High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on&nbsp;neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of&nbsp;the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its&nbsp;influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function161CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465686/2014-1Não tem2014/50909-8; 13/10187–0; 14/10134–7The authors thank the Ministry of Education (MEC), FAPESP - São Paulo Research Foundation, Universidade Estadual de Londrina, Universidade Federal do Rio Grande do Norte and Universidade Federal do ABC for its support. Postdoctoral scholarships to DGSM from the Coordination for the Improvement of Higher Education Personnel (CAPES). Source(s) of financial support: This study was partially funded by grants to MB from NIH (NIH-NIMH 1R01MH111896, NIH-NINDS 1R01NS101362, NIH-NCI U54CA137788/U54CA132378, R03 NS054783) and New York State Department of Health (NYS DOH, DOH01-C31291GG), CEPID/BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology (Process: 13/07559–3) to LML, Brazilian National Research Council (CNPq, Grant # 465686/2014-1) and the São Paulo Research Foundation (Grant # 2014/50909-8) to MSC, and Postdoctoral scholarships to AHO from FAPESP - Sao Paulo Research Foundation (Process: 13/10187–0 and 14/10134–7

Experimental muscle hyperalgesia modulates sensorimotor cortical excitability, which is partially altered by unaccustomed exercise

Impaired corticomotor function is reported in patients with lateral epicondylalgia, but the causal link to pain or musculotendinous overloading is unclear. In this study, sensorimotor cortical changes were investigated using a model of persistent pain combined with an overloading condition. In 24 healthy subjects, the effect of nerve growth factor (NGF)-induced pain, combined with delayed-onset muscle soreness (DOMS), was examined on pain perception, pressure pain sensitivity, maximal force, and sensorimotor cortical excitability. Two groups (NGF alone and NGF + DOMS) received injections of NGF into the extensor carpi radialis brevis (ECRB) muscle at day 0, day 2, and day 4. At day 4, the NGF + DOMS group undertook wrist eccentric exercise to induce DOMS in the ECRB muscle. Muscle soreness scores, pressure pain thresholds over the ECRB muscle, maximal grip force, transcranial magnetic stimulation mapping of the cortical ECRB muscle representation, and somatosensory-evoked potentials from radial nerve stimulation were recorded at day 0, day 4, and day 6. Compared with day 0, day 4 showed in both groups: (1) increased muscle soreness (P < 0.01); (2) reduced pressure pain thresholds (P < 0.01); (3) increased motor map volume (P < 0.01); and (4) decreased frontal N30 somatosensory-evoked potential. At day 6, compared with day 4, only the DOMS + NGF group showed: (1) increased muscle soreness score (P < 0.01); (2) decreased grip force (P < 0.01); and (3) decreased motor map volume (P < 0.05). The NGF group did not show any difference on the remaining outcomes from day 4 to day 6. These data suggest that sustained muscle pain modulates sensorimotor cortical excitability and that exercise-induced DOMS alters pain-related corticomotor adaptation

The Influence of Declarative Processes upon Human Motor Cortex Physiology

Skilled movements require the ability to efficiently extract and manipulate incoming sensory information relating to our body and environment to inform motor output. To facilitate efficient sensory to motor transformations humans have developed highly tuned cognitive abilities featuring constructs such as attention and working memory. Such cognitive constructs support the development of declarative knowledge pertaining to skilled actions. Yet, our understanding of how declarative knowledge shapes the function and reorganization of subconscious procedural knowledge about a skill is limited. Importantly, understanding how declarative strategies may influence motor cortical physiology is an essential step towards understanding why some skills benefit from explicit knowledge while others do not. The purpose of this dissertation was to determine how declarative functions, specifically verbal working memory, shape procedural motor control through modulation of sensory afference. Chapter 1 reviews the role of the motor and somatosensory cortices in motor behavior. The role of attention in the activation of the sensorimotor cortex is then described. Finally, the role of verbal working memory in motor performance is discussed. Previous research looked at the role of working memory from a behavioral perspective, but the studies in this thesis investigated the neural substrates, and notably the sensory afference of the interaction of working memory and control of movement. Chapters 2 through 4 detail a series of studies investigating how working memory load and verbal instructions alter motor cortex physiology and plasticity. Specifically, Chapter 2 demonstrates that engaging verbal working memory processes can change the potential for plasticity in the motor cortex, a substrate of the procedural motor system. Chapter 3 demonstrates that working memory acts upon the motor cortex through intracortical circuits that are distinct from other cognitive functions such as attention. Finally, Chapter 4 extends these results from a model where working memory is a distractor to working memory as a task-relevant construct. Overall, the findings from the studies described in this dissertation demonstrate that working memory has the ability to influence motor cortex physiology through circuits distinct from the circuits affected by attention. Further, the way in which working memory is employed can have important modulatory effects in the motor cortex, which could then impact the acquisition and execution of motor skills. These results lay the groundwork for future studies investigating whether declarative strategies may control and limit procedural learning such that the procedural system serves to perfect the optimal kinematics and dynamics for the imposed strategy even if the imposed strategy results in sub-optimal performance.PHDKinesiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143991/1/lsuzuki_1.pd

Exploring early corticomotor reorganisation

The overarching aim of this thesis was to enhance our understanding of early corticomotor reorganisation in response to novel stimuli (motor skill training and acute pain). To achieve this aim, four primary studies (Chapters 2-5) were conducted and published. Study 1 (Chapter 2) explored the within- and between-session reliability of corticomotor outcomes assessed using rapid TMS mapping (map area, volume, centre of gravity, discrete peaks in corticomotor excitability, and mean motor evoked potential). This study also assessed the validity of rapid mapping by testing its equivalence with traditional mapping methods. Study 2 (Chapter 3) used rapid mapping to investigate corticomotor reorganisation during short-term motor skill learning in thirty individuals. This study demonstrated, for the first time, that reorganisation of lower back muscle representations occurs rapidly (within minutes) in certain individuals. Study 3 (Chapter 4) explored the temporal profile and variability of corticomotor reorganisation in response to acute experimental pain. Findings of this study suggest that early corticomotor responses could be used as an index to predict symptom severity. This could have utility in stratifying individuals according to their likelihood of increased or persistent pain and the development of targeted management strategies. Study 4 (Chapter 5) investigated this possibility using repeated intramuscular injection of nerve growth factor, a novel and clinically-relevant model of musculoskeletal pain. The findings of this study suggest that early rTMS over M1 may expedite recovery following acute musculoskeletal pain or injury. Taken together, this thesis makes a substantial and original contribution to our understanding of neuroplasticity. By evaluating rapid TMS mapping, early corticomotor reorganisation can now be assessed validly and reliably, allowing exploration of early drivers of nervous system plasticity. Decreasing map acquisition times may also increase the utility of TMS beyond research settings, potentially allowing corticomotor reorganisation to be assessed in clinical environments. The experimental studies throughout this thesis provide valuable insight into the temporal profile and modifiability of early corticomotor reorganisation. This work highlights the prognostic and therapeutic utility of exploring early corticomotor reorganisation and the need for further research in this area