Interhemispheric Relationships In Multiple Sclerosis: Evaluation By MEG, EEG, and MRI

Background:  Multiple sclerosis (MS) is a demyelinating disease that leads to compromised axonal conduction and cognitive and physical disabilities. Direct measures of axonal function would therefore help in understanding MS progression and effects of therapies.

Objectives:  This study examined functional aspects of brain integrity in patients with multiple sclerosis, as indexed by magnetoencephalography (MEG), electroencephalography (EEG), and behavioral techniques (i.e., visual-motor reaction times). 

Methods:  We collected reaction times, with MEG and EEG data, from seven MS patients (ages 18-65) during the performance of several visual-motor tests. Patients had varying levels of cognitive and physical disability as well as lesion burden, evaluated through MRI. Their EDSS scores ranged from 1.5 to 8.0, and they had no concurrent diagnoses of other neurological disorders. Our tests presented participants with circles, which randomly flashed to either the right or left visual field. Over subsequent trials, participants were asked to respond to flashes with only their right hand, their left hand, the hand ipsilateral to the flash, or the hand contralateral to the flash. Reaction times and MEG/EEG data of the MS patients were compared against 25 healthy controls (ages 18-40) along the same tasks, allowing us to identify how reaction times and brain processing varied across both groups as tasks became more neurologically demanding.

Results:  Initial data revealed no differences between groups for performance of simple visual-motor tasks. When a consistent right hand motor response was made to a visual stimulus, regardless of visual field of presentation, average reaction times for both groups were about 330 msec, with average interhemispheric transfer times of 7-10 msec. This suggested that there was no dysfunction of the corpus callosum for simple interhemispheric transfer of information in the MS group. However, when participants responded with the hand contralateral to the visual field of presentation, MS patients showed abnormal patterns of brain functioning. Also, while control reaction times slightly increased to about 425 msec, MS patient times doubled to an average of over 650 msec. This effect was seen in all MS patients, regardless of age or level of disability.

Conclusions:  This prolonged processing suggests significant, MS-related callosal dysfunction with respect to coordination and integration of activities between the two brain hemispheres. Additionally, when MEG data for the contralateral hand condition were analyzed using a distributed source model of the brain, MS patients demonstrated prolonged activation of the right somatosensory cortex and left prefrontal region during the period between initial visual stimulation and final motor response. The observed effect on reaction times and cortical activation is sufficiently large that this technique could be developed as a new functional biomarker for axonal injury in MS.