The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortex.

Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control.

Investigating Cerebellar Modulation of Premovement Beta-Band Activity during Motor Adaptation.

Enhancing cerebellar activity influences motor cortical activity and contributes to motor adaptation, though it is unclear which neurophysiological mechanisms contributing to adaptation are influenced by the cerebellum. Pre-movement beta event-related desynchronization (ß-ERD), which reflects a release of inhibitory control in the premotor cortex during movement planning, is one mechanism that may be modulated by the cerebellum through cerebellar-premotor connections. We hypothesized that enhancing cerebellar activity with intermittent theta burst stimulation (iTBS) would improve adaptation rates and increase ß-ERD during motor adaptation. Thirty-four participants were randomly assigned to an active (A-iTBS) or sham cerebellar iTBS (S-iTBS) group. Participants performed a visuomotor task, using a joystick to move a cursor to targets, prior to receiving A-iTBS or S-iTBS, following which they completed training with a 45° rotation to the cursor movement. Behavioural adaptation was assessed using the angular error of the cursor path relative to the ideal trajectory. The results showed a greater adaptation rate following A-iTBS and an increase in ß-ERD, specific to the high ß range (20-30 Hz) during motor planning, compared to S-iTBS, indicative of cerebellar modulation of the motor cortical inhibitory control network. The enhanced release of inhibitory activity persisted throughout training, which suggests that the cerebellar influence over the premotor cortex extends beyond adaptation to other stages of motor learning. The results from this study further understanding of cerebellum-motor connections as they relate to acquiring motor skills and may inform future skill training and rehabilitation protocols.

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning.

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable tool to probe the procedural and declarative influence over sensorimotor integration during skilled motor actions. This manuscript describes the methodology and contributions of short-latency afferent inhibition (SAI) for understanding sensorimotor integration. SAI quantifies the effect of a convergent afferent volley on the corticospinal motor output evoked by transcranial magnetic stimulation (TMS). The afferent volley is triggered by the electrical stimulation of a peripheral nerve. The TMS stimulus is delivered to a location over the primary motor cortex that elicits a reliable motor-evoked response in a muscle served by that afferent nerve. The extent of inhibition in the motor-evoked response reflects the magnitude of the afferent volley converging on the motor cortex and involves central GABAergic and cholinergic contributions. The cholinergic involvement in SAI makes SAI a possible marker of declarative-procedural interactions in sensorimotor performance and learning. More recently, studies have begun manipulating the TMS current direction in SAI to tease apart the functional significance of distinct sensorimotor circuits in the primary motor cortex for skilled motor actions. The ability to control additional pulse parameters (e.g., the pulse width) with state-of-the-art controllable pulse parameter TMS (cTMS) has enhanced the selectivity of the sensorimotor circuits probed by the TMS stimulus and provided an opportunity to create more refined models of sensorimotor control and learning. Therefore, the current manuscript focuses on SAI assessment using cTMS. However, the principles outlined here also apply to SAI assessed using conventional fixed pulse width TMS stimulators and other forms of afferent inhibition, such as long-latency afferent inhibition (LAI).

Specific sensorimotor interneuron circuits are sensitive to cerebellar-attention interactions.

Background: Short latency afferent inhibition (SAI) provides a method to investigate mechanisms of sensorimotor integration. Cholinergic involvement in the SAI phenomena suggests that SAI may provide a marker of cognitive influence over implicit sensorimotor processes. Consistent with this hypothesis, we previously demonstrated that visual attention load suppresses SAI circuits preferentially recruited by anterior-to-posterior (AP)-, but not posterior-to-anterior (PA)-current induced by transcranial magnetic stimulation. However, cerebellar modulation can also modulate these same AP-sensitive SAI circuits. Yet, the consequences of concurrent cognitive and implicit cerebellar influences over these AP circuits are unknown. Objective: We used cerebellar intermittent theta-burst stimulation (iTBS) to determine whether the cerebellar modulation of sensory to motor projections interacts with the attentional modulation of sensory to motor circuits probed by SAI. Methods: We assessed AP-SAI and PA-SAI during a concurrent visual detection task of varying attention load before and after cerebellar iTBS. Results: Before cerebellar iTBS, a higher visual attention load suppressed AP-SAI, but not PA-SAI, compared to a lower visual attention load. Post-cerebellar iTBS, the pattern of AP-SAI in response to visual attention load, was reversed; a higher visual attention load enhanced AP-SAI compared to a lower visual attention load. Cerebellar iTBS did not affect PA-SAI regardless of visual attention load. Conclusion: These findings suggest that attention and cerebellar networks converge on overlapping AP-sensitive circuitry to influence motor output by controlling the strength of the afferent projections to the motor cortex. This interaction has important implications for understanding the mechanisms of motor performance and learning.

Differential experiences of embodiment between body-powered and myoelectric prosthesis users.

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.

The Motor skills At Playtime intervention improves children's locomotor skills: A feasibility study.

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 centres (N = 46; Mage = 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 1,350-min MAP intervention or control condition (outdoor free play) from January to April of 2018. FMS were assessed before and after each programme using both the Test of Gross Motor Development-3rd Edition and skill outcome measures (running speed, hopping speed, jump distance, throwing speed, kicking speed and catching percentage). Intervention implementation feasibility was measured through daily fidelity checks. Fidelity was evaluated as the percentage of intervention sessions that included all explicit intervention criteria. FMS data were analysed using linear mixed modelling. 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.

Concussion-Recovery Trajectories Among Tactical Athletes: Results From the CARE Consortium.

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.

Temporal Dynamics of Corticocortical Inhibition in Human Visual Cortex: A TMS Study.

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.

Probing short-latency cortical inhibition in the visual cortex with transcranial magnetic stimulation: A reliability study.

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.

Verbal working memory modulates afferent circuits in motor cortex.

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.

Brain Network Activation Technology Does Not Assist with Concussion Diagnosis and Return to Play in Football Athletes.

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.

Long-term Effects of Adolescent Sport Concussion Across the Age Spectrum.

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.

Changes in Cortical Plasticity in Relation to a History of Concussion during Adolescence.

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.

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory.

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.

Developmental changes in motor cortex activity as infants develop functional motor skills.

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.

Changes in thresholds for intracortical excitability in chronic stroke: more than just altered intracortical inhibition.

PURPOSE: 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. METHODS: 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: 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. CONCLUSIONS: 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.

Continuous theta burst stimulation over the contralesional sensory and motor cortex enhances motor learning post-stroke.

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.