Abnormal sensory discriminatory processing has been implicated as an endophenotypic marker of isolated dystonia. However, the extent of alterations across the different sensory domains and their commonality in different forms of dystonia are unclear. Based on the previous findings of abnormal temporal but not spatial discrimination in patients with laryngeal dystonia, we investigated sensory processing in the auditory and olfactory domains as potentially additional contributors to the disorder pathophysiology. We tested auditory temporal discrimination and olfactory function, including odor identification, threshold, and discrimination, in 102 laryngeal dystonia patients and 44 healthy controls, using dichotically presented pure tones and the extended Sniffin’ Sticks smell test protocol, respectively. Statistical significance was assessed using analysis of variance with non-parametric bootstrapping. Patients had a lower mean auditory temporal discrimination threshold, with abnormal values found in three patients. Hyposmia was found in 64 patients and anosmia in 2 patients. However, there were no statistically significant differences in either auditory temporal discrimination threshold or olfactory identification, threshold, and discrimination between the groups. A significant positive relationship was found between olfactory threshold and disorder severity based on the Burke–Fahn–Marsden dystonia rating scale. Our findings demonstrate that, contrary to altered visual temporal discrimination, auditory temporal discrimination and olfactory function are likely not candidate endophenotypic markers of laryngeal dystonia.

OBJECTIVE: Isolated dystonia is characterized by abnormal, often painful, postures and repetitive movements due to sustained or intermittent involuntary muscle contractions. Botulinum toxin (BoTX) injections into the affected muscles are the first line of therapy. However, there are no objective predictive markers or standardized tests of BoTX efficacy that can be utilized for appropriate candidate selection prior to treatment initiation. METHODS: We developed a deep learning algorithm, DystoniaBoTXNet, which uses a 3D convolutional neural network architecture and raw structural brain MRI to automatically discover and test a neural network biomarker of BoTX efficacy in 284 patients with four different forms of focal dystonia, including laryngeal dystonia, blepharospasm, cervical dystonia, and writer's cramp. RESULTS: DystoniaBoTXNet identified clusters in superior parietal, inferior/middle frontal, middle orbital gyrus, inferior temporal cortices, corpus callosum, inferior fronto-occipital fasciculus, and anterior thalamic radiation as components of the treatment biomarker. These regions are known to contribute to both dystonia pathophysiology across a broad clinical spectrum of disorder and the central effects of botulinum toxin treatment. Based on its biomarker, DystoniaBoTXNet achieved an overall accuracy of 96.3%, with 100% sensitivity and 86.1% specificity, in predicting BoTX efficacy in patients with isolated dystonia. The algorithmic decision was computed in 19.2 sec per case. INTERPRETATION: DystoniaBoTXNet and its treatment biomarker have a high translational potential as an objective, accurate, generalizable, fast, and cost-effective algorithmic platform for enhancing clinical decision-making for BoTX treatment in patients with isolated dystonia. This article is protected by copyright. All rights reserved.

Objective: Critical decisions are made by effective teams that are characterized by individuals who trust each other and know how to best integrate their opinions. Here, we introduce a multimodal BCI to help collaborative teams of humans and an artificial agent achieve more accurate decisions in assessing danger zones during a pandemic scenario. Approach: Using high-resolution simultaneous EEG/fMRI, we first disentangled the neural markers of decision-making confidence and trust and then employed machine-learning to decode these neural signatures for BCI-augmented team decision-making. We assessed the benefits of BCI on the team's decision-making process compared to the performance of teams of different sizes using the standard majority or weighing individual decisions. Main results: We showed that BCI-assisted teams are significantly more accurate in their decisions than traditional teams, as the BCI is capable of capturing distinct neural correlates of confidence on a trial-by-trial basis. Accuracy and subjective confidence in the context of collaborative BCI engaged parallel, spatially distributed, and temporally distinct neural circuits, with the former being focused on incorporating perceptual information processing and the latter involving action planning and executive operations during decision making. Among these, the superior parietal lobule emerged as a pivotal region that flexibly modulated its activity and engaged premotor, prefrontal, visual, and subcortical areas for shared spatial-temporal control of confidence and trust during decision-making. Significance: Multimodal, collaborative BCIs that assist human-artificial agent teams may be utilized in critical settings for augmented and optimized decision-making strategies.

Task-specificity in isolated focal dystonias is a powerful feature that may successfully be targeted with therapeutic brain-computer interfaces. While performing a symptomatic task, the patient actively modulates momentary brain activity (disorder signature) to match activity during an asymptomatic task (target signature), which is expected to translate into symptom reduction.

Speech production relies on the interplay of different brain regions. Healthy aging leads to complex changes in speech processing and production. Here, we investigated how the whole-brain functional connectivity of healthy elderly individuals differs from that of young individuals. In total, 23 young (aged 24.6 ± 2.2 years) and 23 elderly (aged 64.1 ± 6.5 years) individuals performed a picture naming task during functional magnetic resonance imaging. We determined whole-brain functional connectivity matrices and used them to compute group averaged speech production networks. By including an emotionally neutral and an emotionally charged condition in the task, we characterized the speech production network during normal and emotionally challenged processing. Our data suggest that the speech production network of elderly healthy individuals is as efficient as that of young participants, but that it is more functionally segregated and more modularized. By determining key network regions, we showed that although complex network changes take place during healthy aging, the most important network regions remain stable. Furthermore, emotional distraction had a larger influence on the young group’s network than on the elderly’s. We demonstrated that, from the neural network perspective, elderly individuals have a higher capacity for emotion regulation based on their age-related network re-organization.

Background and Objectives: Laryngeal dystonia (LD) is isolated task-specific focal dystonia selectively impairing speech production. The first choice of LD treatment is botulinum neurotoxin (BoNT) injections into the affected laryngeal muscles. However, whether BoNT has a lasting therapeutic effect on disorder pathophysiology is unknown. We investigated short- and long-term effects of BoNT treatment on brain function in LD patients. Methods: A total of 161 subjects participated in the functional MRI study. Statistical analyses examined central BoNT effects in LD patients who were stratified based on the effectiveness and duration of treatment. Results: LD patients who were treated and benefited from BoNT injections had reduced activity in the left precuneus compared to BoNT-naïve and treatment non-benefiting patients. Additionally, BoNT-treated patients with adductor LD had decreased activity in the right thalamus, whereas BoNT-treated abductor LD patients had reduced activity in the left inferior frontal cortex. No statistically significant differences in brain activity were found between patients with shorter (1-5 years) and longer (13-28 years) treatment durations. However, patients with intermediate treatment duration of 6 to 12 years showed reduced activity in the right cerebellum compared to patients with both shorter and longer treatment durations and reduced activity in the right prefrontal cortex compared to patients with shorter treatment duration. Discussion: Our findings suggest that the left precuneus is the site of short-term BoNT central action in LD patients, whereas the prefrontal-cerebellar axis is engaged in the BoNT response in patients with intermediate treatment duration of 6-12 years. Involvement of these structures points to indirect action of BoNT treatment on the dystonic sensorimotor network via modulation of speech motor sequence planning and coordination.

Dystonia, a debilitating neurological movement disorder, is characterized by involuntary muscle contractions and develops from a complex pathophysiology. Graph theoretical analysis approaches have been employed to investigate functional network changes in patients with different forms of dystonia. In this study, we aimed to characterize the abnormal brain connectivity underlying writer's cramp, a focal hand dystonia. To this end, we examined functional magnetic resonance scans of 20 writer's cramp patients (11 females/nine males) and 26 healthy controls (10 females/16 males) performing a sequential finger tapping task with their non-dominant (and for patients non-dystonic) hand. Functional connectivity matrices were used to determine group averaged brain networks. Our data suggest that in their neuronal network writer's cramp patients recruited fewer regions that were functionally more segregated. However, this did not impair the network's efficiency for information transfer. A hub analysis revealed alterations in communication patterns of the primary motor cortex, the thalamus and the cerebellum. As we did not observe any differences in motor outcome between groups, we assume that these network changes constitute compensatory rerouting within the patient network. In a secondary analysis, we compared patients with simple writer's cramp (only affecting the hand while writing) and those with complex writer's cramp (affecting the hand also during other fine motor tasks). We found abnormal cerebellar connectivity in the simple writer's cramp group, which was less prominent in complex writer's cramp. Our preliminary findings suggest that longitudinal research concerning cerebellar connectivity during WC progression could provide insight on early compensatory mechanisms in WC.

OBJECTIVE: To delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multidisciplinary panel of experts for a 1-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care. METHODS: The participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated. RESULTS: The panel unanimously agreed to adopt the term "laryngeal dystonia" instead of "spasmodic dysphonia" to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology. CONCLUSION: Research priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multicenter, national and international collaborations.