Poster No:
1709
Submission Type:
Abstract Submission
Authors:
Elizabeth Ellis1, Albert Bellmunt Gil1, Jaakko Kungshamn2, Olli Likitalo2, Juho Aaltonen1, Elina Myller2, Susanna Roine2, Pauli Ylikotila2, Juho Joutsa2
Institutions:
1University of Turku, Turku, Finland, 2Turku University Hospital, Turku, Finland
First Author:
Co-Author(s):
Introduction:
Extinction is a common post-stroke deficit characterised by a failure to respond to stimuli presented on one side of the body when a stimulus is simultaneously presented on the other side. Extinction has traditionally been linked to brain lesions damaging temporoparietal regions but there are several cases of extinction following lesions outside these regions, leaving the localisation unclear. Here, we first tested for an association between lesion location and extinction. Next, we looked beyond anatomical location to study the connections disrupted by the lesion, localising a functional brain network underlying extinction. Finally, we sought to examine its relation to neuromodulation targets and underlying neurotransmitter systems.
Methods:
500 patients with a new-onset stroke were prospectively enrolled into an on-going project at Turku University Hospital (Finland). Patients were clinically examined following their stroke, including for extinction in accordance with the standard stroke severity assessment (National Institutes of Health Stroke Scale). To be included as a case of extinction, patients must not have presented with symptoms that may mask or mimic the symptoms of extinction, for example, cases with complete hemianopia were excluded. Traditional voxel-wise lesion symptom mapping analyses were conducted with NiiStat (v1.1) in MATLAB (v R2021a) to test for associations between lesion location and extinction, comparing lesions causing extinction to stroke lesions not causing extinction. Next, the functional connectivity profile of each lesion was computed using resting-state functional connectivity data from 1000 healthy volunteers (Cohen et al., 2021). Connectivity profiles of lesions causing extinction were compared to those not causing extinction, revealing a network of connectivity specific to lesions causing extinction - herein, 'the extinction network'. To explore the potential therapeutic relevance of the network, it was determined whether brain stimulation targets inducing, and relieving extinction symptoms were encompassed by the network. Finally, the extinction network was tested for associations with specific neurotransmitter systems with spatial correlation analyses using JuSpace (Dukart et al., 2021) toolbox in MATLAB.
Results:
Thirty-three patients with extinction were included with 458 cases without extinction included as controls. No lesion location was significantly associated with extinction. Despite this anatomical heterogeneity, lesions causing extinction localised to a specific functional brain network (PFWE < 0.05). This network encompassed regions of the occipital and temporal cortices, the precuneus, striatum, and cerebellum (PFWE < 0.05). In addition, this extinction network included positive connectivity to the portion of the inferior parietal lobe overlapping with the neuromodulation target that has been used to induce extinction symptoms in healthy individuals. Further, the topography of the network was not specific for any single neurotransmitter but aligned with several underlying neurotransmitter systems. There were greater densities of serotonin, GABA, and glutamate neurotransmitters in areas positively connected to lesion locations causing extinction, but greater densities of acetylcholine, dopamine, and serotonin 5HT4 receptors in areas negatively connected to lesion locations causing extinction.
Conclusions:
Lesions causing post-stroke extinction are located inconsistently across the brain but localise to a specific functional brain network. Derived from a large, clinically relevant, sample of post-stroke patients, these results provide strong evidence that extinction is a network-based syndrome. Lesion connectivity, shown to be associated with brain stimulation targets and several underlying neurotransmitter systems, may influence future therapeutic intervention development.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 1
Cortical Anatomy and Brain Mapping
Keywords:
DISORDERS
FUNCTIONAL MRI
Neurological
Other - stroke
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
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Not applicable
Please indicate which methods were used in your research:
Functional MRI
Provide references using APA citation style.
1. Cohen, A., Soussand, L., McManus, P., & Fox, M. (2021). GSP1000 Preprocessed Connectome (V3 ed.). Harvard Dataverse. https://doi.org/doi:10.7910/DVN/ILXIKS
2. Dukart, J., Holiga, S., Rullmann, M., Lanzenberger, R., Hawkins, P. C. T., Mehta, M. A., Hesse, S., Barthel, H., Sabri, O., Jech, R., & Eickhoff, S. B. (2021). JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps. Human Brain Mapping, 42(3), 555–566. https://doi.org/10.1002/hbm.25244
No