Functional MRI Correlates of Intelligence Quotient and Visual-Motor Coordination in Pediatric Multiple Sclerosis
Laura Cacciaguerra1,2,5, Chiara Curatoli1, Carmen Vizzino1, Paola Valsasina1, Maria A. Rocca1,2,5, Massimo Filippi1,2,3,4,5
1Neuroimaging Research Unit, Division of Neuroscience, 2Neurology Unit, 3Neurorehabilitation Unit, 4Neurophysiology Service, IRCCS San Raffaele Scientific Institute, 5Vita-Salute San Raffaele University
To evaluate the neuropsychological profile of pediatric multiple sclerosis (MS) patients and its association with resting-state functional connectivity (RS-FC) abnormalities in cognitive and motor networks.

Pediatric MS differs from adult-onset disease, as the developing brain is characterized by greater compensatory mechanisms, but pathological processes can interfere with ongoing maturational processes.

This 3.0 T RS functional MRI study included 76 pediatric MS patients undergoing a neuropsychological evaluation testing global cognition (intelligence quotient [IQ] from the Wechsler Intelligence Scales), set-shifting (Trial Making Test [TMT] A and B), language (semantic and phonemic fluency tests [SVFT/PVFT]) and visual-motor coordination (Symbol Digit Modalities Test [SDMT], Coding [CD] and Block Design [BD]). Twenty-two age- and sex-matched healthy subjects were used as controls (HC). A seed-based correlation approach was adopted to calculate RS-FC within the executive, language, memory and motor networks. Between-group differences and correlations with cognitive scores were assessed with age- and sex-adjusted full-factorial models. 

In pediatric MS patients, median IQ was 97.5 and 18.4% scored below normative average (IQ<84). Patients most commonly failed CD (21.1%), TMT-B (13.2%) and TMT-A (11.8%). Compared to HC, MS patients had reduced RS-FC of the bilateral caudate nucleus and increased RS-FC of bilateral precentral gyrus in all networks. Patients also showed reduced RS-FC in several network-specific areas, such as the anterior cingulate cortex (language network) and the angular gyrus (memory and motor networks). Decreased RS-FC of the caudate nucleus was associated with higher IQ and better performance at TMT-A/B, but worse performance in BD and CD tests. Decreased RS-FC of the anterior cingulate cortex was associated with higher scores at SVFT, CD and SDMT.

Pediatric MS patients achieve average IQ levels. Reduced RS-FC of the caudate nucleus contributes to global cognitive efficiency but also to patients' fragility in processing speed associated with visual-motor coordination skills.