Papers by Monica A. Perez
J Physiol London, 2007
Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corti... more Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.
Journal of neurotrauma, Jan 20, 2016
We recently demonstrated that the electrical perceptual threshold (EPT) reveals spared sensory fu... more We recently demonstrated that the electrical perceptual threshold (EPT) reveals spared sensory function at lower spinal segments compared with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we investigated whether discrepancies in sensory function detected by both sensory exams change over time following SCI. Forty eight participants with acute (< 1 year), chronic (> 1 to 10 years), and extended-chronic (> 10 years) incomplete cervical SCI and 30 control subjects were tested on dermatomes C2 to T4 bilaterally. EPT values were higher in subjects with acute (2.5±0.8 mA), chronic (2.2±0.7 mA), and extended-chronic (2.8±1.1 mA) SCI compared with controls (1.0±0.1 mA). The EPT exam detected sensory impairments in spinal segments above (2.3±0.9) and below (4.2±2.6) the level detected by the ISNCSCI sensory exam in individuals with acute and chronic SCI, res...
Journal of Neurophysiology, 2015
Interhemispheric interactions through the corpus callosum play an important role in the control o... more Interhemispheric interactions through the corpus callosum play an important role in the control of bimanual forces. However, the extent to which physiological connections between primary motor cortices are modulated during increasing levels of bimanual force generation in intact humans remain poorly understood. Here, we studied coherence between electroencephalographic (EEG) signals and the ipsilateral cortical silent period (iSP), two well-known measures of interhemispheric connectivity between motor cortices, during unilateral and bilateral 10%, 40%, and 70% of maximal isometric voluntary contraction (MVC) into index finger abduction. We found that EEG-EEG coherence in the alpha frequency band decreased while the iSP area increased during bilateral compared with unilateral 40% and 70% but not 10% of MVC. Decreases in coherence in the alpha frequency band correlated with increases in the iSP area and subjects who showed this inverse relation were able to maintain more steady bilateral muscle contractions. To further examine the relationship between the iSP and coherence we electrically stimulated the ulnar nerve at the wrist at the alpha frequency. Electrical stimulation increased coherence in the alpha frequency band and decreased the iSP area during bilateral 70% of MVC. Altogether, our findings demonstrate an inverse relation between alpha oscillations and the iSP during strong levels of bimanual force generation. We suggest that interactions between neural pathways mediating alpha oscillatory activity and transcallosal inhibition between motor cortices might contribute to the steadiness of strong bilateral isometric muscle contractions.
Textbook of Neuromodulation, 2014
PLoS ONE, 2013
Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chroni... more Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI). The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 agematched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs) in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC) into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments) from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI.
Physical Medicine and Rehabilitation Clinics of North America, 2010
clinicians and researchers together to discuss key issues and future directions related to neural... more clinicians and researchers together to discuss key issues and future directions related to neural interface technology 4 . This review classifies neural interface devices and systems into two categories, neural recording systems and neural stimulation systems, based on the direction of information flow. Neural recording systems retrieve information from the nervous system through electrophysiological recording methods, such as electroencephalography (EEG) and microelectrode recording of single-neuron activities. Neural stimulation systems feed information into the nervous system by electrically or magnetically activating or inhibiting neural activity. This is a simplified classification scheme, as certain neural interface devices are capable of both neural recording and stimulation, such as implantable responsive neurostimulators for epilepsy treatment 5,6 . As the term neural interface technology covers a broad range of devices and systems, it is a daunting task to provide a detailed and informative discussion on each device and system in one review paper. Furthermore, there exist multiple books, special journal issues, and review papers that are excellent references for neural interface technology 7-15 . Hence, this paper aims to review neural interface technology from three unique perspectives. First, it will focus primarily on neural interface systems that are currently under active research but have not yet reached clinical practice, hoping to illustrate not only where we are, but also where we will be in the near future. Second, this paper will exemplify neural interface technology with systems that the authors have directly worked with in their rehabilitation research and clinical practice to provide a first-hand view of neural interface technology. Last and the most important, this paper will review neural interface technology in association with neuroplasticity, a foundation for neurological rehabilitation, and demonstrate that those two concepts work symbiotically to improve the quality of life for individuals with disabilities, as illustrated in . Neuroplasticity will help those individuals to make better use of their neural interface devices , and neural interface technology can also promote neuroplasticity for functional recovery 7,20 .
The Journal of Physiology, 2005
Sensory information continuously converges on the spinal cord during a variety of motor behaviour... more Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task and returned to baseline after 10 min. No changes were observed after the control task. To elucidate the mechanisms contributing to the H-reflex depression, we measured the size of the long-latency depression of the soleus H-reflex evoked by peroneal nerve stimulation (D1 inhibition) and the size of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed in the disynaptic reciprocal Ia inhibition. Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) were also unchanged, suggesting that transmission in ascending pathways was unaltered following the visuo-motor skill task. Together these observations suggest that a selective presynaptic control of Ia afferents contributes to the modulation of sensory inputs during acquisition of a novel visuo-motor skill in healthy humans.
The Journal of Physiology, 2006
We have previously demonstrated an increase in the excitability of the leg motor cortical area in... more We have previously demonstrated an increase in the excitability of the leg motor cortical area in relation to acquisition of a visuo-motor task in healthy humans. It remains unknown whether the interaction between corticospinal drive and spinal motoneurones is also modulated following motor skill learning. Here we investigated the effect of visuo-motor skill training involving the ankle muscles on the coupling between electroencephalographic (EEG) activity recorded from the motor cortex (Cz) and electromyographic (EMG) activity recorded from the left tibialis anterior (TA) muscle in 11 volunteers. Coupling in the time (cumulant density function) and frequency domains (coherence) between EEG-EMG and EMG-EMG activity were calculated during tonic isometric dorsiflexion before and after 32 min of training a visuo-motor tracking task involving the ankle muscles or performing alternating dorsi-and plantarflexion movements without visual feedback. A significant increase in EEG-EMG coherence around 15-35 Hz was observed following the visuo-motor skill session in nine subjects and in only one subject after the control task. Changes in coherence were specific to the trained muscle as coherence for the untrained contralateral TA muscle was unchanged. EEG and EMG power were unchanged following the training. Our results suggest that visuo-motor skill training is associated with changes in the corticospinal drive to spinal motorneurones. Possibly these changes reflect sensorimotor integration processes between cortex and muscle as part of the motor learning process.
Journal of Neuroscience, 2014
The motor cortex and the corticospinal system contribute to the control of a precision grip betwe... more The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients.
Journal of Neuroscience, 2013
inhibition was decreased during voluntary contraction compared with rest but there was no effect ... more inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABA B neuronal pathways after human SCI. Thus, cortical GABA B circuits may be less sensitive to baclofen than spinal GABA B circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity.
Neurorehabilitation and Neural Repair, 2010
Motor disability continues to be a major cause of morbidity after stroke. The neural underpinning... more Motor disability continues to be a major cause of morbidity after stroke. The neural underpinnings of disability and of functional recovery are still unclear. Here, we review recent evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into these mechanisms. We briefly discuss the use of TMS in the diagnosis, prognosis, and therapy of post-stroke motor disability. Differently from previous reviews, particular emphasis is placed in the discussion of the use of TMS as a tool to explore in detailed mechanisms of neuroplasticity during spontaneous and treatmentinduced recovery of motor function. TMS can be used to acquire the understanding of these mechanisms required for the development of more rational and clinically useful interventions in stroke neurorehabilitation.
Journal of Neurophysiology, 2012
Bunday KL, Perez MA. Impaired crossed facilitation of the corticospinal pathway after cervical sp... more Bunday KL, Perez MA. Impaired crossed facilitation of the corticospinal pathway after cervical spinal cord injury. In uninjured humans, it is well established that voluntary contraction of muscles on one side of the body can facilitate transmission in the contralateral corticospinal pathway. This crossed facilitatory effect may favor interlimb coordination and motor performance. Whether this aspect of corticospinal function is preserved after chronic spinal cord injury (SCI) is unknown. Here, using transcranial magnetic stimulation, we show in patients with chronic cervical SCI (C 5 -C 8 ) that the size of motor evoked potentials (MEPs) in a resting intrinsic hand muscle remained unchanged during increasing levels of voluntary contraction with a contralateral distal or proximal arm muscle. In contrast, MEP size in a resting hand muscle was increased during the same motor tasks in healthy control subjects. The magnitude of voluntary electromyography was negatively correlated with MEP size after chronic cervical SCI and positively correlated in healthy control subjects. To examine the mechanisms contributing to MEP crossed facilitation we examined short-interval intracortical inhibition (SICI), interhemispheric inhibition (IHI), and motoneuronal behavior by testing F waves and cervicomedullary MEPs (CMEPs). During strong voluntary contractions SICI was unchanged after cervical SCI and decreased in healthy control subjects compared with rest. F-wave amplitude and persistence and CMEP size remained unchanged after cervical SCI and increased in healthy control subjects compared with rest. In addition, during strong voluntary contractions IHI was unchanged in cervical SCI compared with rest. Our results indicate that GABAergic intracortical circuits, interhemispheric glutamatergic projections between motor cortices, and excitability of index finger motoneurons are neural mechanisms underlying, at least in part, the lack of crossed corticospinal facilitation observed after SCI. Our data point to the spinal motoneurons as a critical site for modulating corticospinal transmission after chronic cervical SCI.
Journal of Neurophysiology, 2012
Perez MA, Soteropoulos DS, Baker SN. Corticomuscular coherence during bilateral isometric arm vol... more Perez MA, Soteropoulos DS, Baker SN. Corticomuscular coherence during bilateral isometric arm voluntary activity in healthy humans. Bilateral voluntary contractions involve functional changes in both primary motor cortices. We investigated whether a voluntary contraction controlled by one hemisphere can influence oscillatory processes contralaterally. Corticomuscular coherence was calculated between EEG recorded over the motor cortex hand representation and electromyogram from the first dorsal interosseous muscle when the nondominant hand performed a precision grip task. The dominant arm remained at rest or performed a finger abduction or an elbow flexion task at 10, 40, and 70% of maximal isometric voluntary contraction (MVC). Mean coherence in the 15-to 30-Hz range in the hand performing a precision grip increased during 40% (by 72%) and 70% (by 73%) but not during 10% of MVC in the finger abduction task. Similarly, in the elbow flexion task, mean coherence increased during 40% (by 40%) and 70% (by 48%) but not during 10% of MVC. No differences were observed between the increments in coherence between the finger abduction and elbow flexion tasks at a given force level. We speculate that these results reflect the increased complexity of controlling a fine motor task with one hand while performing a strong contraction with the contralateral hand and suggest that increased oscillatory corticomuscular coupling may contribute to successful task performance.
Journal of Neurophysiology, 2007
Ballet dancers have small soleus (SOL) H-reflex amplitudes, which may be related to frequent use ... more Ballet dancers have small soleus (SOL) H-reflex amplitudes, which may be related to frequent use of cocontraction of antagonistic ankle muscles. Indeed, SOL H-reflexes are depressed during cocontraction compared with plantarflexion at matched background EMG level. We investigated the effect of 30-min training of simultaneous activation of ankle dorsi- and plantarflexor muscles (cocontraction task) on the SOL H-reflex in 10 healthy volunteers. Measurements were taken during cocontraction. After training, there was a significant improvement in the ability of the subjects to perform a stable cocontraction. SOL H-reflex recruitment curves and H-max/M-max ratios were decreased after cocontraction training but not after 30 min of static dorsi or plantarflexion. The decreased H-reflex size correlated with improved motor performance. No changes in SOL and tibialis anterior (TA) EMG activity or EMG power were observed, suggesting that increased presynaptic inhibition of Ia afferents is a likely mechanism for H-reflex depression. In different sessions we measured SOL and TA motor-evoked potentials (MEPs) by using transcranial magnetic stimulation (TMS), TMS-elicited suppression of SOL EMG, and coherence between electroencephalographic (EEG) activity (Cz) and TA and SOL EMG. SOL and TA MEPs were depressed, whereas TMS-elicited suppression of SOL EMG and coherence were increased after training. Decreased excitability of corticospinal neurons due to increased intracortical inhibition seems a likely explanation of these observations. Our results indicate that the depression in H-reflex observed during a cocontraction task can be trained and that repeated performance of tasks involving cocontraction may lead to prolonged changes in reflex and corticospinal excitability.
Journal of Neurophysiology, 2011
Many bilateral motor tasks engage simultaneous activation of distal and proximal arm muscles, but... more Many bilateral motor tasks engage simultaneous activation of distal and proximal arm muscles, but little is known about their physiological interactions. Here, we used transcranial magnetic stimulation to examine motor-evoked potentials (MEPs), interhemispheric inhibition at a conditioning-test interval of 10 (IHI(10)) and 40 ms (IHI(40)), and short-interval intracortical inhibition (SICI) in the left first dorsal interosseous (FDI) muscle during isometric index finger abduction. The right side remained at rest or performed isometric voluntary contraction with the FDI, biceps or triceps brachii, or the tibialis anterior. Left FDI MEPs were suppressed to a similar extent during contraction of the right FDI and biceps and triceps brachii but remained unchanged during contraction of the right tibialis anterior. IHI(10) and IHI(40) were decreased during contraction of the right biceps and triceps brachii compared with contraction of the right FDI. SICI was increased during activation of the right biceps and triceps brachii and decreased during activation of the right FDI. The present results indicate that an isometric voluntary contraction with either a distal or a proximal arm muscle, but not a foot dorsiflexor, decreases corticospinal output in a contralateral active finger muscle. Transcallosal inhibitory effects were strong during bilateral activation of distal hand muscles and weak during simultaneous activation of a distal and a proximal arm muscle, whereas GABAergic intracortical activity was modulated in the opposite manner. These findings suggest that in intact humans crossed interactions at the level of the motor cortex involved different physiological mechanisms when bilateral distal hand muscles are active and when a distal and a proximal arm muscle are simultaneously active.
Journal of Neurophysiology, 2014
Transcallosal inhibitory interactions between proximal representations in the primary motor corte... more Transcallosal inhibitory interactions between proximal representations in the primary motor cortex remain poorly understood. In this study, we used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP; a measure of transcallosal inhibition) in the biceps and triceps brachii during unilateral and bilateral isometric voluntary contractions. Healthy volunteers performed 10% of maximal isometric voluntary elbow flexion or extension with one arm while the contralateral arm remained at rest or performed 30% of maximal isometric voluntary elbow flexion or extension. The iSP was measured in the arm performing 10% contractions, and electromyographic (EMG) recordings were comparable across conditions. The iSP onset and duration in the biceps and triceps brachii were comparable. In both muscles, the iSP depth and area were increased during bilateral contractions of homologous agonist muscles (extension-extension and flexion-flexion) compared with a unilateral contraction, whereas during bilateral contractions of nonhomologous antagonist muscles (extension-flexion and flexion-extension), the iSP depth and area were decreased compared with a unilateral contraction, and sometimes facilitation of EMG was seen. This effect was never observed during bilateral activation of homologous muscles. The size of responses evoked by cervicomedullary electrical stimulation in the arm that made 10% contractions remained unchanged across conditions. Thus transcallosal inhibition targeting triceps and biceps brachii is upregulated by voluntary contraction of the contralateral agonist muscle and downregulated by voluntary contraction of the contralateral antagonist muscle. We speculate that these reciprocal task-dependent interactions between bilateral flexor and extensor arm regions of the motor cortex may contribute to coupling between the arms during motor behavior.
Journal of Applied Physiology, 2013
Optimization of cocontraction of antagonistic muscles around the ankle joint has been shown to in... more Optimization of cocontraction of antagonistic muscles around the ankle joint has been shown to involve plastic changes in spinal and cortical neural circuitries. Such changes may explain the ability of elite ballet dancers to maintain a steady balance during various ballet postures. Here we investigated whether short-term cocontraction training in ballet dancers and nondancers leads to changes in the coupling between antagonistic ankle motor units. Eleven ballet dancers and 10 nondancers were recruited for the study. Prior to training, ballet dancers and nondancers showed an equal amount of coherence in the 15- to 35-Hz frequency band and short-term synchronization between antagonistic tibialis anterior and soleus motor units. The ballet dancers tended to be better at maintaining a stable cocontraction of the antagonistic muscles, but this difference was not significant (P = 0.09). Following 27 min of cocontraction training, the nondancers improved their performance significantly, whereas no significant improvement was observed for the ballet dancers. The nondancers showed a significant increase in 15- to 35-Hz coherence following the training, whereas the ballet dancers did not show a significant change. A group of control subjects (n = 4), who performed cocontraction of the antagonistic muscles for an equal amount of time, but without any requirement to improve their performance, showed no change in coherence. We suggest that improved ability to maintain a stable cocontraction around the ankle joint is accompanied by short-term plastic changes in the neural drive to the involved muscles, but that such changes are not necessary for maintained high-level performance.
Experimental Brain Research, 2005
Repetitive transcranial magnetic stimulation (rTMS) has been shown to induce adaptations in corti... more Repetitive transcranial magnetic stimulation (rTMS) has been shown to induce adaptations in cortical neuronal circuitries. In the present study we investigated whether rTMS, through its effect on corticospinal pathways, also produces adaptations at the spinal level, and what the neuronal mechanisms involved in such changes are. rTMS (15 trains of 20 pulses at 5 Hz) was applied over the leg motor cortical area in ten healthy human subjects. At rest motor evoked potentials (MEPs) in the soleus and tibialis anterior muscles were facilitated by rTMS (at 1.2xMEP threshold). In contrast, the soleus H-reflex was depressed for 1 s at stimulus intensities from 0.92 to 1.2xMEP threshold. rTMS increased the size of the long-latency depression of the soleus H-reflex evoked by common peroneal nerve stimulation and decreased the femoral nerve facilitation of the soleus H-reflex. These observations suggest that the depression of the H-reflex by rTMS can be explained, at least partly, by an increased presynaptic inhibition of soleus Ia afferents. In contrast, rTMS had no effect on disynaptic reciprocal Ia inhibition from ankle dorsiflexors to plantarflexors. We conclude that a train of rTMS may modulate transmission in specific spinal circuitries through changes in corticospinal drive. This may be of relevance for future therapeutic strategies in patients with spasticity.
Experimental Brain Research, 2004
Training-induced changes in cortical excitability may play an important role in rehabilitation of... more Training-induced changes in cortical excitability may play an important role in rehabilitation of gait ability in patients with neurological disorders. In this study, we investigated the effect of a 32-min period of motor skill, non-skill and passive training involving the ankle muscles on leg motor cortical excitability in healthy humans. Transcranial magnetic stimulation (TMS) at a range of intensities was applied to obtain a recruitment curve of the motor evoked potentials (MEPs) in the tibialis anterior (TA) muscle before and after training. We also explored the effect of training on inhibitory and facilitatory cortical circuits by using a paired-pulse TMS technique at intervals of 2.5 ms (short-interval intracortical inhibition, SICI) and 8 ms (intracortical facilitation, ICF). During motor skill training, subjects were instructed to make a cursor follow a series of target lines on a computer screen by performing voluntary ankle dorsi- and plantarflexion movements. Non-skill and passive training consisted of repeated voluntary and assisted dorsi- and plantarflexion movements, respectively. Recruitment curves increased significantly after 32 min of motor skill training but not after non-skill and passive training, suggesting that only skill motor training increases motor cortical excitability. Motor skill training was not accompanied by any changes in the recruitment curves of TA MEPs evoked by transcranial electrical stimulation, suggesting that the increased MEPs to TMS was likely caused by changes in excitability at a cortical site. SICI was decreased after 32 min of motor skill training but no changes were observed in ICF. We conclude that similar plastic changes as have previously been reported for the hand motor following motor skill training may also be observed for the leg motor area. The observed plastic changes appeared to be related to the degree of difficulty in the motor task, and may be of relevance for rehabilitation of gait disorders.
Uploads
Papers by Monica A. Perez