Abstract
Clinical and preclinical studies have established that the hippocampus is hyperactive in schizophrenia, making it a possible biomarker for drug development. Increased hippocampal connectivity, which can be studied conveniently with resting state imaging, has been proposed as a readily accessible corollary of hippocampal hyperactivity. Here, we tested the hypothesis that hippocampal activity and connectivity are increased in patients with schizophrenia. Sixty-three schizophrenia patients and 71 healthy control subjects completed a resting state functional magnetic resonance imaging scan. We assessed hippocampal activity with the amplitude of low frequency fluctuations. We analyzed hippocampal functional connectivity with the default mode network using three common methods: group and single subject level independent component analysis, and seed-based functional connectivity. In patients with schizophrenia, we observed increased amplitude of low frequency fluctuations but normal hippocampal connectivity using independent component and seed-based analyses. Our results indicate that although intrinsic hippocampal activity may be increased in schizophrenia, this finding does not extend to functional connectivity. Neuroimaging methods that directly assess hippocampal activity may be more promising for the identification of a biomarker for schizophrenia.
Highlights
Neuroimaging and postmortem studies indicate that function and structure of the hippocampus are abnormal in schizophrenia [1]
The finding of increased hippocampal amplitude of low frequency fluctuations (ALFF) contrasts with the absence of group differences in intrinsic hippocampal connectivity in our study
ALFF is correlated with baseline cerebral blood flow (CBF) [48] and measures the amplitude of blood oxygen level dependent (BOLD) signal fluctuations in a single voxel, rather than the association between activation of voxels in different brain regions
Summary
Neuroimaging and postmortem studies indicate that function and structure of the hippocampus are abnormal in schizophrenia [1]. The degree of hippocampal hyperactivity has been linked to overall psychopathology [14] and positive symptoms [15, 16], and resolves with antipsychotic treatment [17] This has led to the proposal that hippocampal hyperactivity is a biomarker that can guide the development of new treatments for schizophrenia [6]. The hippocampus is an accessory component of the default mode network and is most often associated with episodic memory and prospective mental scene construction [18] Both hippocampal hyperactivity and default mode network dysconnectivity have been linked to memory deficits and positive symptoms in schizophrenia [1, 19]. We tested the hypothesis that hippocampal activity and connectivity are increased in patients with schizophrenia
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