Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn’t affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.

Background: The possible negative effects of high-heeled shoes on subjective comfort perception and objective biomechanical assessment have been noted. Although shoe inserts have been widely applied in footwear to increase comfort and to reduce the frequency of movement-related injury, no study has attempted to identify insert effectiveness in high heels. The purpose of this study was to determine the effects of heel height and shoe inserts on comfort and biomechanics as represented by plantar pressure and ground reaction force (GRF). Methods: Twenty young female adults performed the test conditions formed by the cross-matching of shoe inserts (shoe without insert and shoe with total contact insert [TCI]) and heel height (a flat, a low heel [3.8 cm] and a high heel [7.6 cm]). Two-way analyses of variance for repeated measures design were used to test condition effects on comfort rating, plantar pressure, and GRF during gait. To determine the biomechanical variables that can predict comfort, a multiple linear regression with stepwise method was done. Results: The results showed that discomfort increased with heel height. In high heels, the plantar pressure in the heel and midfoot shifted to the medial forefoot, and the vertical and anteroposterior GRF increased. Use of the TCI reduced the peak pressure in the medial forefoot. Interestingly, the effectiveness of the TCI was greater in the higher heels than in the lower heels and in flat heels. The peak pressure in the medial forefoot, impact force, and the first peak vertical GRF could explain 75.6% of the variance of comfort in high-heeled gait. Conclusions: These findings suggest that higher heels result in decreased comfort, which can be reflected by both the subjective rating scale and biomechanical variables. Use of a TCI altered the biomechanics and therefore improved the comfort in high-heeled shoes.

At the somatosensory periphery, slowly adapting type 1 (SA1) and rapidly adapting (RA) afferents respond very differently to step indentations: SA1 afferents respond throughout the entire stimulus interval (sustained response), whereas RA afferents respond only at stimulus onset (on response) and offset (off response). We recorded the responses of cortical neurons to step indentations and found many neurons in areas 3b and 1 to exhibit properties that are intermediate between these two extremes: These neurons responded during the sustained portion of the stimulus and also at the offset of the stimulus. Several lines of evidence indicate that these neurons, which exist in large proportions even at these early stages of somatosensory cortical processing, receive input from both populations of afferents. First, we show that many cortical neurons have both a significant sustained response and a significant off response. Second, the strength of the off response is uncorrelated with that of the sustained response, which is to be expected if sustained and off responses stem from different populations of afferent fibers. Third, the bulk of the variance in cortical responses to step indentations can be accounted for using a linear combination of both SA1 and RA responses. Finally, we show that the off response in cortical neurons does not reflect rebound from inhibition. We conclude that the convergence of modality specific input onto individual neurons is common in primary somatosensory cortex and discuss how this conclusion might be reconciled with previous findings.

Invariant representations of stimulus features are thought to play an important role in producing stable percepts of objects. In the present study, we assess the invariance of neural representations of tactile motion direction with respect to other stimulus properties. To this end, we record the responses evoked in individual neurons in somatosensory cortex of primates, including areas 3b, 1, and 2, by three types of motion stimuli, namely scanned bars and dot patterns, and random dot displays, presented to the fingertips of macaque monkeys. We identify a population of neurons in area 1 that is highly sensitive to the direction of stimulus motion and whose motion signals are invariant across stimulus types and conditions. The motion signals conveyed by individual neurons in area 1 can account for the ability of human observers to discriminate the direction of motion of these stimuli, as measured in paired psychophysical experiments. We conclude that area 1 contains a robust representation of motion and discuss similarities in the neural mechanisms of visual and tactile motion processing. When we physically interact with an object, our hands convey information about the shape of the object, its texture, its compliance, and its thermal properties. This information allows us to manipulate tools and to recognize objects based on tactile exploration alone. One of the hallmarks of tactile object recognition is that it involves movement between the skin and the object. In this study, we investigate how the direction in which objects move relative to the skin is represented in the brain. Specifically, we scan a variety of stimuli, including bars and dot patterns, across the fingers of non-human primates while recording the evoked neuronal activity. We find that a population of neurons in somatosensory cortex encodes the direction of moving stimuli regardless of the shape of the stimuli, the speed at which they are scanned across the skin, or the force with which they contact the skin. We show that these neurons can account for our ability to perceive the direction of motion of tactile stimuli.