Alterations in hippocampal connectivity across the psychosis dimension

Abstract

Recent evidence demonstrates that hippocampal hyperactivity helps mediate psychosis. Using resting state functional magnetic resonance imaging (rsfMRI), we examined hippocampal connectivity alterations in individuals with psychosis (PS) versus healthy controls (HC). Because of its putative greater involvement in psychiatric disorders, we hypothesized that the anterior hippocampus network would show greater dysconnectivity in psychosis. We tested rsfMRI connectivity in 88 PS (including 21 with schizophrenia; 40 with schizoaffective disorder; 27 with psychotic bipolar I disorder) and 65 HC. Seed-based voxel-wise connectivity analyses were carried out using whole, anterior, and posterior hippocampal seeds. No significant differences in functional hippocampal connectivity were found across the three conventional diagnoses. PS were then contrasted with HC, showing strong reductions in anterior hippocampal connectivity to anterior neocortical regions, including medial frontal and anterior cingulate cortices, as well as superior temporal gyrus, precuneus, thalamus and cerebellum. Posterior hippocampal seeds also demonstrated decreased connectivity in PS, with fewer dysconnected regions and a posterior/cerebellar distribution. Whole hippocampal outcomes were consistent with anterior/posterior hippocampal connectivity changes. Connectivity alterations did not correlate with cognition, clinical symptoms, or medication effect variables. Our results suggest a psychosis network of decreased hippocampal connectivity with limbic and frontal contributions, independent of diagnostic categories.

Cell-based therapies for the treatment of schizophrenia

“…Indeed, this is consistent with the preclinical data described above where inactivation of the vHipp can reduce dopamine population activity and normalize behavioral correlates of positive symptoms in a rodent model of schizophrenia 21 . Further, hippocampal connectivity is disrupted in schizophrenia patients 40 . Specifically, the anterior hippocampus shows decreased connectivity with regions such as the anterior cingulate and the medial prefrontal cortex 40 .…”

“…Further, hippocampal connectivity is disrupted in schizophrenia patients 40 . Specifically, the anterior hippocampus shows decreased connectivity with regions such as the anterior cingulate and the medial prefrontal cortex 40 .…”

“…Moreover, deficits in connectivity between these regions have been observed in schizophrenia patients 40,56,57 . Indeed, we have previously demonstrated that hippocampal manipulations not only alter behavioral deficits consistent with positive symptoms, but can also regulate cognitive functions dependent on the PFC 58 .…”

Anterior Hippocampal–Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment

“…17,18 To date, few studies have characterized FC of the hippocampus in antipsychotic naive FEP patients by using techniques that differentiate FC along the anterior-posterior axis; however, several studies have assessed hippocampal-brain FC in chronic schizophrenia patients, both unmedicated and medicated. [19][20][21] In this study, we aimed to characterize subregional hippocampal-whole brain FC in antipsychotic naïve FEP subjects using masked-hippocampal-groupindependent component analysis (ICA) with dual regression. 22 This data-driven technique reproducibly segments the hippocampus into independent components (ICs) that occupy distinct subregions along the anterior-posterior axis and display distinct patterns of whole brain FC.…”

Reciprocal Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions

“…Specifically, aberrant connectivity of two key anatomically inter-connected structures, the thalamus and hippocampus, has been implicated in neuropsychiatric disorders (Brown et al, 2017) and schizophrenia in particular (Samudra et al, 2015). The thalamus serves as a critical hub for flow of sensory and higher-order information, facilitating information integration across cortical networks (Guo et al, 2017;Hwang et al, 2017).…”