Understanding Cancer Clinical Trial Participation in Rural Communities: A Qualitative Focus Group Study.

Separate lines of evidence have recently converged in showing significant statistical relationships between patterns of brain connectivity and brain structural features (Fotiadis et al. ; Hong et al. ; Sarwar et al. ). Some investigations in this area of research have focused on people with psychosis or at clinical high-risk for psychosis (CHR-P) (Aberizk et al. ; Prasad et al. ; Harms et al. ). Studies of CHR-P involve the administration of standardized, structured interviews that rate the severity of attenuated psychotic symptoms (e.g., odd beliefs and perceptions) that typically precede frank psychosis (Walker et al. ). In the literature on structure–function coupling in psychosis, the hippocampus has received considerable attention because both hippocampal structural and functional alterations are observed across the spectrum of psychotic psychopathology. Reduced hippocampal volume (HV) is among the most well-replicated brain morphological features of psychotic disorders (Gutman et al. ; van Erp et al. ); it is also observed in first episode psychosis (FEP) and most pronounced in those whose symptoms do not remit within two years of illness onset (McHugo et al. ). Considered together, evidence suggests that reductions in HV are well-established in psychotic disorders (Gutman et al. ), including in FEP (McHugo et al. ), but their timing relative to the onset of psychosis remains unresolved. Meta-analyses do not provide evidence for significant baseline differences in HV between people at CHR-P and HCs (Walter et al. ) or between people at CHR-P who develop psychosis within two years and those who do not (Hinney et al ). More broadly, reduced HV is not prognostic of psychotic illness. It is a common feature in people with bipolar and major depressive disorders (Brosch et al. ), neuroendocrine disease (Burkhardt et al. ), and thought disorder (Stein et al. ). Longer-term follow-up (> 5 years) of people at CHR-P shows that approximately 20% of youth at CHR-P will develop a psychotic disorder, 60% will not remit from CHR-P status, and 70% of those who do not develop psychosis will develop an affective disorder (Cadenhead et al. ). Thus, CHR-P status encompasses a spectrum that warrants further investigation. With respect to function, hippocampal hyperactivity is a risk factor for psychotic disorder and an indicator of acute psychotic illness (Heckers and Konradi ; McHugo et al. ; Modinos et al. ; Schobel et al. ). It remains unknown whether hippocampal hyperactivity in acute and prodromal stages of psychosis is associated with altered hippocampal . We are aware of one previous study that demonstrated hippocampal hyperactivity in FEP relative to HCs, but normal hippocampal connectivity with brain-wide functional networks (e.g., default mode), providing the first direct evidence that hippocampal hyperactivity may not translate to aberrant functional network dynamics (McHugo et al. ). However, the authors of that previous study demonstrated that their results were sensitive to the granularity and location of independent components of brain network connectivity and suggested that future investigations consider individual brain areas as seed regions of interest (ROIs). Indeed, as the literature on hippocampal structure–function coupling has burgeoned, many investigations have adopted a seed-based ROI approach in functional connectivity (FC) analysis. FC is a measure of covariance in brain regional blood oxygenation level-dependent (BOLD) signal, measured during functional magnetic resonance imaging (fMRI), that has informed decades of research on normative brain function and aberrations in psychiatric disorders (Fornito et al. ; Samudra et al. ).