High Stakes in Small Mistakes: Abused Youths’ Brains Show Hypersensitivity to Errors

Emotional and behavioral problems are common among adults who were maltreated as children (1). These maladaptive outcomes appear, at least in part, to reflect enduring changes in brain structure and function that emerge in the wake of severe stressors, such as childhood physical abuse (2). Research that clarifies the extent to which such changes stem from the experience of abuse itself as opposed to the psychiatric conditions that maltreated children often develop, such as posttraumatic stress disorder and depressive disorders, is important.

Indeed, a specific understanding of the path from maltreatment to adverse outcomes could inform maltreatment-related policy and practice, enabling us to implement both more effectively and efficiently. It could, for instance, help us determine where we should target scarce resources in order to best decrease maltreatment and its negative consequences. Do we invest in across-the-board services for all maltreated youths, or do we focus some resources more heavily on individuals who show abuse-related psychopathology? It could also guide our selection of interventions or preventive approaches that are most likely to benefit particular people. If a patient presents with a history of maltreatment but only subthreshold psychiatric symptoms, might one intervention approach be more efficient and effective than another? Research that helps us to answer such questions decisively could have a striking impact on public health.

Why, then, are there so few studies that yield clear evidence about maltreatment and whether it leads directly to changes in brain activity patterns or engenders such changes indirectly, by provoking symptoms that in turn alter the brain? One reason is that research that supports confident inferences about whether neural changes stem from life experiences, from symptoms, or from both is hard to conduct. Recruitment alone is unusually challenging, because participants should ideally be distributed across multiple otherwise-matched groups (non-maltreated/psychiatric disorder, maltreated/psychiatric disorder, non-maltreated/disorder-free, and maltreated/disorder-free). However, although the fourth group (maltreated/disorder-free) is theoretically possible, it is rare to find people with maltreatment histories who are entirely resilient to psychopathology. Thus, including such a group is both impractical and unlikely to yield data that are relevant to more than a few individuals. In addition, researchers must carefully exclude participants with experiences (e.g., drug abuse, brain injury) and characteristics (e.g., neurological anomalies) that could muddy results or introduce irrelevant but potentially influential differences between group members’ brains.

The process of selecting cognitive tasks that facilitate meaningful behavioral and neural comparisons among group members introduces further challenges. Optimal tasks tap discrete cognitive processes that are vulnerable to disruption by early-life maltreatment and also elicit robust, reliable neural response patterns. Furthermore, ideal tasks adapt interactively to each participant’s ability level, becoming harder when a person performs well and easier when a person performs poorly. This feature ensures that no participants experience the same task as particularly difficult or easy.

These are just a few of the issues that complicate studies of neural function and maltreatment; this work is not for the faint of heart. It is thus exciting to see studies that address these issues head-on come to publication. Lim and colleagues, who describe just such a study in this issue of the Journal (3), are to be commended for what they have achieved.

Lim et al. used functional neuroimaging to examine neural activity, indexed as the ratio of deoxygenated to oxygenated blood, throughout the brain while adolescents executed or withheld motor responses in response to rapidly presented cues on a computer screen. Importantly, the task was designed to adjust stimulus presentation rates so that each participant succeeded on only half of the trials when they were cued to withhold a response. The unsuccessful, or “failed inhibition,” trials were of particular interest, because maltreated participants were expected, given their histories of persistent, harsh punishment early in life, to show a distinctive neural hypersensitivity to their own errors.

To test the hypothesis that maltreated youths’ brains would respond more sensitively to behavioral errors than would the brains of non-maltreated youths, the authors compared neuroimaging data obtained during this stop-signal task in three demographically matched, unmedicated/drug-free groups of adolescents—one with documented histories of physical (but not sexual) abuse, one with psychiatric diagnoses but no abuse history, and one with no psychiatric diagnoses and no abuse history. In their analyses, the authors first subtracted the activity observed in each participant’s brain during “go” trials (which did not require inhibition and served as a baseline control condition) from the activity evident in the same participant during failed inhibition trials. Activity evident only during failed inhibition was then averaged across group members, and these averages were compared across groups. Although activity differences appeared in many voxels (units of analysis that each represent roughly a million neurons), only differences whose magnitude exceeded a predetermined threshold, or that extended across sizable clusters of contiguous voxels, were reported.

As the authors had predicted, during failed inhibition trials, maltreated participants showed exaggerated activity relative to both comparison groups in specific brain areas—predominantly clustered within the dorsomedial prefrontal cortex—that previous studies have found to be active when people make behavioral errors. These group differences held up when participants were matched on IQ, response speed, and psychopathology symptoms, each of which could have accounted, at least in part, for the findings. In particular, the maltreated group showed heightened activity in voxel clusters within the supplementary motor area and the adjacent presupplementary motor area relative to both psychiatric and healthy comparison subjects. Previous research in both human and animal studies implicates these components of the supplementary motor complex, particularly the presupplementary motor area, in monitoring for one’s own errors, although they appear also to participate in a more complex array of processes that link cognition and action (4).

The pattern of atypical activation observed in maltreated youths in the Lim et al. study is consistent with previous findings linking early-life adversity to amplified neural responses in brain regions that support monitoring and directing patterns of thought and behavior (e.g., 5). Furthermore, it contrasts markedly with atypical patterns recently observed in people prone to impulsivity, such as adults with cocaine or alcohol dependence, who show diminished activity in the supplementary motor complex relative to healthy and psychiatric controls (6, 7).

Neuroimaging findings are often delicate and ephemeral—what appears in one study is not guaranteed to emerge in the next. However, if Lim and colleagues’ findings regarding regional neural anomalies in maltreated youths can be replicated, a logical next step will be to incorporate such results into systems-level models that integrate structural and functional data across the whole brain. Such work holds promise for identifying comprehensive “neural signatures” associated with maltreatment histories, much like those emerging in the literature for psychiatric conditions, including autism spectrum disorder and attention deficit hyperactivity disorder (8, 9). Although such models are still developing, integrative knowledge about neural signatures associated with such experiences as early-life maltreatment could, in the long term, prove helpful to clinicians as they tailor interventions for patients in their care. In the short term, these findings provide us with information that individual patients may find useful to hear: a hypersensitive response to errors and their potential consequences is not only common among persons who were maltreated during childhood, but it also appears to be related to brain changes that were probably rooted in adaptive responses to a punitive environment.