Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk

Abstract

Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Functional deactivations: Change with age and dementia of the Alzheimer type

“…It will be of particular interest to determine whether such changes can serve as a preclinical marker for Alzheimer's disease, and whether those individuals without dementia who show atypical activation patterns are more likely to convert to dementia. Changes in deactivation patterns have also been reported in other populations whose brain function differs from that of healthy young adults, including patients with amnesia, schizophrenia, or fragile X syndrome (42,(45)(46)(47). In conclusion, these results introduce important opportunities to explore the functional properties of regions showing deactivations, how their dynamic functional properties relate to their baseline metabolic rates, and how they change with age and dementia.…”

Cognitive Function and White Matter Changes Associated with Renal Transplantation

“…The forceps minor connects the lateral and medial surfaces of the frontal lobes, which regulate executive function[19]. Abnormal frontal connectivity is present in mental illness with executive dysfunction[32, 33]. The cingulate gyrus is part of the limbic system located immediately above the corpus callosum and plays a role in executive function along with learning, processing and memory[20].…”

Executive Function, Neural Circuitry, and Genetic Mechanisms in Schizophrenia

“…Investigations of abstract rule inference (Berman et al, 1995; Buchsbaum et al, 2005; Monchi et al, 2001), conflict management and monitoring (Macdonald et al, 2000; Pardo et al, 1990), verbal fluency (Frith et al, 1991; Gourovitch et al, 2000), and working memory (Cohen et al, 1997; Tsuchida and Fellows, 2009) in healthy individuals consistently show reliance on key frontal regions, most notably, the dorsolateral, ventrolateral and anterior cingulate cortices. Abnormal functional measures in each of these regions have been demonstrated in schizophrenia during these same paradigms (Becker et al, 2008; Berman et al, 1986; Callicott et al, 2003b; Kerns et al, 2005; Spence et al, 2000; Weinberger et al, 1986), bolstering the hypothesis of frontal primacy in schizophrenic pathophysiology (Elvevag and Goldberg, 2000; Weinberger et al, 1994) but increasing the imperative to understand how these disparate frontal nodes interact in concert during illness.…”

“…Additional factors, such as specific task paradigm characteristics (Barbalat et al, 2009; Curtis et al, 1999; Holmes et al, 2005; Macdonald et al, 2005; Quintana et al, 2003), clinical heterogeneity, and medication status (see Weiss et al, 2003 versus Weiss et al, 2007 showing greater activation during a modified Stroop paradigm when medicated patients were studied, but the opposite finding when a separate cohort of unmedicated patients was studied) may also play a role. Regardless of the cause of directional discrepancies, because most studies of DLPFC connectivity (covariance with activity in other brain regions) demonstrate abnormal disconnection with other neocortical structures important for executive function (Bassett et al, 2008; Kim et al, 2003; Schlösser et al, 2003; Spence et al, 2000; Tan et al, 2006; Whitfield-Gabrieli et al, 2009; Wolf et al, 2007; Woodward et al, 2009; Yasuno et al, 2005) and because even patients who overactivate the DLPFC still often do not achieve a higher performance on executive tasks than their healthy control comparators, it is clear that DLPFC is dysfunctional in schizophrenia. In the context of the cellular pathological, structural and neuroreceptor imaging DLPFC findings, such altered DLPFC physiology appears to be an expected and robust illness-related phenotype reflecting reduced neurophysiological resources in which microcircuits are either overtaxed or overwhelmed.…”

“…Reduced white matter integrity (fractional anisotropy measured by DTI) in the cingulum bundle, which shows a relationship with impaired Wisconsin Card Sorting Task performance (Kubicki et al, 2003) offers a another reason to predict altered communication between the anterior cingulate and prefrontal regions. In any case, frontocingulate functional dysconnectivity has been explicitly described during verbal fluency (Spence et al, 2000) and modified continuous performance task (Honey et al, 2005) performance in schizophrenia. Further, structural equation modeling of regional D 2/3 receptor binding has shown altered connectivity from other frontal cortical regions (as well as thalamus and parietal cortex) to the anterior cingulate (Yasuno et al, 2005).…”