Addressing reverse inference in psychiatric neuroimaging: Meta-analyses of task-related brain activation in common mental disorders

Abstract

Functional magnetic resonance imaging (fMRI) studies in psychiatry use various tasks to identify case-control differences in the patterns of task-related brain activation. Differently activated regions are often ascribed disorder-specific functions in an attempt to link disease expression and brain function. We undertook a systematic meta-analysis of data from task-fMRI studies to examine the effect of diagnosis and study design on the spatial distribution and direction of case-control differences on brain activation. We mapped to atlas regions coordinates of case-control differences derived from 537 task-fMRI studies in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder comprising observations derived from 21,427 participants. The fMRI tasks were classified according to the Research Domain Criteria (RDoC). We investigated whether diagnosis, RDoC domain or construct and use of regions-of-interest or whole-brain analyses influenced the neuroanatomical pattern of results. When considering all primary studies, we found an effect of diagnosis for the amygdala and caudate nucleus and an effect of RDoC domains and constructs for the amygdala, hippocampus, putamen and nucleus accumbens. In contrast, whole-brain studies did not identify any significant effect of diagnosis or RDoC domain or construct. These results resonate with prior reports of common brain structural and genetic underpinnings across these disorders and caution against attributing undue specificity to brain functional changes when forming explanatory models of psychiatric disorders. Hum Brain Mapp 38:1846-1864, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: Research Domain Criteria; anxiety disorders; bipolar disorder; functional magnetic resonance imaging; major depressive disorder; meta-analyses; obsessive compulsive disorder; schizophrenia.

Figure 1

The top 10 regions among whole‐brain studies across all disorders (ranked by frequency of reported case‐control difference, adjusted for region size). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Percentage of studies within each diagnostic category reporting one or more coordinates within each subcortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Percentage of studies across all diagnoses reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Percentage of studies of schizophrenia reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Percentage of studies of major depression reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 6

Percentage of studies of bipolar disorder reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 7

Percentage of studies of anxiety disorders reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 8

Percentage of studies of obsessive‐compulsive disorder reporting one or more coordinates within each cortical structure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 9

For each region, the contribution of studies that used tasks engaging domains defined by the RDoC project is shown as a proportion of the total number of studies showing case‐control differences in that region. Regional distributions can be compared to the overall RDoC distribution shown in the bars on the right of each figure. [Color figure can be viewed at http://wileyonlinelibrary.com]