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BackgroundIn addition to the typical motor symptoms, a majority of patients suffering from Parkinson's disease experience language impairments. Deep Brain Stimulation of the subthalamic nucleus robustly reduces motor dysfunction, but its impact on language skills remains ambiguous.MethodTo elucidate the impact of subthalamic deep brain stimulation on natural language production, we systematically analyzed language samples from fourteen individuals (three female / eleven male, average age 66.43 ± 7.53 years) with Parkinson's disease in the active (ON) versus inactive (OFF) stimulation condition. Significant ON-OFF differences were considered as stimulation effects. To localize their neuroanatomical origin within the subthalamic nucleus, they were correlated with the volume of tissue activated by therapeutic stimulation.ResultsWord and clause production speed increased significantly under active stimulation. These enhancements correlated with the volume of tissue activated within the associative part of the subthalamic nucleus, but not with that within the dorsolateral motor part, which again correlated with motor improvement. Language error rates were lower in the ON vs. OFF condition, but did not correlate with electrode localization. No significant changes in further semantic or syntactic language features were detected in the current study.ConclusionThe findings point towards a facilitation of executive language functions occurring rather independently from motor improvement. Given the presumed origin of this stimulation effect within the associative part of the subthalamic nucleus, this could be due to co-stimulation of the prefrontal-subthalamic circuit.

Nitrergic neurons of the dorsal raphe nucleus (DRN) may play a role in physiological stress responses. The caudal lateral wings (CLW) are unique compared to other rostral-caudal DRN sub-regions because they contain distinct nitric oxide (NO) synthase (NOS) populations that are independent of tryptophan hydroxylase (TPH). NOS neurons in the CLW are also highly activated during acute restraint stress. However, the effects of acute stress duration on NOS activation in the CLW are unclear. Here NADPH-d, an index of NOS activity, is used to show that sub-regions of the DRN have differential NOS activation in response to 6 hours of restraint stress in rats. We report increased NOS activity through 6 hours of restraint in the caudal lateral wings and ventromedial sub-regions. These data suggest that, NOS neurons may play a dynamic role in the response to stress duration.

OBJECTIVE:Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. METHOD:Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. RESULTS:PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. DISCUSSION:Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

As people increasingly communicate via asynchronous non-spoken modes on mobile devices, particularly text messaging (e.g., SMS), longstanding assumptions and practices of social measurement via telephone survey interviewing are being challenged. In the study reported here, 634 people who had agreed to participate in an interview on their iPhone were randomly assigned to answer 32 questions from US social surveys via text messaging or speech, administered either by a human interviewer or by an automated interviewing system. 10 interviewers from the University of Michigan Survey Research Center administered voice and text interviews; automated systems launched parallel text and voice interviews at the same time as the human interviews were launched. The key question was how the interview mode affected the quality of the response data, in particular the precision of numerical answers (how many were not rounded), variation in answers to multiple questions with the same response scale (differentiation), and disclosure of socially undesirable information. Texting led to higher quality data-fewer rounded numerical answers, more differentiated answers to a battery of questions, and more disclosure of sensitive information-than voice interviews, both with human and automated interviewers. Text respondents also reported a strong preference for future interviews by text. The findings suggest that people interviewed on mobile devices at a time and place that is convenient for them, even when they are multitasking, can give more trustworthy and accurate answers than those in more traditional spoken interviews. The findings also suggest that answers from text interviews, when aggregated across a sample, can tell a different story about a population than answers from voice interviews, potentially altering the policy implications from a survey.

Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.

For word production, we may consciously pursue semantic or phonological search strategies, but it is uncertain whether we can retrieve the different aspects of lexical information independently from each other. We therefore studied the spread of semantic information into words produced under exclusively phonemic task demands.42 subjects participated in a letter verbal fluency task, demanding the production of as many s-words as possible in two minutes. Based on curve fittings for the time courses of word production, output spurts (temporal clusters) considered to reflect rapid lexical retrieval based on automatic activation spread, were identified. Semantic and phonemic word relatedness within versus between these clusters was assessed by respective scores (0 meaning no relation, 4 maximum relation).Subjects produced 27.5 (±9.4) words belonging to 6.7 (±2.4) clusters. Both phonemically and semantically words were more related within clusters than between clusters (phon: 0.33±0.22 vs. 0.19±0.17, p

Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response.

Sex differences in spontaneous sleep amount are largely dependent on reproductive hormones; however, in mice some sex differences in sleep amount during the active phase are preserved after gonadectomy and may be driven by non-hormonal factors. In this study, we sought to determine whether or not these sex differences are driven by sex chromosome complement. Mice from the four core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of phenotype (male or female), were implanted with electroencephalographic (EEG) and electromyographic (EMG) electrodes for the recording of sleep-wake states and underwent a 24-hr baseline recording followed by six hours of forced wakefulness. During baseline conditions in mice whose gonads remained intact, males had more total sleep and non-rapid eye movement sleep than females during the active phase. Gonadectomized FCG mice exhibited no sex differences in rest-phase sleep amount; however, during the mid-active-phase (nighttime), XX males had more spontaneous non-rapid eye movement (NREM) sleep than XX females. The XY mice did not exhibit sex differences in sleep amount. Following forced wakefulness there was a change in the factors regulating sleep. XY females slept more during their mid-active phase siestas than XX females and had higher NREM slow wave activity, a measure of sleep propensity. These findings suggest that the process that regulates sleep propensity is sex-linked, and that sleep amount and sleep propensity are regulated differently in males and females following sleep loss.

BACKGROUND: Verbal Fluency is reduced in patients with Parkinson's disease, particularly if treated with deep brain stimulation. This deficit could arise from general factors, such as reduced working speed or from dysfunctions in specific lexical domains. OBJECTIVE: To test whether DBS-associated Verbal Fluency deficits are accompanied by changed dynamics of word processing. METHODS: 21 Parkinson's disease patients with and 26 without deep brain stimulation of the subthalamic nucleus as well as 19 healthy controls participated in the study. They engaged in Verbal Fluency and (primed) Lexical Decision Tasks, testing phonemic and semantic word production and processing time. Most patients performed the experiments twice, ON and OFF stimulation or, respectively, dopaminergic drugs. RESULTS: Patients generally produced abnormally few words in the Verbal Fluency Task. This deficit was more severe in patients with deep brain stimulation who additionally showed prolonged response latencies in the Lexical Decision Task. Slowing was independent of semantic and phonemic word priming. No significant changes of performance accuracy were obtained. The results were independent from the treatment ON or OFF conditions. CONCLUSION: Low word production in patients with deep brain stimulation was accompanied by prolonged latencies for lexical decisions. No indication was found that the latter slowing was due to specific lexical dysfunctions, so that it probably reflects a general reduction of cognitive working speed, also evident on the level of Verbal Fluency. The described abnormalities seem to reflect subtle sequelae of the surgical procedure for deep brain stimulation rather than of the proper neurostimulation.

BACKGROUND: Severe polyneuropathy has been observed in a number of patients treated for Parkinson's disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect. OBJECTIVE: To investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion. METHODS: In an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n = 15) and with Levodopa/Carbidopa intestinal gel infusion (n = 15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed. RESULTS: Axonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups. CONCLUSION: The results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial.