Exploring neural dysfunction in ‘clinical high risk’ for psychosis: A quantitative review of fMRI studies

Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

“…The majority of these studies show reduced activity in multiple frontal and parietal regions, a pattern that has also been reported in a meta-analysis of 10 fMRI studies (Fusar-Poli, 2012) and a quantitative review of 32 fMRI studies of CHR (both of which included a heterogeneous mix of executive function, memory, and other tasks)(Dutt et al, 2015). The quantitative review by Dutt et al in 2015 included a pooled analysis of 5 studies of the N-back WM task, which showed reduced activity in CHR in the inferior parietal lobule.…”

“…While recent meta-analytic studies of CHR to date report a general pattern of hypoactivity in executive regions in CHR (Dutt et al, 2015; Fusar-Poli, 2012), a large body of work in persons at familial high risk for psychosis and those with schizophrenia suggests that both hypo- and hyperactivity are observed in these populations, with regions of hyperactivity seen as potentially compensatory for deficits in other regions (Minzenberg et al, 2009; Seidman et al, 2006; Thermenos et al, 2013; Whitfield-Gabrieli et al, 2009). The medication-naïve CHR participants in this study were more impaired than the medication-exposed group (e.g., lower intellectual ability and A-CPT interference task performance, lower social and role function, higher SIPS grandiosity scores and higher lifetime drug use), yet they were able perform the N-back task at a level equal to controls.…”

“…Functional magnetic resonance imaging (fMRI) has been used to examine brain activity during the CHR state in response to cognitive tasks, such as working memory (WM), that are reliably impaired in participants with frank psychosis (Dutt et al, 2015) (Fusar-Poli et al, 2011b; Giuliano et al, 2012). WM is the capacity for temporary storage, maintenance and manipulation of information in the absence of perceptual stimulation.…”

“…To our knowledge, 11 fMRI studies of WM in CHR have been reported to date (Dutt et al, 2015; Fusar-Poli, 2012; Fusar-Poli et al, 2010a; Fusar-Poli et al, 2011c; Fusar-Poli et al, 2010b; Morey et al, 2005; Schmidt et al, 2014a; Schmidt et al, 2013; Smieskova et al, 2012; Yaakub et al, 2013). The majority of these studies show reduced activity in multiple frontal and parietal regions, a pattern that has also been reported in a meta-analysis of 10 fMRI studies (Fusar-Poli, 2012) and a quantitative review of 32 fMRI studies of CHR (both of which included a heterogeneous mix of executive function, memory, and other tasks)(Dutt et al, 2015).…”

“…The heterogeneity introduced by medication differences may impact cognitive and MRI study results. In the quantitative review by Dutt et al in 2015, for example, some subjects included in the WM analysis had been exposed to psychotropic medication. Two studies reported that some subjects were on antipsychotic and/or antidepressant medication(Pauly et al, 2010; Smieskova et al, 2012), and three reported that CHR participants were antipsychotic-naïve but did not describe the use of other psychiatric medications.…”