Brain lesions causing parkinsonism versus seizures map to opposite brain networks.

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and used the human connectome to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r = -0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific on a group level (spatial r = -0.51) and on an individual lesion level (average spatial r = -0.042; P < 0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r > 0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.

Brain lesions causing parkinsonism versus seizures map to opposite brain networks.

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and utilized human connectome data to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r =-0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific for lesions causing parkinsonism versus seizures on a group level (spatial r =- 0.51) and on an individual lesion level (average spatial r =-0.042; p<0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r >0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.

The future of brain circuit-targeted therapeutics.

The principle of targeting brain circuits has drawn increasing attention with the growth of brain stimulation treatments such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and focused ultrasound (FUS). Each of these techniques can effectively treat different neuropsychiatric disorders, but treating any given disorder depends on choosing the right treatment target. Here, we propose a three-phase framework for identifying and modulating these targets. There are multiple approaches to identifying a target, including correlative neuroimaging, retrospective optimization based on existing stimulation sites, and lesion localization. These techniques can then be optimized using personalized neuroimaging, physiological monitoring, and engagement of a specific brain state using pharmacological or psychological interventions. Finally, a specific stimulation modality or combination of modalities can be chosen after considering the advantages and tradeoffs of each. While there is preliminary literature to support different components of this framework, there are still many unanswered questions. This presents an opportunity for the future growth of research and clinical care in brain circuit therapeutics.

Neural endophenotypes and predictors of laryngeal dystonia penetrance and manifestation.

Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain unclear. Using an imaging genetics approach, we investigated functional and structural representations of neural endophenotypes underlying the penetrance and manifestation of laryngeal dystonia in families, including 21 probands and 21 unaffected relatives, compared to 32 unrelated healthy controls. We further used a supervised machine-learning algorithm to predict the risk for dystonia development in susceptible individuals based on neural features of identified endophenotypes. We found that abnormalities in prefrontal-parietal cortex, thalamus, and caudate nucleus were commonly shared between patients and their unaffected relatives, representing an intermediate endophenotype of laryngeal dystonia. Machine learning classified 95.2% of unaffected relatives as patients rather than healthy controls, substantiating that these neural alterations represent the endophenotypic marker of dystonia penetrance, independent of its symptomatology. Additional abnormalities in premotor-parietal-temporal cortical regions, caudate nucleus, and cerebellum were present only in patients but not their unaffected relatives, likely representing a secondary endophenotype of dystonia manifestation. Based on alterations in the parietal cortex and caudate nucleus, the machine learning categorized 28.6% of unaffected relative as patients, indicating their increased lifetime risk for developing clinical manifestation of dystonia. The identified endophenotypic neural markers may be implemented for screening of at-risk individuals for dystonia development, selection of families for genetic studies of novel variants based on their risk for disease penetrance, or stratification of patients who would respond differently to a particular treatment in clinical trials.

Effect of Neck Botulinum Neurotoxin Injection on Proprioception and Somatosensory-Motor Cortical Processing in Cervical Dystonia.

Background. Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary contractions of the cervical musculature and is known to be associated with proprioceptive dysfunction in dystonic/nondystonic limbs. Objectives. We examined how neck botulinum neurotoxin (BoNT) injection affects wrist proprioception and the corresponding sensorimotor cortical activity in CD. Method. Wrist position sense acuity of the dominant (right) hand was evaluated in 15 CD and 15 control participants. Acuity measures were a psychophysical position sense discrimination threshold (DT; based on passive joint displacement) and joint position matching error (based on active movement). Cortical activity during the motor preparation period of the active joint position matching was examined using electroencephalography. Results. In their symptomatic state, patients demonstrated a significantly higher wrist proprioceptive DT, indicating an abnormal passive wrist position sense. Yet BoNT injections had no significant effect on this threshold. During active joint position matching, errors were significantly larger in patients, but this difference vanished after the administration of BoNT. Motor preparation of active wrist position matching was associated with a significantly higher rise of ß-band (13-30 Hz) power over contralateral somatosensory-motor cortical areas in patients. This excessive cortical activity significantly declined post-BoNT. Conclusion. Wrist proprioceptive perception during passive/active movements is abnormal in CD. An excessive rise of premotor/motor cortical ß-oscillations during motor planning is associated with this proprioceptive dysfunction. Neck BoNT injections normalized the cortical processing of proprioceptive information from nonsymptomatic limbs, indicating that local injections may affect the central mechanisms of proprioceptive function in CD.

Laryngeal vibration as a non-invasive neuromodulation therapy for spasmodic dysphonia.

Spasmodic dysphonia (SD) is an incurable focal dystonia of the larynx that impairs speech and communication. Vibro-tactile stimulation (VTS) alters afferent proprioceptive input to sensorimotor cortex that controls speech. This proof-of-concept study examined the effect of laryngeal VTS on speech quality and cortical activity in 13 SD participants who vocalized the vowel /a/ while receiving VTS for 29 minutes. In response to VTS, 9 participants (69%) exhibited a reduction of voice breaks and/or a meaningful increase in smoothed cepstral peak prominence, an acoustic measure of voice/speech quality. Symptom improvements persisted for 20 minutes past VTS. Application of VTS induced a significant suppression of theta band power over the left somatosensory-motor cortex and a significant rise of gamma rhythm over right somatosensory-motor cortex. Such suppression of theta oscillations is observed in patients with cervical dystonia who apply effective sensory tricks, suggesting that VTS in SD may activate a similar neurophysiological mechanism. Results of this feasibility study indicate that laryngeal VTS modulates neuronal synchronization over sensorimotor cortex, which can induce short-term improvements in voice quality. The effects of long-term VTS and its optimal dosage for treating voice symptoms in SD are still unknown and require further systematic study.

Atypical somatosensory-motor cortical response during vowel vocalization in spasmodic dysphonia.

OBJECTIVE: Spasmodic dysphonia (SD) is a debilitating voice/speech disorder without an effective cure. To obtain a better understanding of the underlying cortical neural mechanism of the disease we analyzed electroencephalographic (EEG) signals of people with SD during voice production. METHOD: Ten SD individuals and 10 healthy volunteers produced 50 vowel vocalization epochs of 2500 ms duration. Two EEG features were derived: (1) event-related change in spectral power during vocalization relative to rest, (2) inter-regional spectral coherence. RESULTS: During early vocalization (500-1000 ms) the SD group showed significantly larger alpha band spectral power over the left motor cortex. During late vocalization (1000-2500 ms) SD patients showed a significantly larger gamma band coherence between left somatosensory and premotor cortical areas. CONCLUSIONS: Two atypical patterns of cortical activity characterize the pathophysiology of spasmodic dysphonia during voice production: (1) a reduced movement-related desynchronization of motor cortical networks, (2) an excessively large synchronization between left somatosensory and premotor cortical areas. SIGNIFICANCE: The pathophysiology of SD is characterized by an abnormally high synchronous activity within and across cortical neural networks involved in voice production that is mainly lateralized in the left hemisphere.

Vibration-Damping technology in tennis racquets: Effects on vibration transfer to the arm, muscle fatigue and tennis performance.

High vibration transfer from a tennis racquet to the player may cause discomfort, and is hypothesized to influence performance and the onset of muscle fatigue. This study examined a racquet with a novel vibration damping technology (VDT) designed to mitigate frame vibration. Racquet vibration, post-impact vibration transfer to the player, arm electromyographic activity and tennis performance were compared to a non-VDT racquet. Nineteen young adult, competitive tennis players hit forehands and serves until near exhaustion on two days; using one of the two racquets each day. Tri-axial accelerometers mounted to racquet shaft, hand and forearm recorded vibration behaviour. Surface electromyography recorded activity of five arm muscles. In comparison to the non-VDT racquet, the VDT design showed: 1) A significantly lower mean normalised acceleration signal energy at the racquet during unfatigued play (-40%) and at near exhaustion (-34%), which corresponded to a 20-25% lower signal energy at the hand. 2) Reduced signs of arm muscle fatigue at near exhaustion, which was most pronounced in biceps and wrist extensors. 3) Players hit 11% more forehands and placed 40% more hits in the target area at near exhaustion. Conclusion: VDT effectively reduces racquet vibration. Initial evidence indicates that it may delay muscle fatigue, which was associated with increased ball placement accuracy.

Robot-aided assessment of wrist proprioception.

INTRODUCTION: Impaired proprioception severely affects the control of gross and fine motor function. However, clinical assessment of proprioceptive deficits and its impact on motor function has been difficult to elucidate. Recent advances in haptic robotic interfaces designed for sensorimotor rehabilitation enabled the use of such devices for the assessment of proprioceptive function. PURPOSE: This study evaluated the feasibility of a wrist robot system to determine proprioceptive discrimination thresholds for two different DoFs of the wrist. Specifically, we sought to accomplish three aims: first, to establish data validity; second, to show that the system is sensitive to detect small differences in acuity; third, to establish test-retest reliability over repeated testing. METHODOLOGY: Eleven healthy adult subjects experienced two passive wrist movements and had to verbally indicate which movement had the larger amplitude. Based on a subject's response data, a psychometric function was fitted and the wrist acuity threshold was established at the 75% correct response level. A subset of five subjects repeated the experimentation three times (T1, T2, and T3) to determine the test-retest reliability. RESULTS: Mean threshold for wrist flexion was 2.15°± 0.43° and 1.52°± 0.36° for abduction. Encoder resolutions were 0.0075°(flexion-extension) and 0.0032°(abduction-adduction). Motor resolutions were 0.2°(flexion-extension) and 0.3°(abduction-adduction). Reliability coefficients were r T2-T1 = 0.986 and r T3-T2 = 0.971. CONCLUSION: We currently lack established norm data on the proprioceptive acuity of the wrist to establish direct validity. However, the magnitude of our reported thresholds is physiological, plausible, and well in line with available threshold data obtained at the elbow joint. Moreover, system has high resolution and is sensitive enough to detect small differences in acuity. Finally, the system produces reliable data over repeated testing.