Biology subjects

Hughes, C. L.

Publications and source records attributed to Hughes, C. L..

4 recordsLinked to original sources

bioRxiv2026

Temporal modulation of cortical parvalbumin and somatostatin neurons shapes network activation and adaptation during microstimulation

Parvalbumin-positive (PV) and somatostatin-positive (SOM) inhibitory interneurons play distinct and critical roles in cortical sensory processing, yet their activation dynamics during patterned input remain unclear. This study used two-photon calcium imaging to measure how PV and SOM interneurons are activated and regulate layer 2/3 somatosensory cortical activity during prolonged, patterned input with 22 clinically relevant microstimulation patterns divided by temporal pattern (fixed, burst, or dynamic/biomimetic) and amplitude. Activation over time depended on the interaction between microstimulation amplitude, frequency, and duration. For fixed-frequency stimulation, PV neurons were generally more strongly activated than unlabeled neurons, while SOM neurons were more strongly engaged at higher amplitudes and frequencies, corresponding with greater suppression of surrounding populations over time. Burst patterns limited suppression by evoking stronger and more sustained activation than fixed-frequency patterns especially in PV neurons, potentially by reducing SOM feedback. Theta-burst stimulation (TBS) strongly activated and facilitated SOM neurons, which may underlie its therapeutic effects. Dynamic amplitude modulation preserved excitatory-inhibitory balance by eliciting brief, consistent responses that resemble natural sensory input while reducing long-term adaptation. Many findings fit a model in which PV provides fast-adapting feedforward inhibition and SOM provides slower-facilitating feedback. Supporting this model, distant PV neurons reached peak activation earlier than non-PV neurons, and SOM neurons later than non-SOM neurons during stimulation bursts. A simple computational model built on these dynamics reproduced observed responses, including distance-related effects. Neurons recruited directly bypass SOM input onto their dendrites leading to rapid PV-mediated depression but increasing activity across the stimulation pattern. Together, these results inform the design of microstimulation-based sensory restoration and clarify the circuit-level roles of PV and SOM neurons in transient and sustained inhibitory control of somatosensory cortex.

neuroscience↗

bioRxiv2021

Effects of stimulus pulse rate on somatosensory adaptation in the human cortex

BackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of continuous stimulation on percept intensity over time. ObjectiveHere, we evaluate how tactile percepts, evoked by ICMS in the somatosensory cortex of a human participant adapt over time. MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted across approximately one year and linear mixed effects models were used to assess significance. ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within one minute. Intermittent stimulation paradigms with several seconds between stimulus trains also led to decreases in intensity on many electrodes, but never resulted in extinction of sensation after over three minutes of stimulation. Additionally, longer breaks between each pulse train resulted in some recovery of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity. ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts, and given that transient activity in the somatosensory cortex dominates the response to object contact, this stimulation method may mimic natural cortical activity and improve the perception of stimulation over time.

neuroscience↗

bioRxiv2020

Perceptual responses to microstimulation frequency are spatially organized in human somatosensory cortex

Microstimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of a human participant with a cervical spinal cord injury and varied the stimulus amplitude, duration, and frequency. Increasing the amplitude and duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on most electrodes. Electrodes divided into three groups which evoked distinct perceptual qualities that depended on the stimulus frequency and were spatially organized in cortex. These results contribute to our growing understanding of the structure and function of the somatosensory cortex and will facilitate principled development of stimulation strategies for bidirectional BCIs.

neuroscience↗

bioRxiv2019

Restored tactile sensation improves neuroprosthetic arm control

Summary paragraphThe sense of touch is critical for skillful hand control1-3, but is largely missing for people who use prosthetic devices. Instead, prosthesis users rely heavily on visual feedback, even though state transitions that are necessary to skillfully interact with objects, such as object contact, are relayed more precisely through tactile feedback4-6. Here we show that restoring tactile sensory feedback, through intracortical microstimulation of the somatosensory cortex7, enables a person with a bidirectional intracortical brain-computer interface to improve their performance on functional object transport tasks completed with a neurally-controlled prosthetic limb. The participant had full visual feedback and had practiced the task for approximately two years prior to these experiments. Nevertheless, successful trial times on a commonly used clinical upper limb assessment task were reduced from a median time of 20.9 s (13.1 - 40.5 s interquartile range) to 10.2 s (5.4 - 18.1 s interquartile range) when vision was supplemented with microstimulation-evoked cutaneous percepts that were referred to different fingers and were graded in intensity based on real-time prosthesis contact forces. Faster completion times were primarily due to a reduction in the amount of time spent attempting to grasp objects. These results demonstrate the importance of tactile sensations in upper-limb control and the utility of creating bidirectional brain-computer interfaces to restore this stream of information using intracortical microstimulation.

clinical trials↗