A thalamic perspective of consciousness in pharmacological and pathological states in humans
Poster No:
2476
Submission Type:
Abstract Submission
Authors:
Dorottya Szocs1, Dian Lyu2, Rebecca Woodrow1, Andrea I. Luppi3, Peter Coppola1, Judith Allanson1, Ram Adapa1, Guy B. Williams1, JD Pickard1, Adrian Owen4, Lorina Naci5, David Menon1, Emmanuel Stamatakis1
Institutions:
1University of Cambridge, Cambridge, United Kingdom, 2Stanford University, Palo Alto, CA, United States, 3Montreal Neurological Institute, McGill University, Montreal, Québec, Canada, 4Western University, London, Ontario, Canada, 5Trinity College Dublin, Dublin, Ireland
First Author:
Co-Author(s):
Introduction:
The thalamus is involved in modulation of arousal states (M. Shine et al., 2023, Fridman et al., 2022). Recent animal studies investigated the role of distinct thalamic nuclei in pharmacologically induced unconsciousness (Tasserie et al., 2022, Redinbaugh et al., 2020). Human studies highlighted thalamic interactions with the default mode network (DMN) in anaesthesia and disorders of consciousness (DOC) (Demertzi et al., 2019; Luppi et al., 2019). However, only few human studies differentiated the cytoarchitectonically and functionally distinct thalamic nuclei, to elucidate their relevance in altered states of consciousness (Setzer et al., 2022, Weiner et al., 2021, Liu et al., 2013). We investigated thalamic nuclei and their functional relationship to the cortex using functional MRI in both healthy anaesthetised volunteers and patients with disorders of consciousness, with implications for finding potential targets for deep brain stimulation (DBS).
Methods:
We analysed the fMRI data of N=16 healthy controls under deep sedation (mean plasma propofol concentration 2.68µg/mL) and N=22 DOC patients (N=13 minimally conscious state, N=9 unresponsive wakefulness syndrome). All images were pre-processed in SPM12 and CONN. We used a thalamic parcellation atlas based on DW-MRI, where the thalamus is segmented into 7 regions of interest closely matching anatomical subparts (Najdenovska et al., 2018). Thalamic masks corresponded to nuclei (bilaterally): pulvinar (Pu), anterior (Ant), medio-dorsal (MD), ventral-latero-dorsal (VLD), central-lateral, lateral-posterior, medial-pulvinar (CL-LP-MPu), ventral-anterior (VA), and ventral-latero-ventral (VLV). Seed-to-voxel functional connectivity (FC) was computed between each nucleus and the whole brain, with a voxel level threshold of p<0.005 (uncorrected) and cluster level p<0.05 (FWE-corrected for multiple comparisons). Cortical SPM-t maps were derived from contrasts of FC (deep sedation vs. awake and DOC vs. control). To investigate which nucleus had the greatest magnitude of change in FC with loss of consciousness, we computed the average difference in FC (dFC) across the whole brain for the same contrasts as above.
Results:
Cortical SPM-t maps revealed that Pu and VLV nuclei, but not others, increase their FC with DMN regions and decrease their FC with somatomotor (SM)-regions with loss of consciousness in both anaesthesia (Fig. 1a-i, g-i) and DOC (Fig. 2a-i, g-i). All other thalamic nuclei exhibited reversed effects with concomitant loss of consciousness (decreased FC with DMN-regions and increased connectivity with SM-regions). In DOC, most thalamic nuclei were found to disconnect from medial frontal regions (Fig. 2a-g). Box plots display z-scores for anaesthesia (Fig. 1) and DOC group comparisons (Fig. 2). Among all nuclei, Pu had the greatest magnitude of dFC in anaesthesia (Fig. 1h) and VLV had the greatest magnitude of dFC in DOC (Fig. 2h). Linear mixed models for within-subject analysis were used to compare magnitude of change in FC. In anaesthesia, the dFC for Pu was found to be significant in comparison to the rest of nuclei (t = 2.081, p = 0.03861). In DOC, the dFC for VLV was also found to be significant when tested against the rest of nuclei (t = 12.336, p = 2.2e-16).
Conclusions:
We demonstrated, with fMRI, differentiated patterns of thalamic functional disconnections between pharmacological and pathological alterations in consciousness, in healthy volunteers and DOC patients, respectively. Whole-brain connectivity maps revealed that Pu and VLV nuclei in anaesthesia and DOC cohorts increased FC with DMN-regions and decreased FC with SM-regions with loss of consciousness. Additionally, among all nuclei, the Pu (in anaesthesia) and VLV (in DOC) were found to have the strongest FC changes with pharmacological and pathological perturbations of consciousness, providing new evidence in the elucidation of individual thalamic nuclei's relevance in consciousness in both anaesthesia and disorders of consciousness.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Subcortical Structures 2
Perception, Attention and Motor Behavior:
Consciousness and Awareness 1
Keywords:
ADULTS
Consciousness
DISORDERS
FUNCTIONAL MRI
NORMAL HUMAN
Sub-Cortical
Thalamus
Other - Disorders of consciousness (DOC); anaesthesia; thalamic nuclei
1|2Indicates the priority used for review
Provide references using author date format
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Liu, X. (2013), ‘Differential effects of deep sedation with propofol on the specific and nonspecific thalamocortical systems: a functional magnetic resonance imaging study’, Anesthesiology, 118(1), 59–69. https://doi.org/10.1097/ALN.0b013e318277a801
Luppi, A. I. (2019), ‘Consciousness-specific dynamic interactions of brain integration and functional diversity’, Nature Communications, 10(1), 4616. https://doi.org/10.1038/s41467-019-12658-9
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