Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task

Abstract

Mild cognitive impairment has frequently been reported for patients in the early stages of multiple sclerosis. The aim of the present study was to measure whether altered cortical activation during a sustained attention task occurs along with limited extent of neuropsychological problems. Expanded brain activation of multiple sclerosis patients with normal motor function compared with healthy controls during a finger tapping paradigm has previously been reported. Compensatory brain activation in patients with multiple sclerosis compared with normal controls may also be observed when the subjects are performing cognitive functions. In 21 patients with clinically definite relapsing-remitting multiple sclerosis, a psychometric assessment was performed using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite Score (MSFC). In addition, functional MRI was performed during a Paced Visual Serial Addition Task (PVSAT), a visual analogue of the Paced Auditory Serial Addition Task (PASAT). All patients were within 3 years of diagnosis and were not suffering from a relapse at the time of investigation. The multiple sclerosis patients were compared with a control group of 21 healthy volunteers matched for handedness, age, years of education and sex. With regard to psychometric results, the WMS general memory score showed statistically significant differences between patients and controls. We did not find differences for either the MSFC or the PASAT scores. A group analysis of the functional imaging data during the PVSAT revealed different activation patterns for patients compared with control subjects. In healthy volunteers, the main activation was found in the frontal part of the right gyrus cinguli (Brodmann area 32). In patients, the main activation was detected at the right hemispheric frontal cortex (Brodmann areas 6, 8 and 9). In addition, the left hemispheric Brodmann area 39 was activated. We interpret the different patterns of activation, accompanied with intact performance in a sustained attention task of our multiple sclerosis sample compared with healthy controls, as the consequence of compensatory mechanisms. This is an expression of neuronal plasticity during early stages of a chronic disease.

Structural and functional MRI correlates of Stroop control in benign MS

“…Since only the corrected answers were modelled in the statistical analysis and task performance was similar between patients and controls, we can reasonably rule out a possible influence of cognitive impairment and different task performance between patients and controls on our fMRI results. These results are in agreement with those of previous studies which assessed fMRI patterns of activation during the performance of cognitive tasks in patients at the earliest stages of the disease [Audoin et al, 2003] and in those with relapsing course [Hillary et al, 2003;Mainero et al, 2004;Staffen et al, 2002]. Our results are partially in contrast with those of a previous study [Parry et al, 2003] of a mixed group of patients with relapsing remitting (RR) and secondary progressive (SPM) MS, where an increased activation of the L frontal cortex and a decreased activation of the R frontal cortex were found in patients in comparison with controls.…”

Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis

“…Furthermore, EAE shares many pathological features with MS (20). Patients with MS, even at early stages of the disease, have been shown to have sensory deficits (1)(2)(3)(4)(5) and decreased performance on memory tasks with changes in cortical functional MRI activity levels (45). Thus, the early synaptic abnormalities observed in our studies may similarly occur in MS and contribute to the early cortical deficits.…”

Functional MRI in investigating cognitive impairment in multiple sclerosis

“…Working memory has been the most extensively studied domain by means of the Paced Auditory Serial Addition Test (PASAT) or the Paced Visual Serial Addition Task. [7][8][9][10][11][12][13] In patients with a clinically isolated syndrome (CIS) suggestive of MS, an altered pattern of cortical activations has been described during PASAT performance, confirming the presence of cortical reorganization at the earliest clinical stage of disease. 10 An increased recruitment of several cortical areas during PASAT has also been shown in patients with relapsing-remitting (RR) MS and mild cognitive impairment, 11 suggesting that an impaired cognitive task performance in these patients could reflect a decreased function of canonical task-specific areas in the absence of adequate compensatory strategies.…”