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Epidural activity evoked by different forms of brain stimulation
Abstracts / Brain Stimulation 10 (2017) 346e540
Keywords: transcranial magnetic stimulation, spinal cord injury, motor recovery, H-reflex [0810] METHODS TO EXAMINE I-WAVE INTERACTIONS AND EFFECTS OF AFFERENT INPUT R. Chen*. University of Toronto, Canada A single transcranial magnetic stimulation (TMS) pulse to the motor cortex evoked a series of corticospinal volleys known as direct (D) and indirect (I) waves. This talk will discuss methods to assess D and I waves, how they are altered by afferent input and potential clinical implications. TMS with induced current in the posterior-anterior (PA) direction preferentially evokes early (I1) wave whereas anterior-posterior (AP) TMS preferentially evokes late (I3) waves. The interaction between I-waves can be studied with a paired pulse TMS paradigm known as short-interval intracortical facilitation (SICF), with peak facilitations at ~ 1.5, 3.0 and 4.5 ms that correspond to interactions between different I-waves. Afferent input, such as median nerve stimulation, inhibits the motor cortex at about 20 ms, known as short-latency afferent inhibition (SAI). SAI is mediated by acetylcholine and GABA, is altered in Alzheimer’s and Parkinson’s disease and predominately inhibit late I-waves evoked in the PA direction. Unexpectedly, it was found that SAI was greater with TMS in the PA compared to the AP direction. Single motor unit poststimulus time histogram recordings confirmed that the AP TMS preferentially evoked late I-waves, and late I-waves from PA TMS were inhibited by SAI whereas late I-waves from AP TMS were not. These findings suggest that late I-waves generated by AP and PA current are mediated by different circuits. The interactions between SAI and SICF were also investigated. Contrary to expectation, SICF elicited by both AP and PA current directions was facilitated in the presence of SAI. These results are compatible with the finding that projections from sensory to motor cortex terminate in both superficial layers where late I-waves are thought to originate, as well as deeper layers with more direct effect on pyramidal output. This interaction is likely to be relevant to sensorimotor integration and motor control. [0811] I-WAVE INTERACTIONS FOLLOWING HUMAN SPINAL CORD INJURY M.A. Perez*. University of Miami, USA The effect of a CNS injury on methodologies used to assess (D) and indirect (I) waves by using transcranial magnetic stimulation (TMS) of the human motor cortex remain poorly understood. Here, I will discuss the effect of an incomplete cervical spinal cord injury (SCI) on these methodologies. Paired-pulse TMS results in consecutive facilitatory motor evoked potential peaks in surface electromyography that resemble activation of early and late I-waves. We found that after SCI late I-waves aberrantly contributed to spinal motoneuron recruitment. We argue that the later corticospinal inputs on the spinal cord might be crucial for recruitment of motoneurones after human SCI. We have also used coil rotations to examine cortico-cortical contribution to grasping behaviours in humans with and without incomplete SCI. The TMS coil was oriented to induce currents in the brain in the latero-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) direction to preferentially activate corticospinal axons directly and early and late synaptic inputs to corticospinal neurons, respectively. AP-LM MEP latency differences were consistently longer during power grip compared with index finger abduction and precision grip, while PA-LM differences remained similar across tasks. Note that these latency differences across tasks were decreased in humans with SCI. A preferential recruitment of late synaptic inputs to corticospinal neurons may be achieved when humans perform a power grip. This information may contribute to the design of future interventions using TMS following SCI and other motor disorders affecting the corticospinal tract. [0812] COMPUTATIONAL MODELLING OF CORTICAL TRANSCRANIAL MAGNETIC STIMULATION J. Triesch*. JW. Goethe University, Germany
RESPONSES
TO
539
Transcranial magnetic stimulation (TMS) holds great promise for various clinical and basic research applications. Despite decades of research, however, the precise mechanisms through which TMS induces activity in cortical and peripheral structures are still insufficiently understood. Computational models can help to explore putative underlying mechanisms and test their plausibility and consistency. Over the last years, we have been developing and refining such a model, which offers a parsimonious explanation of the mechanisms generating so-called D and I-waves. The model has a simple structure comprising excitatory and inhibitory neurons in cortical layers two and three that project to a population of corticospinal tract neurons in layer five. The model correctly captures the basic findings about D and I-waves and how they are affected by pharmacological interventions. The model also explains the effects of a number of paired-pulse stimulation protocols. More recently, we have extended the model to simulate how TMS over motor cortex drives activity in down-stream motor structures. Our model produces realistic motor evoked potentials (MEPs) and shows how their magnitude is affected by stimulation intensity and the level of voluntary muscle contraction. The model also produces cortical silence periods (CSPs) of realistic lengths and reveals how their duration depends on properties of intra-cortical inhibition. Finally, the model shows how cortical rhythms such as the prominent mu-rhythm of motor cortex contribute to the variability of neural responses to TMS, consistent with the observation that TMS triggered at different phases of the mu-rhythm produces systematically different response magnitudes. Overall, the proposed computational model offers a parsimonious account of the basic effects of TMS on cortical circuits. In the future, this could be exploited for optimizing stimulation protocols for specific clinical or basic research applications. [0813] EPIDURAL ACTIVITY EVOKED BY DIFFERENT FORMS OF BRAIN STIMULATION v. Di Lazzaro*. Policlinico Universitario Campus Bio-Medico, Italy The activity evoked by transcranial electric (TES) and magnetic (TMS) stimulation of the human brain can be visualised directly in patients who have had electrodes’ implanted surgically in the epidural space of the cervical cord for control of pain. The recordings in these patients have shown that a single stimulus to motor cortex evokes a synchronised series of descending activity very similar to those recorded in primates after direct stimulation of the cortical surface. At threshold for producing a muscle contraction, TES evokes a single rapidly conducted volley at short latency that by analogy to the primate data is termed the “D-wave” because it is caused by direct excitation of the axons of corticospinal neurones in the subcortical white matter. These are termed I-waves because they are produced by synaptic activation of corticospinal neurones. The effect of TMS with an orientation of the induced current in the brain perpendicular to the line of the central sulcus and flowing in a posterior to anterior direction (PA), is very similar apart from one unexpected finding, which is that the threshold difference between activation of direct and indirect activation of corticospinal neurones is reversed. At threshold for evoking a muscle twitch, PA TMS pulses evoke only I-waves; D-waves are only elicited at much higher intensities. Thus even though TES and TMS evoke electrical pulses of similar amplitude and duration are induced in the brain, they preferentially activate different targets. Overall, the characteristics of the epidural activity evoked by different forms of stimulation suggest that different populations of neurons can be activated by non-invasive brain stimulation. [0818] TDCS CAN ALLEVIATE THE EFFECTS OF POOR SLEEP ON COGNITION A. Sterr*, J. Ebajemito. University of Surrey, UK Background: Transcranial direct current stimulation (tDCS) is an affordable and easy-to-use technology used to influence brain function. In recent years, the method has gained immense popularity as a research tool in cognitive neuroscience, and most importantly, as an intervention to boost learning and cognitive performance. While the overarching evidence-base suggests that tDCS can be an effective cognitive enhancer, lack of replicability and large individual differences pose a major challenge. In addition
Keywords: transcranial magnetic stimulation, spinal cord injury, motor recovery, H-reflex [0810] METHODS TO EXAMINE I-WAVE INTERACTIONS AND EFFECTS OF AFFERENT INPUT R. Chen*. University of Toronto, Canada A single transcranial magnetic stimulation (TMS) pulse to the motor cortex evoked a series of corticospinal volleys known as direct (D) and indirect (I) waves. This talk will discuss methods to assess D and I waves, how they are altered by afferent input and potential clinical implications. TMS with induced current in the posterior-anterior (PA) direction preferentially evokes early (I1) wave whereas anterior-posterior (AP) TMS preferentially evokes late (I3) waves. The interaction between I-waves can be studied with a paired pulse TMS paradigm known as short-interval intracortical facilitation (SICF), with peak facilitations at ~ 1.5, 3.0 and 4.5 ms that correspond to interactions between different I-waves. Afferent input, such as median nerve stimulation, inhibits the motor cortex at about 20 ms, known as short-latency afferent inhibition (SAI). SAI is mediated by acetylcholine and GABA, is altered in Alzheimer’s and Parkinson’s disease and predominately inhibit late I-waves evoked in the PA direction. Unexpectedly, it was found that SAI was greater with TMS in the PA compared to the AP direction. Single motor unit poststimulus time histogram recordings confirmed that the AP TMS preferentially evoked late I-waves, and late I-waves from PA TMS were inhibited by SAI whereas late I-waves from AP TMS were not. These findings suggest that late I-waves generated by AP and PA current are mediated by different circuits. The interactions between SAI and SICF were also investigated. Contrary to expectation, SICF elicited by both AP and PA current directions was facilitated in the presence of SAI. These results are compatible with the finding that projections from sensory to motor cortex terminate in both superficial layers where late I-waves are thought to originate, as well as deeper layers with more direct effect on pyramidal output. This interaction is likely to be relevant to sensorimotor integration and motor control. [0811] I-WAVE INTERACTIONS FOLLOWING HUMAN SPINAL CORD INJURY M.A. Perez*. University of Miami, USA The effect of a CNS injury on methodologies used to assess (D) and indirect (I) waves by using transcranial magnetic stimulation (TMS) of the human motor cortex remain poorly understood. Here, I will discuss the effect of an incomplete cervical spinal cord injury (SCI) on these methodologies. Paired-pulse TMS results in consecutive facilitatory motor evoked potential peaks in surface electromyography that resemble activation of early and late I-waves. We found that after SCI late I-waves aberrantly contributed to spinal motoneuron recruitment. We argue that the later corticospinal inputs on the spinal cord might be crucial for recruitment of motoneurones after human SCI. We have also used coil rotations to examine cortico-cortical contribution to grasping behaviours in humans with and without incomplete SCI. The TMS coil was oriented to induce currents in the brain in the latero-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) direction to preferentially activate corticospinal axons directly and early and late synaptic inputs to corticospinal neurons, respectively. AP-LM MEP latency differences were consistently longer during power grip compared with index finger abduction and precision grip, while PA-LM differences remained similar across tasks. Note that these latency differences across tasks were decreased in humans with SCI. A preferential recruitment of late synaptic inputs to corticospinal neurons may be achieved when humans perform a power grip. This information may contribute to the design of future interventions using TMS following SCI and other motor disorders affecting the corticospinal tract. [0812] COMPUTATIONAL MODELLING OF CORTICAL TRANSCRANIAL MAGNETIC STIMULATION J. Triesch*. JW. Goethe University, Germany
RESPONSES
TO
539
Transcranial magnetic stimulation (TMS) holds great promise for various clinical and basic research applications. Despite decades of research, however, the precise mechanisms through which TMS induces activity in cortical and peripheral structures are still insufficiently understood. Computational models can help to explore putative underlying mechanisms and test their plausibility and consistency. Over the last years, we have been developing and refining such a model, which offers a parsimonious explanation of the mechanisms generating so-called D and I-waves. The model has a simple structure comprising excitatory and inhibitory neurons in cortical layers two and three that project to a population of corticospinal tract neurons in layer five. The model correctly captures the basic findings about D and I-waves and how they are affected by pharmacological interventions. The model also explains the effects of a number of paired-pulse stimulation protocols. More recently, we have extended the model to simulate how TMS over motor cortex drives activity in down-stream motor structures. Our model produces realistic motor evoked potentials (MEPs) and shows how their magnitude is affected by stimulation intensity and the level of voluntary muscle contraction. The model also produces cortical silence periods (CSPs) of realistic lengths and reveals how their duration depends on properties of intra-cortical inhibition. Finally, the model shows how cortical rhythms such as the prominent mu-rhythm of motor cortex contribute to the variability of neural responses to TMS, consistent with the observation that TMS triggered at different phases of the mu-rhythm produces systematically different response magnitudes. Overall, the proposed computational model offers a parsimonious account of the basic effects of TMS on cortical circuits. In the future, this could be exploited for optimizing stimulation protocols for specific clinical or basic research applications. [0813] EPIDURAL ACTIVITY EVOKED BY DIFFERENT FORMS OF BRAIN STIMULATION v. Di Lazzaro*. Policlinico Universitario Campus Bio-Medico, Italy The activity evoked by transcranial electric (TES) and magnetic (TMS) stimulation of the human brain can be visualised directly in patients who have had electrodes’ implanted surgically in the epidural space of the cervical cord for control of pain. The recordings in these patients have shown that a single stimulus to motor cortex evokes a synchronised series of descending activity very similar to those recorded in primates after direct stimulation of the cortical surface. At threshold for producing a muscle contraction, TES evokes a single rapidly conducted volley at short latency that by analogy to the primate data is termed the “D-wave” because it is caused by direct excitation of the axons of corticospinal neurones in the subcortical white matter. These are termed I-waves because they are produced by synaptic activation of corticospinal neurones. The effect of TMS with an orientation of the induced current in the brain perpendicular to the line of the central sulcus and flowing in a posterior to anterior direction (PA), is very similar apart from one unexpected finding, which is that the threshold difference between activation of direct and indirect activation of corticospinal neurones is reversed. At threshold for evoking a muscle twitch, PA TMS pulses evoke only I-waves; D-waves are only elicited at much higher intensities. Thus even though TES and TMS evoke electrical pulses of similar amplitude and duration are induced in the brain, they preferentially activate different targets. Overall, the characteristics of the epidural activity evoked by different forms of stimulation suggest that different populations of neurons can be activated by non-invasive brain stimulation. [0818] TDCS CAN ALLEVIATE THE EFFECTS OF POOR SLEEP ON COGNITION A. Sterr*, J. Ebajemito. University of Surrey, UK Background: Transcranial direct current stimulation (tDCS) is an affordable and easy-to-use technology used to influence brain function. In recent years, the method has gained immense popularity as a research tool in cognitive neuroscience, and most importantly, as an intervention to boost learning and cognitive performance. While the overarching evidence-base suggests that tDCS can be an effective cognitive enhancer, lack of replicability and large individual differences pose a major challenge. In addition