All behavior is proximally caused by the brain, but the neural causes of most complex behaviors are still not understood. Much of our ignorance stems from the fact that complex behavior depends on distributed neural control. Unlike a reflex, where the arc from sensation to action can be traced through a few synapses, most volitional behavior involves a dense causal web through which stimuli, memories, beliefs, and other factors exert their effects. Disruption anywhere in this causal web can produce effects that are difficult to trace back to their origin. Against this background, the finding that focal lesions of the ventromedial prefrontal cortex could lead to immoral and even criminal behavior generated considerable surprise and interest (1, 2). While a number of rare cases have now been described in whom a focal lesion caused criminality, these are neither very consistent (the lesions occur in several different anatomical locations) nor at all reliable (only a small fraction of patients, for any lesion location, show criminal behavior). To explain the effects of a lesion on criminal behavior, we need to understand what it is that the lesion does to the rest of the brain, a network-level understanding of lesion effects now provided by the new study of Darby et al. in PNAS (3).
A Disconnection ApproachDarby et al. (3) began by searching the literature for cases documenting criminal behavior following a focal brain lesion. They found 17 of these, with lesions predominantly including the prefrontal cortex but also other regions. To estimate the distal effects of such brain damage, lesion network mapping (4) was used, showing which other brain regions, in healthy brains, would normally be functionally connected with the location of the lesion. This approach effectively treats the brain of the lesion patient as equivalent to a healthy brain in which all those regions functionally connected to the lesion site have been instantaneously affected. To do this, Darby et al. (3) leveraged a large reference dataset of restingstate functional MRI (fMRI) data from healthy individuals [from the Brain Genomics Superstruct Project (5)]. From each lesion patient a map was produced showing where, in this resting-state dataset of healthy individuals, the lesion site had strong functional connectivity. Maps of these functionally connected regions were then overlapped across the patients, producing a composite map showing all of the places in a healthy brain that were predicted to be impacted by the lesions. This innovative approach (4, 6) takes seriously the notion of a disconnection syndrome, a term popularized by Norman Geschwind (7) in the 1960s: it is the idea that behavioral impairments can be caused by the disruption of the connections between brain regions rather than by damage to one particular region itself.The composite connectivity map based on positive correlations in the resting-state dataset in fact included many of the regions that, when themselves lesioned, were associated with criminality: the ventromedial and orbi...