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.

The morphometric co‐atrophy networking of schizophrenia, autistic and obsessive spectrum disorders

“…In line with these data a recent study by our research group demonstrated that SCZD, OCSD and ASD do not show distinctive patterns of GM alterations; rather, these three spectra showed a common pattern, which can be divided into two clusters of alterations extending across the insulae, medial thalamic and the cingulate cortices (Cauda, et al, 2017). This finding was also recently supported by a study on functional alterations (Sprooten, et al, 2017), which has showed that very few functional differences can be statistically observed in a variety of psychiatric conditions (i.e., schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder). Of note, this specific pattern of alterations common to SCZD, OCSD, and ASD is probably not only shared by these three spectra, but also by other psychiatric disorders (Buckholtz & Meyer-Lindenberg, 2012;Caspi, et al, 2014;Crossley, et al, 2014;McTeague, et al, 2016).…”

Motor system dysfunction in the schizophrenia diathesis: Neural systems to neurotransmitters

“…Basic motor control and behavior are linked with a rich set of cortical and sub-cortical brain regions (10), an aspect that is appropriately recognized in the Research Domain Criteria constructs matrix (129). Whether the explication of domain related effects will ultimately inform and transform the diagnostic concept of schizophrenia, is itself an open question (130, 131), yet one worthy of investigation.…”

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

“…Given the critical role of the amygdala in anxiety and consistently observed hyperresponsivity in this region in anxiety-related disorders [18, 36, 37], previous rt-fMRI NF studies trained subjects to downregulate neural activity in this region and demonstrated that this strategy has the potential to enhance ER and attenuate anxious arousal [38-41]. In line with current neurocircuitry models of ER, successful downregulation of the amygdala was accompanied by increased functional connectivity between the amygdala and prefrontal regulatory regions in both, healthy subjects [39, 42] as well as patient populations with exaggerated anxiety [40, 43].…”