Disrupted thalamic FC explained the altered level of consciousness induced by ketamine
Poster No:
634
Submission Type:
Abstract Submission
Authors:
Tara Chand1, Meng Li2, Yuan Cao3, Zümrüt Duygu Sen4, Lena Danyeli5, Nooshin Javaheripour5, Vinod Kumar6, Martin Walter5
Institutions:
1Jindal Institute of Behavioural Sciences, O. P. Jindal Global University, Sonipat, Haryana, India, 2Jena University Hospital, Jena, Germany, 3Jena University Hospital, Jena, Turingia, 4Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Thuringen, 5Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Thuringia, 6MPI for Biological Cybernetics, Tübingen, Baden Württemberg
First Author:
Tara Chand
Jindal Institute of Behavioural Sciences, O. P. Jindal Global University
Sonipat, Haryana, India
Jindal Institute of Behavioural Sciences, O. P. Jindal Global University
Sonipat, Haryana, India
Co-Author(s):
Zümrüt Duygu Sen
Department of Psychiatry and Psychotherapy, Jena University Hospital
Jena, Thuringen
Department of Psychiatry and Psychotherapy, Jena University Hospital
Jena, Thuringen
Nooshin Javaheripour
Department of Psychiatry and Psychotherapy, Jena University Hospital
Jena, Thuringia
Department of Psychiatry and Psychotherapy, Jena University Hospital
Jena, Thuringia
Introduction:
The therapeutic potential of a single subanesthetic dose of ketamine in various mental illnesses, particularly treatment-resistant depression (TRD), has gained significant attention in the past decade (Kryst et al 2020). Beyond the rapid onset of therapeutic efficacy, ketamine administration can induce altered states of consciousness, which is known as dissociative states, encompassing disorientation, confusion, sensory perception changes (such as visual or auditory hallucinations), and feelings of detachment. The vital role of the thalamus in the ketamine-induced loss and return of consciousness, as well as altered states of consciousness, has been broadly reported (Krystal et al. 1994). Although the regional effect of ketamine on thalamic nuclei has been reported (Ferrer et al 1973; Rogers et al 2004), to date, it remains unclear how changes in the thalamo-cortical interactions lead to ketamine-induced dissociative states on the level of thalamus functional anatomy. This study aimed to investigate resting-state functional connectivity changes within the thalamus functional anatomy (Kumar et al., 2017) and their relation to ketamine-induced dissociative states.
Methods:
In a randomized, double-blind, placebo-controlled, crossover study, thirty-five healthy males (mean age ± standard deviation (SD) = 25.08 ± 4.18 years) underwent 7T high-field functional MRI scans before and one day after ketamine or placebo infusions. fMRI data was acquired using echo-planar imaging (EPI) sequence with the following parameters: TE = 25 ms, TR = 1500 ms, flip angle = 70 °, FoV = 212 mm, 60 slices, isotropic voxel size = 2 mm3, multi-band acceleration factor = 3, grappa acceleration factor PE = 2. The data underwent preprocessing using fMRIPrep, and rsFC was calculated using parcels from the functional anatomy atlas of the human thalamus (Kumar et al., 2017). To examine ketamine's effect on seed-based rsFC in the different parcels of the thalamus functional anatomy, a within-subject flexible factorial ANOVA was performed for each functional parcel separately in SPM, assessing the main effects of session (baseline vs. infusion), treatment (placebo vs. ketamine), and their interaction. Additionally, rsFC values from significant clusters were correlated with subjective consciousness levels measured by the score of Oceanic Boundlessness score (OB) from the five-dimensional altered states of consciousness.
Results:
Within-subject flexible factorial ANOVA revealed a significant treatment * session interaction (clusterwise FWE-corrected at p < 0.05) in the FC of four thalamic parcel (bilateral 08, left 02, and 15) to the medial/inferior frontal gyrus (Figure 01; pFWE-cluster corrected, initial height threshold p< 0.001). The FC of left 15 and right 08 to the right-medial frontal gyrus during infusion showed significant negative correlations [left 15 (r = -38, p= 0.27), and right 08 (r= -42, p= 0.013)] with subjective consciousness measured by the OB score (Figure 02).
·Figure 1: The FC of four thalamic subnuclei (bilateral 08 (A, D), left 02 (B), and 15 (C)) to the inferior frontal gyrus showed a significant treatment variation by session.
·Figure 2: showing a significant association of the FC between four thalamic sub nuclies to IFG during infusion with subjective feeling of the consciousness as measured with the OSE score.
Conclusions:
The ketamine show the changes in the thalamo-cortical functional connectivity between the specific thalamus nuclei (VA, PuI, VL, CL, VPL) with medial/inferior frontal gyrus, and right-medial frontal gyrus. Whereas the ketamine-impacted nuclei associate with the arousal, awareness, sensory, and visual processing (Kumar et.al. 2017, 2022). The CL is an intralaminar nucleus, enables rapid interactions between brainstem and cortex, and has been implicated in the arousal, awareness, and disorders of consciousness (Kumar et.al. 2017). Thalamic nuclei and their involvement in cortico-striatal-thalamo-cortical loops and their changes might be the essential component in ketamine-induced altering consciousness due to their role in salience processing and cortex gating.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Consciousness
FUNCTIONAL MRI
Thalamus
1|2Indicates the priority used for review
Provide references using author date format
Kryst, J. et al. (2020) Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: A meta-analysis of randomized clinical trials. Pharmacol. Rep. 72, 543–562 .
Krystal, J. et al. (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of general psychiatry
Kumar, V.; van Oort, E.; Scheffler, K.; Beckmann, C.; Grodd, W.:(2017) Functional Anatomy of the Human Thalamus at Rest. NeuroImage 147, pp. 678 - 691
Rogers, R., Wise, R. G., Painter, D. J., Longe, S. E. & Tracey, I. (2004) An Investigation to Dissociate the Analgesic and Anesthetic Properties of Ketamine Using Functional Magnetic Resonance Imaging. Anesthesiology 100, 292–301
Kumar, V.J., Beckmann, C.F., Scheffler, K. et al.(2022) Relay and higher-order thalamic nuclei show an intertwined functional association with cortical-networks. Commun Biol 5, 1187 .