Neuroscience and mental health

Deep Brain Stimulation (DBS), besides an effective therapeutic tool, is a fascinating physiological "window" on human subcortical structures. In fact, local field potential (LFPs) recordings in patients provide an amount of physiological data on basal ganglia, especially in relation to their motor, cognitive and affective functions. In this study we aimed to assess a novel methodological approach for estimating the

Background: Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higherorder cognition. Objective: We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. Method: We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. Results: In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. Conclusion: Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions.

Background: Post hoc analyses of placebo-controlled studies suggest that memantine treatment may benefit language and conversation abilities of patients' with Alzheimer's disease (AD). This study prospectively evaluated the effects of memantine on functional communication in patients with moderate AD. Methods: Native English-speaking outpatients (N¼265) with AD (MMSE range: 10-19) participated in a 12-week, international, double-blind, randomized, placebo-controlled study of memantine (20 mg/day) versus placebo. Concurrent cholinesterase inhibitor treatment, stable throughout the study, was permitted but not required. The primary outcome was the baseline-to-endpoint score change on the Functional Linguistic Communication Inventory (FLCI), a patient performance measure; secondary outcome was the baseline-to-endpoint score change on the combined Social Communication and Communication of Basic Needs subscales of the American Speech-Language-Hearing Association Functional Assessment Communication Skills for Adults (ASHA FACS), a caregiver assessment. Primary analysis was based on the intent-to-treat population and the last observation carried forward (LOCF) approach, performed using a two-way ANCOVA model with treatment group and study center as factors, and baseline score as covariate. Further analyses were based on the observed cases (OC) and the mixed-effects model with repeated measures (MMRM; FLCI only). Safety and tolerability were assessed by recording treatment-emergent adverse events (TEAEs). Results: Patients treated with memantine (n¼133) demonstrated a statistically significant (LOCF) improvement on the FLCI at Weeks 4 and 8, and trend at Week 12 (placebo: -0.6; memantine: 0.7; P¼0.070) when compared with patients treated with placebo (n¼124); improvement on the ASHA FACS was significant at Weeks 8 and 12 (placebo: -5.3; memantine: 0.5; P¼0.022). Analyses based on OC (FLCI; ASHA FACS) and MMRM (FLCI) yielded similar results. Memantine was well tolerated; only dizziness and restlessness were reported by 2% of memantine patients and at an incidence twice that observed in the placebo group. Conclusions: Treatment of patients with moderate AD with memantine improves functional communication skills which can be recognized by caregivers.