Person: Vial Undurraga, Felipe
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Vial Undurraga
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Felipe
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Publication KCNN2 Mutation in Pediatric Tremor Myoclonus Dystonia Syndrome with Electrophysiological Evaluation(2022) Lavenstein, Bennett; McGurrin, Patrick; Attaripour, Sanaz; Vial Undurraga, Felipe; Hallett, MarkBackground: Here we combine clinical, electrophysiological, and genetic findings to phenotype an unusual childhood movement disorder in a patient with a rare form of KCNN2 mutation. Case report: A 10-year-old male presented with a clinical syndrome of tremor and myoclonus. Electrophysiology demonstrated muscle activity indicative of myoclonus dystonia, an observation that was not appreciated clinically. Genetic testing revealed an abnormality in the KCNN 2 gene, not present in the parents, known to cause dystonia, as the etiology. Discussion: The value of utilizing noninvasive, electrophysiological recording in pediatric movement disorders expands the precision of diagnosis, potentially informing treatment when correlated with clinical and genetic findings.Publication Physiology of Tremor Reduction by Putting the Hands Together in Essential Tremor(2022) McGurrin, Patrick; Vial Undurraga, Felipe; Osterholt, Thomas; Norato, Gina; Khan, Imran; Haubenberger, Dietrich; Ehrlich, Debra; Hallett, MarkBackground: Background Essential tremor is a common movement disorder, characterized by 4ā12 Hz tremor of the hands and arms that can affect many activities of daily living. It has been reported by patients that when performing tasks bimanually their tremor is reduced, but why this happens is unknown. Objectives: Objectives We measured patientsā tremors in different conditions when performed with 1 hand and 2 hands to observe if bimanual task performance changes the characteristics of the tremor. Methods: Methods A total of 10 patients with essential tremor participated in the study. Electromyographic electrodes were attached bilaterally to the wrist flexor and extensor muscles, and accelerometers were attached to the dorsum of the hands. For each condition, holding a cup, wingbeat, and extending both arms up, data were collected with a single hand and bimanually with the hands touching. Results: Results When the hands were touching, there was a significant decrease in both accelerometric and electromyographic power at the tremor frequency. In addition, there was a decrease in coherence between accelerometer and electromyography on the same side. There was no change in the tremor frequency. Conclusions: Conclusions Tremor amplitude does decrease when the hands are together. Together, the characteristics underlying the decrease in tremor amplitude may indicate a decrease in power of the central oscillator driving the tremor, which we speculate is attributed to the differences in unimanual and bimanual motor control. However, given the small sample size, we note that future hypothesis-driven studies with an a priori power analysis will be required to further explore this phenomenon.Publication Multimodal neuroimaging of fatigability development(2025) Bedard, Patrick; Knutson, Kristine; McGurrin, Patrick; Vial Undurraga, Felipe; Popa, Traian; Horovitz, Silvina; Hallett, Mark; Nath, Avindra; Walitt, BrianFatigability refers to the inability of the neuromuscular system to generate enough force to produce movements to meet task challenges. Fatigability has a central and a peripheral component linked via the neuromuscular system, but how these two components interact as fatigue develops lacks a complete understanding. The effects of fatigability are experienced in healthy humans but also accompany various disorders, often exacerbating their symptoms. We studied how fatigability develops in the neuromuscular system using multimodal neuroimaging. We recruited healthy participants to perform a fatiguing grip force task, while recording force, electromyography of forearm muscles (EMG), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) in 30-second blocks of grip task alternating with 30 seconds of rest. The task entailed maintaining 50% of the maximum force. We combined EMG and EEG to compute corticomuscular coherence and combined EEG and fMRI to compute EEG-informed fMRI. We selected eight task blocks specific to each participant to represent how the neuromuscular system adapted from pre-fatigability to actual fatigability. Those included five blocks for pre-fatigability in which participants could generate enough force to match the required 50% of maximum force and three blocks when the force fell below that limit. Across blocks of the grip force task, we observed changes in the neuromuscular system that preceded grip force changes. We found that electromyography of arm muscles shifted from high to low frequency, EEG in the channel covering the contralateral sensorimotor area increased steadily up to the fifth block and then plateaued, and fMRI signal also increased in the cerebellum. Corticomuscular coherence increased within each of the 30-second blocks of the grip task. EEG-informed fMRI revealed areas of the brain that the traditional regression did not, including the bilateral sensorimotor cortex, temporal-parietal junction, and supplementary motor area. Thus, as fatigability developed, the neuromuscular system experienced changes earlier than the actual behavior. While we found evidence for fatigability of central and peripheral origins, peripheral fatigue seems to occur first.Publication Patterns of brain activity in choice or instructed go and no-go tasks(2025) Attaripour, Sanaz; McGurrin, Patrick; Vial Undurraga, Felipe; Hallett, MarkThe goal of this study was to investigate the decision making process for choosing what movements to make. We used electroencephalography (EEG) to investigate patterns of the contingent negative variation (CNV) associated with free-choice decisions to move or abstain, comparing them to conditions where actions were commanded. Our primary hypothesis was that choice tasks would differ significantly from each other and exhibit EEG patterns akin to their command-driven counterparts after the decisions were made, at least, in the 50 ms block of time prior to movement. A secondary analysis evaluated post hoc comparisons of time, in 50 ms blocks, to understand the temporal development of the CNV for each condition. We also conducted an exploratory analysis of EEG event-related desynchronization (ERD) to identify patterns of brain activity associated with the decision-making process. This approach was taken due to the exploratory nature of our hypotheses concerning the spatial and temporal characteristics of EEG activity during these free-choice versus commanded tasks. We studied 12 right-handed healthy volunteers (7 women, mean age 53 years, range 39-73 years) with no prior history of neurological or major psychiatric illness. A CNV paradigm encompassing commanded and choice tasks was devised, with a 2500 ms interval between S1 and S2, while recording EEG and electromyography (EMG). S1 provided full information about the upcoming task, which was to be executed at the time of S2. We assessed CNV and explored whole scalp EEG activity, including both voltage as well as power in the alpha and beta frequency ranges. Clear and similar CNVs were observed for command and choice go tasks prior to the movements, contrasting with near-zero CNVs for the command and choice no-go tasks. Separation of CNVs for command go and no-go tasks occurred around 1600 ms post-S1, and choice CNVs separated about 2150 ms post-S1. Exploratory analysis revealed that beta power provided information about decision and preparation processes much earlier. The left dorsolateral prefrontal cortex (DLPFC) exhibited the initial sign of decision approximately 500 ms post-S1 for all tasks, with subsequent preparation for movement or restraint involving distinct activity in various brain regions. The localization of effects in the left DLPFC was determined by visual analysis of the informative electrode sites. The CNVs separate about 2 s after S1, and it appears that this process represents preparation for movement (or no movement). Exploration of the beta activity suggests an earlier decision process which leads eventually to subsequent task preparation and activation. Choice decisions lag slightly behind command decisions, with the CNV apparently reflecting motor implementation rather than the decision-making process. In a simple motor task with an exploratory analysis, both commanded and choice-based decisions are rapidly initiated in the left DLPFC. While the CNV distinguishes between go and no-go conditions, it primarily appears to signify preparation for implementation of the task following the earlier decision. Further controlled studies will be needed to confirm these results.