Alternation of Neuronal Feature Selectivity Induced by Paired Optogenetic-Mechanical Stimulation in the Barrel Cortex

Paired stimulation has been applied to modulate neuronal functions in the primary somatosensory cortex but its utility in the alternation of tuning function, such as direction tuning for whisker stimuli, remains unclear. In the present study, we attempted to manipulate feature preferences in barrel cortical neurons using repetitive paired whisker deflection combined with optogenetic stimulation and to obtain optimal parameters that can induce neuroplasticity. We found no significant response changes across stimulus parameters, such as onset asynchronies and paired directions. Only when paired stimulation was applied in the nonpreferred direction of the principal whisker of a neuron, were the neuron’s responses enhanced in that direction. Importantly, this effect was only observed when the optogenetic stimulus preceded the mechanical stimulus. Our findings indicate that repetitive paired optogenetic-mechanical stimulation can induce in vivo neuroplasticity of feature selectivity in limited situations.

Effect of Channel Interaction on Vocal Cue Perception in Cochlear Implant Users

Speech intelligibility in multitalker settings is challenging for most cochlear implant (CI) users. One possibility for this limitation is the suboptimal representation of vocal cues in implant processing, such as the fundamental frequency (F0), and the vocal tract length (VTL). Previous studies suggested that while F0 perception depends on spectrotemporal cues, VTL perception relies largely on spectral cues. To investigate how spectral smearing in CIs affects vocal cue perception in speech-on-speech (SoS) settings, adjacent electrodes were simultaneously stimulated using current steering in 12 Advanced Bionics users to simulate channel interaction. In current steering, two adjacent electrodes are simultaneously stimulated forming a channel of parallel stimulation. Three such stimulation patterns were used: Sequential (one current steering channel), Paired (two channels), and Triplet stimulation (three channels). F0 and VTL just-noticeable differences (JNDs; Task 1), in addition to SoS intelligibility (Task 2) and comprehension (Task 3), were measured for each stimulation strategy. In Tasks 2 and 3, four maskers were used: the same female talker, a male voice obtained by manipulating both F0 and VTL (F0+VTL) of the original female speaker, a voice where only F0 was manipulated, and a voice where only VTL was manipulated. JNDs were measured relative to the original voice for the F0, VTL, and F0+VTL manipulations. When spectral smearing was increased from Sequential to Triplet, a significant deterioration in performance was observed for Tasks 1 and 2, with no differences between Sequential and Paired stimulation. Data from Task 3 were inconclusive. These results imply that CI users may tolerate certain amounts of channel interaction without significant reduction in performance on tasks relying on voice perception. This points to possibilities for using parallel stimulation in CIs for reducing power consumption.

Paired motor cortex and spinal cord epidural stimulation strengthens sensorimotor connections and improves forelimb function after cervical spinal cord injury in rats

Associative plasticity occurs when two stimuli converge on a common neural target. We sought to use the strong convergence between motor and sensory systems in the spinal cord to restore movement after spinal cord injury (SCI). We developed a paired motor cortex and dorsal spinal cord stimulation protocol to target this interaction called spinal cord associative plasticity (SCAP). Subthreshold spinal cord stimulation strongly augments motor cortex evoked potentials at the time they are paired, but only when they arrive synchronously in the spinal cord. We tested the hypothesis that this paired stimulation effect depended on cortical descending motor and spinal cord proprioceptive afferents. Selective inactivation of either of these pathways fully abrogated the paired stimulation effect. We then found that repetitive pairing in awake rats increased spinal excitability for hours after pairing ended. To apply this protocol as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical SCI as in un-injured rats, demonstrating that spared connections after SCI are sufficient to support this plasticity. When 30 minutes of paired stimulation was done over 10 days, the effect of pairing was sustained for weeks. In addition, H-reflex modulation improved, showing decreased hyperreflexia that also persisted for weeks. Importantly, repetitive paired stimulation supported enhanced recovery of forelimb dexterity in rats after SCI with no augmentation of injury-induced neuropathic pain. We conclude that SCAP strengthens sensory-motor connections within the spinal cord, resulting in decreased hyperreflexia and improved forelimb function after SCI.Significance StatementDespite evidence that electrical stimulation of spared nervous system connections can facilitate recovery after SCI, strongly overlapping sensory and motor connections in the spinal cord have not been targeted for therapy. Here we demonstrate a robust paired stimulation paradigm that depends on corticofugal and proprioceptive afferent convergence in the spinal cord. The paradigm, termed SCAP for spinal cord associative plasticity, produced large-scale physiological changes in a preclinical model of cervical SCI. Importantly, SCAP caused lasting improvements in dexterity and decreased hyperreflexia in rats with SCI. Thus, we have determined the neural circuits that drive SCAP and have preclinical evidence for its efficacy to restore function after incomplete cervical SCI, the most common SCI in people.

Plastic Changes in Primate Motor Cortex Following Paired Peripheral Nerve Stimulation

Repeated paired stimulation of two peripheral nerves can produce lasting changes in motor cortical excitability, but little is known of the underlying neuronal basis. Here we trained two macaque monkeys to perform selective thumb and index finger abduction movements. Neural activity was recorded from the contralateral primary motor cortex during task performance, and following stimulation of the ulnar and median nerves, and the nerve supplying the extensor digitorum communis (EDC) muscle. Responses were compared before and after one hour of synchronous or asynchronous paired ulnar/median nerve stimulation. Task performance was significantly enhanced after asynchronous, and impaired after synchronous stimulation. The amplitude of short latency neural responses to median and ulnar nerve stimulation was increased after asynchronous stimulation; later components were reduced after synchronous stimulation. Synchronous stimulation increased neural activity during thumb movement and decreased it during index finger movement; asynchronous stimulation decreased activity during both movements. To assess how well neural activity could separate behavioral or sensory conditions, linear discriminant analysis was used to decode which nerve was stimulated, or which digit moved. Decoding accuracy for nerve stimulation was decreased after synchronous, and increased after asynchronous paired stimulation. Decoding accuracy for task performance was decreased after synchronous, but unchanged after asynchronous paired stimulation. Paired stimulation produces changes in motor cortical circuits which outlast the stimulation. Some of these changes depend on precise stimulus timing.

Transcutaneous spinal direct current stimulation shows no effect on paired stimulation suppression of the somatosensory cortex

Transcutaneous spinal direct current stimulation (tsDCS) is a safe and convenient method of neuromodulation. It has been proven to alter sensory processing at cervicomedullary level by amplitude changes of the P30 response of tibial nerve somatosensory evoked potentials (TN SEPs). With knowledge that tsDCS affects cortical circuits, we hypothesized that tsDCS may also affect intracortical excitability of the somatosensory cortex assessed by paired stimulation suppression (PSS). Fourteen healthy men were included in this prospective, single-blinded, placebo-controlled crossover study. Single (SS) and paired stimulation (PS) TN SEPs were recorded over the scalp before, immediately as well as 30 and 60 min after applying 15 min of tsDCS over the twelfth thoracic vertebra. Each volunteer underwent three independent and randomized sessions of either cathodal, anodal or sham stimulation. tsDCS showed no effect on peak-to-peak amplitudes or latencies of cortical P40-N50 response after SS. Furthermore, tsDCS failed to induce significant changes on amplitude ratios of PSS, thus showing no impact on intracortical excitability of the somatosensory cortex in healthy subjects. Further research is required to reveal the different mechanisms and to strengthen clinical use of this promising technique.

Effect of Channel Interaction on Vocal Cue Perception in Cochlear Implant Users

Speech intelligibility in multi-talker settings is challenging for most CI users. One possibility for this limitation is the suboptimal representation of vocal cues in implant processing, such as the fundamental frequency (F0), and the vocal tract length (VTL). Previous studies suggested that while F0 perception depends on both spectral and temporal cues, VTL perception relies largely on spectral cues. To investigate how spectral smearing in CIs affects vocal cue perception in speech-on-speech (SoS) settings, parallel channels were simultaneously stimulated in 14 Advanced Bionics users to simulate channel interaction. Three such patterns were created: Sequential (stimulation of 2 simultaneous electrodes), Paired (4 electrodes), and Triplet stimulation (6 electrodes). F0 and VTL just-noticeable differences (JNDs; task 1), in addition to SoS intelligibility (task 2) and comprehension (task 3) were measured for each stimulation strategy. In tasks 2 and 3, four maskers were used: the same female talker, a male voice obtained by manipulating both F0 and VTL (F0+VTL) of the original female speaker, a voice where only F0 was manipulated, and a voice where only VTL was manipulated. JNDs were measured relative to the original voice for the F0, VTL, and F0+VTL manipulations. When spectral smearing was increased, a significant deterioration in performance was observed for all tasks, with no differences between Sequential and Paired stimulation. These results imply that CI users may tolerate certain amounts of channel interaction without significant reduction in performance on tasks relying on voice perception. This points to possibilities for utilizing parallel stimulation in CIs for reducing power consumption.

Facial motor evoked potential with paired transcranial magnetic stimulation: prognostic value following microvascular decompression for hemifacial spasm

OBJECTIVEMicrovascular decompression (MVD) is widely considered the treatment of choice for hemifacial spasm (HFS), but not all patients immediately benefit from it. Numerous electrophysiological tests have been employed to monitor the integrity of the facial nerve prior to, during, and after MVD treatment. The authors sought to verify if facial motor evoked potential (FMEP) with paired transcranial magnetic stimulation (pTMS) can be utilized as a tool to predict prognosis following MVD for HFS.METHODSFMEP using pTMS was performed preoperatively and postoperatively for 527 HFS patients who underwent an MVD treatment. Various interstimuli intervals (ISIs), which included 2, 10, 20, 25, 30, 75, and 100 msec, were applied for each paired stimulation and pTMS(%) was obtained. A graph of pTMS(%) versus each ISI was drawn for every patient and its pattern was analyzed in accordance with patients’ clinical outcomes.RESULTSWith ISIs of 75 and 100 msec, pTMS(%) was physiologically further inhibited, whereas it was relatively facilitated under ISIs of 20, 25, and 30 msec; loss of this specific pattern, that is, further inhibition-relative facilitation, indicated impaired integrity of the facial nerve. Those patients who immediately benefited from an MVD and experienced no relapse tended to show proper restoration of this further inhibition-relative facilitation pattern (p = 0.01). Greater resemblance between the physiological pattern of pTMS(%) and postoperative pTMS(%) was correlated to better outcome (p = 0.019).CONCLUSIONSA simple linear graph of pTMS(%) versus each ISI may be a helpful tool to predict prognosis for HFS following an MVD.