George M. Opie

A single bout of aerobic exercise promotes motor cortical neuroplasticity

Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.

Age-related Differences in Short- and Long-interval Intracortical Inhibition in a Human Hand Muscle

BACKGROUND Effects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude. OBJECTIVE To investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes. METHODS In 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%-150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS. RESULTS When pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle. CONCLUSIONS Advancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle.

Modulation of short- and long-interval intracortical inhibition with increasing motor evoked potential amplitude in a human hand muscle

OBJECTIVE The aim of the current study was to investigate the effect of increasing test motor evoked potential (MEP) amplitude on short- (SICI) and long-interval intracortical inhibition (LICI) at rest and during activation of the first dorsal interosseous (FDI) muscle. METHODS In 22 young subjects, a conditioning-test transcranial magnetic stimulation (TMS) paradigm was used to assess SICI and LICI at 5 different test TMS intensities (110-150% motor threshold) in resting and active FDI. In 9 additional subjects, SICI and LICI data were quantified when the test MEP amplitude represented specific proportions of the maximal compound muscle action potential (Mmax) in each subject. RESULTS Test TMS intensity influenced SICI and LICI in rest and active FDI muscle. The normalised test MEP amplitude (%Mmax) did not influence SICI at rest, whereas there was a decrease in LICI at rest and an increase in SICI in active FDI with an increased normalised test MEP amplitude (%Mmax). CONCLUSIONS Our results demonstrate differential effects of normalised test MEP amplitude (%Mmax) on SICI and LICI in resting and active FDI muscle. SIGNIFICANCE Estimation of SICI and LICI under some circumstances may be influenced by the normalised test MEP amplitude in subject populations with different Mmax characteristics.

Motor cortex plasticity induced by theta burst stimulation is impaired in patients with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a respiratory condition occurring during sleep characterised by repeated collapse of the upper airway. Patients with OSA show altered brain structure and function that may manifest as impaired neuroplasticity. We assessed this hypothesis in 13 patients with moderate‐to‐severe OSA and 11 healthy control subjects. Transcranial magnetic stimulation was used to induce and measure neuroplastic changes in the motor cortex by assessing changes in motor‐evoked potentials (MEPs) in a hand muscle. Baseline measurements of cortical excitability included active (AMT) and resting motor thresholds (RMT), and the maximal stimulator output producing a 1‐mV MEP. Intracortical inhibition (ICI) was investigated with short‐ and long‐interval ICI paradigms (SICI and LICI, respectively), and neuroplastic changes were induced using continuous theta burst stimulation (cTBS). At baseline, differences were found between groups for RMT (9.5% maximal stimulator output higher in OSA) and 1‐mV MEPs (10.3% maximal stimulator output higher in OSA), but not AMT. No differences were found between groups for SICI or LICI. The response to cTBS was different between groups, with control subjects showing an expected reduction in MEP amplitude after cTBS, whereas the MEPs in patients with OSA did not change. The lack of response to cTBS suggests impaired long‐term depression‐like neuroplasticity in patients with OSA, which may be a consequence of sleep fragmentation or chronic blood gas disturbance in sleep. This reduced neuroplastic capacity may have implications for the learning, retention or consolidation of motor skills in patients with OSA.

Increased intracortical inhibition in elderly adults with anterior-posterior current flow: a TMS study

OBJECTIVE All previous studies using TMS to assess short-interval intracortical inhibition (SICI) in older adults have used a conventional coil orientation, which produces posterior-to-anterior (PA) current flow in the motor cortex. However, no studies have examined SICI in older adults by reversing the coil to induce anterior-to-posterior (AP) current flow, which is considered more sensitive at detecting SICI. Therefore, we investigated age-related changes in SICI using both PA and AP TMS across different conditioning stimulus intensities and muscle activation states. METHODS In 22 young and 20 older adults, SICI was assessed using PA and AP coil orientations, across a range of conditioning stimulus intensities (70-90% active motor threshold), and whilst participants kept their first dorsal interosseous (FDI) muscle either relaxed or active (2N force). RESULTS There were no age-related differences in SICI using conventional PA TMS in resting or active FDI muscle. However, SICI was increased in elderly participants when assessed with reverse coil AP TMS in resting FDI. CONCLUSIONS Coil orientation is a key factor to consider when assessing age-related differences in SICI. SIGNIFICANCE Reverse coil AP TMS can reveal age-related changes in SICI, which were previously not evident with conventional PA TMS. This may have implications for the assessment of SICI in some clinical populations that may show subtle differences in SICI circuitry.

Investigating TMS-EEG Indices of Long-Interval Intracortical Inhibition at Different Interstimulus Intervals

BACKGROUND Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes. OBJECTIVE This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP). METHODS In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI100) and 150 ms (LICI150), while TEPs were recorded using simultaneous high-definition EEG. RESULTS Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced amplitude following LICI100 (P = 0.03) but not LICI150 (P = 0.3). In contrast, the N100 and P180 were significantly reduced by LICI at both intervals (all P-values < 0.05). In addition, topographical analyses suggested that the global change in P30, N40 and P180 differed between LICI conditions. CONCLUSIONS These findings suggest that LICI100 and LICI150 reflect complex measurements of cortical inhibition with differential contributions from comparable circuits.

Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation

Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.

Age-related changes in corticospinal excitability and intracortical inhibition after upper extremity motor learning : A systematic review and meta-analysis

It is unclear how old age affects the neuronal mechanisms of motor learning. We reviewed the neuronal mechanisms of how healthy old and young adults acquire motor skills as assessed with transcranial magnetic stimulation. Quantitative meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed by upper extremity muscles in 132 healthy old and 128 young adults, revealed that the motor practice-induced increase in corticospinal excitability (CSE) is task-dependent but not age-dependent, with an increase in CSE in both age groups after visuomotor but not ballistic training. In addition, short-interval intracortical inhibition (SICI) is reduced in old but not young adults, but only after visuomotor practice. In addition, correlation analyses in 123 old and 128 young adults showed that the magnitude of motor skill acquisition did not correlate with increases in CSE or decreases in SICI in either age group. Thus, there are subtle age-related differences in use-dependent plasticity but increases in CSE or decreases in SICI are not related to motor skill acquisition in healthy young or old adults.

Intracortical Inhibition Assessed with Paired-Pulse Transcranial Magnetic Stimulation is Modulated during Shortening and Lengthening Contractions in Young and Old Adults

BACKGROUND The modulation of intracortical inhibition is thought to be impaired in older adults, which may contribute to their reduced fine motor control, particularly during lengthening muscle contractions. OBJECTIVE To quantify the magnitude of intracortical inhibition and movement performance during postural, shortening and lengthening contractions of a hand muscle in young and old adults. METHODS In 18 young (23.2 ± 4.2) and 16 old (70.6 ± 6.5) subjects, paired-pulse transcranial magnetic stimulation (TMS) was used to assess short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) during a movement task involving the first dorsal interosseous muscle. The task required a constant load (50 g) to be slowly lifted and lowered using the index finger while single- or paired-pulse TMS was delivered during the shortening or lengthening contraction. RESULTS Relative to postural contractions, SICI during shortening contractions was reduced by 29% in young subjects (P < 0.0001) and 43% in old subjects (P < 0.0001), whereas SICI during lengthening contractions was reduced by 11% in young subjects (P = 0.0004) and 33% in old subjects (P < 0.0001). Furthermore, SICI was significantly less in older adults during lengthening contractions (P-values < 0.01). For LICI, inhibition was not influenced by contraction type in old subjects, but was increased by 11% during shortening contractions (P < 0.0001) and by 9% during lengthening contractions in young subjects (P = 0.0008). In addition, old subjects showed significantly less LICI than young subjects in each movement phase (both P-values < 0.05). CONCLUSIONS Shortening and lengthening contractions with a constant load are associated with a modulation of GABAergic inhibition that is altered by healthy ageing.

Modulating motor cortical neuroplasticity with priming paired associative stimulation in young and old adults

OBJECTIVE To examine the effect of priming paired associative stimulation (PAS) on the modulation of motor cortex (M1) plasticity in young and old adults. METHODS Fifteen young (20-27yrs) and 15 old (61-79yrs) subjects participated in 3 experimental sessions, with each session involving two consecutive PAS protocols separated by 10mins. The first (priming) protocol was either PASLTP (ISI=N20 latency+2ms), PASLTD (ISI=N20 latency-10ms), or PASControl (ISI=100ms), whereas the second (test) protocol was always PASLTP. Changes in M1 excitability were assessed from motor evoked potentials (MEPs) in a hand muscle. RESULTS In young subjects, MEPs were larger after PASLTP+PASLTP than PASLTD+PASLTP (P<0.0001) and PASControl+PASLTP (P=0.0008), whereas the response to PASControl+PASLTP was not different to PASLTD+PASLTP (P=0.3). In old subjects, MEPs were smaller after PASLTP+PASLTP compared with PASControl+PASLTP (P=0.02), whereas PASLTD+PASLTP was similar to PASControl+PASLTP (P=0.08). Age-related comparisons within each priming condition showed that the response to PASLTP+PASLTP was significantly greater in young subjects (P=0.03). CONCLUSION Data show that priming with PASLTP was effective in young but not old subjects. SIGNIFICANCE These findings suggest a limited utility of priming PAS for augmenting plasticity induction in old adults.