Aberrant structure and connectivity of the claustrum in the early stages of schizophrenia
Poster No:
521
Submission Type:
Abstract Submission
Authors:
Rebecca Hippen1,2, Jil Wendt1,2, Antonia Neubauer1,2,3, Aurore Menegaux1,2, Christian Sorg1,2,4
Institutions:
1Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM, Munich, Germany, 2TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM, Munich, Germany, 3Center for Neuropathology and Prion Research, University Hospital Munich, LMU, Munich, Germany, 4Department of Psychiatry, School of Medicine and Health, TUM, Munich, Germany
First Author:
Rebecca Hippen
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Co-Author(s):
Jil Wendt
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Antonia Neubauer
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM|Center for Neuropathology and Prion Research, University Hospital Munich, LMU
Munich, Germany|Munich, Germany|Munich, Germany
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM|Center for Neuropathology and Prion Research, University Hospital Munich, LMU
Munich, Germany|Munich, Germany|Munich, Germany
Aurore Menegaux
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany
Christian Sorg
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM|Department of Psychiatry, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany|Munich, Germany
Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, TUM|TUM-NIC Neuroimaging Center, School of Medicine and Health, TUM|Department of Psychiatry, School of Medicine and Health, TUM
Munich, Germany|Munich, Germany|Munich, Germany
Introduction:
Schizophrenia is a debilitating psychiatric condition affecting all domains of life, presenting with positive (e.g. delusions, hallucinations) and negative (e.g. anhedonia) symptoms. Furthermore, the disorder is characterised by cognitive impairments, which can arise as early as ten years before psychotic symptoms (Kahn et al., 2015). Schizophrenia is associated with widespread aberrant connectivity (Wang et al., 2012), which already becomes apparent in the early stages of the disorder (Shon et al., 2018). The claustrum, a small bilateral grey matter region located between insula and putamen, is one of the most highly connected structures of the forebrain (Torgerson et al., 2015; Wendt et al., 2024). It is suggested to be functionally relevant for attention and salience processing, slow-wave sleep (Smith et al., 2020) as well as memory consolidation (Medina et al., 2024), overlapping with deficient functional areas in schizophrenia. A previous post-mortem study has reported a decreased volume of the claustrum in patients with schizophrenia (Bernstein et al., 2016). We hypothesised altered microstructure and cortical connectivity of the claustrum and an association with cognitive impairment in people with recent-onset schizophrenia.
Methods:
Structural (MPRAGE, 0.8mm resolution) and diffusion MRI (1.5mm resolution, b1500 and b3000 s/mm2, 46 directions each) data from 48 patients with non-affective early psychosis (NA-EP), who had been diagnosed with schizophrenia or related disorders in the previous five years, and 48 age- and sex-matched healthy controls from the Human Connectome Project for Early Psychosis was preprocessed and analysed using FSL. Specifically, T1-weighted images were bias-corrected and denoised, and diffusion MR images were corrected for motion, susceptibility-induced distortions and eddy currents before fitting a diffusion tensor model to generate fractional anisotropy (FA) maps. An automated, deep learning based approach (Li et al., 2021) was used to segment the claustrum on T1-weighted images. Microstructure of the claustrum was assessed by computing average claustrum FA, and structural connectivity was analysed by constructing ipsilateral claustrum-cortex streamlines with probabilistic tractography. Episodic memory and language function were assessed with the NIH Toolbox Picture Sequence Memory Test and Picture Vocabulary Test.
Results:
We found significantly reduced volumes of the claustrum relative to total intracranial volume in both left (p=0.024) and right (p=0.0188) hemisphere of NA-EP subjects compared to healthy controls (Fig. 1). In these patients, relative claustrum volumes were significantly correlated with Picture Sequence Memory Test performance (left: r=0.407, p=0.01825; right: r=0.359, p=0.0197). NA-EP subjects also presented with a significantly lower mean FA of the left claustrum (p=0.0351; Fig. 1). Furthermore, connection probability was reduced between both left and right claustrum and ipsilateral temporal association cortices (left: p=0.0095; right: p=0.0451; Fig. 2), which was associated with reduced performance on the Picture Vocabulary Test (left: r=0.359, p=0.0167; right: r=0.383, p=0.0102).
Conclusions:
Our results demonstrate structural alterations of the claustrum in patients with non-affective early psychosis, as well as dysconnectivity between the claustrum and the temporal cortex. The findings are associated with impaired episodic memory and language functioning, suggesting a pathophysiological role of the claustrum in cognitive deficits in the early stages of schizophrenia.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 2
Keywords:
Schizophrenia
Other - non-affective early psychosis, diffusion-weighed imaging, probabilistic tractography, claustrum
1|2Indicates the priority used for review
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2. Kahn, R. S. et al. (2015). Schizophrenia. Nature Reviews Disease Primers, 1(1), 15067.
3. Li, H. et al. (2021). Automated claustrum segmentation in human brain MRI using deep learning. Human Brain Mapping, 42(18), 5862–5872.
4. Medina, C. et al. (2024). The role of the claustrum in the acquisition, consolidation and reconsolidation of memories in mice. Scientific Reports, 14(1), 24409.
5. Shon, S.-H. et al. (2018). Deterioration in Global Organization of Structural Brain Networks in Schizophrenia: A Diffusion MRI Tractography Study. Frontiers in Psychiatry, 9, 272.
6. Smith, J. B. et al. (2020). The claustrum. Current Biology, 30(23), R1401–R1406.
7. Torgerson, C. M. et al. (2015). The DTI connectivity of the human claustrum. Human Brain Mapping, 36(3), 827–838.
8. Wang, Q. et al. (2012). Anatomical insights into disrupted small-world networks in schizophrenia. NeuroImage, 59(2), 1085–1093.
9. Wendt, J. et al. (2024). Human Claustrum Connections: Robust In Vivo Detection by DWI ‐Based Tractography in Two Large Samples. Human Brain Mapping, 45(14), e70042.