Utpal Saha

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.

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

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.

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.

Pallidal deep brain stimulation modulates cortical excitability and plasticity

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.

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 Parkinsons 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.

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.

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.

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

HighlightsSimilar STN frequency‐specific changes for the control of spoken and manual responses.Suggesting generalizable processes of response control across effectors.STN alpha band is related to slowing responses and beta band is related to stopping.Right‐lateralized STN beta profile during vocal stopping, implications for stuttering. ABSTRACT 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.

Event-related deep brain stimulation of the subthalamic nucleus affects conflict processing: Event-Related STN DBS

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.

P15-20 Movement related potentials and oscillatory activities in the human internal globus pallidus during voluntary movements

Method: Repeat the task, which is tracing the dots of square and circle by pencil in each hands, and measure the brain wave of that time. The measurement of brain wave was based on Ten-twenty electrode system. Brain wave was recorded from the part of F3, F4, C3, C4. Data is taken into the personal computer by sampling frequency 1 kHz by using the DAQ terminal-410 (INTERCROSS Co. Ltd. Tokyo). Result: When the writing operation began, a decrease of a wave was seen from the each part compared with the resting time, and it has increased gradually along with the proficient of operation which is to say motor learning. The change of the amount of the brain wave and increase of a wave in F3 and F4 was larger than C3 and C4. This tendency was more remarkable in non-dominant hand than that of dominant hand. Conclusion: Generally, it is said that the a wave will increase when the mental load decreases. We can say that a mental load decreased gradually as the motor learning advances, and it led to an increase of the a wave. The change of a wave was remarkable in non-dominant hand. This is because the learning effect appears remarkably in non-dominant hand than the dominant hand, which is used habitually. This study shows the possibility that the proficient of operation, that is, motor learning can caught in the numerical value by the brain wave measurement.