No abstract

The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

No abstract

It has long been recognized that the amplitude of the P300 component of event-related brain potentials is sensitive to the degree to which eliciting stimuli are surprising to the observers (Donchin, 1981). While Squires et al. (1976) showed and modeled dependencies of P300 amplitudes from observed stimuli on various time scales, Mars et al. (2008) proposed a computational model keeping track of stimulus probabilities on a long-term time scale. We suggest here a computational model which integrates prior information with short-term, long-term, and alternation-based experiential influences on P300 amplitude fluctuations. To evaluate the new model, we measured trial-by-trial P300 amplitude fluctuations in a simple two-choice response time task, and tested the computational models of trial-by-trial P300 amplitudes using Bayesian model evaluation. The results reveal that the new digital filtering (DIF) model provides a superior account of the trial-by-trial P300 amplitudes when compared to both Squires et al.’s (1976) model, and Mars et al.’s (2008) model. We show that the P300-generating system can be described as two parallel first-order infinite impulse response (IIR) low-pass filters and an additional fourth-order finite impulse response (FIR) high-pass filter. Implications of the acquired data are discussed with regard to the neurobiological distinction between short-term, long-term, and working memory as well as from the point of view of predictive coding models and Bayesian learning theories of cortical function.

Though somatotopic encoding of function is a prominent feature in brain structures involved in sensori-motor processing, it has not been well established for the human cerebellum. We delineated the representation of hand, foot and tongue movements in the anterior cerebellar lobe of eight healthy subjects using dynamic high-resolution MRI sensitized to changes in cerebral blood oxygenation (CBO). Activation was determined by pixel-by-pixel correlation of signal intensity time courses with the performance protocol. All subjects showed task-related signal increases in an ipsilateral region during distal limb movements. For the hand task, the centre of activation was located in the intermediate hemispheric portion of Larsell lobules H IV-V. Foot movements activated areas within the central lobule, Larsell lobules II-III, medial and anterior to the corresponding hand areas in all subjects. Responses for tongue movements were less consistent across subjects but found in areas posterior to the respective individual hand representation.

No abstract

Autosomal dominant spinocerebellar ataxias (SCA) are a group of clinically and genetically heterogeneous neurodegenerative disorders which lead to progressive cerebellar ataxia. A gene responsible for SCA type 2 has been mapped to human chromosome 12 and the disease causing mutation has been identified as an unstable and expanded (CAG)n trinucleotide repeat. We investigated the (CAG)n repeat length of the SCA2 gene in 842 patients with sporadic ataxia and in 96 German families with dominantly inherited SCA which do not harbor the SCA1 or MJD1/SCA3 mutation, respectively. The SCA2 (CAG)n expansion was identified in 71 patients from 54 families. The (CAG)n stretch of the affected allele varied between 36 and 64 trinucleotide units. Significant repeat expansions occurred most commonly during paternal transmission. Analysis of the (CAG)n repeat lengths with the age of onset in 41 patients revealed an inverse correlation. Two hundred and forty-one apparently healthy octogenerians carried alleles between 16 and 31 repeats. One 50-year old, healthy individual had 34 repeats; she had transmitted an expanded allele to her child. The small difference between 'normal' and disease alleles makes it necessary to define the extreme values of their ranges. With one exception, the trinucleotide expansion was not observed in 842 ataxia patients without a family history of the disease. The SCA2 mutation causes the disease in nearly 14% of autosomal dominant SCA in Germany.

We studied syllabic timing in patients with ataxia (10 with cerebellar atrophy, 6 with Friedreich's ataxia) under two conditions: in a "natural" sentence production context and in the context of a rapid syllable repetition task. The two tasks included comparable articulatory maneuvers. We measured syllable durations from the speech signal and analyzed variables describing average syllabic rate and within-trial variation of syllable durations. Among the observed measures, slowed syllable repetition was a particularly powerful predictor of the severity of dysarthric impairment. In sentence production, patients often performed at normal syllabic rates. Irregular pacing of syllable repetitions was frequent. Different patterns of between-articulator variation emerged in the two tasks. All patients except one were slower in rapid repetitive articulation than in sentence production. These data suggest that sentence production and rapid repetitive articulation are governed by basically different motor processes. The disproportionate slowing of ataxic patients in the repetitive task can be ascribed to adaptation to novel motor tasks being impaired in cerebellar disease.