Theta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal ...of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments. In Experiment 1, participants received 600, 1200, 1800, or sham (600) iTBS (4 visits, counterbalanced, left motor cortex, 80% active threshold). In Experiment 2, participants received 600, 1200, 1800, 3600, or sham (600) cTBS (5 visits, counterbalanced). Motor evoked potentials (MEP) were measured in 10-min increments for 60 min. For iTBS, there was a significant interaction between dose and time (F = 3.8296, p = 0.01), driven by iTBS (1200) which decreased excitability for up to 50 min (t = 3.1267, p = 0.001). For cTBS, there was no overall interaction between dose and time (F = 1.1513, p = 0.33). Relative to sham, cTBS (3600) increased excitability for up to 60 min (t = 2.0880, p = 0.04). There were no other significant effects of dose relative to sham in either experiment. Secondary analyses revealed high within and between subject variability. These results suggest that iTBS (1200) and cTBS (3600) are, respectively, the most effective doses for decreasing and increasing cortical excitability.
Background
Although ET is a phenomenologically heterogeneous condition, thalamic DBS appears to be equally effective across subtypes. We hypothesized stimulation sites optimized for individuals with ...essential tremor (ET) would differ from individuals with essential tremor plus syndrome (ET-plus). We examined group differences in optimal stimulation sites within the ventral thalamus and their overlap of with relevant white matter tracts. By capturing these differences, we sought to determine whether ET subtypes are associated with anatomically distinct neural pathways.
Methods
A retrospective chart review was conducted on ET patients undergoing VIM DBS at MUSC between 01/2012 and 02/2022. Clinical, demographic, neuroimaging, and DBS stimulation parameter data were collected. Clinical characteristics and pre-DBS videos were reviewed to classify ET and ET-plus cohorts. Patients in ET-plus cohorts were further divided into ET with dystonia, ET with ataxia, and ET with others. DBS leads were reconstructed using Lead-DBS
1
and the volume of tissue activated (VTA) overlap was performed using normative connectomes. Tremor improvement was measured by reduction in a subscore of tremor rating scale (TRS) post-DBS lateralized to the more affected limb.
Results
Sixty-eight ET patients were enrolled after initial screening, of these 10 ET and 24 ET-plus patients were included in the final analyses. ET group had an earlier age at onset (
p
= 0.185) and underwent surgery at a younger age (
p
= 0.096). Both groups achieved effective tremor control. No significant differences were found in lead placement or VTA overlap within ventral thalamus. The VTA center of gravity (COG) in the ET-plus cohort was located dorsal to that of the ET cohort. No significant differences were found in VTA overlap with the dentato-rubral-thalamic (DRTT) tracts or the ansa lenticularis. Dystonia was more prevalent than ataxia in the ET-plus subgroups (
n
= 18 and
n
= 5, respectively). ET-plus with dystonia subgroup had a more medial COG compared to ET-plus with ataxia.
Conclusion
VIM DBS therapy is efficacious in patients with ET and ET-plus. There were no significant differences in optimal stimulation site or VTA overlap with white-matter tracts between ET, ET-plus and ET-plus subgroups.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the ...discovery that non-invasive transcranial magnetic stimulation (TMS) can cause dopamine release in PD patients, there has been growing interest in the use of TMS to fill existing gaps in the treatment continuum for PD. This review evaluates the safety and efficacy of a unique multifocal, bilateral Deep TMS protocol, which has been evaluated as a tool to address motor and non-motor symptoms of PD. Six published clinical trials have delivered a two-stage TMS protocol with an H-Coil targeting both the prefrontal cortex (PFC) and motor cortex (M1) bilaterally (220 PD patients in total; 108 from two randomized, sham-controlled studies; 112 from open label or registry studies). In all studies TMS was delivered to M1 bilaterally (Stage 1) and then to the PFC bilaterally (Stage 2) with approximately 900 pulses per stage. For Stage 1 (M1), two studies delivered 10 Hz at 90% motor threshold (MT) while four studies delivered 1 Hz at 110% MT. For Stage 2 (PFC), all studies delivered 10 Hz at 100% MT. The results suggest that this two-stage Deep TMS protocol is a safe, moderately effective treatment for motor symptoms of PD, and that severely impaired patients have the highest benefits. Deep TMS also improves mood symptoms and cognitive function in these patients. Further research is needed to establish optimal dosing and the long-term durability of treatment effects.
In pre-clinical animal models of Parkinson's disease (PD), vagus nerve stimulation (VNS) can rescue motor deficits and protect susceptible neuronal populations. Transcutaneous auricular vagus nerve ...stimulation (taVNS) has emerged as a non-invasive alternative to traditional invasive cervical VNS. This is the first report summarizing the safety, feasibility, and preliminary efficacy of repeated sessions of taVNS in participants with PD.
To evaluate the feasibility, safety, and possible efficacy of taVNS for motor and non-motor symptoms in mild to moderate PD.
This is a double-blind, sham controlled RCT (NCT04157621) of taVNS in 30 subjects with mild to moderate PD without cognitive impairment. Participants received 10, 1-h taVNS sessions (25 Hz, 200% of sensory threshold, 500 μs pulse width, 60 s on and 30 s off) over a 2-week period. Primary outcome measures were feasibility and safety of the intervention; secondary outcomes included the MDS-UPDRS, cognitive function and self-reported symptom improvement.
taVNS treatment was feasible, however, daily in-office visits were reported as being burdensome for participants. While five participants in the taVNS group and three in the sham group self-reported one or more minor adverse events, no major adverse events occurred. There were no group differences on blood pressure and heart rate throughout the intervention. There were no group differences in MDS-UPDRS scores or self-reported measures. Although global cognitive scores remained stable across groups, there was a reduction in verbal fluency within the taVNS group.
taVNS was safe, and well-tolerated in PD participants. Future studies of taVNS for PD should explore at-home stimulation devices and optimize stimulation parameters to reduce variability and maximize engagement of neural targets.
•No long-term serious adverse events 6–12 months following tDCS in children with cerebral palsy.•Remotely-instructed tDCS in children with cerebral palsy was feasible in the home setting.•Future ...studies may now investigate fully-remote teleneuromodulation interventions in this pediatric population.
Highlights • Cocaine users are consistently less accurate on basic finger-tapping tasks. • They have lower frontal-striatal connectivity during all levels of task difficulty. • As task difficulty ...increases, both controls and cocaine users make more errors. • However, network connectivity degrades with difficulty in users but not controls.
The objective of this study was to evaluate ON-state resting state functional connectivity (FC) from the mesencephalic locomotor regions (MLR) to distributed sensorimotor cortical regions in patients ...with Freezing of Gait (FOG) and its association with gait performance.
54 individuals with PD were recruited for this study (50% of whom had FOG). All individuals received a resting state functional MRI in the ON state, and underwent a series of gait assessments during single and dual task conditions. FC with the MLR was calculated using a whole brain seed to voxel approach wherein the left and right MLR seeds were extracted from a published atlas. General linear regression was used to determine differences in connectivity between the individuals with (‘freezers’) and without (‘non-freezers’) FOG as well as the correlation between MLR connectivity and gait performance in the freezers.
Freezers had significantly higher MLR connectivity to a network of sensorimotor regions compared to non-freezers. Additionally, among the freezers, higher FC with these regions was related to longer single-task and dual-task performance. There were no regions in which non-freezers had higher connectivity than freezers (p < 0.05, FWE corrected clusters for all analyses).
These data support the hypothesis that freezers have significantly higher ON-state FC between the MLR and a network of cortical structures than non-freezers. Additionally, this elevated connectivity is directly related to worsening FOG severity. These data add to a theoretical foundation which suggests that cortical hyperconnectivity to the MLR is central to the underlying pathophysiology of FOG.
•Cortico-mesencephalic functional connectivity is increased in Freezing of Gait.•Increased cortico-mesencephalic connectivity correlates with worsening gait in freezers.•Increased cortico-mesencephalic connectivity persists in the ON state in freezers.
Freezing of gait (FOG) is a prevalent and debilitating feature of Parkinson's Disease (PD). The subthalamic nucleus (STN) is a center for controlled locomotion and a common DBS target. The objective ...of this study was to identify STN circuitry associated with FOG response to dopaminergic medication. In this study, we compare BOLD functional connectivity of the subthalamic nucleus (STN) in participants with and without dopa-responsive FOG.
55 PD participants either with FOG (n = 38) or without FOG (n = 17) were recruited. Among FOG participants 22 were dopa-responsive and 16 were dopa-unresponsive. STN whole-brain connectivity was performed using CONN toolbox. The relationship between the degree of self-reported FOG dopa-response and STN connectivity was evaluated using partial correlations corrected for age, disease duration, and levodopa equivalent daily dose.
Right STN connectivity with the cerebellar locomotor region and the temporal/occipital cortex was greater in the dopa-responsive FOG group (voxel threshold p < 0.01, FWE corrected p < 0.05). Left STN connectivity with the occipital cortex was greater in the dopa-responsive FOG group and connectivity with the postcentral gyrus was greater in the dopa-unresponsive FOG group. Strength of connectivity to these regions correlated with l-dopa induced improvement in UPDRS Item-14 (FOG), but not UPDRS Part-III (overall motor score).
We demonstrate that dopa-unresponsive FOG is associated with changes in BOLD functional connectivity between the STN and locomotor as well as sensory processing regions. This finding supports the conceptual framework that effective treatment for freezing of gait likely requires the engagement of both locomotor and sensory brain regions.
Pediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, ...as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance.
Here, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey.
We expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP.
October 8, 2021( https://clinicaltrials.gov/ct2/show/NCT05071586 ).
•Remotely-instructed tDCS is safe and tolerable in children and young adults with cerebral palsy.•Participants and caregivers reported and demonstrated that at-home tDCS setup was feasible.•Results ...support further studies to evaluate efficacy of remotely-instructed tDCS in children.
PDF
