Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

Background DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. Objective To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. Methods We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. Results First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. Conclusions STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

BACKGROUND DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. OBJECTIVE To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. METHODS We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. RESULTS First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. CONCLUSIONS STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features

Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area.

Enhanced dopamine (DA) neurotransmission from the ventral tegmental area (VTA) to the ventral striatum is thought to drive drug self-administration and mediate positive reinforcement. We examined neuronal firing rates in slices of mouse midbrain following adolescent binge-like alcohol drinking and find that prior alcohol experience greatly enhanced the sensitivity to excitation by ethanol itself (10-50 mM) in a subset of ventral midbrain DA neurons located in the medial VTA. This enhanced response after drinking was not associated with alterations of firing rate or other measures of intrinsic excitability. In addition, the phenomenon appears to be specific to adolescent drinking, as mice that established a drinking preference only after the onset of adulthood showed no change in alcohol sensitivity. Here we demonstrate not only that drinking during adolescence induces enhanced alcohol sensitivity, but also that this DA neuronal response occurs over a range of alcohol concentrations associated with social drinking in humans

Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study.

Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers