Increased Thalamocortical Connectivity in Schizophrenia Correlates With Sleep Spindle Deficits: Evidence for a Common Pathophysiology.
Functional connectivity
Schizophrenia
Sleep
Sleep spindles
Thalamic reticular nucleus
Thalamus
Journal
Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
02
2019
revised:
06
04
2019
accepted:
24
04
2019
pubmed:
3
7
2019
medline:
28
3
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
Converging evidence implicates abnormal thalamocortical interactions in the pathophysiology of schizophrenia. This evidence includes consistent findings of increased resting-state functional connectivity of the thalamus with somatosensory and motor cortex during wake and reduced spindle activity during sleep. We hypothesized that these abnormalities would be correlated, reflecting a common mechanism: reduced inhibition of thalamocortical neurons by the thalamic reticular nucleus (TRN). The TRN is the major inhibitory nucleus of the thalamus and is abnormal in schizophrenia. Reduced TRN inhibition would be expected to lead to increased and less filtered thalamic relay of sensory and motor information to the cortex during wake and reduced burst firing necessary for spindle initiation during sleep. Overnight polysomnography and resting-state functional connectivity magnetic resonance imaging were performed in 26 outpatients with schizophrenia and 30 demographically matched healthy individuals. We examined the relations of sleep spindle density during stage 2 non-rapid eye movement sleep with connectivity of the thalamus to the cortex during wakeful rest. As in prior studies, patients with schizophrenia exhibited increased functional connectivity of the thalamus with bilateral somatosensory and motor cortex and reduced sleep spindle density. Spindle density inversely correlated with thalamocortical connectivity, including in somotosensory and motor cortex, regardless of diagnosis. These findings link two biomarkers of schizophrenia-the sleep spindle density deficit and abnormally increased thalamocortical functional connectivity-and point to deficient TRN inhibition as a plausible mechanism. If TRN-mediated thalamocortical dysfunction increases risk for schizophrenia and contributes to its manifestations, understanding its mechanism could guide the development of targeted interventions.
Sections du résumé
BACKGROUND
Converging evidence implicates abnormal thalamocortical interactions in the pathophysiology of schizophrenia. This evidence includes consistent findings of increased resting-state functional connectivity of the thalamus with somatosensory and motor cortex during wake and reduced spindle activity during sleep. We hypothesized that these abnormalities would be correlated, reflecting a common mechanism: reduced inhibition of thalamocortical neurons by the thalamic reticular nucleus (TRN). The TRN is the major inhibitory nucleus of the thalamus and is abnormal in schizophrenia. Reduced TRN inhibition would be expected to lead to increased and less filtered thalamic relay of sensory and motor information to the cortex during wake and reduced burst firing necessary for spindle initiation during sleep.
METHODS
Overnight polysomnography and resting-state functional connectivity magnetic resonance imaging were performed in 26 outpatients with schizophrenia and 30 demographically matched healthy individuals. We examined the relations of sleep spindle density during stage 2 non-rapid eye movement sleep with connectivity of the thalamus to the cortex during wakeful rest.
RESULTS
As in prior studies, patients with schizophrenia exhibited increased functional connectivity of the thalamus with bilateral somatosensory and motor cortex and reduced sleep spindle density. Spindle density inversely correlated with thalamocortical connectivity, including in somotosensory and motor cortex, regardless of diagnosis.
CONCLUSIONS
These findings link two biomarkers of schizophrenia-the sleep spindle density deficit and abnormally increased thalamocortical functional connectivity-and point to deficient TRN inhibition as a plausible mechanism. If TRN-mediated thalamocortical dysfunction increases risk for schizophrenia and contributes to its manifestations, understanding its mechanism could guide the development of targeted interventions.
Identifiants
pubmed: 31262708
pii: S2451-9022(19)30108-9
doi: 10.1016/j.bpsc.2019.04.012
pmc: PMC6688951
mid: NIHMS1528782
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
706-714Subventions
Organisme : NIMH NIH HHS
ID : K24 MH099421
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH067720
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH092638
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001102
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH048832
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023043
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023401
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR019307
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007901
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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