Sean K. Meehan

Implicit Sequence-Specific Motor Learning After Subcortical Stroke is Associated with Increased Prefrontal Brain Activations: An fMRI Study

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. Hum Brain Mapp, 2011.

Role of the primary somatosensory cortex in motor learning: An rTMS study

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.

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.

5 Hz repetitive transcranial magnetic stimulation over the ipsilesional sensory cortex enhances motor learning after stroke

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

Interhemispheric enhancement of somatosensory cortical excitability through contralateral repetitive transcranial magnetic stimulation.

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.

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.

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning.

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 transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. 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 rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence‐specific learning with 1 Hz rTMS 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.

Changes in Intracortical Excitability After Transient Ischemic Attack Are Associated With ABCD2 Score

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 ABCD2 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 ABCD2 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 ABCD2 score.

Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors

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.

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.