Altered hippocampal centrality and dynamic anatomical covariance of intracortical microstructure in first episode psychosis

Abstract

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2–4 visits over 3–15 months) were acquired for 27 FEP and 29 age‐ and sex‐matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair‐wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin‐rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles.

Neurocognitive functions in persistent negative symptoms following a first episode of psychosis

“…Duan et al, 2020;Matsumoto et al, 2001;Rajarethinam et al, 2001). In a recent paper (Makowski et al, 2020a) used a novel brain imaging measure of the nature of hippocampal connectivity with the rest of the brain (termed hippocampal centrality) and examined the hypothesis that longitudinal changes in the hippocampal circuit are altered in FEP and that such changes are associated with negative symptoms and verbal memory. Importantly, this study observed that lower centrality (or reduced coupling) of the hippocampal circuit with other cortical networks was associated with worse negative symptoms over time, a relationship that was mediated by changes in verbal memory.…”

“…Based on our preliminary report with a smaller sample of 136 FEP patients (Hovington et al, 2013), and our more recent work on verbal memory and negative symptoms (e.g. Makowski et al, 2020a;Makowski et al, 2020b), we hypothesized that verbal memory will significantly differ between the PNS and non-PNS groups. Given that there is a dearth of knowledge of sPNS patients, we also explored functioning, symptom and antipsychotics use in this group.…”

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome

“…This technique has further shed light on multiscale interactions between the hippocampus and manifestscale measures in psychosis. By grouping nodes of the hippocampus together into a hippocampal module, Makowski et al (16) showed that longitudinal structural covariance-based connectivity between the hippocampal module and large-scale brain networks (17) is significantly reduced in FEP in comparison to healthy controls. At the manifest-scale, such a reduction in hippocampalcortical connectivity was associated with more severe negative symptoms, as mediated by impaired episodic memory (16).…”

“…By grouping nodes of the hippocampus together into a hippocampal module, Makowski et al (16) showed that longitudinal structural covariance-based connectivity between the hippocampal module and large-scale brain networks (17) is significantly reduced in FEP in comparison to healthy controls. At the manifest-scale, such a reduction in hippocampalcortical connectivity was associated with more severe negative symptoms, as mediated by impaired episodic memory (16). Using longitudinal data, Makowski et al (16) thus 5 characterized a multiscale disease progression from hippocampal-cortical dysconnectivity to episodic memory and negative symptoms for the first time.…”

Network properties of intracortical myelin associated with psychosocial functioning in bipolar I disorder

“…24,25 Previous studies have shown that structural covariance networks derived from cortical myelin values align to a significant extent with functional connectivity networks. 26,27 Several studies have observed significant structural network changes in other brain disorders such as schizophrenia/ psychosis, 28,29 obsessive-compulsive disorder, 30 mild traumatic brain injury, 31 Parkinson's disease, 32 Alzheimer's disease 33 and binge drinking. 34 To our knowledge, no studies to date have examined structural covariance networks of cortical myelin in relation to psychosocial functioning in BD.…”