Cortical modulations before lower limb motor blocks are associated with freezing of gait in Parkinson's disease: an EEG source localization study.

BACKGROUND: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. METHODS: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. RESULTS: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. CONCLUSIONS: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG.

Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

BACKGROUND: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. OBJECTIVES: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. METHODS: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band. RESULTS: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. CONCLUSIONS: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society.

Fronto-subthalamic phase synchronization and cross-frequency coupling during conflict processing.

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed "hold-your-horses" role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC.

Event-related deep brain stimulation of the subthalamic nucleus affects conflict processing.

OBJECTIVE: Many lines of evidence suggest that response conflict recruits brain regions in the cortical-basal ganglia system. Within the basal ganglia, deep brain recordings from the subthalamic nucleus (STN) have shown that conflict triggers a transient increase in low-frequency oscillations (LFOs; 2-8Hz). Here, we deployed a new method of delivering short trains of event-related deep brain stimulation (DBS) to the STN to test the causal role of the STN and its associated circuits in conflict-related processing. METHODS: In a double-blind design, we stimulated the STN in patients with Parkinson disease by locking brief trains of DBS to specific periods of the trial within a Stroop task. RESULTS: Stimulation had a specific effect on conflict compared to nonconflict trials by relatively speeding responses on conflict trials (ie, reducing the Stroop effect, defined as the difference in reaction time between conflict and nonconflict trials) when it was delivered in the preresponse period in the preparation phase. Stimulation also increased errors when it was delivered early in the response window. This latter result corresponded to the timing of the conflict-induced increase in LFOs observed in the absence of stimulation but was not directly related to the reduction in the Stroop effect. INTERPRETATION: These results support the theory that the time of LFO increase recorded from the STN corresponds to a conflict-processing function. They also provide one of the first demonstrations of event-related DBS of the STN in humans during a cognitive control paradigm. Ann Neurol 2018;84:515-526.

Pallidal deep brain stimulation modulates cortical excitability and plasticity.

OBJECTIVE: Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves symptoms in dystonia patients. However, the physiological effects produced by GPi DBS are not fully understood. In particular, how a single-pulse GPi DBS changes cortical circuits has never been investigated. We studied the modulation of motor cortical excitability and plasticity with single-pulse GPi DBS in dystonia patients with bilateral implantation of GPi DBS. METHODS: The cortical evoked potentials from DBS were recorded with electroencephalography. Transcranial magnetic stimulation with a conditioning test paired-pulse paradigm was used to investigate the effect of GPi DBS on the primary motor cortex. How GPi DBS might modulate the motor cortical plasticity was tested using a paired associative stimulation paradigm with repetitive pairs of GPi DBS and motor cortical stimulation at specific time intervals. RESULTS: GPi stimulation produced 2 peaks of cortical evoked potentials with latencies of ∼10 and ∼25 milliseconds in the motor cortical area. Cortical facilitation was observed at ∼10 milliseconds after single-pulse GPi DBS, and cortical inhibition was observed after a ∼25-millisecond interval. Repetitive pairs of GPi stimulation with cortical stimulation at these 2 time intervals produced long-term potentiation-like effects in the motor cortex. INTERPRETATION: Single-pulse DBS modulates cortical excitability and plasticity at specific time intervals. These effects may be related to the mechanism of action of DBS. Combination of DBS with cortical stimulation with appropriate timing has therapeutic potential and could be explored in the future as a method to enhance the effects of neuromodulation for neurological and psychiatric diseases. Ann Neurol 2018;83:352-362.

Stop-related subthalamic beta activity indexes global motor suppression in Parkinson's disease.

BACKGROUND: Rapid action stopping leads to global motor suppression. This is shown by studies using transcranial magnetic stimulation to measure corticospinal excitability of task-unrelated effectors (e.g., from the hand during speech stopping). We hypothesize that this global suppression relates to the STN of the basal ganglia. Several STN local field potential studies in PD patients have shown increased ß-band power during successful stopping. OBJECTIVES: Here, we aimed to test whether this STN ß-band activity indexes global motor suppression measured by transcranial magnetic stimulation. METHODS: We studied 9 medicated PD patients (age, 47-67 years; mean, 55.8; 3 female) who were implanted with STN-DBS electrodes. Participants performed a vocal stop-signal task (i.e., they had to occasionally stop a vocal response) while we simultaneously recorded local field potentials from right STN and delivered transcranial magnetic stimulation to primary motor cortex to measure corticospinal excitability from a task-unrelated hand muscle (first dorsal interosseous). RESULTS: Replicating previous results, STN ß-band power was increased (P < 0.005) and corticospinal excitability was reduced (P = 0.024; global motor suppression) during successful stopping. As hypothesized, global motor suppression was greater for successful stop trials with higher STN ß-power (median split: P = 0.043), which was further evident in a negative correlation between single-trial STN ß-power and corticospinal excitability (mean, r = -0.176; P = 0.011). CONCLUSION: These findings link stopping-related global motor suppression to STN ß-band activity through simultaneous recordings of STN and corticospinal excitability. The results support models of basal ganglia function that propose the STN has broad motor suppressive effects. © 2016 International Parkinson and Movement Disorder Society.

Modulation of Beta oscillations in the subthalamic nucleus with prosaccades and antisaccades in Parkinson's disease.

Increased oscillations in the beta band are thought to be related to motor symptoms of Parkinson's disease (PD). Previous studies have shown that beta-band desynchronization in the subthalamic nucleus (STN) is reduced just before and during limb movements. While the STN is part of the basal ganglia (BG)-thalamocortical circuit controlling limb movements, it is also part of the BG-brainstem projection controlling saccadic eye movements. Late-stage PD patients have deficits in saccades in addition to difficulties with limb movements arising from impaired functions of the BG. We investigated saccade-related changes in beta-band (15-30 Hz) oscillatory activities in the human STN while PD patients performed visually guided prosaccades and antisaccades, the latter requiring suppression of reflexive responses and volitional initiation of saccades. We recorded local field potentials from deep brain stimulation electrodes implanted in the STN in human PD patients 1-5 d after surgery and compared prosaccades and antisaccades with these and with limb movements. Saccade-related beta-band desynchronizations were observed just before and during saccades in all subjects, suggesting that reduction of beta-band oscillatory activity in the STN is related to preparation and execution of saccades. Furthermore, beta-band desynchronizations for antisaccades started earlier, were sustained for longer periods, were of greater magnitude, and were observed more often than prosaccades. Beta-band desynchronization in the STN may reflect the additional processes associated with suppression of reflexive responses and volitional execution of saccades in the opposite direction.

Short- and long-latency interhemispheric inhibitions are additive in human motor cortex.

Transcranial magnetic stimulation (TMS) of the human primary motor cortex (M1) at suprathreshold strength results in inhibition of M1 in the opposite hemisphere, a process termed interhemispheric inhibition (IHI). Two phases of IHI, termed short-latency interhemispheric inhibition (SIHI) and long-latency interhemispheric inhibition (LIHI), involving separate neural circuits, have been identified. In this study we evaluated how these two inhibitory processes interact with each other. We studied 10 healthy right-handed subjects. A test stimulus (TS) was delivered to the left M1, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle. Contralateral conditioning stimuli (CCS) were applied to the right M1 either 10 ms or 50 ms prior to the TS, inducing SIHI and LIHI, respectively, in the left M1. The effects of SIHI and LIHI alone, and SIHI and LIHI delivered together, were compared. The TS was adjusted to produce 1-mV or 0.5-mV MEPs when applied alone or after CCS. SIHI and LIHI were found to be additive when delivered together, irrespective of the strength of the TS. The interactions were affected neither by varying the strength of the conditioning stimulus producing SIHI nor by altering the current direction of the TS. Small or opposing interactions, however, may not have been detected. These results support previous findings suggesting that SIHI and LIHI act through different neural circuits. Such inhibitory processes may be used individually or additively during motor tasks and should be studied as separate processes in functional studies.

Inferring cognitive state underlying conflict choices in verbal Stroop task using heterogeneous input discriminative-generative decoder model.

Objective. The subthalamic nucleus (STN) of the basal ganglia interacts with the medial prefrontal cortex (mPFC) and shapes a control loop, specifically when the brain receives contradictory information from either different sensory systems or conflicting information from sensory inputs and prior knowledge that developed in the brain. Experimental studies demonstrated that significant increases in theta activities (2-8 Hz) in both the STN and mPFC as well as increased phase synchronization between mPFC and STN are prominent features of conflict processing. While these neural features reflect the importance of STN-mPFC circuitry in conflict processing, a low-dimensional representation of the mPFC-STN interaction referred to as a cognitive state, that links neural activities generated by these sub-regions to behavioral signals (e.g. the response time), remains to be identified.Approach. Here, we propose a new model, namely, the heterogeneous input discriminative-generative decoder (HI-DGD) model, to infer a cognitive state underlying decision-making based on neural activities (STN and mPFC) and behavioral signals (individuals' response time) recorded in ten Parkinson's disease (PD) patients while they performed a Stroop task. PD patients may have conflict processing which is quantitatively (may be qualitative in some) different from healthy populations.Main results. Using extensive synthetic and experimental data, we showed that the HI-DGD model can diffuse information from neural and behavioral data simultaneously and estimate cognitive states underlying conflict and non-conflict trials significantly better than traditional methods. Additionally, the HI-DGD model identified which neural features made significant contributions to conflict and non-conflict choices. Interestingly, the estimated features match well with those reported in experimental studies.Significance. Finally, we highlight the capability of the HI-DGD model in estimating a cognitive state from a single trial of observation, which makes it appropriate to be utilized in closed-loop neuromodulation systems.

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex.

INTRODUCTION: There is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. OBJECTIVE: The aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. METHODS: An 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. RESULTS: tbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. CONCLUSION: The findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

The nature and time course of cortical activation following subthalamic stimulation in Parkinson's disease.

We studied the time course and nature of interactions between the subthalamic nucleus (STN) and the motor cortex in 8 Parkinson disease (PD) patients with chronically implanted STN deep-brain stimulation (DBS) electrodes. We first identified the cortical evoked potentials following STN stimulation. The most consistent potential was positive wave with peak latency of 22.2 +/- 1.2 ms from stimulation of clinically effective contacts. We then stimulated the motor cortex with transcranial magnetic stimulation (TMS) at 2-15 ms and at the latency of the evoked potential ( approximately 23 ms) following STN DBS. TMS induced currents in 3 directions: lateral-medial (LM) direction activated corticospinal axons directly, posterior-anterior (PA), and anterior-posterior (AP) directions activated corticospinal neurons transynaptically. Motor-evoked potentials (MEP) elicited by AP and PA TMS were facilitated at short (2-4 ms) and medium latencies (21-24 ms). However, MEPs elicited by LM TMS were not modified by STN DBS. Short-latency antidromic stimulation of the corticosubthalamic projections and medium latency transmission likely through the basal ganglia-thalamocortical circuit led to cortical evoked potentials and increased motor cortex excitability at specific intervals following STN stimulation at clinically effective contacts. Cortical activation may be related to the clinical effects of STN DBS in PD.

Motor blocks during bilateral stepping in Parkinson's disease and effects of dopaminergic medication.

INTRODUCTION: Freezing of gait (FOG) is a complex symptom in Parkinson's disease (PD) that manifests during walking as limited forward progression despite the intention to walk. It is unclear if lower limb motor blocks (LLMB) that occur independently from FOG are related to overground FOG and the effects of dopaminergic medications. METHODS: Nineteen patients with PD were tested on two separate days in the dopaminergic medication "on" and "off" states. The patients completed a series of freezing-provoking tasks while videotaped. Raters assessed videos for FOG presence using Movement Disorders Society Unified Parkinson's Disease Rating Scale item 3.11 score greater than or equal to 1 and FOG severity using the standardized FOG score. Whilst seated in a virtual environment, patients and 20 healthy controls stepped in right-left sequence on foot pedals. Frequency and percent time in LLMB were assessed for accurate classification of FOG presence and correlation to the FOG score. RESULTS: Frequency and percent time spent in LLMB predicted the presence of FOG in both medication states. Percent time spent in LLMB correlated with FOG severity in both medication states. LLMB frequency predicted FOG severity in the "off" state only. CONCLUSIONS: LLMB during bilateral stepping in a virtual environment predicted the presence and severity of FOG in PD in both "on" and "off" medication states. These findings support the use of this non-walking paradigm to detect and assess FOG in PD patients unable or unsafe to walk.

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5-12 Hz) are important in cognition. METHODS: We tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients' peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation. RESULTS: Acute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions. CONCLUSION: Here, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.

Solvent-driven structural topology involving energetically significant intra- and intermolecular chelate ring contacts and anticancer activities of Cu(ii) phenanthroline complexes involving benzoates: experimental and theoretical studies.

Two new coordination solids [Cu2(µ2-Bz)4(CH3OH)2][Cu2(η2-Bz)2(phen)2(H2O)2]·(NO3)2 (1) and [Cu(phen)(H2O)(Bz)(η2-Bz)] (2) (phen = 1,10-phenanthroline; Bz = benzoate) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (IR, UV-vis-NIR and ESR) and single crystal X-ray diffraction techniques. Change of the solvent from methanol to DMF results in changes in the architectures that are triggered by a change from square pyramidal to octahedral coordination at the divalent metal centers for complexes 1 and 2 respectively. The structural topology of the complexes is established by the interplay of strong O-H⋯O and weak C-H⋯O, C-H⋯C, π-π stacking interactions. Unconventional parallel intramolecular and anti-parallel intermolecular contacts involving the chelate rings (CR) also stabilize the structures. The energetic analyses of the structures evidence that the parallel arrangement is energetically favoured which is likely due to the presence of the Cu⋯Cu cuprophilic interaction in 1 that is not established in 2. Compound 1 exhibits the highest antibacterial activity against Rhizobium leguminosarum among the tested cultures. In vitro cytotoxicity and apoptosis studies were carried out for compounds 1 and 2 on malignant Dalton's lymphoma cell line (DL). Both compounds showed a significant effect on the decrease in cell viability as compared to a control, while compound 2 induced remarkable cytotoxicity towards DL cells. Treatment also showed the appearance of membrane blebbing, chromatin condensation and fragmented nuclei which are typical characteristic features of apoptotic cell death. Furthermore, a docking study revealed that both compounds docked in the active sites of all the cancer target proteins under study. Moreover, SAR analysis revealed that oxygen and nitrogen atoms of compound 1 and the oxygen atoms of compound 2 are crucial for biological activities.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences.

OBJECTIVE: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research. METHODS: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed. RESULTS: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event. CONCLUSIONS: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

Stopping and slowing manual and spoken responses: Similar oscillatory signatures recorded from the subthalamic nucleus.

Response control in the forms of stopping and slowing responses is thought to be implemented by a frontal-subcortical network, which includes the subthalamic nucleus (STN). For manual control, stopping is linked to STN beta (13-30 Hz) and slowing responses are linked to lower frequencies (<12 Hz). Whether similar STN oscillatory activities are associated with the control of spoken responses is not clear. We studied 16 patients with STN LFP recordings during manual and vocal stop signal tasks in two experiments. We found increased beta activities for stopping spoken responses, similar to manual stopping. However, unlike manual stopping, stopping spoken responses elicited a right-lateralized beta power increase, which may be related to previously reported hyperactivity of right-sided motor control regions in stuttering. We additionally studied STN power changes associated with slowing responses in the same stop-signal tasks by comparing slower vs. faster go trials. Now, rather than beta, there was an alpha power increase after Go cues, which remained elevated only in slower Go trials in both the vocal and manual tasks. These data show that different types of response control are generalizable across effectors and relate to different frequencies recorded from the STN.

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case.

OBJECTIVE: To evaluate the safety of repetitive transcranial magnetic stimulation (rTMS) in patients with implanted subdural cortical electrodes. METHODS: We performed ex-vivo experiments to test the temperature, displacement and current induced in the electrodes with single pulse transcranial magnetic stimulation (TMS) from 10 to 100% of stimulator output and tested a typical rTMS protocol used in a clinical setting. We then used rTMS to the motor cortex to treat a patient with refractory post-herpetic neuralgia who had previously been implanted with a subdural motor cortical electrode for pain management. The rTMS protocol consisted of ten sessions of 2000 stimuli at 20Hz and 90% of resting motor threshold. RESULTS: The ex-vivo study showed an increase in the coil temperature of 2°C, a maximum induced charge density of 30.4µC/cm2/phase, and no electrode displacement with TMS. There was no serious adverse effect associated with rTMS treatment of the patient. Cortical tremor was observed in the intervals between trains of stimuli during one treatment session. CONCLUSIONS: TMS was safe in a patient with implanted Medtronic Resume II electrode (model 3587A) subdural cortical electrode. SIGNIFICANCE: TMS may be used as a therapeutic, diagnostic or research tool in patients this type of with implanted cortical electrodes.

Reduced dorsal premotor cortex and primary motor cortex connectivity in older adults.

Motor functions decline with increasing age. The underlying mechanisms are still unclear and are likely to be multifactorial. There is evidence for disruption of white matter integrity with age, which affects cortico-cortical connectivity. Studies with transcranial magnetic stimulation found both inhibitory and facilitatory connections from dorsal premotor cortex (PMd) to the ipsilateral primary motor cortex (M1) in young adults. We investigated whether aging affects this connectivity in 15 older and 15 young healthy adults. Transcranial magnetic stimulation in a paired-pulse paradigm was used to test the connectivity between left PMd and M1. Motor evoked potential in the right first dorsal interosseous muscle was recorded. We found that both the inhibitory effect with low intensity PMd stimulation and the facilitatory effect with high intensity PMd stimulation observed in young adults were decreased in older adults. We conclude that the connectivity between PMd and ipsilateral M1 is reduced in older adults.