Abstract Details

Title Resting State Effective Connectivity Abnormalities of the Papez Circuit Contribute to Explain Worse Cognitive Performances in Multiple Sclerosis Patients

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 300

Objective To investigate abnormalities of resting state (RS) effective connectivity (EC) between regions of the Papez circuit in multiple sclerosis (MS) and their relationship with cognitive performances.

Background The Papez circuit is central to memory and emotional processes. However, little is known about causal connectivity between its regions and its involvement in MS.

Design/Methods Sixty-two MS patients and 64 healthy controls (HC) underwent 3.0T 3D T1-weighted and RS functional MRI scanning. Subjects also underwent neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). The Papez circuit was constructed by placing regions of interest in the bilateral hippocampus subiculum, entorhinal cortex and anterior thalamic nuclei, as well as in the anterior cingulate (ACC) and posterior cingulate cortex (PCC). RS EC analysis was performed using SPM12 and dynamic causal modelling; RS EC differences between groups were investigated using parametric empirical bayes models. Correlations of RS EC abnormalities with global and domain-specific BRB-N Z-scores were tested.

Results Compared to HC, MS patients showed (posterior probability>0.95) higher inhibitory EC between the right entorhinal cortex and the right subiculum, and lower EC from the ACC to the PCC, from left to right subiculum, from left anterior thalamus to ACC, and within ACC and PCC. Lower RS EC within the ACC was correlated with better attention scores (p=0.04), while lower RS EC from the ACC to the PCC was associated with worse visuospatial memory, verbal semantic fluency and global cognition (p<0.03), and lower RS EC from the left to the right subiculum was related to worse verbal memory (p=0.02). Finally, higher inhibitory RS EC from the right entorhinal cortex to the right subiculum was correlated with worse verbal semantic fluency (p=0.02).

Conclusions

MS patients showed widespread RS EC alterations within the Papez circuit. Reduced RS EC involving cingulate cortices and hippocampal formations contributed to explain worse cognitive performances.

Authors/Disclosures
Maria A. Rocca (Neuroimaging Research Unit) PRESENTER	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.
	No disclosure on file
	No disclosure on file
Paola Valsasina	Paola Valsasina has nothing to disclose.
Massimo Filippi, MD, FAAN (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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