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BACKGROUND. Interventions are needed to teach fundamental motor skills (FMS) to preschoolers. There is a need to design more practical and effective interventions that can be successfully implemented by non-motor experts and fit within the existing gross motor opportunities such as outdoor free play at the preschool. The purpose of this study was to evaluate the feasibility and efficacy of a non-motor expert FMS intervention that was implemented during outdoor free play, Motor skills At Playtime (MAP). METHODS. Participants were preschoolers from two Head Start Centers (N = 46; M(age) = 4.7 ± 0.46 years; 41% boys) and were divided into a MAP (n = 30) or control (outdoor free play; n = 16) group. Children completed either a 1350-minute MAP intervention or control condition (outdoor free play) from January to April of 2018. FMS were assessed before and after each program. using both the Test of Gross Motor Development-3(rd) Edition (Ulrich, 2019) and skill outcome measures (running speed, hopping speed, jump distance, throwing speed, kicking speed, and catching percentage). Intervention implementation feasibility was measures through daily fidelity checks. Fidelity was evaluated as the percentage of intervention sessions that included all explicit intervention criteria. FMS data were analyzed using linear mixed modeling. Models were fit with fixed effects of time and treatment, covariates of sex and height, and a random intercept for each individual. RESULTS. The non-motor expert was feasibly able to implement MAP with high fidelity (> 93%). There was a significant treatment effect for MAP on process and product locomotor FMS (p< 0.05), and a trend for a treatment effect for MAP on total process FMS (p = 0.07). CONCLUSION. Results support that MAP was successfully implemented by a non-motor expert and led to improvements in children’s FMS, especially locomotor FMS.

Context Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately. Objective To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion. Design Cohort study. Setting Three US military service academies. Patients or Other Participants A total of 10 604 cadets at participating US military service academies enrolled in the study and completed a baseline evaluation and up to 5 postinjury evaluations. A total of 726 cadets (451 men, 275 women) sustained concussions during the study period. Main Outcome Measure(s) Number of days from injury (1) until the participant became asymptomatic and (2) to complete the RTA protocol. Results Varsity athlete cadets took less time than nonvarsity cadets to become asymptomatic (hazard ratio [HR] = 1.75, 95% confidence interval = 1.38, 2.23). Cadets who reported less symptom severity on the Sport Concussion Assessment Tool, third edition (SCAT3), within 48 hours of concussion had 1.45 to 3.77 times shorter symptom-recovery durations than those with more symptom severity. Similar to symptom duration, varsity status was associated with a shorter RTA-protocol duration (HR = 1.74, 95% confidence interval = 1.34, 2.25), and less symptom severity on the SCAT3 was associated with a shorter RTA-protocol duration (HR range = 1.31 to 1.47). The academy that the cadet attended was associated with the RTA-protocol duration (P < .05). Conclusions The initial total number of symptoms reported and varsity athlete status were strongly associated with symptom and RTA-protocol durations. These findings suggested that external (varsity status and academy) and injury (symptom burden) factors influenced the time until RTA.

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials. OBJECTIVE: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements. INTERVENTIONS: Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change in short-interval intracortical inhibition (SICI; SICI(−1) was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies. RESULTS: A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI(−1) increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI(−1) did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, −2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

Background Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. Methods The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. Results Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70–2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07–1.78). Previous concussion was associated with 1.98 (95% CI: 1.65–2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87–11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. Conclusions Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention. Electronic supplementary material The online version of this article (10.1186/s40621-018-0178-3) contains supplementary material, which is available to authorized users.

Objectives We aimed to describe the bedside registered nurses perceived competence, attitudes, and challenges surrounding the management of patients with left ventricular assist devices (LVAD) in the intensive care unit (ICU) and stepdown unit (SDU). Research methodology/design An exploratory research was employed using a survey. Setting Bedside participants were recruited via an electronic recruitment flyer circulated in online professional and social networking sites. Main outcome measures Items consisted of a numeric rating scale, measuring competence and attitudes related to the management of patients with left ventricular assist devices. The one open-ended question asked the participants to write responses regarding challenges in left ventricular assist device care. Data were analysed using quantitative and qualitative analytics software. Results A total of 36 intensive care unit and 35 stepdown unit bedside nurse (n = 71) from six regions of the United States responded. Overall mean scores for competency and attitude domains were ≥ 7.0. Intensive care nurses scored higher in competence and attitude when compared to stepdown unit nurses care of short-term left ventricular assist devices. Competence and attitude were positively associated with years of experience. Five themes related to challenges in care were identified. Conclusion Overall, bedside nurses had satisfactory competence and attitudes surrounding the care of hospitalised left ventricular assist device patients.

Verbal instruction and strategies informed by declarative memory are key to performance and acquisition of skilled actions. We previously demonstrated that anatomically distinct sensory-motor inputs converging on the corticospinal neurons of motor cortex are differentially sensitive to visual attention load. However, how loading of working memory shapes afferent input to motor cortex is unknown. This study used short-latency afferent inhibition (SAI) to probe the effect of verbal working memory upon anatomically distinct afferent circuits converging on corticospinal neurons in the motor cortex. SAI was elicited by preceding a suprathreshold transcranial magnetic stimulus (TMS) with electrical stimulation of the median nerve at the wrist while participants mentally rehearsed a two- or six-digit numeric memory set. To isolate different afferent intracortical circuits in motor cortex SAI was elicited, using TMS involving posterior-anterior (PA) or anterior-posterior (AP) monophasic current. Both PA and AP SAI were significantly reduced during maintenance of the six-digit compared to two-digit memory set. The generalized effect of working memory across anatomically distinct circuits converging upon corticospinal neurons in motor cortex is in contrast to the specific sensitivity of AP SAI to increased attention load. The common response across the PA and AP SAI circuits to increased working memory load may reflect an indiscriminate perisomatic mechanism involved in the voluntary facilitation of desired and/or suppression of unwanted actions during action selection or response conflict.

OBJECTIVE: To evaluate neuroelectric and cognitive function relative to a season of football participation. Cognitive and neuroelectric function declines are hypothesized to be present in football athletes. DESIGN: Observational SETTING: Athletic fields and research laboratory. PATIENTS (OR PARTICIPANTS): 77 high school athletes (15.9+0.9years, 178.6+7.2cm, 74.4+14.7Kg, and 0.8+0.8 self-reported concussions) participating in football (n=46) and non-contact sports (n=31). INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS): All athletes completed pre-, mid, and post-season assessments of cognitive and neuroelectric function, self-reported symptoms and quality of life. All athletes participated in their respective sports without intervention, while head impact exposure in football athletes was tracked using the Head Impact Telemetry (HIT) System. MAIN OUTCOME MEASUREMENTS: Cognitive performance was based on Cogstate Computerized Cognitive Assessment Tool Processing Speed, Attention, Learning, Working Memory Speed and Working Memory Accuracy scores. ElMindA Brain Network Activation Amplitude, Synchronization, Timing and Connectivity BNA scores demarcated neuroelectric performance. Quality of life was assessed on the Health Behavior Inventory and Satisfaction with Life Scale and symptoms on the SCAT3 inventory. RESULTS: Football and control sport athletes did not show declines in cognitive or neuroelectric function, quality of life measures, or symptom reports across a season of sport participation. CONCLUSIONS: These findings refute the notion that routine football participation places athletes at risk for acute cognitive declines. The lack of impairment may be associated with no association with head impacts and cognitive function, increased physical activity offsetting any declines, and/or test sensitivity. How these findings are associated with long term cognitive function is unknown.

Background Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics. Objective Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals. Methods Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes. Results Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions. Conclusions TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex.

The brain activity changes during infancy that underpin the emergence of functional motor skills, such as reaching and stepping, are not well understood. The current study used functional near-infrared spectroscopy (fNIRS) to examine the hemodynamic response across the frontal, mid-coronal plane (sensorimotor cortex) and external occipital protuberance (cerebellar cortex) regions of typically developing infants (5 to 13 months) during reach-to-grasp or supported treadmill stepping behaviour. Motor ability was assessed using the third edition of the Motor Subscale of the Bayley Scales of Infant Development (BSID-III). Infants with enhanced motor ability demonstrated greater oxy-hemoglobin (HbO) concentration in the contralateral anterior mid-coronal and frontal-dorsal areas during right-handed reach-to-grasp. During bilateral reaching behavior, infants with enhanced motor ability showed greater HbO increases in right frontal-dorsal regions and lower HbO increases in left anterior mid-coronal areas. In contrast, infants' motor ability was associated with changes in de-oxyhemoglobin (HbR) concentration in the ipsilateral anterior mid-coronal, contralateral frontal and left external occipital protuberance regions during left-handed reaching behavior. These relationships between upper limb hemodynamics and infant motor ability are consistent with increased lateralization and cognitive-motor coupling as motor skills emerge. During stepping behavior, infants with enhanced motor ability demonstrated smaller increases in HbR concentration in the bilateral external occipital protuberance region consistent with an emerging efficiency as cruising and independent stepping behavior is still nascent. Together, the current results identify several distinct neural markers of functional motor ability during infancy that may be relevant to diagnostic testing and rehabilitation of developmental movement disorders.

Purpose Myocardial recovery after left ventricular device (LVAD) implantation is important to identify; however, identifying predictors of successful LVAD decommissioning, and recurrence of heart failure remains a challenge. Methods We performed a retrospective analysis on individuals who underwent a protocolized echocardiographic and invasive hemodynamic turn-down study. Patients were selected based on normalized hemodynamics, clinical stability and LVEDD Results A total of 12 patients underwent the LVAD weaning protocol. Of those patients, 42% (5/12) underwent LVAD decommissioning with sustained recovery (SR) (median 13 months) while 58% (7/12) failed recovery (FR) by requiring LVAD re-implantation after decommissioning or failed turn-down study precluding LVAD decommission. In FR versus SR patients LV-end systolic (LVESD) and -end diastolic (LVEDD) diameter were higher at the start (LVESD 4.8 ± 0.4 FR vs 3.5 ± 0.3 SR, p Conclusion In our cohort of LVAD turn-down studies, we were able to identify echo parameters, invasive hemodynamics, and LVAD pump parameters that differed between patients with failed and sustained recovery.

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

Background:This study examined the effects of three different treatment doses of a motor skill intervention (the Children’s Health Activity Motor Program [CHAMP]) on changes in preschoolers’ motor performance.Methods:Onehundred and nine children were divided into one of four groups: control and three CHAMP dosage groups: T1, 660 min; T2, 720 min; or T3, 900 min. Motor performance was assessed before and after the intervention using the Test of Gross Motor Development, 2nd Edition (TGMD-2). We used a 2 (time) × 4 (treatment) mixed-measures ANOVA to determine interaction and main effects. Significant interactions were decomposed using separate one-way between groups ANOVAs at each time point followed by Tukey’s post hoc tests.Results:Results revealed a significant time × treatment interaction (F3, 100 = 16.79; p < .001). There were no differences across treatment groups before the intervention (F3, 100 = .075, p < .90), but after the intervention the control group had significantly lower TMGD-2 scores compared with all three CHAMP intervention groups (F3, 100 = 9.92, p < .001, all post hoc tests, p < .001). Posttreatment differences can be attributed to greater improvements in motor performance following the CHAMP intervention regardless of specific dosage.Conclusions:Motor performance scores for all children who completed CHAMP significantly improved.

Prosthesis embodiment, the perception of a prosthesis as part of one’s body, may be an important component of functional recovery for individuals with upper limb absence. This work determined whether embodiment differs between body-powered and myoelectric prosthesis users. In a sample of nine individuals with transradial limb absence, embodiment was quantified using a survey regarding prosthesis ownership and agency. The extent to which the prosthesis affected the body schema, the representation of the body’s dimensions, was assessed using limb length estimation. Because body-powered prostheses offer proprioceptive feedback that myoelectric prostheses do not, it was hypothesized that both measures would reveal stronger embodiment of body-powered prostheses. However, our results did not show differences across the two prosthesis designs. Instead, body schema was influenced by several patient-specific characteristics, including the cause of limb absence (acquired or congenital) and hours of daily prosthesis wear. These results indicate that regular prosthesis wear and embodiment are connected, regardless of the actual prosthesis design. Identifying whether embodiment is a direct consequence of regular prosthesis use would offer insight on how individuals with limb absence could modify their behavior to more fully embody their prosthesis.

Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. We measured the size of the visual disturbance (phosphene) evoked by stimulating visual cortex with a fixed intensity, supra-threshold test stimulus (TS) when that TS was preceded by a sub-threshold conditioning stimulus (CS). We manipulated the inter-stimulus interval (ISI) and assessed how the size of the phosphene elicited by the fixed-intensity TS changed as a function of interval for two different CS intensities (45% and 75% of phosphene threshold). At 45% of threshold, the CS produced uniform suppression of the phosphene elicited by the TS across ISIs ranging from 2 to 200 ms. At 75% of threshold, the CS did not have a significant effect on phosphene size across the 2–15 ms intervals. Intervals of 50–200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.

Purpose Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. We aimed to assess the efficacy of tolvaptan in this population in a prospective, randomized study. Methods We conducted a prospective, randomized, non-blinded study of LVAD recipients with post-operative hyponatremia (Na Results A total of 33 patients were consented, 30 of whom developed post-operative hyponatremia. Two were excluded due to new onset renal failure requiring hemodialysis prior to development of hyponatremia. Of 28 eligible patients (21% women, 54% Black, 32% ischemic cardiomyopathy) 15 were randomized to tolvaptan (TLV), and 13 were randomized to standard care alone (No-TLV). Patients in TLV had a significant increase in Na from randomization to discharge, 133 (IQR 132-134) to 135 mEq/L (IQR 134-137), p=0.018, while those in No-TLV did not have a significant change in Na, 133 (IQR 132-134) to 134 mEq/L (IQR 132-136), p=0.15 (1A). There were no significant differences in renal function in either arm of the study: eGFR 76 (IQR 51-99) to 80 mL/min/1.73m2 (IQR 66-90), p=0.97 in TLV versus eGFR 78 (IQR 56-115) to 115 mL/min/1.73m2 (IQR 56-120), p=0.13 in No-TLV (1B). Patients in TLV had significantly more urine output than those in No-TLV during their first 24 hours of hyponatremia (3294 vs 2155 mL, p=0.043) and during last 24 hours of hyponatremia prior to sodium correction (4177 vs 2739 mL, p Conclusion Tolvaptan improves Na in hyponatremic post-operative LVAD patients when compared to those not receiving tolvaptan without adversely impacting renal function.

Purpose Anticoagulation with coumarin derivatives in left ventricular assist device (LVAD) patients is essential to prevent hemocompatibility related adverse events (HRAEs), but is challenging due to inter- and intra-individual variability of dose response and small therapeutic window. The aim of this study was to describe differences in quality of anticoagulation, HRAEs, and outcomes in users of phenprocoumon and warfarin. Methods This retrospective, multicenter study included 179 patients (Age: 57.4±11.8 yrs, female: 23.5%, BMI: 28.6±5.9kg/m2, HM3/HVAD: 50.8%/49.2%) implanted at the Medical University of Vienna (n=102 phenprocoumon) and University of Chicago (n=77 warfarin), between 2014 and 2018. Primary outcome was INR TTR during one-year after first follow-up visit (FFUV), secondary outcomes included all-cause mortality, freedom from- and the evaluation of independent risk factors for the occurrence of HRAEs. Results During follow-up, phenprocoumon vs. warfarin users had a significantly higher TTR (64.9±16.1% vs. 37.7±21.8%, p Conclusion Despite similar working mechanism of phenprocoumon and warfarin, differences in pharmacokinetics may affect anticoagulation quality. Gender, time between INR tests, absence of beta blockers and GI bleeding pre-implant are independent risk factors for HRAEs during LVAD support.

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants’ confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function.

Purpose Driveline infections in patients with left ventricular assist devices (LVAD) have long been an adverse event that has been difficult to eliminate. Driveline infections lead to an increased morbidity and mortality and a decrease in quality of life for patients. This review served to determine if using antibiotics as prophylactic therapy can affect infection rates and increase survival in patients who have had trauma or manipulation of the driveline. Trauma or manipulation can consist of a controller drop, driveline tug. Methods A retrospective chart review was done at a large academic medical center. We reviewed all patients implanted with an LVAD within the past 5 years. Patients were divided by infection vs non-infection; patients were then evaluated by who was treated with prophylactic antibiotic therapy and who developed an infection post antibiotic therapy compared to patients that developed an infection with no prophylactic therapy. We then reviewed survival rates within that cohort of patients. Results A total of 258 patients were evaluated for driveline infection. Of those, 73 (28%) patients had developed a driveline infection. Of those 73, 62 (84%) were not treated with prophylactic antibiotic therapy and 11 (15%) received prophylactic antibiotics. Mortality within the group of patients with no prophylaxis therapy was 25 (40%) vs 1 (9%) p=0.03 in the patients that were treated with prophylaxis antibiotic therapy. Conclusion Prophylactic antibiotic therapy can be useful to prevent driveline infections and increase survival in patients with a known controller drop or driveline tug. Further studies should be done to evaluate further prophylactic antibiotic therapy in other cohorts of patients.

Purpose It is well-documented that tobacco smoking has significant cardiovascular ramifications. However, the effects of tobacco smoking upon Ventricular Assist Device (VAD) implant outcomes are understudied. We aimed to ascertain the effort that institutions devote to smoking cessation programs for VAD patients and the success of these programs. Methods Using Survey Monkey®, a 13-question survey was created and distributed to 26 VAD institutions. Examples of multiple-choice questions included: 1) the volume of VAD patients at the respondent's center, 2) the patient population with active or past use of tobacco, 3) the presence and breadth of smoking cessation programs, and 4) the respondents’ views on program success. Results Respondents (n=15, 58%) stated that more male patients (n=12,75%) were smokers at the time of implantation. The most prevalent ages of tobacco smoking among patients were nearly evenly distributed between the ages of 35-70, but one institution reported the most common age as below 35 years. While pre-implant smoking cessation was not required at most programs (n=13, 87%), nearly all (n=14, 93%) offered cessation therapy after implant, with half of the respondents viewing the programs as effective. There was no apparent correlation between feelings of effectiveness and the category of tobacco smoking cessation therapy (Figure 1). Several respondents indicated that tobacco smoking cessation programs are not effective in Destination Therapy patients, while Bridge-to-Candidacy offers an incentive for compliance. Conclusion Although tobacco smoking is not a contraindication for device implantation, our data suggests programs are dedicated to utilizing smoking cessation strategies for patients. However, no definitive strategy was identified in successful tobacco smoking cessation programs in our study, pointing to the need for research. Additionally, studies of standards, protocols, and team involvement are areas that could provide data to improve the outcomes of tobacco smoking cessation among VAD patients.

Purpose International shared care can provide access to advanced options for patients in various parts of the world with end stage heart failure who are deemed high risk surgical candidates. We sought to describe the process utilized to provide successful, co-managed, culturally sensitive international shared care. Methods A retrospective analysis was performed to evaluate outcomes and hemocompatability related adverse event (HRAE) rates of a successful international shared care model between a large, academic medical center in the United States (US) and two shared care hospitals located in two countries in the Middle East. Results After training at the implant site is completed by the shared care team, a partnership can continue remotely. Ongoing communication with the International office ensures a streamlined process for referrals, successful transition for a patient to return home, co-management of adverse events, and continued education for patients, families, and shared care providers. This partnership resulted in 109 patient referrals since 2016. 7 patients were discharged from the hospital on centrifugal flow ventricular assist devices (HM3 n=3 or HVAD n=4) with 100% survival at 6 months and 85% of patients returned home (n=6). Since discharge, there has been 100% freedom from stroke or thrombosis related adverse events compared to IMACs 69.1% at 6 months for patients on isolated centrifugal flow device. Additional adverse events include 1 driveline infection (14%) and 1 outpatient GI bleed (14%). Conclusion International shared care provides access to advanced heart failure therapies in other countries and co-management facilitates improved patient outcomes with lower HRAE rates. Quality VAD care can be shared, regardless of language or location. Further application of this model in other countries should be further employed and evaluated.

Purpose Left Ventricular Assist Devices (LVAD) is a growing form of therapy for patients with advanced heart failure. While LVAD patient volumes grow, the need for additional education both for the patients and hospitals has grown. The implementation of dedicated LVAD educators into LVAD programs can be beneficial for program quality indicators as well as patient outcomes. Methods Retrospective chart review at a large academic University, comparing median length of stay, driveline infection rates, unplanned readmission's, and one year survival from between 2017 and 2018 when a dedicated LVAD educator was implemented into the program. Results The implementation of a dedicated LVAD educator occurred January of 2018. Outcome results were evaluated for 2017 prior to the educator and 2018 after implantation of the educator. The volumes for 2017 and 2018 were similar at 47 and 63 respectively. Outcomes evaluated included median length of stay from implant of LVAD to discharge from hospital which decreased from 20.5 days to 18.9 days. Driveline infections rates decreased from 23.81% to 17.71%. Unplanned readmission's decreased from 3.53% to 2.91% and one year survival between the two groups remained comparable at 93.74% and 92.81%. Acuity of the patients was comparable in both groups and programmatic staffing remained unchanged otherwise. Conclusion Incorporating a dedicated LVAD educator into LVAD programs proves to be beneficial by decreasing length of stay, decrease driveline infection rates, decrease unplanned readmission while maintaining overall one year survival.

Purpose Left ventricular assist device (LVAD) implantation for patients refusing blood transfusion presents a distinct challenge. This study summarizes our center's experience in clinical outcomes of LVAD implantation for patients who refuse blood transfusion. Methods The cohort included 21 Jehovah's Witness (JW) patients who underwent an LVAD implantation between 2008-2019. Non-JW patients (N=427) served as a control. We previously established the perioperative optimization protocol for JW patients. The protocol includes preoperative optimization of hemoglobin (Hb) level with a goal of >12 g/dl using iron, vitamin B12, and erythropoietin. There are also protocolized intraoperative techniques and postoperative management to minimize blood loss. Results Hb levels in eight patients (38.1%) were successfully optimized (as defined by Hb>12g/dl) before surgery in the JW group. In-hospital mortality was 14.3% (3/21) in the JW group, and 11.7% (50/427) in the non- JW group (p=0.35). One-year survival was similar between in the JW group and the non- JW group (79.3±9.3% vs. 68.1±2.4%, p=0.43). Causes of mortality during the follow-up period in the JW group included stroke (N=4), right-sided heart failure (N=2), device thrombosis, sepsis, gastrointestinal bleeding (GIB), and unknown (N=1), respectively. Freedom from GIB at 1 year was 83.9± 8.5% in the JW group and 74.9±2.4% in the non-JW group (Log-Rank p=0.95). Overall, 5 patients suffered from GIB during follow up in the JW group. Three of them required esophagogastroduodenoscopy or endovascular catheterization to obtain hemostasis with medical therapy including intravenous iron, erythropoietin, and octreotide. Conclusion The clinical outcomes of LVAD implantation for patients refusing blood transfusion were comparable to those who accepted blood transfusions. LVAD therapy for such a patient population is feasible in select patients and is facilitated with the use of perioperative optimization protocols.

Skilled performance and acquisition is dependent upon afferent input to motor cortex. The present study used short-latency afferent inhibition (SAI) to probe how manipulation of sensory afference by attention affects different circuits projecting to pyramidal tract neurons in motor cortex. SAI was assessed in the first dorsal interosseous muscle while participants performed a low or high attention-demanding visual detection task. SAI was evoked by preceding a suprathreshold transcranial magnetic stimulus with electrical stimulation of the median nerve at the wrist. To isolate different afferent intracortical circuits in motor cortex SAI was evoked using either posterior-anterior (PA) or anterior-posterior (PA) monophasic current. In an independent sample, somatosensory processing during the same attention-demanding visual detection tasks was assessed using somatosensory-evoked potentials (SEP) elicited by median nerve stimulation. SAI elicited by AP TMS was reduced under high compared to low visual attention demands. SAI elicited by PA TMS was not affected by visual attention demands. SEPs revealed that the high visual attention load reduced the fronto-central P20-N30 but not the contralateral parietal N20-P25 SEP component. P20-N30 reduction confirmed that the visual attention task altered sensory afference. The current results offer further support that PA and AP TMS recruit different neuronal circuits. AP circuits may be one substrate by which cognitive strategies shape sensorimotor processing during skilled movement by altering sensory processing in premotor areas.

Background Concussion diagnosis and management remains a largely subjective process. This investigation sought to evaluate the utility of a novel neuroelectric measure for concussion diagnosis and return to play decision-making. Hypothesis Brain Network Activation (BNA) scores obtained within 72-h of injury will be lower than the athlete’s preseason evaluation and that of a matched control athlete; and the BNA will demonstrate ongoing declines at the return to play and post-season time points, while standard measures will have returned to pre-injury and control athlete levels. Design Case–control study. Methods Football athletes with a diagnosed concussion (n = 8) and matched control football athletes (n = 8) completed a preseason evaluation of cognitive (i.e., Cogstate Computerized Cognitive Assessment Tool) and neuroelectric function (i.e., BNA), clinical reaction time, SCAT3 self-reported symptoms, and quality of life (i.e., Health Behavior Inventory and Satisfaction with Life Scale). Following a diagnosed concussion, injured and control athletes completed post-injury evaluations within 72-h, once asymptomatic, and at the conclusion of the football season. Results Case analysis of the neuroelectric assessment failed to provide improved diagnostics beyond traditional clinical measures. Statistical analyses indicated significant BNA improvements in the concussed and control groups from baseline to the asymptomatic timepoint. Conclusion With additional attention being placed on rapid and accurate concussion diagnostics and return to play decision-making, the addition of a novel neuroelectric assessment does not appear to provide additional clinical benefit at this time. Clinicians should continue to follow the recommendations for the clinical management of concussion with the assessment of the symptom, cognitive, and motor control domains.

Background:Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings.Methods:A multi-site database, including motor symptom assessments conducted in 487 patients from palliative care, adult and old age consultation-liaison psychiatry services was used to document motor activity disturbances as per the Delirium Motor Checklist (DMC). Latent class analysis (LCA) was used to identify the class structure underpinning DMC data and also items for a brief subtyping scale. The concordance of the abbreviated scale was then compared with the original Delirium Motor Subtype Scale (DMSS) in 375 patients having delirium as per the American Psychiatric Association's Diagnostic and Statistical Manual (4th edition) criteria.Results:Latent class analysis identified four classes that corresponded closely with the four recognized motor subtypes of delirium. Further, LCA of items (n = 15) that loaded >60% to the model identified four features that reliably identified the classes/subtypes, and these were combined as a brief motor subtyping scale (DMSS-4). There was good concordance for subtype attribution between the original DMSS and the DMSS-4 (κ = 0.63).Conclusions:The DMSS-4 allows for rapid assessment of clinical subtypes in delirium and has high concordance with the longer and well-validated DMSS. More consistent clinical subtyping in delirium can facilitate better delirium management and more focused research effort.

Background: Research in sport concussion has increased greatly over the previous decade due to increased scientific interest as well as the media and political spotlight that has been cast on this injury. However, a dearth of literature is available regarding the long-term (>1 year after concussion) effects of adolescent concussion on cognitive and motor performance of high school athletes. Purpose: To evaluate the potential for long-term effects of concussion sustained during high school on cognitive and motor performance across the lifespan. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Adults with (n = 30) and without (n = 53) a concussion history were recruited in 3 age groups: younger (18-30 years; n = 43), middle-aged (40-50 years; n = 18), and older (≥60 years; n = 22). Each participant completed a computerized neurocognitive assessment and continuous tracking and discrete temporal auditory tasks with the hand and foot. Root mean squared error and timing variability were derived from the tracking and temporal auditory tasks, respectively. Data were analyzed by regression analyses for each recorded variable. Results: The analysis revealed significant age effects on neurocognitive task, continuous tracking task, and discrete auditory timing task performance ( P values < .05). No concussion history or interaction (concussion history by age) effects were found for performance on any task ( P values > .05). Conclusion: While longitudinal investigations are still needed, this cross-sectional study failed to identify any observable effect of adolescent concussion history on cognition or motor performance with age.

Adolescence and early adulthood is a critical period for neurophysiological development potentially characterized by an increased susceptibility to the long-term effects of traumatic brain injury. The current study investigated differences in motor cortical physiology and neuroplastic potential across a cohort of young adults with adolescent concussion history and those without. Transcranial magnetic stimulation (TMS) was used to assess motor evoked potential (MEP) amplitude, short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) before and after intermittent theta burst stimulation (iTBS). Pre-iTBS, MEP amplitude, but not SICI or ICF, was greater in the concussion history group. Post-iTBS, the expected increase in MEP amplitude and ICF was tempered in the concussion history group. Change in SICI was variable within the concussion history group. Post hoc assessment revealed that SICI was significantly lower in individuals whose concussion was not diagnosed at the time of injury compared to both those without a concussion history or whose concussion was medically diagnosed. Concussive impacts during adolescence appear to result in a persistent reduction of the ability to modulate facilitatory motor networks. Failure to report/identify concussive impacts close to injury during adolescence also appears to produce persistent change in inhibitory networks. These findings highlight the potential long-term impact of adolescent concussion upon motor cortical physiology.

Knowledge of the properties that govern the effectiveness of transcranial magnetic stimulation (TMS) interventions is critical to clinical application. Extrapolation to clinical populations has been limited by high inter-subject variability and a focus on intrinsic muscles of the hand in healthy populations. Therefore, the current study assessed variability of continuous theta burst stimulation (cTBS), a patterned TMS protocol, across an agonist-antagonist pair of extrinsic muscles of the hand. Secondarily, we assessed whether concurrent agonist contraction could enhance the efficacy of cTBS. Motor evoked potentials (MEP) were simultaneously recorded from the agonist flexor (FCR) and antagonist extensor (ECR) carpi radialis before and after cTBS over the FCR hotspot. cTBS was delivered with the FCR relaxed (cTBS-Relax) or during isometric wrist flexion (cTBS-Contract). cTBS-Relax suppressed FCR MEPs evoked from the FCR hotspot. However, the extent of FCR MEP suppression was strongly correlated with the relative difference between FCR and ECR resting motor thresholds. cTBS-Contract decreased FCR suppression but increased suppression of ECR MEPs elicited from the FCR hotspot. The magnitude of ECR MEP suppression following cTBS-Contract was independent of the threshold-amplitude relationships observed with cTBS-Relax. Contraction alone had no effect confirming the effect of cTBS-Contract was driven by the interaction between neuromuscular activity and cTBS. Interactions across muscle representations should be taken into account when predicting cTBS outcomes in healthy and clinical populations. Contraction during cTBS may be a useful means of focusing aftereffects when differences in baseline excitability across overlapping agonist-antagonist cortical representations may mitigate the inhibitory effect of cTBS.

The current study investigated the contributions of contralesional primary somatosensory cortex (S1c) to motor learning deficits post-stroke. For three days, continuous theta burst (cTBS) was delivered over the contralesional hemisphere prior to practicing a serial targeting task. cTBS was delivered over either S1c, contralesional primary motor cortex (M1c) or as control stimulation (n=4/group). Change in motor ability was assessed from initial performance to a delayed retention test using a serial targeting task and a subset of items from the Wolf Motor Function Test. Practice preceded by cTBS over either M1c or S1c resulted in large decreases in movement time compared to practice preceded by control stimulation. M1c cTBS resulted in larger decreases in peak velocity and peak acceleration compared to control and S1c cTBS. In contrast, S1c cTBS resulted in larger reductions in time to initiate movement and time to complete the WMFT compared to control and M1c cTBS. These preliminary findings suggest that stimulation of either M1c or S1c can enhance the benefits of practice. However, changes in M1c and S1c excitability may contribute to different aspects of post-stroke motor deficits that may differentially impact rehabilitation.

Objectives Somatosensory evoked potentials (SEPs) were used to index somatosensory–somatosensory interhemispheric interactions and highlight potential mechanisms by which TMS alters contralateral somatosensory cortex excitability. Methods Fifteen healthy individuals participated in three sessions on separate days. On each day participants received either: (1) continuous theta burst (cTBS), (2) 1 Hz repetitive transcranial magnetic stimulation (rTMS) or (3) control TMS over left somatosensory cortex. SEPs from right somatosensory cortex were recorded before and after TMS while participants were at rest, performed sensorimotor tracking or the sustained attention to response task (SART). Left-handed tracking performance was also indexed. Results N20–P27 amplitude was increased following 1 Hz rTMS while participants were at rest. This increased amplitude was not observed during right-handed tracking or the SART. N20–P27 amplitude was not influenced by cTBS or control TMS. P15–N20 and N34–P50 SEP components were not influenced by TMS. Right- and left-handed tracking performance was not transiently influenced by TMS. Conclusions The results support TMS induced somatosensory–somatosensory interactions and offer converging evidence for an intercortical, rather that intracortical, mechanism that mediates contralateral sensory processing. These interactions appear to be dependent on concurrent attention/task demands. Significance Somatosensory–somatosensory interactions are reflected by intercortical mechanisms that are state and task dependent.

Background and Purpose— A transient ischemic attack (TIA) is a brief ischemic episode characterized by rapid clinical resolution and not associated with permanent cerebral infarction. Whether changes in intracortical excitability persist and are related to clinical predictors of stroke risk after TIA remains unknown. Methods— Participants were individuals with clinically resolved motor TIA with no structural lesions and healthy age-matched control participants. Single and paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability. Recruitment curves for percent inhibition and facilitation were used to derive excitability thresholds. Correlations between threshold asymmetries and ABCD 2 score were performed. Results— Results showed a significant 3-way interaction with reduced inhibition and enhanced facilitation in the affected compared with unaffected hemisphere after TIA. No significant differences were present in healthy participants. Asymmetries in intracortical inhibition and facilitation were significantly correlated with ABCD 2 score. Conclusions— The present study is the first, to our knowledge, to demonstrate altered intracortical inhibition and facilitation in the affected hemisphere after TIA. These changes occurred on average 2 weeks after clinical signs of TIA resolved and in the absence of structural lesions and were not present in healthy age-matched control participants. Furthermore, this study is the first, to our knowledge, to report that changes in intracortical excitability after TIA are associated with ABCD 2 score.

Performance of efficient and precise movement requires the proper planning of motor parameters as well as the integration of sensory feedback. This study tests the hypothesis that the frontal components of the median nerve somatosensory-evoked potentials are differentially modulated, depending on (i) the stage of motor preparation and (ii) the moving limb. Participants were instructed to make intermittent voluntary contractions with either their right or left hands while receiving median nerve stimulation to the right wrist only. The results indicate that the frontal N30 demonstrated a significant increase in amplitude during the execution, but not the preparation, of a movement contralateral to median nerve stimulation. These data have implications for interhemispheric control of sensory information within the primary and premotor cortices.

Recent perceptual neuroimaging studies have shown that intermodal selective attention extracts relevant information from one modality at the expense of another at the level of unimodal sensory cortex. The present paper sought 1) to determine the effects of intermodal selective attention on primary somatosensory cortex (S1) during continuous sensorimotor transformations, 2) to investigate the interactions of spatial relationship between the target and distracter modalities on S1 and 3) to identify any potential modulators during continuous sensorimotor transformations. Functional MRI was acquired while participants (n=10) received simultaneous vibrotactile and visuospatial stimulation. In each condition, participants tracked either vibrotactile stimulation (25 Hz), applied to the right index finger with variable intensity, or a visuospatial stimulus, a centrally presented dial where the spatial position of a needle randomly moved, by applying graded force to a force sensing resistor. The distracter modality either originated from a location that was spatially related or distinct to the target that guided movement. Vibrotactile tracking resulted in decreased S1 activation relative to when it was task-irrelevant. Neither S1 activity nor tracking performance was influenced by spatial relationship. In addition the superior parietal lobe/precuneus (BA 7), inferior parietal lobe (BA 40), precentral gyrus (BA 6) and secondary visual areas (BA 18 and 19) may modulate the extraction of task-relevant information while the insula (BA 13) may do so during cases of spatial conflict. We conclude that modulation of S1 is important to the proper execution of sensory-guided movements and that sensorimotor requirements determine the mechanisms of intermodal selective attention.

Despite extensive research examining overt behavioral changes of motor skills in infants, the neural basis underlying the emergence of functional motor control has yet to be determined. We used functional near-infrared spectroscopy (fNIRS) to record hemodynamic activity of the primary motor cortex (M1) from 22 infants (11 six month-olds, 11 twelve month-olds) as they reached for an object, and stepped while supported over a treadmill. Based on the developmental systems framework, we hypothesized that as infants increased goal-directed experience, neural activity shifts from a diffused to focal pattern. Results showed that for reaching, younger infants showed diffuse areas of M1 activity that became focused by 12 months. For elicited stepping, younger infants produced much less M1 activity which shifted to diffuse activity by 12 months. Thus, the data suggest that as infants gain goal-directed experience, M1 activity emerges, initially showing a diffuse area of activity, becoming refined as the behavior stabilizes. Our data begin to document the cortical activity underlying early functional skill acquisition.

Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm.

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, p0.0005], 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.

The purpose of the present study was to assess changes in thresholds for the onset of short intracortical inhibition (SICI) and intracortical facilitation (ICF) in individuals with chronic stroke compared to age-matched healthy adults and evaluate the relationship between these thresholds and motor function in the chronic stroke group.Paired-pulse transcranial magnetic stimulation was used to derive thresholds for the onset of SICI and ICF in 12 neurologically healthy and 12 individuals with chronic stroke. Motor evoked potentials were elicited by a test stimulus of fixed intensity preceded by a conditioning stimulus ranging from 0%-125% of active motor threshold to generate recruitment curves. Regression functions were fit to these recruitment curves to identify thresholds for the onset of SICI and ICF. Mixed measures analysis of variance was used to compare thresholds for each hemisphere within and between groups.Results showed a significant three-way interaction between Group (stroke, healthy), Hemisphere (ipsilesional, contralesional) and Stimulus interval (2 ms, 12 ms). Significant differences in the thresholds for the onset of both SICI and ICF were present in individuals with chronic stroke, with no between hemisphere differences for the control group. When compared to age-matched controls, comparisons revealed significant reductions in ipsilesional, but not contralesional thresholds for the onset of ICF, and significant reductions in contralesional, but not ipsilesional, thresholds for the onset of SICI in individuals with chronic stroke. In addition, as thresholds for ICF and SICI in stroke patients approached the level of healthy adults, higher function on the Wolf Motor Function Test was observed.Reduced thresholds for the onset of SICI and ICF observed in the present study indicate that both inhibitory and facilitatory systems mediate changes in cortical excitability in chronic stroke patients. The association between higher onset thresholds and motor function in the stroke group also suggests that these thresholds have potential utility for tracking functional motor improvements in patients with chronic stroke. This study provides new insights to further characterize changes in intracortical neurotransmission that play an important role in modulating neuroplasticity and the potential relationship between inhibitory and facilitatory networks and motor function post-stroke.

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence specific learning. Thirty-three participants were assigned to one of three groups of repetitive TMS over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following repetitive TMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz repetitive TMS over the PMd during the early consolidation period immediately following practice compared to control or 5 Hz repetitive TMS. Enhanced sequence specific learning with 1 Hz repetitive TMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence specific learning of a visuomotor task and offer converging evidence for competing memory systems.

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and nine individuals with chronic, right focal subcortical stroke performed a continuous joystick-based tracking task during an initial functional magnetic resonance images (fMRI) session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequence during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased blood oxygenation level dependent (BOLD) response in left dorsal premotor cortex (PMd; BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. This study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke.

Background Previous literature has shown that the frontal N30 is increased during movement of the hand contralateral to median nerve stimulation. This finding was a result of non-dominant left hand movement in right-handed participants. It is unclear however if the effect depends upon non-dominant hand movement or if this is a generalized phenomenon across the upper-limbs. This study tests the effect of dominant and non-dominant hand movement upon contralateral frontal and parietal somatosensory evoked potentials (SEPs) and further tests if this relationship persists in left hand dominant participants. Median nerve SEPs were elicited from the wrist contralateral to movement in both right hand and left hand dominant participants alternating the movement hand in separate blocks. Participants were required to volitionally squeeze (~ 20% of a maximal voluntary contraction) a pressure-sensitive bulb every ~3 seconds with the hand contralateral to median nerve stimulation. SEPs were continuously collected during the task and individual traces were grouped into time bins relative to movement according to the timing of components of the Bereitschaftspotential. SEPs were then averaged and quantified from both FCZ and CP3/4 scalp electrode sites during both the squeeze task and at rest. Results The N30 is facilitated during non-dominant hand movement in both right and left hand dominant individuals. There was no effect for dominant hand movement in either group. Conclusions N30 amplitude increase may be a result of altered sensory gating from motor areas known to be specifically active during non-dominant hand movement.

Somatosensation is thought to play an important role in skilled motor learning. The present study investigated how healthy adults learn a continuous implicit motor task when somatosensation is altered by 1 Hz repetitive transcranial magnetic stimulation (rTMS) delivered over the primary somatosensory cortex (S1). Twenty-seven right-handed participants enrolled in a two-part experiment. In Experiment 1, we verified that 20 min of 1 Hz rTMS over S1 disrupted cutaneous somatosensation (indexed by two-point discrimination) in the wrist/hand; the impact of 1 Hz rTMS on wrist proprioception (tested by limb-position matching) was variable. Sham rTMS had no effect on either measure. We exploited these effects in Experiment 2 by pairing either 1 Hz or sham rTMS with practice of a continuous tracking task over two separate sessions on different days. Implicit motor learning was indexed on a third, separate retention test day when no rTMS was delivered. Across practice in Experiment 2, both the 1 Hz and sham rTMS groups showed improved tracking performance; however, 1 Hz rTMS was associated with less accurate tracking and smaller improvements in performance. Importantly, at the no rTMS retention test the effects of altering sensation with stimulation over S1 were still evident in the persistently less accurate tracking behavior of the 1 Hz rTMS group. The current study shows that disruption of somatosensation during task practice impairs the magnitude of change associated with motor learning, perhaps through the development of an inaccurate internal model.

Previous research has shown that information from one sensory modality has the potential to influence activity in a different modality, and these crossmodal interactions can occur early in the cortical sensory processing stream within sensory‐specific cortex. In addition, it has been shown that when sensory information is relevant to the performance of a task, there is an upregulation of sensory cortex. This study sought to investigate the effects of simultaneous bimodal (visual and vibrotactile) stimulation on the modulation of primary somatosensory cortex (SI), in the context of a delayed sensory‐to‐motor task when both stimuli are task‐relevant. It was hypothesized that the requirement to combine visual and vibrotactile stimuli would be associated with an increase in SI activity compared to vibrotactile stimuli alone. Functional magnetic resonance imaging (fMRI) was performed on healthy subjects using a 3T scanner. During the scanning session, subjects performed a sensory‐guided motor task while receiving visual, vibrotactile, or both types of stimuli. An event‐related design was used to examine cortical activity related to the stimulus onset and the motor response. A region of interest (ROI) analysis was performed on right SI and revealed an increase in percent blood oxygenation level dependent signal change in the bimodal (visual + tactile) task compared to the unimodal tasks. Results of the whole‐brain analysis revealed a common fronto‐parietal network that was active across both the bimodal and unimodal task conditions, suggesting that these regions are sensitive to the attentional and motor‐planning aspects of the task rather than the unimodal or bimodal nature of the stimuli. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.