Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

Parkinsonian daytime sleep-wake classification using deep brain stimulation lead recordings.

Excessive daytime sleepiness is a recognized non-motor symptom that adversely impacts the quality of life of people with Parkinson's disease (PD), yet effective treatment options remain limited. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for PD motor signs. Reliable daytime sleep-wake classification using local field potentials (LFPs) recorded from DBS leads implanted in STN can inform the development of closed-loop DBS approaches for prompt detection and disruption of sleep-related neural oscillations. We performed STN DBS lead recordings in three nonhuman primates rendered parkinsonian by administrating neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Reference sleep-wake states were determined on a second-by-second basis by video monitoring of eyes (eyes-open, wake and eyes-closed, sleep). The spectral power in delta (1-4 Hz), theta (4-8 Hz), low-beta (8-20 Hz), high-beta (20-35 Hz), gamma (35-90 Hz), and high-frequency (200-400 Hz) bands were extracted from each wake and sleep epochs for training (70% data) and testing (30% data) a support vector machines classifier for each subject independently. The spectral features yielded reasonable daytime sleep-wake classification (sensitivity: 90.68 ± 1.28; specificity: 88.16 ± 1.08; accuracy: 89.42 ± 0.68; positive predictive value; 88.70 ± 0.89, n = 3). Our findings support the plausibility of monitoring daytime sleep-wake states using DBS lead recordings. These results could have future clinical implications in informing the development of closed-loop DBS approaches for automatic detection and disruption of sleep-related neural oscillations in people with PD to promote wakefulness.

Semi-automated approaches to optimize deep brain stimulation parameters in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) is a treatment option for Parkinson's disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available. New approaches to optimizing a patient's stimulation parameters, that can also handle the increasing complexity of new electrode and stimulator designs, is needed. METHODS: To improve DBS parameter programming, we explored two semi-automated optimization approaches: a Bayesian optimization (BayesOpt) algorithm to efficiently determine a patient's optimal stimulation parameter for minimizing rigidity, and a probit Gaussian process (pGP) to assess patient's preference. Quantified rigidity measurements were obtained using a robotic manipulandum in two participants over two visits. Rigidity was measured, in 5Hz increments, between 10-185Hz (total 30-36 frequencies) on the first visit and at eight BayesOpt algorithm-selected frequencies on the second visit. The participant was also asked their preference between the current and previous stimulation frequency. First, we compared the optimal frequency between visits with the participant's preferred frequency. Next, we evaluated the efficiency of the BayesOpt algorithm, comparing it to random and equal interval selection of frequency. RESULTS: The BayesOpt algorithm estimated the optimal frequency to be the highest tolerable frequency, matching the optimal frequency found during the first visit. However, the participants' pGP models indicate a preference at frequencies between 70-110 Hz. Here the stimulation frequency is lowest that achieves nearly maximal suppression of rigidity. BayesOpt was efficient, estimating the rigidity response curve to stimulation that was almost indistinguishable when compared to the longer brute force method. CONCLUSIONS: These results provide preliminary evidence of the feasibility to use BayesOpt for determining the optimal frequency, while pGP patient's preferences include more difficult to measure outcomes. Both novel approaches can shorten DBS programming and can be expanded to include multiple symptoms and parameters.

Directional deep brain stimulation leads reveal spatially distinct oscillatory activity in the globus pallidus internus of Parkinson's disease patients.

The goal of this study was to characterize the spectral characteristics and spatial topography of local field potential (LFP) activity in the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease utilizing directional (segmented) deep brain stimulation (dDBS) leads. Data were collected from externalized dDBS leads of three patients with idiopathic Parkinson's disease after overnight withdrawal of parkinsonian medication at rest and during a cued reach-to-target task. Oscillatory activity across lead contacts/segments was examined in the context of lead locations and contact orientations determined using co-registered preoperative 7 Tesla (T) MRI and postoperative CT scans. Each of the three patients displayed a unique frequency spectrum of oscillatory activity in the pallidum, with prominent peaks ranging from 5 to 35 Hz, that modulated variably across subjects during volitional movement. Despite subject-specific spectral profiles, a consistent finding across patients was that oscillatory power was strongest and had the largest magnitude of modulation during movement in LFPs recorded from segments facing the postero-lateral "sensorimotor" region of GPi, whereas antero-medially-directed segmented contacts facing the internal capsule and/or anterior GPi, had relatively weaker LFP power and less modulation in the 5 to 35 Hz. In each subject, contact configurations chosen for clinically therapeutic stimulation (following data collection and blinded to physiology recordings), were in concordance with the contact pairs showing the largest amplitude of LFP oscillations in the 5-35 Hz range. Although limited to three subjects, these findings provide support for the hypothesis that the sensorimotor territory of the GPi corresponds to the site of maximal power of oscillatory activity in the 5 to 35 Hz and provides the greatest benefit in motor signs during stimulation in the GPi. Variability in oscillatory activity across patients is likely related to Parkinson's disease phenotype as well as small differences in recording location (i.e. lead location), highlighting the importance of lead location for optimizing stimulation efficacy. These data also provide compelling evidence for the use of LFP activity for the development of predictive stimulation models that may optimize patient benefits while reducing clinic time needed for programming.

Effect of Cue Timing and Modality on Gait Initiation in Parkinson Disease With Freezing of Gait.

OBJECTIVE: To examine the effects of cue timing, across 3 sensory modalities, on anticipatory postural adjustments (APAs) during gait initiation in people with Parkinson disease (PD). DESIGN: Observational study. SETTING: Biomechanics research laboratory. PARTICIPANTS: Individuals with idiopathic PD (N=25; 11 with freezing of gait [FOG]) were studied in the off-medication state (12-h overnight withdrawal). INTERVENTIONS: Gait initiation was tested without cueing (self-initiated) and with 3 cue timing protocols: fixed delay (3s), random delay (4-12s), and countdown (3-2-1-go, 1-s intervals) across 3 sensory modalities (acoustic, visual, and vibrotactile). MAIN OUTCOME MEASURES: The incidence and spatiotemporal characteristics of APAs during gait initiation were analyzed, including vertical ground reaction forces and center of pressure. RESULTS: All cue timings and modalities increased the incidence and amplitude of APAs compared with self-initiated stepping. Acoustic and visual cues, but not vibrotactile stimulation, improved the timing of APAs. Fixed delay or countdown timing protocols were more effective at decreasing APA durations than random delay cues. Cue-evoked improvements in APA timing, but not amplitude, correlated with the level of impairment during self-initiated gait. Cues did not improve the late push-off phase in the FOG group. CONCLUSIONS: External cueing improves gait initiation in PD regardless of cue timing, modality, or clinical phenotype (with and without FOG). Acoustic or visual cueing with predictive timing provided the greatest improvements in gait initiation; therefore, these protocols may provide the best outcomes when applied by caregivers or devices.

Subliminal gait initiation deficits in rapid eye movement sleep behavior disorder: A harbinger of freezing of gait?

BACKGROUND: Muscle activity during rapid eye movement sleep is markedly increased in people with rapid eye movement sleep behavior disorder and people with Parkinson's disease (PD) who have freezing of gait. This study examined whether individuals with rapid eye movement sleep behavior disorder who do not have a diagnosis of PD show abnormalities in gait initiation that resemble the impairments observed in PD and whether there is a relationship between these deficits and the level of rapid eye movement sleep without atonia. METHODS: Gait initiation and polysomnography studies were conducted in 4 groups of 10 participants: rapid eye movement sleep behavior disorder, PD with and without freezing of gait, and controls. RESULTS: Significant reductions were seen in the posterior shift of the center of pressure during the propulsive phase of gait initiation in the groups with rapid eye movement sleep behavior disorder and PD with freezing of gait when compared with controls and PD nonfreezers. These reductions negatively correlated with the amount of rapid eye movement sleep without atonia. The duration of the initial dorsiflexor muscle burst during gait initiation was significantly reduced in both PD groups and the rapid eye movement sleep behavior disorder cohort. CONCLUSIONS: These results provide evidence that people with rapid eye movement sleep behavior disorder, prior to a diagnosis of a degenerative neurologic disorder, show alterations in the coupling of posture and gait similar to those seen in PD. The correlation between increased rapid eye movement sleep without atonia and deficits in forward propulsion during the push-off phase of gait initiation suggests that abnormities in the regulation of muscle tone during rapid eye movement sleep may be related to the pathogenesis of freezing of gait. © 2016 International Parkinson and Movement Disorder Society.

Neural processes mediating the preparation and release of focal motor output are suppressed or absent during imagined movement.

Movements that are executed or imagined activate a similar subset of cortical regions, but the extent to which this activity represents functionally equivalent neural processes is unclear. During preparation for an executed movement, presentation of a startling acoustic stimulus (SAS) evokes a premature release of the planned movement with the spatial and temporal features of the tasks essentially intact. If imagined movement incorporates the same preparatory processes as executed movement, then a SAS should release the planned movement during preparation. This hypothesis was tested using an instructed-delay cueing paradigm during which subjects were required to rapidly release a handheld weight while maintaining the posture of the arm or to perform first-person imagery of the same task while holding the weight. In a subset of trials, a SAS was presented at 1500, 500, or 200 ms prior to the release cue. Task-appropriate preparation during executed and imagined movements was confirmed by electroencephalographic recording of a contingent negative variation waveform. During preparation for executed movement, a SAS often resulted in premature release of the weight with the probability of release progressively increasing from 24 % at -1500 ms to 80 % at -200 ms. In contrast, the SAS rarely (<2 % of trials) triggered a release of the weight during imagined movement. However, the SAS frequently evoked the planned postural response (suppression of bicep brachii muscle activity) irrespective of the task or timing of stimulation (even during periods of postural hold without preparation). These findings provide evidence that neural processes mediating the preparation and release of the focal motor task (release of the weight) are markedly attenuated or absent during imagined movement and that postural and focal components of the task are prepared independently.

Degraded expression of learned feedforward control in movements released by startle.

Recent work has shown that preplanned motor programs can be rapidly released via fast conducting pathways using a startling acoustic stimulus. Our question was whether the startle-elicited response might also release a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Our initial investigation using adaptation to robotically produced forces showed some evidence of this, but the results were potentially confounded by co-contraction caused by startle. In this study, we eliminated this confound by asking subjects to make reaching movements in the presence of a visual distortion. Results show that a startle stimulus (1) decreased performance of the recently learned task and (2) reduced after-effect magnitude. Since the recall of learned control was reduced, but not eliminated during startle trials, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation. These findings have implications for motor training in areas such as piloting, teleoperation, sports, and rehabilitation.

Slow-wave sleep dysfunction in mild parkinsonism is associated with excessive beta and reduced delta oscillations in motor cortex.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5-3 Hz) power was reduced (p = 0.038) whereas beta (8-35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = -0.65, p < 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD.

Pause time alters the preparation of two-component movements.

Targeted reciprocal aiming movements are pervasive in everyday life, but it is unclear how the timing parameters between task elements affect the preparation of these movements. This study used a loud (124 dB) startling acoustic stimulus (SAS) to probe how changes in the pause time between the outward and return components of a reciprocal aiming task affected the preparatory state of the motor system. Participants performed a visually guided wrist extension-flexion task to a target located at 20° from the start position and were instructed to pause the movement within the wrist extension target zone for either 50, 200, or 500 ms. A SAS was presented during 25 % of trials before either the onset of the wrist extension (out) or flexion (return) components of the task to determine how motor preparation was affected by task requirements. Results showed that the presentation of a SAS prior to the initial outward movement led to significantly earlier onsets of both the outward and return components (p < .05), indicating that the pause time in the planned action was pre-planned. For the longer (200, 500 ms) pause-time conditions, a SAS delivered prior to returning from the target region triggered the return portion of the movement early. These findings suggest that the shortest pause-time movement (50 ms) was preplanned as a single action, whereas for reciprocal movements with longer pause times at least the initial part of the movement and the timing of the pause were preplanned and integrated, while the return portion was more independent.

Self-triggered assistive stimulus training improves step initiation in persons with Parkinson's disease.

BACKGROUND: Prior studies demonstrated that hesitation-prone persons with Parkinson's disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure. OBJECTIVE: This study investigated the effects of long-term stimulus exposure. METHODS: Two groups of hesitation-prone subjects with Parkinson's disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length. RESULTS: Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements. CONCLUSIONS: The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure.

Startle-induced rapid release of a gait initiation sequence in Parkinson's disease with freezing of gait.

OBJECTIVE: Freezing of gait (FOG) in Parkinson's disease (PD) is characterized by the inability to initiate stepping, despite the intention to do so. This study used a startling acoustic stimulus paradigm to examine if the capacity to select, prepare and initiate gait under simple and choice reaction time conditions are impaired in people with PD and FOG. METHODS: Thirty individuals (10 PD with FOG, 10 PD without FOG, and 10 controls) performed an instructed-delay gait initiation task under simple and choice reaction time conditions. In a subset of trials, a startle stimulus (124 dB) was presented 500 ms before the time of the imperative go-cue. Anticipatory postural adjustments preceding and accompanying gait initiation were quantified. RESULTS: The presentation of a startling acoustic stimulus resulted in the rapid initiation of an anticipatory postural adjustment sequence during both the simple and choice reaction time tasks in all groups. CONCLUSIONS: The neural capacity to prepare the spatial and temporal components of gait initiation remains intact in PD individuals with and without FOG. SIGNIFICANCE: The retained capacity to prepare anticipatory postural adjustments in advance may explain why external sensory cues are effective in the facilitation of gait initiation in people with PD with FOG.

Postural instability in Parkinson's disease assessed with clinical "pull test" and standardized postural perturbations: effect of medication and body weight support.

OBJECTIVE: This experiment tested if balance performance differed between a standardized treadmill surface perturbation task and a clinical pull test and was affected by medication or the presence of body weight support in people with Parkinson's disease (PD). METHODS: Twenty-seven individuals were tested (14 PD in both ON- and OFF-medication states). Clinical pull test and rapid forward (backward fall) translations of the support surface were applied to induce postural reactions requiring at least 1 step to restore balance. The effects of pull type (clinical vs. treadmill), partial bodyweight support (0 vs 20% body weight) and group (control, PD ON-meds and PD OFF-meds) on reactive stepping as well as practice/learning effect were examined. The number of steps taken and the first step duration were entered in linear repeated-measures mixed-effect models separately. RESULTS: The effects of pull type, group, and bodyweight support were all significant in both metrics, as was ON- vs. OFF-medication. A significant interaction term (group x pull type) was found in the first step duration, showing that the group difference was greater in treadmill compared to the clinical pull test. A significant practice effect was also observed within and across testing sessions. CONCLUSIONS: A standardized treadmill perturbation performed slightly better than the classical pull test in distinguishing between groups, and partial weight support did not substantially degrade the test's performance to detect the balance deficits in people with PD.

Excessive cortical beta oscillations are associated with slow-wave sleep dysfunction in mild parkinsonism.

Increasing evidence associates slow-wave sleep (SWS) dysfunction with neurodegeneration. Using a within-subject design in the nonhuman primate model of Parkinson's disease (PD), we found that reduced SWS quantity in mild parkinsonism was accompanied by elevated beta and reduced delta power during SWS in the motor cortex. Our findings support excessive beta oscillations as a mechanism for SWS dysfunction and will inform development of neuromodulation therapies for enhancing SWS in PD.

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson's Disease patients.

Introduction: Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined. Methods: We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery. Results: Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization. Discussion: Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.

The early release of planned movement by acoustic startle can be delayed by transcranial magnetic stimulation over the motor cortex.

Previous studies have shown that preplanned movements can be rapidly released when a startling acoustic stimulus (SAS) is presented immediately prior to, or coincident with, the imperative signal to initiate movement. Based on the short latency of the onset of muscle activity (typically in less than 90 ms) and the frequent co-expression of startle responses in the neck and eye muscles, it has been proposed that the release of planned movements by a SAS is mediated by subcortical, possibly brainstem, pathways. However, a role for cortical structures in mediating these responses cannot be ruled out based on timing arguments alone. We examined the role of the cortex in the mediation of these responses by testing if a suprathreshold transcranial magnetic stimulation applied over the primary motor cortex, which suppresses voluntary drive and is known to delay movement initiation, could delay the release of movement by a SAS. Eight subjects performed an instructed-delay task requiring them to make a ballistic wrist movement to a target in response to an acoustic tone (control task condition). In a subset of trials subjects received one of the following: (1) suprathreshold TMS over the contralateral primary motor cortex 70 ms prior to their mean response time on control trials (TMS(CT)), (2) SAS 200 ms prior to the go cue (SAS), (3) suprathreshold TMS 70 ms prior to the mean SAS-evoked response time (TMS(SAS)), or (4) TMS(SAS) and SAS presented concurrently (TMS+SAS). Movement kinematics and EMG from the wrist extensors and flexors and sternocleidomastoid muscles were recorded. The application of TMS(CT) prior to control voluntary movements produced a significant delay in movement onset times (P < 0.001) (average delay = 37.7 ± 12.8 ms). The presentation of a SAS alone at -200 ms resulted in the release of the planned movement an average of 71.7 ± 2.7 ms after the startling stimulus. The early release of movement by a SAS was significantly delayed (P < 0.001, average delay = 35.0 ± 12.9 ms) when TMS(SAS) and SAS were presented concurrently. This delay could not be explained by a prolonged suppression of motor unit activity at the spinal level. These findings provide evidence that the release of targeted ballistic wrist movements by SAS is mediated, in part, by a fast conducting transcortical pathway via the primary motor cortex.

Can People with Parkinson's Disease Self-Trigger Gait Initiation? A Comparison of Cueing Strategies.

BACKGROUND: An external cue can markedly improve gait initiation in people with Parkinson's disease (PD) and is often used to overcome freezing of gait (FOG). It is unknown if the effects of external cueing are comparable if the imperative stimulus is triggered by the person receiving the cue (self-triggered) or an external source. OBJECTIVE: Two experiments were conducted to compare the effects of self- versus externally triggered cueing on anticipatory postural adjustments (APAs) during gait initiation in people with PD. METHODS: In experiment 1, 10 individuals with PD and FOG initiated gait without a cue or in response to a stimulus triggered by the experimenter or by the participant. Experiment 2 compared self- versus externally triggered cueing across three groups: healthy young adults (n = 16), healthy older adults (n = 11), and a group with PD (n = 10). RESULTS: Experiment 1: Externally triggered cues significantly increased APA magnitudes compared to uncued stepping, but not when the same cue was self-triggered. Experiment 2: APAs were not significantly improved with a self-triggered cue compared to un-cued stepping in both the PD and healthy older adult groups, but the young adults showed a significant facilitation of APA magnitude. CONCLUSION: The effectiveness of an external cue on gait initiation in people with PD and older adults is critically dependent upon whether the source of the trigger is endogenous (self-produced) or exogenous (externally-generated). These results may explain why cueing interventions that rely upon self-triggering of the stimulus are often ineffective in people with PD.