Abstract Details

Title Abnormal Thalamic Functional Connectivity Correlates With Cardiorespiratory Fitness and Physical Activity in Progressive Multiple Sclerosis

Topic Neuro-rehabilitation

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-011

Objective

To assess thalamic structural and functional MRI alterations and investigate their correlations with physical activity (PA) and cardiorespiratory fitness (CRF) levels in progressive MS (PMS) patients.

Background

Patients with PMS have insufficient levels of PA and CRF, which showed some associations with measures of structural MRI damage. Functional MRI (fMRI) correlates of reduced PA/fitness have never been explored. Given the role of thalamus in motor planning, sensory processing and cognition, abnormal thalamic resting state (RS) functional connectivity (FC) might explain PA/fitness levels in these patients.

Design/Methods

Ninety-one PMS patients performed a cardiopulmonary exercise test and wore an accelerometer for 7 days to assess PA/CRF levels. They underwent, together with 37 matched healthy controls (HC), a structural and RS fMRI acquisition at 3.0T, used to derive whole-brain and thalamic atrophy and thalamic RS FC. Between-group comparisons of MRI measures and their correlations with PA/CRF variables were assessed.

Results

PMS patients had whole-brain and subcortical atrophy compared to HC (all p<0.001). Patients showed decreased intra- and inter-thalamic RS FC, decreased RS FC of the thalamus with caudate nucleus, cerebellum and anterior cingulate cortex (ACC), and increased thalamic RS FC with the hippocampus and some occipital regions. Lower CRF correlated with lower white matter volume (r=range 0.28;0.31, p=range 0.003;0.01), decreased thalamic RS FC with the ACC (r=range 0.22;0.28, p=range 0.01;0.04), and increased thalamic RS FC with the hippocampus, calcarine cortex, and lingual gyrus (r=range -0.26;-0.21, p=range 0.01;0.04). Lower PA correlated with decreased inter-thalamic RS FC (r=0.27, p=0.02), and increased thalamic RS FC with the hippocampus (r=-0.3, p=0.01) and lingual gyrus (r=-0.23, p=0.04).

Conclusions

Only white matter atrophy correlated with CRF. Conversely, abnormal RS FC in the thalamic network showed various maladaptive associations with PA/CRF in PMS patients. Thalamic RS FC might be used to monitor the efficacy of rehabilitative and disease-modifying treatments in PMS patients.

Authors/Disclosures
Tetsu Morozumi, PT (Ospedale San Raffaele S.r.l.) PRESENTER	Mr. Morozumi has nothing to disclose.
Francesco Romano (San Raffaele Hospital)	Francesco Romano has nothing to disclose.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Paola Valsasina	Paola Valsasina has nothing to disclose.
Maria P. Amato, PhD (Ospedale Di Careggi)	Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOU Careggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene BMS. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche.
Giampaolo Brichetto, MD, PhD (Italian MS Society)	Giampaolo Brichetto, MD, PhD has received personal compensation for serving as an employee of Italian MS Society.
Nicolo Bruschi	Mr. Bruschi has nothing to disclose.
Jeremy S. Chataway, MD	Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janseen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NerveGen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis.
Nancy Chiaravalloti	The institution of Nancy Chiaravalloti has received research support from NIH. The institution of Nancy Chiaravalloti has received research support from NIDILRR.
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for onsulting or Advisory Boards: Alexion, Antisense Therapeutics/Percheron, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Genzyme, Genentech, Immunic, Klein-Buendel Incorporated, Kyverna Therapeutics, Inc. , Linical, Merck/Serono, Noema, Neurogenesis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Revelstone Consulting, Roche, SAB Biotherapeutics, Sapience Therapeutics, Scott&Scott LLP, Tenmile.. Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, AMO Pharma, Argenx, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb, CSL Behring, Cynata Therapeutics, DiamedicaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhibrix, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Merck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Holdings, Prothena Biosciences, Novartis, Pipeline Therapeutics (Contineum), Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Ulrik Dalgas	Ulrik Dalgas has received personal compensation for serving as an employee of Roche. Ulrik Dalgas has received personal compensation for serving as an employee of Bristol Meyers Squibb.
John DeLuca, PhD, ABPP (Kessler Foundation)	Dr. DeLuca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. DeLuca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. DeLuca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. DeLuca has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. DeLuca has received research support from Biogen.
Rachel A. Farrell, MD (National Hospital for Neurology and Neurosurgery)	The institution of Dr. Farrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma / Jazz. The institution of Dr. Farrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz.
Peter Feys	Peter Feys has nothing to disclose.
Jennifer Freeman	Jennifer Freeman has nothing to disclose.
	No disclosure on file
Cecilia Meza (Sunnybrook Research Institute)	Cecilia Meza has nothing to disclose.
Amber Salter, PhD (UT Southwestern Medical Center)	Dr. Salter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gryphon Bio. Dr. Salter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abata Therapeutics. Dr. Salter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sora Neuroscience. Dr. Salter has stock in Owl Therapeutics. The institution of Dr. Salter has received research support from National Multiple Sclerosis Society. The institution of Dr. Salter has received research support from Department of Defense Congressionally Directed Medical Research Program. The institution of Dr. Salter has received research support from Consortium of Multiple Sclerosis Centers.
Brian Sandroff	The institution of Brian Sandroff has received research support from NIH, NIDILRR, National MS Society.
Anthony Feinstein, MD (Sunnybrook Health Sciences Centre)	Anthony Feinstein, MD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis, Biogen, Roche and Sanofi-Genzyme. The institution of Anthony Feinstein, MD has received research support from Multiple Sclerosis Society of Canada. Anthony Feinstein, MD has received publishing royalties from a publication relating to health care.
	No disclosure on file
Massimo Filippi, MD, F�鶹��ýӳ�� (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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