really thinking about during the 4-8 sec interval following a stingy offer? Do we have yet another example of reverse inference here?

Below is a figure generated from entering the x, y, z coordinates from the right insular focus shown above into the Sleuth program (available at, which searched the available database of papers for matches. The resulting list of coordinates and experiments was then imported into the GingerALE program, which performed a meta-analysis via the activation likelihood estimation (ALE) method (see this PDF). 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.

Perhaps the control subjects in the King-Casas et al. study were muttering to themselves about the stingy offer. Maybe they were engaging working memory processes to a greater extent on those trials. Or maybe they were remembering a time when they were shortchanged at the grocery store. Do we conclude, then, that the BPD subjects did not do any of those things? Or that they engaged those types of processes to an equivalent extent after low and high offers?

To summarize, the extrapolation about the insula and social norm violations was based on a handful of trials from 38 different control participants. I'll leave you with a few questions to ponder. Can the study can really say anything specific about the insular response on those low $ offers? Do we trust that the rest of the brain is completely silent on the matter? We do know that the BPD group scored lower than controls on a self-report measure of trust (the Interpersonal Trust Scale), but do we know what they were really thinking about during the trust game? At the end of the day, does this finding "give psychiatrists a better diagnostic tool and a brain area to target with therapy or drugs when treating BDP"?

What do you think?


1 Note that these 6 monetary bins were formed from a total of 10 trials per dyad.

2 See The Right and The Good and The Insula for discussion of yet another Science paper; this one localized the concept of fairness to the insula.


B. King-Casas, C. Sharp, L. Lomax-Bream, T. Lohrenz, P. Fonagy, P. R. Montague (2008). The Rupture and Repair of Cooperation in Borderline Personality Disorder Science, 321 (5890), 806-810 DOI: 10.1126/science.1156902

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