Tasnuva Hoque

COMPARISON OF THREE METHODS OF TARGETING THE SUBTHALAMIC NUCLEUS FOR CHRONIC STIMULATION IN PARKINSON'S DISEASE

OBJECTIVE The success of subthalamic nucleus (STN) surgery for Parkinsons disease depends on accuracy in target determination. The objective of this study was to determine which of the following techniques was most accurate and precise in identifying the location for stimulation in STN deep brain stimulation surgery that is most clinically effective: direct targeting, indirect targeting using the positions of the anterior and posterior commissures, or a technique using the red nucleus (RN) as an internal fiducial marker. METHODS We reviewed 14 patients with Parkinsons disease treated with bilateral STN deep brain stimulation (28 STN targets). Electrode implantation was based on direct and indirect targeting using two-dimensional magnetic resonance imaging with refinement using microelectrode recording. Optimal settings, including the contacts used, were determined during the clinical follow-up. The position of the best contact was defined with postoperative magnetic resonance imaging. This location was compared with the modified direct, indirect, and RN-based targets. The mean distances between the targets and the final position of the optimal contact were calculated. The accuracy and variance of each target were analyzed. RESULTS The mean position of the best contact was x = 12.12 (standard deviation [SD], 1.45 mm), y = -2.41 (SD, 1.63 mm), and z = -2.39 (SD, 1.49 mm) relative to the midcommissural point. The mean distance between the optimal contact position and the planned target was 3.19 mm (SD, 1.19 mm) using the RN-based method, 3.42 mm (SD, 1.34 mm) using indirect targeting, and 4.66 mm (SD, 1.33 mm) using a modified direct target. The mean distance between the optimal contact and the RN-based target was significantly smaller than the mean distance between the optimal contact and the direct target (post hoc with Tamhanes correction, P < 0.001) but not between the optimal contact and the indirect target. The RN-based target had the smallest variance (F test, P < 0.001), indicating greater precision. CONCLUSION The use of the RN as an internal fiducial marker for targeting the optimal region of STN stimulation was reliable and closely approximates the position of the electrode contact that provides the optimal clinical results.

Two Phases of Interhemispheric Inhibition between Motor Related Cortical Areas and the Primary Motor Cortex in Human

Interhemispheric inhibition (IHI) refers to the neurophysiological mechanism in which one hemisphere of the brain inhibits the opposite hemisphere. IHI can be studied by transcranial magnetic stimulation using a conditioning-test paradigm. We investigated IHI from 5 motor related cortical areas in the right hemisphere to the left primary motor cortex (M1). These areas are hand and face representations of M1, dorsal premotor cortex, somatosensory cortex, and dorsolateral prefrontal cortex. Test stimulus was delivered to the left M1 and conditioning stimulus (CS) was delivered to one of 5 motor related cortical areas in the right hemisphere. The time course of IHI, effects of different CS intensities and current directions on IHI were tested. Maximum IHI was found at interstimulus intervals of approximately 10 ms (short latency IHI, SIHI) and approximately 50 ms (long latency IHI, LIHI) for the motor related areas tested. LIHI could be elicited over a wide range of CS intensities, whereas SIHI required higher CS intensities. We conclude that there are 2 distinct phases of IHI from motor related cortical areas to the opposite M1 through the corpus callosum, and they are mediated by different neuronal populations.

Involvement of the Basal Ganglia and Cerebellar Motor Pathways in the Preparation of Self-Initiated and Externally Triggered Movements in Humans

The subthalamic nucleus (STN) is part of the cortico-basal ganglia (BG)–thalamocortical circuit, whereas the ventral lateral nucleus of the thalamus (VL) is a relay nucleus in the cerebello-dentato-thalamocortical (CTC) pathway. Both pathways have been implicated in movement preparation. We compared the involvement of the STN and VL in movement preparation in humans by recording local field potentials (LFPs) from seven patients with Parkinsons disease with deep-brain stimulation (DBS) electrodes in the STN and five patients with tremor and electrodes in VL. LFPs were recorded from DBS electrodes and scalp electrodes simultaneously while the patients performed self-paced and externally cued (ready, go/no-go) movements. For the self-paced movement, a premovement-related potential was observed in all patients from scalp, STN (phase reversal, five of six patients), and VL (phase reversal, five of five patients) electrodes. The onset times of the potentials were similar in the cortex, STN, and VL, ranging from 1.5 to 2 s before electromyogram onset. For the externally cued movement, an expectancy potential was observed in all patients in cortical and STN electrodes (phase reversal, six of six patients). The expectancy potential was recorded from the thalamic electrodes in four of five patients. However, phase reversal occurred only in one case, and magnetic resonance imaging showed that this contact was outside the VL. The cortico-BG–thalamocortical circuit is involved in the preparation of both self-paced and externally cued movements. The CTC pathway is involved in the preparation of self-paced but not externally cued movements, although the pathway may still be involved in the execution of these movements.

Bi-directional interhemispheric inhibition during unimanual sustained contractions

BackgroundThe interaction between homologous muscle representations in the right and left primary motor cortex was studied using a paired-pulse transcranial magnetic stimulation (TMS) protocol known to evoke interhemispheric inhibition (IHI). The timecourse and magnitude of IHI was studied in fifteen healthy right-handed adults at several interstimulus intervals between the conditioning stimulus and test stimulus (6, 8, 10, 12, 30, 40, 50 ms). IHI was studied in the motor dominant to non-dominant direction and vice versa while the right or left hand was at rest, performing isometric contraction of the first dorsal interosseous (FDI) muscle, and isometric contraction of the FDI muscle in the context of holding a pen.ResultsCompared with rest, IHI was reduced at all ISIs during contraction of either type (with or without the context of pen). IHI was reduced bi-directionally without evidence of hemispheric dominance. Further, contraction of the hand contralateral to the conditioning and test pulse yielded similar reductions in IHI.ConclusionThese data provide evidence for bi-directional reduction of IHI during unimanual contractions. During unimanual, sustained contractions of the hand, the contralateral and ipsilateral motor cortices demonstrate reduced inhibition. The data suggest that unimanual movement decreases inhibition bi-directionally across motor hemispheres and offer one explanation for the observation of ipsilateral M1 activity during hand movements.

Impaired interhemispheric inhibition in writer's cramp

Objectives: Reduced cortical inhibition is a feature of focal hand dystonia and this likely contributes to excessive muscle contractions. Inhibition from the opposite hemisphere, known as interhemispheric inhibition (IHI), was studied bidirectionally in 7 right-handed patients with writers cramp (WC) and age-matched healthy controls in a cross-sectional physiologic study. Methods: IHI was measured with paired transcranial magnetic stimulation with the conditioning stimulus applied to the motor cortex and the test stimulus applied to the contralateral motor cortex. Surface EMG was measured in right and left first dorsal interosseous muscles during rest, and while holding a pen between the thumb and index finger at 20% maximum voluntary contraction with the right dystonia-affected hand. The time course and magnitude of IHI was studied at interstimulus intervals of 6, 8, 10, 12, 30, 40, and 50 msec between the conditioning stimulus and test stimulus. Results: In WC at rest, IHI was significantly reduced in the dystonia-affected right hand (IHI from right to left motor cortex) at both short (SIHI, 10–12 msec) and long (LIHI, 30–40 msec) intervals compared to the unaffected hand. Compared to controls, SIHI and LIHI were reduced in the dystonia-affected hand only. There was no difference in IHI between controls and WC during the task of holding a pen. Conclusions: In WC, both SIHI and LIHI are reduced in the dystonia-affected hand compared to the unaffected hand and to healthy controls. Impaired IHI may contribute to excessive muscle contraction in WC.

Dopamine alters tactile perception in Parkinson's disease.

BACKGROUND Abnormal somatosensory processing may contribute to motor impairments observed in Parkinsons disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception. METHODS Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinsons disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli. RESULTS Temporal order judgment in PD patients of and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactical acuity in controls and in PD patients off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications. CONCLUSIONS These findings suggest that dopamine in PD reduces cortico-cortical connectivity with SI and this leads to changes in tactical sensitivity.

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.

Altered somatosensory processing in Parkinson's disease and modulation by dopaminergic medications

BACKGROUND Somatosensory abnormalities contribute to the pathophysiology of Parkinsons disease (PD). The goal of this study was to identify abnormalities in the tactile-evoked activation of the somatosensory and motor cortices in PD, and in a sensorimotor circuit that traverses both of these cortical loci. The second goal was to investigate the impact of dopaminergic medication on these measures. METHODS Individuals with PD (n = 10, age 61 ± 8 years) and aged-matched controls (n = 11, age 52.3 ± 10.4 years) were studied. PD subjects were studied on and off dopaminergic medications. Using high-resolution functional magnetic resonance, imaging data was acquired over the primary somatosensory and motor cortices during passively delivered, computer-automated tactile stimulation of digits 2 and 5 of the more affected hand in PD and the analogous hand in controls. Short and long-latency afferent inhibition (SAI, LAI) were assessed via median nerve stimulation followed by transcranial magnetic stimulation over the motor cortical representation of the first dorsal interosseous muscle. RESULTS Compared to controls, PD subjects demonstrated diminished activation within the somatosensory cortex, reduced LAI and normal SAI, of which all were insensitive to dopaminergic medications. In addition to improving motor symptoms, dopaminergic medications reduced the hyperactivity observed within primary motor cortex in PD. CONCLUSIONS Somatosensory processing is deficient in PD. Reduction in tactile-evoked activation within primary motor cortex may contribute to improvement in motor symptoms with dopaminergic medications.