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Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring., Competing Interests: KJ, GP, SB, BL, JV, and RD’A are associated with HealthTech Connex and have a financial interest in the NeuroCatch Platform. JV was employed by Healthcode Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jones, Frizzell, Fickling, Pawlowski, Brodie, Lakhani, Venter and D’Arcy.)

Background: Non-invasive neuromodulation using translingual neurostimulation (TLNS) has been shown to advance rehabilitation outcomes, particularly when paired with physical therapy (PT). Together with motor gains, patient-reported observations of incidental improvements in cognitive function have been noted. Both studies in healthy individuals and case reports in clinical populations have linked TLNS to improvements in attention-related cognitive processes. We investigated if the use of combined TLNS/PT would translate to changes in objective neurophysiological cognitive measures in a real-world clinical sample of patients from two separate rehabilitation clinics., Methods: Brain vital signs were derived from event-related potentials (ERPs), specifically auditory sensation (N100), basic attention (P300), and cognitive processing (N400). Additional analyses explored the attention-related N200 response given prior evidence of attention effects from TLNS/PT. The real-world patient sample included a diverse clinical group spanning from mild-to-moderate traumatic brain injury (TBI), stroke, Multiple Sclerosis (MS), Parkinson's Disease (PD), and other neurological conditions. Patient data were also acquired from a standard clinical measure of cognition for comparison., Results: Results showed significant N100 variation between baseline and endpoint following TLNS/PT treatment, with further examination showing condition-specific significant improvements in attention processing (i.e., N100 and N200). Additionally, CogBAT composite scores increased significantly from baseline to endpoint., Discussion: The current study highlighted real-world neuromodulation improvements in neurophysiological correlates of attention. Overall, the real-world findings support the concept of neuromodulation-related improvements extending beyond physical therapy to include potential attention benefits for cognitive rehabilitation., Competing Interests: SF, GP, SB, and RD’A have financial and/or business interests in HealthTech Connex, which may be affected by the research reported in this manuscript. JV was employed by company Healthcode. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kirby, Jones, Fickling, Pawlowski, Brodie, Boyd, Venter, Moser, Kalsi-Ryan, Medvedev and D’Arcy.)

Background: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication., Methods: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data., Results: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10 -4 ). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10 -7 ) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10 -7 )., Conclusions: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAV CNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAV CNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg -1 initial bolus, 10 mcg kg -1 min -1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg -1 bolus, 5 mcg kg -1 min -1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg -1 remifentanil over 30 s, then 1.5 mg kg -1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAV CNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAV CNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAV CNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAV CNS . This effect should be considered when using the WAV CNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.

Background: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on myocardial repolarization, which is important given that the drug is listed as a possible risk factor for torsades de pointes. We investigated the effect of 3 different doses of dexmedetomidine on myocardial repolarization and transmural dispersion in children undergoing elective surgery with total IV anesthesia., Methods: Sixty-four American Society of Anesthesiologists I-II children 3-10 years of age were randomized to receive dexmedetomidine 0.25 µg/kg, 0.5 µg/kg, 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds, after induction of anesthesia. Pre- and postintervention 12-lead electrocardiograms were recorded. The interval between the peak and the end of the electrocardiogram T wave (Tp-e; transmural dispersion) and heart rate-corrected QT intervals (myocardial repolarization) were measured by a pediatric electrophysiologist blinded to group allocation. Data were analyzed using an analysis of covariance regression model. The study was powered to detect a 25-millisecond difference in Tp-e., Results: Forty-eight children completed the study, with data analyzed from 12 participants per group. There were no instances of dysrhythmias. Tp-e values were unaffected by dexmedetomidine administration at any of the studied doses (F = 0.09; P = .96). Mean (99% CI) within-group differences were all <2 milliseconds (-5 to 8). Postintervention, corrected QT interval increased in the control group, but decreased in some dexmedetomidine groups (F = 7.23; P < .001), specifically the dexmedetomidine 0.5 and 0.75 µg/kg doses. Within groups, the mean (99% CI) differences between pre- and postintervention corrected QT interval were 12.4 milliseconds (-5.8 to 30.6) in the control group, -9.0 milliseconds (-24.9 to 6.9) for dexmedetomidine 0.25 µg/kg, -18.6 milliseconds (-33.7 to -3.5) for dexmedetomidine 0.5 µg/kg, and -14.1 milliseconds (-27.4 to -0.8) for dexmedetomidine 0.75 µg/kg., Conclusions: Of the bolus doses of dexmedetomidine studied, none had an effect on Tp-e and the dexmedetomidine 0.5 and 0.75 µg/kg doses shortened corrected QT intervals when measured at 1 minute after dexmedetomidine bolus injection during total IV anesthesia. There is no evidence for an increased risk of torsades de pointes in this context.

Objective: The goal of this paper was to optimize robust PID control for propofol anesthesia in children aged 5-10 years to improve performance, particularly to decrease the time of induction of anesthesia while maintaining robustness., Methods: We analyzed results of a previous study conducted by our group to identify opportunities for system improvement. Allometric scaling was introduced to reduce the interpatient variability and a new robust PID controller was designed using an optimization-based method. We evaluated this optimized design in a clinical study involving 16 new cases., Results: The optimized controller design achieved the performance predicted in simulation studies in the design stage. Time of induction of anesthesia was median [Q1, Q3] 3.7 [2.3, 4.1] min and the achieved global score was 13.4 [9.9, 16.8]., Conclusion: Allometric scaling reduces the interpatient variability in this age group and allows for improved closed-loop performance. The uncertainty described by the model set, the predicted closed-loop responses, and the predicted robustness margins are realistic. The system meets the design objectives of improved speed of induction of anesthesia while maintaining robustness and improving clinically relevant system behavior., Significance: Control system optimization and ongoing system improvements are essential to the development of a clinically relevant commercial device. This paper demonstrates the validity of our approach, including system modeling, controller optimization, and pre-clinical testing in simulation.

Background: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on blood glucose and serum potassium concentrations, which are relevant due to the associations of derangements of both parameters with undesired outcomes. We investigated the effects of 3 different doses of dexmedetomidine on these outcomes in a randomized controlled trial in children undergoing elective surgery., Methods: Sixty-four American Society of Anesthesiologists I-II children were randomized to receive either dexmedetomidine 0.25 µg/kg, dexmedetomidine 0.5 µg/kg, dexmedetomidine 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds after induction of anesthesia. Changes in plasma glucose and serum potassium concentrations were measured in venous blood sampled before and at 15 and 30 minutes after study drug administration. Data were plotted within and between groups and analyzed using a constrained longitudinal data approach., Results: Forty-nine children completed the study. Mean glucose levels at 15 and 30 minutes were elevated with estimated changes from baseline of 0.37 mmol/L (95% CI, 0.29-0.45 mmol/L) and 0.05 mmol/L (95% CI, 0.00-0.10 mmol/L), respectively. At 15 minutes, there was a linear dose-response relationship (1.07 mmol/L/μg/kg [95% CI, 0.57-1.58 mmol/L/μg/kg]), but there was no appreciable effect of dexmedetomidine at 30 minutes (0.15 mmol/L/μg/kg [95% CI, -0.40 to 0.70 mmol/L/μg/kg]). Potassium levels were depressed relative to baseline, with a mean difference at 15 minutes of -0.20 mEq/L (95% CI, -0.28 to -0.12 mEq/L) and at 30 minutes of -0.12 mEq/L (95% CI, -0.15 to -0.08 mEq/L), but there was no appreciable effect of dexmedetomidine at either time., Conclusions: Small elevations in glucose and decreases in potassium were observed after induction of anesthesia in children. The elevation in glucose at 15 minutes depended on the dose of dexmedetomidine administered. These preliminary data warrant further investigation.

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAV CNS ) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAV CNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAV CNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring.

Background: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs., Methods: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I-III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS., Results: Data were analyzed for 127 patients, of median (range) age 64 (22-86) years, undergoing surgical procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6-90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II., Conclusions: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions.

Closed-loop control of anesthesia based on continuous feedback from processed electroencephalography adjusts drug dosing to target a desired depth of hypnosis during dynamic clinical circumstances, freeing the anesthesiologist to focus on more complex tasks. We describe a case of closed-loop control of total intravenous anesthesia in which a sudden loss of blood required immediate intervention. This case illustrates that closed-loop control of drug delivery maintained an appropriate depth of hypnosis during a rapidly changing surgical situation, and that processed electroencephalography may be a useful adjunct indicator for cerebral hypoperfusion.

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Respiratory depression in children receiving postoperative opioid infusions is a significant risk because of the interindividual variability in analgesic requirement. Detection of respiratory depression (or apnea) in these children may be improved with the introduction of automated acoustic respiratory rate (RR) monitoring. However, early detection of adverse events must be balanced with the risk of alarm fatigue. Our objective was to evaluate the use of acoustic RR monitoring in children receiving opioid infusions on a postsurgical ward and identify the causes of false alarm and optimal alarm thresholds., Methods: A video ethnographic study was performed using an observational, mixed methods approach. After surgery, an acoustic RR sensor was placed on the participant's neck and attached to a Rad87 monitor. The monitor was networked with paging for alarms. Vital signs data and paging notification logs were obtained from the central monitoring system. Webcam videos of the participant, infusion pump, and Rad87 monitor were recorded, stored on a secure server, and subsequently analyzed by 2 research nurses to identify the cause of the alarm, response, and effectiveness. Alarms occurring within a 90-second window were grouped into a single-alarm response opportunity., Results: Data from 49 patients (30 females) with median age 14 (range, 4.4-18.8) years were analyzed. The 896 bedside vital sign threshold alarms resulted in 160 alarm response opportunities (44 low RR, 74 high RR, and 42 low SpO2). In 141 periods (88% of total), for which video was available, 65% of alarms were deemed effective (followed by an alarm-related action within 10 minutes). Nurses were the sole responders in 55% of effective alarms and the patient or parent in 20%. Episodes of desaturation (SpO2 < 90%) were observed in 9 patients: At the time of the SpO2 paging trigger, the RR was >10 bpm in 6 of 9 patients. Based on all RR samples observed, the default alarm thresholds, to serve as a starting point for each patient, would be a low RR of 6 (>10 years of age) and 10 (4-9 years of age)., Conclusions: In this study, the use of RR monitoring did not improve the detection of respiratory depression. An RR threshold, which would have been predictive of desaturations, would have resulted in an unacceptably high false alarm rate. Future research using a combination of variables (e.g., SpO2 and RR), or the measurement of tidal volumes, may be needed to improve patient safety in the postoperative ward.

Objective: To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke., Methods: Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated., Results: Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p<0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p<0.01). Both transcallosal prefrontal tract FA (ΔR(2)=0.12, p=0.04) and NL-iSPmean (ΔR(2)=0.09, p=0.04) accounted for unique variance in motor impairment level., Conclusions: Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke., Significance: Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may facilitate mechanisms of motor learning. In a recent single-blind, pseudo-randomized study, we showed that 5-Hz rTMS over ipsilesional primary somatosensory cortex followed by practice of a skilled motor task enhanced motor learning compared with sham rTMS + practice in individuals with chronic stroke. However, the beneficial effect of stimulation was inconsistent. The current study examined how differences in sensorimotor cortex morphology might predict rTMS-related improvements in motor learning in these individuals. High-resolution T1-weighted magnetic resonance images were acquired and processed in FreeSurfer using a newly developed automated, whole brain parcellation technique. Gray matter and white matter volumes of the ipsilesional primary somatosensory and motor cortices were extracted. A significant positive association was observed between the volume of white matter in the primary somatosensory cortex and motor learning-related change, exclusively in the group that received active 5-Hz rTMS. A regression model with age, gray matter and white matter volumes as predictors was significant for predicting motor learning-related change in individuals who received active TMS. White matter volume predicted the greatest amount of variance (47.6%). The same model was non-significant when volumes of the primary motor cortex were considered. We conclude that white matter volume in the cortex underlying the TMS coil may be a novel predictor for behavioral response to 5-Hz rTMS over the ipsilesional primary somatosensory followed by motor practice., (© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Brain injury after intracerebral hemorrhage (ICH) arises from numerous contributors, of which some also play essential roles. Notably, thrombin production, needed to stop bleeding, also causes acute cell death and edema. In some rodent models of ICH, peri-hematoma neurons die over weeks. Hence we evaluated whether thrombin is responsible for this chronic degeneration. Functional impairments after ICH also result from sub-lethal damage to neurons, especially the loss of dendrites. Thus, we evaluated whether thrombin infusion alone, a reductionist model of ICH, causes similar injury., Methods: Adult rats had a modest intra-striatal infusion of thrombin (1 U) or saline followed by a behavioral test, to verify impairment, 7 days later. After this they were euthanized and tissue stained with Golgi-Cox solution to allow the assessment of dendritic morphology in striatal neurons. In a second experiment, rats survived 7 or 60 days after thrombin infusion in order to histologically determine lesion volume., Results: Thrombin caused early cell death and considerable atrophy in surviving peri-lesion neurons, which had less than half of their usual numbers of branches. However, total tissue loss was comparable at 7 (24.1 mm3) and 60 days (25.6 mm3)., Conclusion: Thrombin infusion causes early cell death and neuronal atrophy in nearby surviving striatal neurons but thrombin does not cause chronic tissue loss. Thus, the chronic degeneration found after ICH in rats is not simply and solely due to acute thrombin production. Nonetheless, thrombin is an important contributor to behavioral dysfunction because it causes cell death and substantial dendritic injury.

The neurophysiological mechanism of interhemispheric inhibition (IHI) between the human primary sensory cortices (S1s) is poorly understood. Here we used a paired median nerve somatosensory evoked potential protocol to observe S1-S1 IHI from the dominant to the nondominant hemisphere with electroencephalography. In 10 healthy, right-handed individuals, we compared mean peak-to-peak amplitudes of five somatosensory evoked potential components (P14/N20, N20/P25, P25/N30, N30/P40, and P40/N60) recorded over the right S1 after synchronous versus asynchronous stimulation of the right and left median nerves. Asynchronous conditioning + test stimuli (CS+TS) were delivered at interstimulus intervals of 15, 20, 25, 30, and 35 ms. We found that, in relation to synchronous stimulation, when a CS to the left S1 preceded a TS to the right S1 at the short intervals (15 and 20 ms) the amplitude of the cortical N20/P25 complex was significantly depressed, whereas at the longer intervals (25, 30, and 35 ms) significant inhibition was observed for the thalamocortical P14/N20 as well as the cortical N20/P25 components. We conclude that the magnitude of S1 IHI appears to depend on the temporal asynchrony of bilateral inputs and the specific timing is likely reflective of a direct transcallosal mechanism. Employing a method that enables direct S1 IHI to be reliably quantified may provide a novel tool to assess potential IHI imbalances in individuals with neurological damage, such as stroke., (Copyright © 2014 the American Physiological Society.)

Sensory feedback is critical for motor learning, and thus to neurorehabilitation after stroke. Whether enhancing sensory feedback by applying excitatory repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional primary sensory cortex (IL-S1) might enhance motor learning in chronic stroke has yet to be investigated. The present study investigated the effects of 5 Hz rTMS over IL-S1 paired with skilled motor practice on motor learning, hemiparetic cutaneous somatosensation, and motor function. Individuals with unilateral chronic stroke were pseudo-randomly divided into either Active or Sham 5 Hz rTMS groups (n = 11/group). Following stimulation, both groups practiced a Serial Tracking Task (STT) with the hemiparetic arm; this was repeated for 5 days. Performance on the STT was quantified by response time, peak velocity, and cumulative distance tracked at baseline, during the 5 days of practice, and at a no-rTMS retention test. Cutaneous somatosensation was measured using two-point discrimination. Standardized sensorimotor tests were performed to assess whether the effects might generalize to impact hemiparetic arm function. The active 5 Hz rTMS + training group demonstrated significantly greater improvements in STT performance {response time [F (1, 286.04) = 13.016, p < 0.0005], peak velocity [F (1, 285.95) = 4.111, p = 0.044], and cumulative distance [F (1, 285.92) = 4.076, p = 0.044]} and cutaneous somatosensation [F (1, 21.15) = 8.793, p = 0.007] across all sessions compared to the sham rTMS + training group. Measures of upper extremity motor function were not significantly different for either group. Our preliminary results suggest that, when paired with motor practice, 5 Hz rTMS over IL-S1 enhances motor learning related change in individuals with chronic stroke, potentially as a consequence of improved cutaneous somatosensation, however no improvement in general upper extremity function was observed.