Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia

Abstract

Background:Schizophrenia has been associated with disturbances of thalamic functioning. In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-d-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity.Methods:Based on the ketamine model of psychosis, we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan. Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind, randomized, placebo-controlled, crossover design.Results:Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network, more precisely, an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.Conclusions:Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists.

Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects

“…Moreover, the thalamus is emerging as a key subcortical node exhibiting altered functional connectivity following ketamine administration in healthy human subjects, with both increased global connectivity (Joules et al 2015) and increased connectivity with sensory and temporal cortices specifically (Hoflich et al 2015) being recently reported and consistent with observations in schizophrenic subjects. Findings of altered cerebral blood flow in schizophrenic subjects include increased perfusion in the thalamus but decreases in frontal cortical regions (Ota et al 2014;Zhu et al 2015).…”

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI

“…HC healthy control subjects, rMD remitted depressed subjects, aMD acute depressed patients fMRI-1 functional magnetic resonance imaging session one, HAM-D 24 Hamilton Depression Rrating Scale (24 item version), HAM-A Hamilton Anxiety Rating Scale, BDI Beck Depression Index, CGI Clinical Global Impression scale, f female, m male, y years, m months, r right, l left a p-value chi-square test b p-value analysis of variance c p-value t-test d for detiailed medication see supplementary Table S5 e only one patient Antidepressant effects on the pulvinar and the thalamus are substantiated in other fMRI tasks [29][30][31]. Moreover, thalamocortical connectivity was altered upon ketamine administration [32] and transracial magnetic stimulation to the dorsolateral prefrontal cortex elevated activity in the pulvinar nuclei [33]. These results corroborate reduction of pulvinar hyperactivity by antidepressants, which might not be specific to a pain fMRI paradigm, but a more general effect of antidepressant efficacy.…”

Thalamo-cortical communication, glutamatergic neurotransmission and neural oscillations: A unique window into the origins of ScZ?

“…Moreover, several resting-state fMRI studies reported increased functional connectivity between thalamus and cortical regions (Anticevic et al, 2013a;Hoflich et al, 2015;Klingner et al, 2014;Woodward et al, 2012), albeit some report mixed findings (Woodward et al, 2012). …”