Working memory deficits in multiple sclerosis: a controlled study with auditory P600 correlates

Cognitive impairment is a common clinical feature of multiple sclerosis (MS), occurring in up to 65% of patients with this disorder. ^{1, 2} Repeatedly, it has been suggested that the cognitive impairment in MS patients is strongly associated with limitations in work and social activities. ³

Recent neuropsychological studies provided evidence indicating that working memory (WM) deficits may be involved in MS. ^{4, 5} However, brain mechanisms underlying these deficits continue to be a subject of ongoing investigation, as their patterning and specificity still remain unclear. This is particularly evident in psychophysiological research. The existing evidence indicates that the multifocal demyelination of MS leads to a disruption of the multiple interconnected brain areas, which form the substrate of the working memory. ^{5- 7}

Event related potentials (ERPs) provide a valuable means for studying brain-behaviour relations. ⁸

Pelosi et al , recording both auditory and visual ERPs during the memorising as well as the recognition and matching of digits of a short-term memory paradigm, found that early MS patients as compared with healthy controls displayed a delay of the N270/N290 waves and a decreased amplitude of the major positivities (P400/P560). ⁷ Although these abnormalities have been referred to with regard to both modalities, abnormal changes were more noticeable in the auditory modality. The delay of the negative waves has been interpreted as "an index of slowed processing between stimulus presentation and motor response selection", while the reduction of the amplitudes as "a manifestation of either the allocation of attentional resources to cope with the increasing task demands or a desynchronization of decision making and/or response selection and execution". It should be noted that in this study only three leads were used, namely Fz, Cz, and Pz.

The P600 component of ERPs or late positive potentials (elicited between 500 and 800 ms or later after warning stimuli) is accepted as reflecting the completion of any synchronised operation immediately after target detection. In other words, it signals "the second pass parsing processes" of information processing. Specifically, its amplitude is considered as an index of the cost of reprocessing, while its latency as a function of onset and duration of parsing processes. ^{9, 10} Furthermore, it has been suggested that the P600 component may be related to WM. ¹¹