High-Resolution Focused Ultrasound Neuromodulation Induces Limb-Specific Motor Responses in Mice in Vivo.

Ultrasound can modulate activity in the central nervous system, including the induction of motor responses in rodents. Recent studies investigating ultrasound-induced motor movements have described mostly bilateral limb responses, but quantitative evaluations have failed to reveal lateralization or differences in response characteristics between separate limbs or how specific brain targets dictate distinct limb responses. This study uses high-resolution focused ultrasound (FUS) to elicit motor responses in anesthetized mice in vivo and four-limb electromyography (EMG) to evaluate the latency, duration and power of paired motor responses (n = 1768). The results indicate that FUS generates target-specific differences in electromyographic characteristics and that brain targets separated by as little as 1 mm can modulate the responses in individual limbs differentially. Exploiting these differences may provide a tool for quantifying the susceptibility of underlying neural volumes to FUS, understanding the functioning of the targeted neuroanatomy and aiding in mechanistic studies of this non-invasive neuromodulation technique.

Effects of intense pulsed light in microstomia in patients with systemic sclerosis: A pilot study.

INTRODUCTION: The effects of intense pulsed light (IPL) on collagen structures are well known in the treatment of photodamaged skin. OBJECTIVE: The objective of this study was to investigate the effect of IPL on sclerotic skin by treating patients with microstomia due to systemic sclerosis. METHODS AND MATERIALS: 13 patients all with microstomia and systemic sclerosis were treated with IPL, PR (530-750 nm filter) and/or VL (555-950 nm filter) applicator. They were treated in the perioral area 8 times with 3-4 weeks of interval and follow-up for 6 months. The outcomes were the inter-incisal distance and the inter-ridge distance. RESULTS: A significant increase in mouth opening of 4.1 mm (95% confidence interval, 1726-6638, p < 0.005) was found in the inter-ridge distance when comparing the distance before treatment with the distance at six-month follow-up. No significant difference was found in the inter-incisal distance. The patients experienced improved mobility and better control of lip movements after the treatments. CONCLUSION: IPL can improve the inter-ridge distance between the lips in patients with microstomia due to systemic sclerosis but does not affect the inter-incisal distance, which is also dependent on the mobility of the mandibular joints. This treatment can be considered an adjunctive therapy in patients with microstomia due to systemic sclerosis.

Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.

Estimation of the spatial profile of neuromodulation and the temporal latency in motor responses induced by focused ultrasound brain stimulation.

This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected using 2-deoxy-2-[¹8F]fluoro-D-glucose PET immediately after FUS sonication on the unilateral thalamic area of Sprague-Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (SD) ms from the onset of sonication. When compared with latencies of other nonultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the nonelectrical modes of neuromodulation, making it a distinctive brain stimulation method.

Subthalamic stimulation improves orienting gaze movements in Parkinson's disease.

OBJECTIVE: To determine the effect of subthalamic stimulation on visually triggered eye and head movements in patients with Parkinson's disease (PD). METHODS: We compared the gain and latency of visually triggered eye and head movements in 12 patients bilaterally implanted into the subthalamic nucleus (STN) for severe PD and six age-matched control subjects. Visually triggered movements of eye (head restrained), and of eye and head (head unrestrained) were recorded in the absence of dopaminergic medication. Bilateral stimulation was turned OFF and then turned ON with voltage and contact used in chronic setting. The latency was determined from the beginning of initial horizontal eye movements relative to the target onset, and the gain was defined as the ratio of the amplitude of the initial movement to the amplitude of the target movement. RESULTS: Without stimulation, the initiation of the head movement was significantly delayed in patients and the gain of head movement was reduced. Our patients also presented significantly prolonged latencies and hypometry of visually triggered saccades in the head-fixed condition and of gaze in head-free condition. Bilateral STN stimulation with therapeutic parameters improved performance of orienting gaze, eye and head movements towards the controls' level CONCLUSIONS: These results demonstrate that visually triggered saccades and orienting eye-head movements are impaired in the advanced stage of PD. In addition, subthalamic stimulation enhances amplitude and shortens latency of these movements. SIGNIFICANCE: These results are likely explained by alteration of the information processed by the superior colliculus (SC), a pivotal visuomotor structure involved in both voluntary and reflexive saccades. Improvement of movements with stimulation of the STN may be related to its positive input either on the STN-Substantia Nigra-SC pathway or on the parietal cortex-SC pathway.

Corticospinal facilitation during first and third person imagery.

Motor imagery can be defined as the covert rehearsal of movement. Previous research with transcranial magnetic stimulation (TMS) has demonstrated that motor imagery increases the corticospinal excitability of the primary motor cortex in the area corresponding to the representation of the muscle involved in the imagined movement. This research, however, has been limited to imagery of oneself in motion. We extend the TMS research by contrasting first person imagery and third person imagery of index finger abduction-adduction movements. Motor evoked potentials were recorded from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) during single pulse TMS. Participants performed first and third person motor imagery, visual imagery, and static imagery. Visual imagery involved non biological motion while static imagery involved a first person perspective of the unmoving hand. Relative to static imagery, excitability during imagined movement increased in FDI but not ADM. The facilitation in first person imagery adds to previous findings. A greater facilitation of MEPs recorded from FDI was found in third person imagery where the action was clearly attributable to another person. We interpret this novel result in the context of observed action and imagined observation of self action, and attribute the result to activation of mirror systems for matching the imagined action with an inner visuo-motor template.

TENS to the posterior aspect of the legs decreases postural sway during stance.

The purpose of this study was to examine the effect of Transcutaneous Electrical Nerve Stimulation (TENS) applied to the posterior aspect of the legs, on postural sway during stance. Thirty healthy subjects were tested while standing on a force platform under four stimulation conditions: no TENS, bilateral TENS, and unilateral left and right TENS. Thirty-second long tests, employing detection threshold amplitudes, were performed in three blocks. In each block, the four conditions were applied both with and without vision in a random order. The results indicate that the application of TENS brought about a decrease in postural sway as expressed by average sway velocity, in addition to a decrease in the absolute values of maximal and minimal medio-lateral and anterior-posterior velocity. Thus, similar to sub-threshold random electrical noise, it appears that the application of low-amplitude TENS to the lower limbs decreases postural sway during stance. Considering the ease of TENS application and the high prevalence of postural disorders, the potential clinical significance of this observation is to be determined by further studies.

Low frequency rTMS effects on sensorimotor synchronization.

Previous studies using low frequency (1 Hz) rTMS over the motor and premotor cortex have examined repetitive movements, but focused either on motor aspects of performance such as movement speed, or on variability of the produced intervals. A novel question is whether TMS affects the synchronization of repetitive movements with an external cue (sensorimotor synchronization). In the present study participants synchronized finger taps with the tones of an auditory metronome. The aim of the study was to examine whether motor and premotor cortical inhibition induced by rTMS affects timing aspects of synchronization performance such as the coupling between the tap and the tone and error correction after a metronome perturbation. Metronome sequences included perturbations corresponding to a change in the duration of a single interval (phase shifts) that were either small and below the threshold for conscious perception (10 ms) or large and perceivable (50 ms). Both premotor and motor cortex stimulation induced inhibition, as reflected in a lengthening of the silent period. Neither motor nor premotor cortex rTMS altered error correction after a phase shift. However, motor cortex stimulation made participants tap closer to the tone, yielding a decrease in tap-tone asynchrony. This provides the first neurophysiological demonstration of a dissociation between error correction and tap-tone asynchrony in sensorimotor synchronization. We discuss the results in terms of current theories of timing and error correction.

Functional electrostimulation of muscles as a method for restoring motor functions.

The main functions of a method of functional electrical stimulation of muscles (FES) are described: diagnostic, prognostic, and therapeutic. The main indication for using the FES method is a deficiency of muscle function, which may be organic (due to lesions to neuromuscular structures) or functional (associated with relaxation of the muscular apparatus). The five most significant functions of the FES method were established: 1) identification of correctable movements and stimulable muscles; 2) identification of the amplitude and time program for stimulation; 3) stimulation regimes for pathological gaits; 4) stimulation parameters; 5) positioning of skin electrodes on the human body. Using the example of two severe central nervous system pathologies (spinal cord lesions in the lumbosacral area and hemiparesis of cerebral origin), the positive effects of FES on the process of motor rehabilitation of this category of patients were demonstrated.

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces akinesia in Parkinson's disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L-dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS-items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L-dopa test than in the pure STN-DBS condition. Other akinesia items and the time for build-up of lifting force were equally improved in both conditions. This suggests that routine STN-DBS might not be equally effective on all aspects of fine motor functions.

Characteristics of microwave evoked body movements in mice.

Microwave evoked body movements were studied in mice. A resonant cavity was used to provide head and neck exposure of the mouse to pulsed and gated continuous wave (CW) 1.25 GHz microwaves. No difference in response to pulsed and gated CW stimuli of equal average power was found. The incidence of the microwave evoked body movements increased proportionally with specific absorption (dose) when the whole-body average specific absorption rate was at a constant level (7300 W/kg). Under a constant average specific absorption rate, the response incidence reached a plateau at 0.9 kJ/kg. For doses higher than 0.9 kJ/kg, response incidence was proportional to the specific absorption rate and reached a plateau at 900 W/kg. Body movements could be evoked by a single microwave pulse. The lowest whole-body specific absorption (SA) tested was 0.18 kJ/kg, and the corresponding brain SA was 0.29 kJ/kg. Bulk heating potentials of these SAs were less than 0.1 degree C. For doses higher than 0.9 kJ/kg, the response incidence was also proportional to subcutaneous temperature increment and subcutaneous heating rate. The extrapolated absolute thresholds (0% incidence) were 1.21 degrees C temperature increment and 0.24 degree C/s heating rate. Due to high subcutaneous heating rates, these microwaves must be perceived by the mouse as an intense thermal sensation but not a pain sensation because the temperature increment was well below the threshold for thermal pain. Results of the present study should be considered in promulgation of personnel protection guideline against high peak power but low average power microwaves.

[Characteristics of the effect of a constant electromagnetic field on reparative processes in spinal cord injuries]. / Osobennosti vozdeistviia postoiannogo élektromagnitnogo polia na vosstanovite'lnye protsessy pri travmakh spinnogo mozga.

In 171 white rats the spinal cord was completely sectioned in the upper thoracic region. In 46 control rats an early crude spinal cord scar was identified which precluded the growth of nervous fibers. On the contrary, in animals exposed to constant magnetic field a smooth spinal cord scar was found with collaterals of anterior spinal arteria, recrease of the destruction zone and nervous fiber growth across the scar, This resulted in restored hind paw motility by 56 +/- 4.8% as related to control rats in which motility did not restore. Magnet therapy applied as a part in combined restitutional therapy in 104 patients in early restitution period yielded a 46.15 +/- 4.89% to 76.32 +/- 4.87% increase in the rate of restoration of motor and sensory functions. With the therapy applied in late periods, the restitution was 48.1 +/- 5.6% and 78.1 +/- 3.9%, respectively. The magnetic field is considered as a reparation booster in spinal cord trauma applicable in any stage of the disease.

[Somaticoautonomic functions of rabbits exposed to an ultrahigh-frequency electromagnetic field at acupuncture points]. / Izuchenie somatovegetativnykh funktsii u krolikov pri deistvii élektromagnitnogo polia sverkhvysokoi chastoty na tochki akupunktury.

The action of electromagnetic field of ultrahigh frequency with power from 1 to 1000 mwt and acupuncture on the functional state of rabbits under the tooth pulp irritation conditions has been investigated. The action on the points has been established to be accompanied by decrease of the rythm breathing irregularity and motion of animals jaws. The most effectiveness during the action of the field has been registered with power 1-20 mwt that corresponds to the effectiveness of acupuncture. However during the action of the field the frequency of breathing does not change while during acupuncture it increases. This fact points out the differences of the mechanism of normalized effect of these species influence on acupuncture points. The point of view concerning the invariable information action of fields upon the points and the system of points as constantly acting communication channel between an organism and the environment is under discussion.