Fronto-parietal hypo-activation during working memory independent of structural abnormalities: Conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients

Abstract

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline. Therefore the emergent view is that fronto-parietal deficits in function and structure characterize HR-S. However, it is unknown if fronto-parietal sub-regions in which fMRI-measured hypo-activity might be observed are precisely those regions of the cortex in which gray matter deficits are also observed. To investigate this question we conducted conjoint analyses of fronto-parietal function and structure in HR-S (n=19) and controls (n=24) with no family history of psychoses using fMRI data during a continuous working memory task (2 Back), and sMRI collected in the same session. HR-S demonstrated significantly reduced BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral parietal cortex (BA 7/40). Sub-regions of interest were created from the significant fronto-parietal functional clusters. Analyses of gray matter volume from volume-modulated gray matter segments in these clusters did not reveal significant gray matter differences between groups. The results suggest that functional impairments in adolescent HR-S can be independent of impairments in structure, suggesting that the relationship between impaired function and structure is complex. Further studies will be needed to more closely assess whether impairments in function and structure provide independent or interacting pathways of vulnerability in this population.

Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder

“…Structural MR images were pre-processed using the Statistical Parametric Mapping (SPM) diffeomorphic image registration algorithm (DARTEL) in SPM8 (Friston et al, 1995; Ashburner, 2007; Diwadkar et al, 2011). DARTEL optimizes the fidelity of shape-based deformations applied to fit native images in stereotactic space, and performs favorably relative to other non-linear deformation algorithms (Klein et al, 2009).…”

Preserved Working Memory and Altered Brain Activation in Persons at Risk for Psychosis

“…The equivalence of behavior between the at-risk and comparison groups, despite differences in education, across all three conditions allowed us to attribute the altered patterns of activation to the at-risk mental state (23,29,31,54), as opposed to poorer performance in at-risk participants. Additionally, the comparability of performance across medicated and nonmedicated participants reassures us that the imaging findings were unlikely to be a result of antidepressant therapy.…”

Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

“…These implications generalize to both the cingulate gyrus and the putamen, each of which have been implicated in attention processing, finger tapping, or both (Diwadkar et al, 2011; Fan et al, 2005; Ullen et al, 2003). …”

“…Moreover, studies demonstrate that the structure is also engaged during obligatory attention tasks (Alho et al, 2014), suggesting that the common bases of hyper-modulation reflects an interface between exaggerated motor and attention control in OCD. The basal ganglia have been previously implicated in both finger-tapping tasks (Witt et al, 2008) and in the executive attention network (Diwadkar et al, 2011). Studies indicate that the basal ganglia are activated during rhythmic finger movements to externally guided stimuli (Bednark et al, 2015), suggestive of complimentary functionality to the core motor system.…”