Upgraded Cherenkov time-of-flight detector for the AFP project.

We present the results of our performance studies of the upgraded Cherenkov time-of-flight (ToF) detector for the AFP (ATLAS Forward Proton) project. The latest version consists of solid L-shaped fused silica bars, new customized ALD-coated micro-channel plate photomultipliers (MCP-PMTs) miniPlanacon XPM85112-S-R2D2 with an extended lifetime which operate at low gains (order of 103), and an updated construction. The improvements were aimed to increase the efficiency, the lifetime as well as the radiation hardness of the detector which has been designed to operate in high radiation areas (above 400 kGy/year). The detector was finally tested at the CERN-SPS test-beam facility (120 GeV π+ particles) in August 2021 prior to its installation at the Large Hadron Collider (LHC) at CERN. Measurements proved the detector kept its inner timing resolution of 20 ps despite the rather low gain of its photodetector and reduced optical throughput caused by inevitable changes in the detector geometry.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Interplay between speech and gait variables in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: A long-term instrumental assessment.

OBJECTIVE: To evaluate correlations between speech and gait parameters in the long term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's disease (PD) patients. METHODS: This observational study included consecutive PD patients treated with bilateral STN-DBS. Axial symptoms were evaluated using a standardized clinical-instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented Timed Up and Go (iTUG) test, respectively. Disease motor severity was evaluated with the total score and subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. RESULTS: Twenty-five PD patients with a 5-year median follow-up after surgery (range 3-7 years) were included (18 males; disease duration at surgery: 10.44 [SD 4.62] years; age at surgery: 58.40 [SD 5.73] years). In the off-stimulation/off-medication and on-stimulation/on-medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait; whereas in the on-stimulation/on-medication condition only, patients with the poorer voice quality were also the worst to perform the sit to stand and gait phases of the iTUG. Conversely, patients with the higher speech rate performed well in the turning and walking phases of the iTUG. CONCLUSIONS: This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN-DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.

npSCOPE: A New Multimodal Instrument for In Situ Correlative Analysis of Nanoparticles.

Over the last few decades, nanoparticles have become a key element in a number of scientific and technological fields, spanning from materials science to life sciences. The characterization of nanoparticles or samples containing nanoparticles, in terms of morphology, chemical composition, and other parameters, typically involves investigations with various analytical tools, requiring complex workflows and extending the duration of such studies to several days or even weeks. Here, we report on the development of a new unique in situ correlative instrument, allowing us to answer questions about the shape, size, size distribution, and chemical composition of the nanoparticles using a single probe. Combining various microscopic and analytical capabilities in one single instrument allows a considerable increase in flexibility and a reduction in the duration of such complex investigations. The new instrument is based on focused ion beam microscopy technology using a gas field ion source as a key enabler and combining it with specifically developed secondary ion mass spectrometry and scanning transmission ion microscopy technology. We will present the underlying concept, the instrument and its main components, and proof-of-concept studies performed on this novel instrument. For this purpose, different pure titanium dioxide nanoparticle samples were investigated. Furthermore, the distribution and localization of the nanoparticles in biological model systems were studied. Our results demonstrate the performance and usefulness of the instrument for nanoparticle investigations, paving the way for a number of future applications, in particular, nanotoxicological research.

Acoustic, perceptual and clinical correlates of speech and voice in isolated dystonia: Preliminary findings.

BACKGROUND: Hyperkinetic dysarthria is often present in isolated dystonia (ID) and is still understudied. Four main clusters of deviant speech dimensions in dystonia hyperkinetic dysarthria were initially provided: articulatory inaccuracy, phonatory stenosis, prosodic excess and prosodic insufficiency. AIM: The aim of our exploratory study was to provide preliminary data on both perceptual and acoustic analyses in relation to three out of these four main clusters. METHODS & PROCEDURES: Eleven patients with ID and 11 healthy controls (HC) participated in this study. Clinical/perceptual assessments and acoustic analyses of speech recordings were performed, the latter allowing for the analysis of parameters referring to aerophonatory control, voice quality, prosodic features and speech intelligibility estimated by nine listeners. Between-group statistical comparisons were performed (Wilcoxon tests, p < 0.05). Single-case differences between each patient and the control group were also carried out (effect size index and t < 0.05). OUTCOMES & RESULTS: Between-group comparisons confirmed the presence of a 'phonatory stenosis'; in addition, deficit in aerophonatory control and hypophonia was also displayed. 'Prosodic insufficiency' was confirmed, but not at the individual level. 'Prosodic excess' manifested only in patients with marked and severe dysarthria. Correlations between altered maximum phonation time, loudness variation, speech and articulatory rates on the one hand, and several clinical speech assessments on the other hand, were also found. CONCLUSIONS & IMPLICATIONS: From these findings, altogether, perceptual characteristics of hyperkinetic dysarthria, as suggested by Darley et al., were quantified by the acoustic parameters we measured. As regards to our data obtained in a small participant sample, we would suggest that Darley et al.'s clusters of excess and insufficiency prosody should be questioned in future studies involving larger numbers of dystonic patients. Our study provides novel and preliminary results that demonstrate the relevance of using quantitative measures to further characterise speech/voice deficits in patients with ID.

The impact of when, what and how predictions on auditory speech perception.

An impressive number of theoretical proposals and neurobiological studies argue that perceptual processing is not strictly feedforward but rather operates through an interplay between bottom-up sensory and top-down predictive mechanisms. The present EEG study aimed to further determine how prior knowledge on auditory syllables may impact speech perception. Prior knowledge was manipulated by presenting the participants with visual information indicative of the syllable onset (when), its phonetic content (what) and/or its articulatory features (how). While when and what predictions consisted of unnatural visual cues (i.e., a visual timeline and a visuo-orthographic cue), how prediction consisted of the visual movements of a speaker. During auditory speech perception, when and what predictions both attenuated the amplitude of N1/P2 auditory evoked potentials. Regarding how prediction, not only an amplitude decrease but also a latency facilitation of N1/P2 auditory evoked potentials were observed during audiovisual compared to unimodal speech perception. However, when and what predictability effects were then reduced or abolished, with only what prediction reducing P2 amplitude but increasing latency. Altogether, these results demonstrate the influence of when, what and how visually induced predictions at an early stage on cortical auditory speech processing. Crucially, they indicate a preponderant predictive role of the speaker's articulatory gestures during audiovisual speech perception, likely driven by attentional load and focus.

Psychosocial Impact of Dysarthria: The Patient-Reported Outcome as Part of the Clinical Management.

BACKGROUND: Dysarthria in neurological disorders can have psychosocial consequences. The dysarthric speaker's perspective towards the disorder's psychosocial impact is essential in its global assessment and management. For such purposes, assessment tools such as the Dysarthria Impact Profile (DIP) are indispensable. OBJECTIVE: We aimed to confirm the relevance of using the DIP to quantify the psychosocial consequences of dysarthria in neurological diseases. METHODS: We studied 120 participants, 15 healthy controls and 105 patients with different kinds of dysarthria induced by several neurological disorders (Parkinson's disease [PD], Huntington's disease, dystonia, cerebellar ataxia, progressive supranuclear palsy [PSP], multiple system atrophy, lateral amyotrophic sclerosis). All participants underwent a cognitive evaluation and a speech intelligibility assessment and completed three self-reported questionnaires: the 36-Item Short Form Health Survey, the Voice Handicap Index (VHI), and the DIP. RESULTS: The psychometric properties of the DIP were confirmed, including internal consistency (α = 0.93), concurrent validity (correlation with the VHI: r = -0.77), and discriminant validity (accuracy = 0.93). Psychosocial impact of dysarthria was revealed by the DIP for all patients. Intelligibility loss was found strongly correlated with the psychosocial impact of dysarthria: for a similar level of intelligibility impairment, the DIP total score was similar regardless of the pathological group. However, our findings suggest that the psychosocial impact measured by the DIP could be partially independent from the severity of dysarthria (indirectly addressed here via speech intelligibility): the DIP was able to detect patients without any intelligibility impairment, but with a psychosocial impact. CONCLUSIONS: All patients reported a communication complaint, attested by the DIP scores, despite the fact that not all patients, notably PD, ataxic, and PSP patients, had an intelligibility deficit. The DIP should be used in clinical practice to contribute to a holistic evaluation and management of functional communication in patients with dysarthria.

Stimulation of the pedunculopontine nucleus area in Parkinson's disease: effects on speech and intelligibility.

Improvement of gait disorders following pedunculopontine nucleus area stimulation in patients with Parkinson's disease has previously been reported and led us to propose this surgical treatment to patients who progressively developed severe gait disorders and freezing despite optimal dopaminergic drug treatment and subthalamic nucleus stimulation. The outcome of our prospective study on the first six patients was somewhat mitigated, as freezing of gait and falls related to freezing were improved by low frequency electrical stimulation of the pedunculopontine nucleus area in some, but not all, patients. Here, we report the speech data prospectively collected in these patients with Parkinson's disease. Indeed, because subthalamic nucleus surgery may lead to speech impairment and a worsening of dysarthria in some patients with Parkinson's disease, we felt it was important to precisely examine any possible modulations of speech for a novel target for deep brain stimulation. Our results suggested a trend towards speech degradation related to the pedunculopontine nucleus area surgery (off stimulation) for aero-phonatory control (maximum phonation time), phono-articulatory coordination (oral diadochokinesis) and speech intelligibility. Possibly, the observed speech degradation may also be linked to the clinical characteristics of the group of patients. The influence of pedunculopontine nucleus area stimulation per se was more complex, depending on the nature of the task: it had a deleterious effect on maximum phonation time and oral diadochokinesis, and mixed effects on speech intelligibility. Whereas levodopa intake and subthalamic nucleus stimulation alone had no and positive effects on speech dimensions, respectively, a negative interaction between the two treatments was observed both before and after pedunculopontine nucleus area surgery. This combination effect did not seem to be modulated by pedunculopontine nucleus area stimulation. Although limited in our group of patients, speech impairment following pedunculopontine nucleus area stimulation is a possible outcome that should be considered before undertaking such surgery. Deleterious effects could be dependent on electrode insertion in this brainstem structure, more than on current spread to nearby structures involved in speech control. The effect of deep brain stimulation on speech in patients with Parkinson's disease remains a challenging and exploratory research area.

From micrographia to Parkinson's disease dysgraphia.

Micrographia, an abnormal reduction in writing size, is a specific behavioral deficit associated with Parkinson's disease (PD). In recent years, the availability of graphic tablets has made it possible to study micrographia in unprecedented detail. Consequently, a growing number of studies show that PD patients also exhibit impaired handwriting kinematics. Is micrographia still the most characteristic feature of PD-related handwriting deficits? To answer this question, we identified studies that investigated handwriting in PD, either with conventional pencil-and-paper measures or with graphic tablets, and we reported their findings on key spatiotemporal and kinematic variables. We found that kinematic variables (velocity, fluency) differentiate better between control participants and PD patients, and between off- and on-treatment PD patients, than the traditional measure of static writing size. Although reduced writing size is an important feature of PD handwriting, the deficit is not restricted to micrographia stricto sensu. Therefore, we propose the term PD dysgraphia, which encompasses all deficits characteristic of Parkinsonian handwriting. We conclude that the computerized analysis of handwriting movements is a simple and useful tool that can contribute to both diagnosis and follow-up of PD.

Delivering Multidisciplinary Rehabilitation Care in Parkinson's Disease: An International Consensus Statement.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD. OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was to develop a consensus statement regarding the incorporation of rehabilitation in PD care. METHODS: The Task Force, comprised of international multidisciplinary experts in PD and rehabilitation and people directly affected by PD, met virtually to discuss topics such as rehabilitative services, existing therapy guidelines and rehabilitation literature in PD, and gaps and needs. A systematic, interactive, and iterative process was used to develop consensus-based statements on core components of PD rehabilitation and discipline-specific interventions. RESULTS: The expert-based consensus statement outlines key tenets of rehabilitative care including its multidisciplinary approach and discipline-specific guidance for occupational therapy, physical therapy, speech language pathology/therapy, and psychology/neuropsychology across all PD stages. CONCLUSIONS: Rehabilitative interventions should be an essential component in the comprehensive treatment of PD, from diagnosis to advanced disease. Greater education and awareness of the benefits of rehabilitative services for people with PD and their care partners, and further evidence-based and scientific study are encouraged.

Do Acoustic Characteristics of Dysarthria in People With Parkinson's Disease Differ Across Languages?

PURPOSE: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. METHOD: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). RESULTS: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. CONCLUSIONS: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

Levodopa does not change cerebral vasoreactivity in Parkinson's disease.

The aim of this work was to study cerebral vasoreactivity to hypercapnia in Parkinson's disease (PD) before and after levodopa administration. The prospective study was conducted in 20 patients presenting with PD, using 3T blood oxygenation level-dependent (BOLD) functional MRI (fMRI) covering the whole brain. The hypercapnic stimulus was block-designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L-dopa dose (ON). Ten age-matched controls were enrolled for between-group comparisons. Analyses were conducted with a random effects model and corrected for multiple comparisons. No adverse reaction to the hypercapnic stimulus was reported. However, 10 patients and 2 controls were excluded because of incomplete protocol realization, inappropriate hypercapnic stimulus, or excessive movements, leaving 10 patients and 8 controls for further analyses. The hypercapnic stimulus increased whole-brain BOLD signal of 1.48% ± 0.06% (mean ± standard error) in controls, 1.59% ± 0.05% in patients OFF, and 1.62% ± 0.09% in patients ON. Regions of interest analyses showed a signal increase in gray matter of 2.60% ± 0.16% in controls, 2.89% ± 0.21% in patients OFF, and 2.87% ± 0.12% in patients ON. No global or regional significant difference was detected, when comparing patients OFF and ON L-dopa, or between patients and controls. Contrary to Alzheimer's disease, the vasoreactivity to hypercapnia was normal in PD before and after L-dopa administration, compared to controls. This negative result is an important finding, especially for neuroscientists using fMRI to investigate motricity and cognition, discarding a significant confounding effect.

Phoneme Representation and Articulatory Impairment: Insights from Adults with Comorbid Motor Coordination Disorder and Dyslexia.

Phonemic processing skills are impaired both in children and adults with dyslexia. Since phoneme representation development is based on articulatory gestures, it is likely that these gestures influence oral reading-related skills as assessed through phonemic awareness tasks. In our study, fifty-two young dyslexic adults, with and without motor impairment, and fifty-nine skilled readers performed reading, phonemic awareness, and articulatory tasks. The two dyslexic groups exhibited slower articulatory rates than skilled readers and the comorbid dyslexic group presenting with an additional difficulty in respiratory control (reduced speech proportion and increased pause duration). Two versions of the phoneme awareness task (PAT) with pseudoword strings were administered: a classical version under time pressure and a delayed version in which access to phonemic representations and articulatory programs was facilitated. The two groups with dyslexia were outperformed by the control group in both versions. Although the two groups with dyslexia performed equally well on the classical PAT, the comorbid group performed significantly less efficiently on the delayed PAT, suggesting an additional contribution of articulatory impairment in the task for this group. Overall, our results suggest that impaired phoneme representations in dyslexia may be explained, at least partially, by articulatory deficits affecting access to them.

A study on the correlations between acoustic speech variables and bradykinesia in advanced Parkinson's disease.

Background: Very few studies have assessed the presence of a possible correlation between speech variables and limb bradykinesia in patients with Parkinson's disease (PD). The objective of this study was to find correlations between different speech variables and upper extremity bradykinesia under different medication conditions in advanced PD patients. Methods: Retrospective data were collected from a cohort of advanced PD patients before and after an acute levodopa challenge. Each patient was assessed with a perceptual-acoustic analysis of speech, which included several quantitative parameters [i.e., maximum phonation time (MPT) and intensity (dB)]; the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items); and a timed test (a tapping test for 20 s) to quantify upper extremity bradykinesia. Pearson's correlation coefficient was applied to find correlations between the different speech variables and the tapping rate. Results: A total of 53 PD patients [men: 34; disease duration: 10.66 (SD 4.37) years; age at PD onset: 49.81 years (SD 6.12)] were included. Levodopa intake increased the MPT of sustained phonation (p < 0.01), but it reduced the speech rate (p = 0.05). In the defined-OFF condition, MPT of sustained phonation positively correlated with both bilateral mean (p = 0.044, r-value:0.299) and left (p = 0.033, r-value:0.314) tapping. In the defined-ON condition, the MPT correlated positively with bilateral mean tapping (p = 0.003), left tapping (p = 0.003), and right tapping (p = 0.008). Conclusion: This study confirms the presence of correlations between speech acoustic variables and upper extremity bradykinesia in advanced PD patients. These findings suggest common pathophysiological mechanisms.

Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson's disease.

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson's Disease (PD). However, the effects of STN-DBS on speech are still debated, particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced PD patients treated with bilateral STN-DBS. Each patient was assessed before surgery through a neurological evaluation and a perceptual-acoustic analysis of speech and re-assessed in the long-term in different stimulation and drug conditions. The primary outcome was the percentage change of speech intelligibility obtained by comparing the postoperative on-stimulation/off-medication condition with the preoperative off-medication condition. Twenty-five PD patients treated with bilateral STN-DBS with a 5-year follow-up were included. In the long-term, speech intelligibility stayed at the same level as preoperative values when compared with preoperative values. STN-DBS induced a significant acute improvement of speech intelligibility (p < 0.005) in the postoperative assessment when compared to the on-stimulation/off-medication and off-stimulation/off-medication conditions. These results highlight that STN-DBS may handle speech intelligibility even in the long-term.

At-Home Training With a Rhythmic Video Game for Improving Orofacial, Manual, and Gait Abilities in Parkinson's Disease: A Pilot Study.

Rhythm disorders are consistently reported in Parkinson's disease (PD). They manifest across motor domains, such as in orofacial (oral diadochokinesis), manual (finger tapping), and gait tasks. It is still unclear, however, whether these disorders are domain- and task-specific, or result from impaired common mechanisms supporting rhythm processing (general dysrhythmia). We tested the possibility that an at-home intervention delivered via a rhythmic video game on tablet improves motor performance across motor domains in PD. Patients with PD (n = 12) played at home a rhythmic video game (Rhythm Workers) on tablet, in which they finger-tapped to the beat of music, for 6 weeks. A control group (n = 11) played an active non-rhythmic video game (Tetris). A third group (n = 10) did not receive any intervention. We measured rhythmic abilities in orofacial, manual and gait motor domains, as well as rhythm perception, before and after the intervention. Patients who performed the rhythmic training improved their orofacial and manual rhythmic performance. This beneficial effect was linked to improved rhythm perception only following the rhythmic training period. We did not observe any improvement in rhythmic abilities in the other two groups. In this pilot study, we demonstrated that at-home intervention with a rhythmic video game using finger tapping can have beneficial effects on motor performance across different motor domains (manual and orofacial). This finding provides evidence of a general dysrhythmia in PD and paves the way to technology-driven interventions aiming at alleviating rhythm-related motor deficits in PD.

Demonstration of non-destructive and isotope-sensitive material analysis using a short-pulsed laser-driven epi-thermal neutron source.

Neutrons are a valuable tool for non-destructive material investigation as their interaction cross sections with matter are isotope sensitive and can be used complementary to x-rays. So far, most neutron applications have been limited to large-scale facilities such as nuclear research reactors, spallation sources, and accelerator-driven neutron sources. Here we show the design and optimization of a laser-driven neutron source in the epi-thermal and thermal energy range, which is used for non-invasive material analysis. Neutron resonance spectroscopy, neutron radiography, and neutron resonance imaging with moderated neutrons are demonstrated for investigating samples in terms of isotope composition and thickness. The experimental results encourage applications in non-destructive and isotope-sensitive material analysis and pave the way for compact laser-driven neutron sources with high application potential.

Functional magnetic resonance imaging exploration of combined hand and speech movements in Parkinson's disease.

Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values < 0.05, familywise error corrected), between-group, and between-task comparisons (regional activations significant at P values < 0.001, uncorrected, with cluster size > 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task.

Modulation of dysarthropneumophonia by low-frequency STN DBS in advanced Parkinson's disease.

BACKGROUND: Parkinsonian dysarthria (as typically characterized by hypophonia, monotony of pitch, and rhythm abnormalities) is often accompanied by gait disturbances. The long-term effect of subthalamic nucleus deep brain stimulation (STN DBS) on dysarthria remains unclear. METHODS: Given STN DBS's known improvement of gait disorders, we analyzed speech intelligibility and aerodynamic and acoustic parameters in 11 advanced PD patients in three double-blind, randomized conditions: "defined Off," 60 Hz STN DBS and 130 Hz STN DBS. RESULTS: An improvement in aerodynamic speech parameters during 60 Hz STN DBS was accompanied by significant clinical benefit. CONCLUSIONS: Chronic treatment with low-frequency STN DBS may have a beneficial impact on dysarthropneumophonia, even in advanced PD patients.