Resting State Functional Connectivity Signatures of MRgFUS Vim Thalamotomy in Parkinson's Disease: A Preliminary Study

Movement-related potentials (MRPs) were recorded from subdural electrodes chronically implanted in the interhemispheric fissure in two patients being evaluated for epilepsy surgery. Different types of movements (finger, foot, tongue and vocalization) were executed. Foot movements elicited a clearly defined, well-localized slow negativity or positivity (Bereitschaftspotential, BP) preceding electromyogram (EMG) onset. These BPs were seen from the contralateral primary motor foot area and also from bilateral supplementary motor areas (SMAs) with equivalent amplitudes and temporal evolutions. A steeper potential [negative slope (NS')] occurred about 300 ms before EMG onset and the motor potential (MP) started 100 ms before EMG onset. Negative slopes and MPs also arose from the contralateral primary motor area as well as from the bilateral SMAs. Finger movements elicited well-localized BPs and NS' which were generated from the bilateral SMAs, but were of higher amplitude on the contralateral SMA. Motor potentials started 50 ms prior to EMG onset and arose exclusively from the contralateral SMA. Tongue protrusions and vocalizations also elicited BP, NS' and MP which were seen in the bilateral SMAs. Movement-related potentials for different types of movements had a somatotopic distribution in the SMA, which was consistent with the SMA somatotopic organization defined by electrical simulation. Movement-related potentials for tongue movements and vocalization had a similar distribution and waveform. It was concluded that bilateral SMAs generate well-defined MRPs consistent with the assumption that the SMA plays a significant role in the organization of voluntary movements. However, the MRPs from the bilateral SMAs do not have characteristics which are different from those of the primary motor area. This suggests the hypothesis of 'supplementary' function for SMA, and does not support the hypothesis of 'supramotor' function.

Introduction: Parkinson’s disease (PD) reduces an individual’s capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual tasks (DTs) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods: Data were obtained from 34 individuals with PD and 47 healthy older adults including (1) demographics (age, sex), (2) disease severity (Movement Disorder Society – Unified Parkinson’s Disease Rating Scale [MDS-UPDRS], Hoehn and Yahr, levodopa equivalent daily dose [LEDD]), (3) cognition (Montreal Cognitive Assessment), (4) LEDD, (5) single-task and DT performance during a DT-timed-up-and-go test utilizing a serial subtraction task, and (6) cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT effect was greater than the previously determined mean value for healthy older adults (μ = –74.2). Nonparametric testing using Quade’s ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group and the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results: The highDT group had thicker cortices than the lowDT group in the right primary somatosensory cortex (p = 0.001), bilateral primary motor cortices (p ≤ 0.001, left; p = 0.002, right), bilateral supplementary motor areas (p = 0.001, left; p < 0.001, right), and mean of the bilateral hemispheres (p = 0.001, left; p < 0.001, right). Of note, left primary cortex thickness (p = 0.002), left prefrontal cortex thickness (p < 0.001), and right supplementary motor area thickness (p = 0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT effect (p = 0.011) beyond the influence of covariates. Conclusions: These results suggest regions underlying DT performance, specifically, a convergence of neural control relying on sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD. Introduction: Parkinson’s disease (PD) reduces an individual’s capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual tasks (DTs) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods: Data were obtained from 34 individuals with PD and 47 healthy older adults including (1) demographics (age, sex), (2) disease severity (Movement Disorder Society – Unified Parkinson’s Disease Rating Scale [MDS-UPDRS], Hoehn and Yahr, levodopa equivalent daily dose [LEDD]), (3) cognition (Montreal Cognitive Assessment), (4) LEDD, (5) single-task and DT performance during a DT-timed-up-and-go test utilizing a serial subtraction task, and (6) cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT effect was greater than the previously determined mean value for healthy older adults (μ = –74.2). Nonparametric testing using Quade’s ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group and the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results: The highDT group had thicker cortices than the lowDT group in the right primary somatosensory cortex (p = 0.001), bilateral primary motor cortices (p ≤ 0.001, left; p = 0.002, right), bilateral supplementary motor areas (p = 0.001, left; p < 0.001, right), and mean of the bilateral hemispheres (p = 0.001, left; p < 0.001, right). Of note, left primary cortex thickness (p = 0.002), left prefrontal cortex thickness (p < 0.001), and right supplementary motor area thickness (p = 0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT effect (p = 0.011) beyond the influence of covariates. Conclusions: These results suggest regions underlying DT performance, specifically, a convergence of neural control relying on sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson’s disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including central hemorrhagic necrosis with surrounding cytotoxic edema and a rim of mostly unaffected vasogenic edema with some reactive and reparative processes. Overall, this case demonstrates the correlation of postoperative imaging findings with the subacute neuropathological findings after MRgFUS for PD.

Altered resting-state cerebral blood flow and its relationship with molecular architecture in tremor dominant Parkinson's disease.

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, andthe correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum_crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

BackgroundDepression is the most common non-motor symptom in patients with Parkinson’s disease (PD) with unknown mechanisms, but the diagnostic criteria of PD with depression (PDD) are not uniform.PurposeThe aim of the study was to investigate interhemispheric interactions between PDD patients and patients with PD without depression (PDND).MethodsThe voxel-mirrored homotopic connectivity (VMHC) combined with the seed-based method was used to investigate intrinsic resting-state functional connectivity (RSFC) in 33 PDD patients, 60 PDND, and 47 healthy controls (HCs).ResultsPDD patients exhibited a decreased VMHC in the bilateral medial frontal gyrus and paracentral lobule (MFG/PCL) than did PDND patients. Parkinson’s disease with depression had a decreased VMHC in the bilateral precentral gyrus than had PDND and HC (p < 0.05). Parkinson’s disease with depression had a decreased homotopic RSFC from the medial frontal gyrus (MFG)/PCL to the contralateral supplementary motor area (SMA) than had PDND (p < 0.05). The decreased homotopic RSFC from the right MFG/PCL to the left SMA was negatively correlated with Hamilton Depression Rating Scale scores (p < 0.05), but not with illness duration, Beck’s Depression Inventory, and Unified Parkinson’s Disease Rating Scale in PD patients.ConclusionsOur findings indicated that the occurrence of depression in Parkinson’s disease is associated with the dysfunctional connectivity from the MFG/PCL to the contralateral SMA, which could be used as potential neuroimaging markers for the diagnosis of depression in PD patients.

Thalamic stroke may result in cognitive and linguistic problems, but the underlying mechanism remains unknown. Especially, it is still a matter of debate why thalamic aphasia occasionally occurs and then mostly recovers to some degree. We begin with a brief overview of the cognitive dysfunction and aphasia, and then review previous hypotheses of the underlying mechanism. We introduced a unique characteristic of relatively transient “word retrieval difficulty” of patients in acute phase of thalamic stroke. Word retrieval ability involves both executive function and speech production. Furthermore, SMA aphasia and thalamic aphasia may resemble in terms of the rapid recovery, thus suggesting a shared neural system. This ability is attributable to the supplementary motor area (SMA) and inferior frontal cortex (IFG) via the frontal aslant tract (FAT). To explore the possible mechanism, we applied unique hybrid neuroimaging techniques: single-photon emission computed tomography (SPECT) and functional near-infrared spectroscopy (f-NIRS). SPECT can visualize the brain distribution associated with word retrieval difficulty, cognitive disability or aphasia after thalamic stroke, and f-NIRS focuses on SMA and monitors long-term changes in hemodynamic SMA responses during phonemic verbal task. SPECT yielded common perfusion abnormalities not only in the fronto–parieto–cerebellar–thalamic loop, but also in bilateral brain regions such as SMA, IFG and language-relevant regions. f-NIRS demonstrated that thalamic stroke developed significant word retrieval decline, which was intimately linked to posterior SMA responses. Word retrieval difficulty was rapidly recovered with increased bilateral SMA responses at follow-up NIRS. Together, we propose that the cognitive domain affected by thalamic stroke may be related to the fronto–parieto–cerebellar–thalamic loop, while the linguistic region may be attributable to SMA, IFG and language-related brain areas. Especially, bilateral SMA may play a crucial role in the recovery of word retrieval, and right language-related region, including IFG, angular gyrus and supramarginal gyrus may determine recovery from thalamic aphasia.

EMG-driven robot hand training can facilitate motor recovery in chronic stroke patients by restoring the interhemispheric balance between motor networks. However, the underlying mechanisms of reorganization between interhemispheric regions remain unclear. This study investigated the effective connectivity (EC) between the ventral premotor cortex (PMv), supplementary motor area (SMA), and primary motor cortex (M1) using Dynamic Causal Modeling (DCM) during motor tasks with the paretic hand. Nineteen chronic stroke subjects underwent 20 sessions of EMG-driven robot hand training, and their Action Reach Arm Test (ARAT) showed significant improvement ( β =3.56, [Formula: see text]). The improvement was correlated with the reduction of inhibitory coupling from the contralesional M1 to the ipsilesional M1 (r=0.58, p=0.014). An increase in the laterality index was only observed in homotopic M1, but not in the premotor area. Additionally, we identified an increase in resting-state functional connectivity (FC) between bilateral M1 ( β =0.11, p=0.01). Inter-M1 FC demonstrated marginal positive relationships with ARAT scores (r=0.402, p=0.110), but its changes did not correlate with ARAT improvements. These findings suggest that the improvement of hand functions brought about by EMG-driven robot hand training was driven explicitly by task-specific reorganization of motor networks. Particularly, the restoration of interhemispheric balance was induced by a reduction in interhemispheric inhibition from the contralesional M1 during motor tasks of the paretic hand. This finding sheds light on the mechanistic understanding of interhemispheric balance and functional recovery induced by EMG-driven robot training.

Benefits of intensive speech treatment have been documented for a range of speech signs in English speakers with Parkinson's Disease (PD). However, the answer to a critical question that whether the same treatment benefits speech variables including intelligibility in Mandarin speakers is still unclear. In order to develop a targeted speech treatment for Mandarin speakers with PD, we reviewed the efficacy of intensive speech treatment to improve vocal loudness and functional communication and discuss possible explanations for efficacy on Mandarin speakers with PD. Literatures about intensive speech treatment for Mandarin speakers with PD were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Database for Chinese Technical Periodicals (VIP) Database. Search strategy was (voice therapy OR speech therapy OR voice treatment OR speech treatment OR voice training OR speech training OR voice rehabilitation OR speech rehabilitation OR Lee Silverman voice treatment OR intensive speech treatment) and (Parkinson's disease) and (Mandarin speakers OR Chinese OR Chinese people). Five randomized controlled trials were selected and possible explanations for efficacy on individuals with PD are discussed. Further research directions are suggested. The existing evidence from treatment efficacy studies of intensive speech treatment provides support for improving vocal loudness, speech intelligibility, pitch and rate in Mandarin speakers with PD. Our future research will continue to work to conduct a large sample multicenter randomized controlled trial to provide high quality evidence and understand the basic mechanisms accompanying treatment-related change.

The supplementary motor area (SMA) syndrome is a frequently encountered clinical phenomenon associated with surgery of the dorsomedial prefrontal lobe. The region has a known motor sequencing function and the dominant pre-SMA specifically is associated with more complex language functions; the SMA is furthermore incorporated in the negative motor network. The SMA has a rich interconnectivity with other cortical regions and subcortical structures using the frontal aslant tract (FAT) and the frontostriatal tract (FST). The development of the SMA syndrome is positively correlated with the extent of resection of the SMA region, especially its medial side. This may be due to interruption of the nearby callosal association fibres as the contralateral SMA has a particular important function in brain plasticity after SMA surgery. The syndrome is characterized by a profound decrease in interhemispheric connectivity of the motor network hubs. Clinical improvement is related to increasing connectivity between the contralateral SMA region and the ipsilateral motor hubs. Overall, most patients know a full recovery of the SMA syndrome, however a minority of patients might continue to suffer from mild motor and speech dysfunction. Rarely, no recovery of neurological function after SMA region resection is reported.

U.S. 4,758,619 Anti-blocking agent for film composition

P021 Differential clinical and neurophysiological outcomes after premotor rTMS in Parkinson’s disease

Large-extent movements (LEMs) are vital for daily activities, and their recovery remains a challenge in neurorehabilitation due to inevitable loading on muscles. Since inhibitory cTBS may facilitate recovery but also disrupt task control, we ask whether a previously identified linear relationship between load and cortical activation would retain, after cTBS over the contralateral supplementary motor area (SMA). It will set a benchmark for choosing resistance during brain stimulation. Hemodynamic activities of SMA and M1 during LEMs were monitored by functional Near-Infrared Spectroscopy (fNIRS) in this study. Twelve healthy participants received 40s of cTBS over SMA, before and after which the participants were instructed to complete LEMs with varying loads (0, 3, and 15 pounds) repetitively. When lifting 0-pound and 3-pound weights, the β of the left SMA and M1 increased significantly after cTBS (p < 0.05). Also, the random intercepts of individual subjects increased significantly in the left SMA, left M1, and right SMA, but the slopes were not significantly affected by cTBS. Data also showed a significant positive correlation between the intercept of left M1, right SMA&M1 areas and age (all p < 0.05). Despite cTBS-induced inhibition, the supplementary motor area (SMA) exhibited enhanced fNIRS responses to increased loads, and the positive correlation between load inertia and motor-cortical activation remained unaltered.

To investigate the role of interhemispheric β-synchronization in the selection of motor effectors, we trained two monkeys to memorize and perform multiple two-movement sequences that included unimanual repetition and bimanual switching. We recorded local field potentials simultaneously in the bilateral supplementary motor area (SMA) and pre-SMA to examine how the β-power in both hemispheres and the interhemispheric relationship of β-oscillations depend on the prepared sequence of arm use. We found a significant ipsilateral enhancement of β-power for bimanual switching trials in the left hemisphere and an enhancement of β-power in the right SMA while preparing for unimanual repetition. Furthermore, interhemispheric synchrony in the SMA was significantly more enhanced while preparing unimanual repetition than while preparing bimanual switching. This enhancement of synchrony was detected in terms of β-phase but not in terms of modulation of β-power. Furthermore, the assessment of the interhemispheric phase difference revealed that the β-oscillation in the hemisphere contralateral to the instructed arm use significantly advanced its phase relative to that in the ipsilateral hemisphere. There was no arm use-dependent shift in phase difference in the pairwise recordings within each hemisphere. Both neurons with and without arm use-selective activity were phase-locked to the β-oscillation. These results imply that the degree of interhemispheric phase synchronization as well as phase differences and oscillatory power in the β-band may contribute to the selection of arm use depending on the behavioral conditions of sequential arm use.NEW & NOTEWORTHY We addressed interhemispheric relationships of β-oscillations during bimanual coordination. While monkeys prepared to initiate movement of the instructed arm, β-oscillations in the contralateral hemisphere showed a phase advance relative to the other hemisphere. Furthermore, the sequence of arm use influenced β-power and the degree of interhemispheric phase synchronization. Thus the dynamics of interhemispheric phases and power in β-oscillations may contribute to the specification of motor effectors in a given behavioral context.

Auditory entrainment of motor responses in older adults with and without Parkinson’s disease: An MEG study