Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

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.

The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1.

Autoantibodies (AB) against N-methyl-D-aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood-brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF-serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non-brain-binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an 'immunoprecipitator'; simultaneous injection of NMDAR1 AB and the non-brain-binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF.

Functional electrical stimulation through direct 4-channel nerve stimulation to improve gait in multiple sclerosis: a feasibility study.

BACKGROUND: Gait dysfunction due to lower limb central paralysis, frequently involving drop foot, is a common cause of disability in multiple sclerosis and has been treated with transcutaneous functional electrical stimulation (FES). We provide here the first report of 4-channel semi-implantable FES of the peroneal nerve which has been successfully used for rehabilitation in patients following stroke. METHODS: FES was implemented via a 4-channel semi-implantable closed-loop system (ActiGait(®), ©Ottobock), generating dorsiflexion in drop foot. Walking distance, gait symmetry (temporospatial gait analyses, Vicon Motion Systems(®)), gait velocity (10 m walking test) and quality of life (SF-36 questionnaire) were measured to evaluate the therapeutic benefit of this system in two patients with progressive MS. RESULTS: Walking distance increased from 517 to 1884 m in Patient 1 and from 52 to 506 m in Patient 2. Gait velocity did not change significantly in Patient 1 and increased from 0.6 to 0.8 m/s in Patient 2. Maximum deviations of center of mass from the midline to each side changed significantly after 3 months of stimulation compared to baseline, decreasing from 15 to 12 mm in Patient 1 and from 47 to 37 mm in Patient 2. Both patients experienced reduced pain and fatigue and benefits to quality of life. Adverse events did not occur during the observation period. CONCLUSION: We conclude that implantable 4-channel FES systems are not only feasible but present a promising new alternative for treating central drop foot in MS patients.

Event-related potentials and EMDR treatment of post-traumatic stress disorder.

Ten patients suffering from post-traumatic stress disorder (PTSD) following a severe traumatic event, were assessed with event-related brain potentials (ERPs) in a modified oddball paradigm containing auditory standard, target, and novel tones. ERPs were assessed before and after a treatment session using the eye movement desensitization and reprocessing method. Compared to a control group that underwent sham treatment, ERPs of the patients showed a reduction of the P3a component in the post-treatment recording, suggesting a reduced orienting to novel stimuli and reduced arousal level after the treatment. Moreover, psychometric assessment revealed a marked improvement of the PTSD symptoms after treatment.

Disturbed monitoring and response inhibition in patients with Gilles de la Tourette syndrome and co-morbid obsessive compulsive disorder.

OBJECTIVE: Fronto-striatal dysfunction has been discussed as underlying symptoms of Tourette syndrome (TS) with co-morbid Obsessive Compulsive Disorder (OCD). This suggests possible impairments of executive functions in this disorder, which were therefore targeted in the present study. METHODS: A comprehensive series of neuropsychological tests examining attention, memory and executive functions was performed in a group of 14 TS/OCD in co-occurrence with OCD patients and a matched control group. RESULTS: While attentional and memory mechanisms were not altered, TS/OCS patients showed deficits in executive functions predominantly in the areas of response inhibition and action monitoring. CONCLUSIONS: These findings provide further evidence for a substantial impairment of the frontal-striatal-thalamic-frontal circuit. We propose that the deficits in monitoring, error detection and response inhibition constitute the major impairment of TS/OCD patients in the cognitive domain.

The costs of freedom: an ERP -- study of non-canonical sentences.

OBJECTIVES: The present investigation explored the electrophysiological correlates of working memory during sentence comprehension. METHODS: Event-related brain potentials (ERP) were recorded from 29 channels in 22 subjects, while they read German sentences having subject-first (canonical) or object-first (non-canonical) word orders. RESULTS: Three different ERP effects were observed: a negativity (maximum at Fc5) differentiating unambiguous object-first and subject-first sentences, interpreted as reflecting the demands of the object-first sentences on working memory; a second negativity (maximum at F7) to the subject noun-phrase in object-first sentences, interpreted as indicating retrieval of verbal material. Finally, a parietal positivity was found for ambiguous sentences that turned out to have a non-canonical word order, which was interpreted as indicating revision and reevaluation processes. CONCLUSIONS: The present data underscore the different roles of working memory in comprehension.