Non-invasive Brain Stimulation to Characterize and Alter Motor Function after Spinal Cord Injury

Advances in transcranial magnetic stimulation (TMS) now permit the precise assessment of circuitry in human motor cortices that contribute to movement. Further, TMS approaches are used to promote neural plasticity within cortical and spinal circuitry in an attempt to create short-term changes in motor control. This review is focused on the application of TMS techniques in the study of characterizing and promoting neural plasticity within individuals presenting with chronic spinal cord injury. We review TMS research performed in individuals with SCI and consider new opportunities for the use of TMS approaches to promote neural plasticity for improving motor recovery

Physical activity levels determine exercise-induced changes in brain excitability.

Emerging evidence suggests that regular physical activity can impact cortical function and facilitate plasticity. In the present study, we examined how physical activity levels influence corticospinal excitability and intracortical circuitry in motor cortex following a single session of moderate intensity aerobic exercise. We aimed to determine whether exercise-induced short-term plasticity differed between high versus low physically active individuals. Participants included twenty-eight young, healthy adults divided into two equal groups based on physical activity level determined by the International Physical Activity Questionnaire: low-to-moderate (LOW) and high (HIGH) physical activity. Transcranial magnetic stimulation was used to assess motor cortex excitability via motor evoked potential (MEP) recruitment curves for the first dorsal interosseous (FDI) muscle at rest (MEPREST) and during tonic contraction (MEPACTIVE), short-interval intracortical inhibition (SICI) and facilitation (SICF), and intracortical facilitation (ICF). All dependent measures were obtained in the resting FDI muscle, with the exception of AMT and MEPACTIVE recruitment curves that were obtained during tonic FDI contraction. Dependent measures were acquired before and following moderate intensity aerobic exercise (20 mins, ~60% of the age-predicted maximal heart rate) performed on a recumbent cycle ergometer. Results indicate that MEPREST recruitment curve amplitudes and area under the recruitment curve (AURC) were increased following exercise in the HIGH group only (p = 0.002 and p = 0.044, respectively). SICI and ICF were reduced following exercise irrespective of physical activity level (p = 0.007 and p = 0.04, respectively). MEPACTIVE recruitment curves and SICF were unaltered by exercise. These findings indicate that the propensity for exercise-induced plasticity is different in high versus low physically active individuals. Additionally, these data highlight that a single session of aerobic exercise can transiently reduce inhibition in the motor cortex regardless of physical activity level, potentially priming the system for plasticity induction

Alterations in Motor Cortical Representation of Muscles Following Incomplete Spinal Cord Injury in Humans

(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation of arm muscles, and determined whether anatomical shifts in these representations occur, and investigated the symmetry in organization between the two hemispheres.; (2) Methods: Transcranial magnetic stimulation (TMS) was used to map the representation of the biceps, flexor carpi radialis and abductor pollicis brevis (APB) bilaterally in nine individuals with chronic incomplete cervical spinal cord injury and nine aged- and handed-matched uninjured controls. TMS was delivered over a 6 × 5 point grid that encompassed M1 using an intensity specific to the resting motor threshold for each muscle tested.; (3) Results: Results indicate that, compared to controls, muscle representations in SCI are shifted medially but preserve a general somatotopic arrangement, and that territory dedicated to the APB muscle is greater.; (4) Conclusions: These findings demonstrate differences in the organization of M1 between able-bodied controls and those with incomplete cervical SCI. This altered organization may have future implications in understanding the functional deficits observed in SCI and rehabilitation techniques aimed at restoring function

Exploring Behavioral Correlates of Afferent Inhibition

(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior

Experimental timeline.

<p>Measures of resting motor threshold (RMT), active motor threshold (AMT), motor evoked potential (MEP) recruitment curves obtained at rest (MEP_REST) and during ~10% MVC (MEP_ACTIVE), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were acquired prior to (T₀) and ten minutes following the cessation of exercise (T₁).The order of dependent measure acquisition was pseudo-randomized across participants using a Williams Square design. The exercise intervention began following the assembly of the heart rate (HR) monitor and involved 5 minutes of cycling warm-up, 20 minutes of moderate-intensity exercise (50–70% of age-predicted maximal heart rate (HR)) and 5 minutes of cycling cool-down. During the 20-minute exercise, resistance was adjusted online to maintain HR in the target range. HR was recorded every 2 minutes as shown.</p

Thresholds and recruitment curves.

<p><b>(A)</b> Group-averaged MEP_REST recruitment curves (with standard errors) at T₀ and T₁ for the LOW (N = 14) and HIGH (N = 13) groups. TMS intensity is defined as the percentage of RMT. Solid and dashed lines indicate pre (T₀) and post (T₁) values, respectively. <b>(B)</b> Histograms displaying TIME x GROUP interaction for group-averaged MEP_REST amplitude (with standard error; LOW: N = 14, HIGH: N = 13). The asterisk indicates a significant increase in MEP_REST amplitudes. <b>(C)</b> Histograms displaying TIME x GROUP interaction for group-averaged MEP_REST AURC (with standard error; LOW: N = 14, HIGH: N = 14). The asterisk indicates a significant increase in MEP_REST AURC. <b>(D)</b> Group-averaged MEP_ACTIVE recruitment curves (with standard errors) at T₀ and T₁ for the LOW (N = 14) and HIGH (N = 13) group. TMS intensity is defined as the percentage of the active motor threshold (AMT). Solid and dashed lines indicate pre (T₀) and post (T₁) values, respectively.</p

Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury

Intermittent theta burst stimulation (iTBS) is intended primarily to alter corticospinal excitability, creating an attractive opportunity to alter neural output following incomplete spinal cord injury (SCI). This study is the first to assess the effects of iTBS in SCI. Eight individuals with chronic incomplete SCI were studied. Sham or real iTBS was delivered (to each participant) over primary motor and somatosensory cortices in separate sessions. Motor-evoked potential (MEP) recruitment curves were obtained from the flexor carpi radialis muscle before and after iTBS. Results indicate similar responses for iTBS to both motor and somatosensory cortex and reduced MEPs in 56.25% and increased MEPs in 25% of instances. Sham stimulation exceeded real iTBS effects in the remaining 18.25%. It is our opinion that observing short-term neuroplasticity in corticospinal output in chronic SCI is an important advance and should be tested in future studies as an opportunity to improve function in this population. We emphasize the need to re-consider the importance of the direction of MEP change following a single session of iTBS since the relationship between MEP direction and motor function is unknown and multiple sessions of iTBS may yield very different directional results. Furthermore, we highlight the importance of including sham control in the experimental design. The fundamental point from this pilot research is that a single session of iTBS is often capable of creating short-term change in SCI. Future sham-controlled randomized trials may consider repeat iTBS sessions to promote long-term changes in corticospinal excitability

Acute high-intensity and moderate-intensity interval exercise do not change corticospinal excitability in low fit, young adults.

Previous research has demonstrated a lack of neuroplasticity induced by acute exercise in low fit individuals, but the influence of exercise intensity is unclear. In the present study, we assessed the effect of acute high-intensity (HI) or moderate-intensity (MOD) interval exercise on neuroplasticity in individuals with low fitness, as determined by a peak oxygen uptake (VO2peak) test (n = 19). Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability via area under the motor evoked potential (MEP) recruitment curve before and following training. Corticospinal excitability was unchanged after HI and MOD, suggesting no effect of acute exercise on neuroplasticity as measured via TMS in sedentary, young individuals. Repeated bouts of exercise, i.e., physical training, may be required to induce short-term changes in corticospinal excitability in previously sedentary individuals