Event-related brain potentials (EMS) were recorded while normal German subjects read either simple declarative sen- tences made up from real German words, or sentences that contained German pseudo-words instead of nouns and verbs. The verb (pseudo-verb) of the sentences disagreed in number with the subject noun (pseudo-noun) in 50% of the sentences. The subjects had the task either to read the sentences for an interspersed memory test (memory condition, pseudeword sentences only) or to make a syntactic judgment after each real-word/pseudo-word sentence. While in the real-word condition a late and widespread positivity resembling the previously described syntactic positive shift was found for the disagreeing verbs, a negativity with an onset latency of about 300 msec was seen for the disagreeing pseudo-verbs. In the pseudo-word conditions no positivity followed the initial negativity. This dissociation of negative and positive waves occurring in response to morphosyntactic mismatches by the pseudo/real-word manipulation suggests that the positive shift is a concomitant of a recomputation routine initiated to account for the number incongruency. This routine is based upon the semantics of the sentence and therefore is not observed in the pseudo-word conditions. The earlier negativity, on the other hand, appears to be a more direct index of morphosyntactic incongruency.
Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.
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