Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output

Abstract

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in sub-cortical motor pathways such as the reticulospinal tract could help to boost recovery after damage (e.g. stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation; TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20 and 30 minutes after stimulus pairing ended, TMS responses were enhanced, indicating the induction of long-term potentiation. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared to other available paradigms.SIGNIFICANCE STATEMENT:Induction of plasticity by neurostimulation protocols may be promising to enhance functional recovery after damage such as following stroke, but current protocols mainly target cortical circuits. In this study, we developed a novel paradigm which may generate long-term changes in connections between cortex and brainstem. This could provide an additional tool to modulate and improve recovery.

Neural coordination of bilateral hand movements: evidence for an involvement of brainstem motor centres

“…Several facts speak against a cortical influence on the coupling‐like response: first, LAS‐related effects seem to be weak during muscle contraction (Chen et al., 2016). Second, a relevant cortical suppression at 50 ms after LAS (Furubayashi et al., 2000; Tazoe & Perez, 2017; Germann et al., 2023) should modulate the coupling‐like response without startle, but not the shifted one with startles. Third, the similarity of the responses to LAS and ES makes a LAS‐induced cortical extra‐effect implausible.…”

Age‐related changes in reticulospinal contributions to anticipatory postural adjustments between back extensors and abdominal muscles

“…Additionally, our results were in keeping with other studies demonstrating shortening in movement onset in both the arm and the trunk during forward reaching (Yang et al., 2019 ) and rapid unilateral shoulder flexion (Tsao et al., 2009 ). It is suggested that the shortening in motor response is due to engagement of subcortical structures such as the reticular formation, which mediates spinal interneurons and motoneurons via the reticulospinal tract and thereby influences spinal excitability (Carlsen & Maslovat, 2019 ; Germann et al., 2023 ; Yeomans & Frankland, 1995 ).…”

Moving toward elucidating alternative motor pathway structures post-stroke: the value of spinal cord neuroimaging

“…In the acoustic startle response, an unexpected acoustic stimulus is delivered, and electromyography (EMG) is recorded from proximal upper extremity muscles to quantify drive from the reticulospinal system ( 99 ). The technique has been successfully used in animal models ( 100 – 103 ) and clinical ( 104 – 106 ) studies to identify the involvement of reticulospinal pathways. Using the startle response, it has been suggested that reticulospinal pathways are involved in spasticity ( 107 ) and have enhanced function in severely impaired patients ( 75 ); although contradictory findings have also been reported ( 108 , 109 ).…”