Characterization of multi-channel intraneural stimulation in transradial amputees.

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency.

To reveal how cells exit human pluripotency, we designed a CRISPR-Cas9 screen exploiting the metabolic and epigenetic differences between naïve and primed pluripotent cells. We identify the tumor suppressor, Folliculin(FLCN) as a critical gene required for the exit from human pluripotency. Here we show that FLCN Knock-out (KO) hESCs maintain the naïve pluripotent state but cannot exit the state since the critical transcription factor TFE3 remains active in the nucleus. TFE3 targets up-regulated in FLCN KO exit assay are members of Wnt pathway and ESRRB. Treatment of FLCN KO hESC with a Wnt inhibitor, but not ESRRB/FLCN double mutant, rescues the cells, allowing the exit from the naïve state. Using co-immunoprecipitation and mass spectrometry analysis we identify unique FLCN binding partners. The interactions of FLCN with components of the mTOR pathway (mTORC1 and mTORC2) reveal a mechanism of FLCN function during exit from naïve pluripotency.

Heart rate variability at bedtime predicts subsequent sleep features.

Getting enough sleep during the night is important for preventing adverse short- and long-term health outcomes. The sympathetic-parasympathetic autonomic balance, characteristics of the pre-bed time resting period, correlates with sleep efficiency. We investigated in healthy subjects whether Low/High Frequencies (LF/HF) and other Heart Rate Variability (HRV) metrics, extracted in the period immediately before sleep onset, are able to predict quality/architecture sleep parameters in the sample group and in the Evening-Intermediate- chronotype subgroups. Linear correlations were found between HRV metrics and the investigated quality/architecture sleep parameters. The possibility to predict sleep parameters from the HRV metrics while falling asleep might pave the way to behavioral interventions during the bedtime period to increase the quality of sleep.

Bilateral cortical representation of tactile roughness.

Roughness is the most important feature for texture discrimination. Here we investigate how the bilateral cortical representation of touch is modulated by tactile roughness by analyzing the neural responses elicited by stimuli with various coarseness levels ranging from fine to medium. A prolonged stimulation was delivered to 10 healthy subjects by passively sliding tactile stimuli under the fingertip while recording the EEG to study the modulation of Somatosensory Evoked Potentials (SEPs) as well as activity in the theta and alpha bands. Elicited long-latency SEPs, namely bilateral P100-N140 and frontal P240 were consistent across stimuli. On the contrary, the temporal lag N140 - P240 was nonlinearly modulated both in contralateral and ipsilateral sides, in agreement with literature. Using a time-frequency analysis approach, we identified a theta band power increase in the [0 0.5]s interval and a partially overlapped power decrease in the alpha band which lasted throughout the stimulation. The estimated time these two phenomena were overlapped was comparable across stimuli, whereas a linear decrease in alpha band amplitude was reported when increasing the stimulus roughness in both contralateral and ipsilateral sides. This study showed that the selected tactile stimuli generated physiological bilateral responses that were modulated in a diversified way according to the stimulus roughness and side. Specifically, we identified sensory processing features (i.e., theta and alpha time overlap) invariant to the stimulus roughness (i.e., associated to a basic cortical mechanism of touch) and roughness-dependent cortical outputs comparable in the contralateral and ipsilateral sides that confirm a bilateral processing of tactile information.

Long-latency components of somatosensory evoked potentials during passive tactile perception of gratings.

Perception of tactile stimuli elicits Somatosensory Evoked Potentials (SEPs) that can be recorded via non-invasive electroencephalography (EEG). However, it is not yet clear how SEPs localization, shape and latency are modulated by different stimuli during mechanical tactile stimulation of fingertips. The aim of this work is thus to characterize SEPs generated by the tactile perception of gratings during dynamic passive stimulation of the dominant fingertip by means of a mechatronic platform. Results show that a random sequence of stimuli elicited SEPs with two long-latency components: (i) a negative deflection around 140 ms located in the frontal-central-parietal side in the contralateral hemisphere; (ii) a positive deflection around 250 ms located in the frontal-central midline. Time-frequency analysis revealed significant continuous bilateral desynchronization in the alpha band throughout the passive stimulation. These results are a fundamental step towards building a model of brain responses during perception of tactile stimuli for future benchmarking studies.