Sensory information to motor cortices: Effects of motor execution in the upper-limb contralateral to sensory input.

Performance of efficient and precise motor output requires proper planning of movement parameters as well as integration of sensory feedback. Peripheral sensory information is projected not only to parietal somatosensory areas but also to cortical motor areas, particularly the supplementary motor area (SMA). These afferent sensory pathways to the frontal cortices are likely involved in the integration of sensory information for assistance in motor program planning and execution. It is not well understood how and where sensory information from the limb contralateral to motor output is modulated, but the SMA is a potential cortical source as it is active both before and during motor output and is particularly involved in movements that require coordination and bilateral upper-limb selection and use. A promising physiological index of sensory inflow to the SMA is the frontal N30 component of the median nerve (MN) somatosensory-evoked potential (SEP), which is generated in the SMA. The SMA has strong connections with ipsilateral areas 2, 5 and secondary somatosensory cortex (S2) as well as ipsilateral primary motor cortex (M1). As such, the SMA proves a fruitful candidate to assess how sensory information is modulated across the upper-limbs during the various stages of motor output. This thesis inquires into how somatosensory information is modulated in both the SMA and primary somatosensory cortical areas (S1) during the planning and execution of a motor output contralateral to sensory input across the upper-limbs, and further, how and what effect ipsilateral primary motor cortex (iM1) has upon modulation of sensory inputs to the SMA

Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain

Background: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization.Objective/Hypothesis: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). Methods: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. Results: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. Conclusions: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options

Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study

Abstract Background Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation. Results Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area or the dorsal premotor cortex. Conclusions Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions. Trial registration ClinicalTrials.gov NCT03634631 08/14/1

Transcranial Focused Ultrasound Modulates Intrinsic and Evoked EEG Dynamics

Background: The integration of EEG recordings and transcranial neuromodulation has provided a useful construct for noninvasively investigating the modification of human brain circuit activity. Recent evidence has demonstrated that focused ultrasound can be targeted through the human skull to affect the amplitude of somatosensory evoked potentials and its associated spectral content. Objective/hypothesis: The present study tests whether focused ultrasound transmitted through the human skull and targeted to somatosensory cortex can affect the phase and phase rate of cortical oscillatory dynamics. Methods: A computational model was developed to gain insight regarding the insertion behavior of ultrasound induced pressure waves in the human head. The instantaneous phase and phase rate of EEG recordings before, during, and after transmission of transcranial focused ultrasound (tFUS) to human somatosensory cortex were examined to explore its effects on phase dynamics. Results: Computational modeling results show the skull effectively reinforces the focusing of tFUS due to curvature of material interfaces. Neurophysiological recordings show that tFUS alters the phase distribution of intrinsic brain activity for beta frequencies, but not gamma. This modulation was accompanied by a change in phase rate of both beta and gamma frequencies. Additionally, tFUS modulated phase distributions in the beta band of early sensory-evoked activity but did not affect late sensory-evoked activity, lending support to the spatial specificity of tFUS for neuromodulation. This spatial specificity was confirmed through an additional experiment where the ultrasound transducer was moved 1 cm laterally from the original cortical target. Conclusions: Focused ultrasonic energy can alter EEG oscillatory dynamics through local mechanical perturbation of discrete cortical circuits. (C) 2014 The Authors. Published by Elsevier Inc

Pulsed ultrasound differentially stimulates somatosensory circuits in humans as indicated by EEG and FMRI.

Peripheral somatosensory circuits are known to respond to diverse stimulus modalities. The energy modalities capable of eliciting somatosensory responses traditionally belong to mechanical, thermal, electromagnetic, and photonic domains. Ultrasound (US) applied to the periphery has also been reported to evoke diverse somatosensations. These observations however have been based primarily on subjective reports and lack neurophysiological descriptions. To investigate the effects of peripherally applied US on human somatosensory brain circuit activity we recorded evoked potentials using electroencephalography and conducted functional magnetic resonance imaging of blood oxygen level-dependent (BOLD) responses to fingertip stimulation with pulsed US. We found a pulsed US waveform designed to elicit a mild vibration sensation reliably triggered evoked potentials having distinct waveform morphologies including a large double-peaked vertex potential. Fingertip stimulation with this pulsed US waveform also led to the appearance of BOLD signals in brain regions responsible for somatosensory discrimination including the primary somatosensory cortex and parietal operculum, as well as brain regions involved in hierarchical somatosensory processing, such as the insula, anterior middle cingulate cortex, and supramarginal gyrus. By changing the energy profile of the pulsed US stimulus waveform we observed pulsed US can differentially activate somatosensory circuits and alter subjective reports that are concomitant with changes in evoked potential morphology and BOLD response patterns. Based on these observations we conclude pulsed US can functionally stimulate different somatosensory fibers and receptors, which may permit new approaches to the study and diagnosis of peripheral nerve injury, dysfunction, and disease

PUNS-M stimulates BOLD contrast signals in somatosensory detection and discrimination networks.

<p>Grand average fMRI BOLD responses obtained from five subjects in response to left finger (<i>red-yellow</i> LUT) and right finger (<i>blue</i>-<i>green</i> LUT) stimulation with PUNS-M waveforms (L  =  Left, R  =  right). Anatomical areas shown were significantly activated (p<0.001). The <i>yellow</i> numbers correspond to MNI slices in respective views while <i>white</i> labels indicate anatomical regions abbreviated as follows: SMg  =  supramarginal gyrus; S1  =  primary somatosensory cortex; Op  =  parietal operculum; Th  =  thalamus; aMCC  =  anterior middle cingulate cortex; Put  =  putamen; SMA  =  supplementary motor area; In  =  Insula; Cdt  =  Caudate.</p

Summary of evoked potential data obtained in response to right fingertip stimulation with pulsed US and vibrotactile sources.

<p>Summary of evoked potential data obtained in response to right fingertip stimulation with pulsed US and vibrotactile sources.</p

Pulsed ultrasonic neurostimulation elicits ultrasound-evoked potentials.

<p>(<b>A</b>) Grand average of ultrasound-evoked potentials (USEPs) recorded from five subjects using a 64 channel EEG in response to right (<i>black traces</i>) and left (<i>cyan traces</i>) fingertip stimulation using a PUNS-M waveform are shown in a top-view of the whole-head. The channels indicated by the <i>red square</i> are shown at a higher gain in <b>B</b>. The <i>vertical dashed lines</i> represent the onset of stimulation and the EEG traces illustrate a time period from 100 msec pre-stimulus to 1000 msec post-stimulus. (<b>B</b>) Grand average USEPs from electrode sites C3, CZ, and C4 shown in <b>A</b>, but at a higher amplitude and temporal gain. The <i>vertical dotted lines</i> show time points of interest for which average voltage maps are shown in <b>C</b> and labels (P1, N1, N2, and P2) indicate potentials of interest. (<b>C</b>) Topographic voltage maps from time-points corresponding to <i>vertical dotted lines</i> in <b>B</b> illustrate grand average USEPs obtained in response to PUNS-M stimulation of the left (<i>top</i>) and right (<i>bottom</i>) fingers.</p