Paired-pulse Stimulation Research Articles

The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study.

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior-anterior (PA) and anterior-posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI.

Recording of pig neuronal activity in the comparative context of the awake human brain

Gyriform mammals display neurophysiological and neural network activity that other species exhibit only in rudimentary or dissimilar form. However, neural recordings from large mammals such as the pig can be anatomically hindered and pharmacologically suppressed by anesthetics. This curtails comparative inferences. To mitigate these limitations, we set out to modify electrocorticography, intracerebral depth and intracortical recording methods to study the anesthetized pig. In the process, we found that common forms of infused anesthesia such as pentobarbital or midazolam can be neurophysiologic suppressants acting in dose-independent fashion relative to anesthetic dose or brain concentration. Further, we corroborated that standard laboratory conditions may impose electrical interference with specific neural signals. We thus aimed to safeguard neural network integrity and recording fidelity by developing surgical, anesthesia and noise reduction methods and by working inside a newly designed Faraday cage, and evaluated this from the point of view of neurophysiological power spectral density and coherence analyses. We also utilized novel silicon carbide electrodes to minimize mechanical disruption of single-neuron activity. These methods allowed for the preservation of native neurophysiological activity for several hours. Pig electrocorticography recordings were essentially indistinguishable from awake human recordings except for the small segment of electrical activity associated with vision in conscious persons. In addition, single-neuron and paired-pulse stimulation recordings were feasible simultaneously with electrocorticography and depth electrode recordings. The spontaneous and stimulus-elicited neuronal activities thus surveyed can be recorded with a degree of precision similar to that achievable in rodent or any other animal studies and prove as informative as unperturbed human electrocorticography.

TU-128. The role of caffeine in cortical excitability measured with paired-pulse transcranial magnetic stimulation

TU-128. The role of caffeine in cortical excitability measured with paired-pulse transcranial magnetic stimulation

Bifurcations in the Firing of Neuronal Population Caused by a Small Difference in Pulse Parameters During Sustained Stimulations in Rat Hippocampus in Vivo.

The bifurcation of neuronal firing is one of important nonlinear phenomena in the nervous system and is characterized by a significant change in the rate or temporal pattern of neuronal firing on responding to a small disturbance from external inputs. Previous studies have reported firing bifurcations for individual neurons, not for a population of neurons. We hypothesized that the integrated firing of a neuronal population could also show a bifurcation behavior that should be important in certain situations such as deep brain stimulations. The hypothesis was verified by experiments of rat hippocampus in vivo. Stimulation sequences of paired-pulses with two different inter-pulse-intervals (IPIs) or with two different pulse intensities were applied on the alveus of hippocampal CA1 region in anaesthetized rats. The amplitude and area of antidromic population spike (APS) were used as indices to evaluate the differences in the responses of neuronal population to the different pulses in stimulations. During sustained paired-pulse stimulations with a high mean pulse frequency such as ∼130 Hz, a small difference of only a few percent in the two IPIs or in the two intensities was able to generate a sequence of evoked APSs with a substantial bifurcation in their amplitudes and areas. Small differences in the excitatory inputs can cause nonlinearly enlarged differences in the induced firing of neuronal populations. The novel dynamics and bifurcation of neuronal responses to electrical stimulations provide important clues for developing new paradigms to extend neural stimulations to treat more diseases.

Is it possible to compare inhibitory and excitatory intracortical circuits in face and hand primary motor cortex?

Face muscles are important in a variety of different functions, such as feeding, speech and communication of non‐verbal affective states, which require quite different patterns of activity from those of a typical hand muscle. We ask whether there are differences in their neurophysiological control that might reflect this. Fifteen healthy individuals were studied. Standard single‐ and paired‐pulse transcranial magnetic stimulation (TMS) methods were used to compare intracortical inhibitory (short interval intracortical inhibition (SICI); cortical silent period (CSP)) and excitatory circuitries (short interval intracortical facilitation (SICF)) in two typical muscles, the depressor anguli oris (DAO), a face muscle, and the first dorsal interosseous (FDI), a hand muscle. TMS threshold was higher in DAO than in FDI. Over a range of intensities, resting SICF was not different between DAO and FDI, while during muscle activation SICF was stronger in FDI than in DAO (P = 0.012). At rest, SICI was stronger in FDI than in DAO (P = 0.038) but during muscle contraction, SICI was weaker in FDI than in DAO (P = 0.034). We argue that although many of the difference in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting SICI in DAO, may reflect fundamental differences in the physiology of the two muscle groups. Key points Transcranial magnetic stimulation (TMS) single‐ and paired‐pulse protocols were used to investigate and compare the activity of facilitatory and inhibitory intracortical circuits in a face (depressor anguli oris; DAO) and hand (first dorsal interosseous; FDI) muscles. Several TMS intensities and interstimulus intervals were tested with the target muscles at rest and when voluntarily activated.At rest, intracortical inhibitory activity was stronger in FDI than in DAO. In contrast, during muscle contraction inhibitory activity was stronger in DAO than in FDI. As many previous reports have found, the motor evoked potential threshold was higher in DAO than in FDI.Although many of the differences in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting short interval intracortical inhibition in DAO, may reflect fundamental differences in the physiology of the two muscle groups.

Spatially bivariate EEG-neurofeedback can manipulate interhemispheric inhibition.

Human behavior requires inter-regional crosstalk to employ the sensorimotor processes in the brain. Although external neuromodulation techniques have been used to manipulate interhemispheric sensorimotor activity, a central controversy concerns whether this activity can be volitionally controlled. Experimental tools lack the power to up- or down-regulate the state of the targeted hemisphere over a large dynamic range and, therefore, cannot evaluate the possible volitional control of the activity. We addressed this difficulty by using the recently developed method of spatially bivariate electroencephalography (EEG)-neurofeedback to systematically enable the participants to modulate their bilateral sensorimotor activities. Here, we report that participants learn to up- and down-regulate the ipsilateral excitability to the imagined hand while maintaining constant contralateral excitability; this modulates the magnitude of interhemispheric inhibition (IHI) assessed by the paired-pulse transcranial magnetic stimulation (TMS) paradigm. Further physiological analyses revealed that the manipulation capability of IHI magnitude reflected interhemispheric connectivity in EEG and TMS, which was accompanied by intrinsic bilateral cortical oscillatory activities. Our results show an interesting approach for neuromodulation, which might identify new treatment opportunities, e.g., in patients suffering from a stroke.

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex

PurposeAcute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex.MethodsEleven healthy, right-handed participants completed two testing sessions: (1) AIH (comprising 3 min in hypoxia [fraction of inspired oxygen ~ 10%] and 2 min in normoxia repeated over five cycles) and (2) normoxia (NOR) (equivalent duration to AIH). Single- and paired-pulse transcranial magnetic stimulations were delivered to the primary motor cortex, before and 0, 25, and 50 min after AIH and normoxia.ResultsThe mean nadir in arterial oxygen saturation was lower (p < 0.001) during the cycles of AIH (82.5 ± 4.9%) than NOR (97.8 ± 0.6%). There was no significant difference in corticospinal excitability, intracortical facilitation, or intracortical inhibition between AIH and normoxia conditions at any time point (all p > 0.05). There was no association between arterial oxygen saturation and changes in corticospinal excitability after AIH (r = 0.05, p = 0.87).ConclusionOverall, AIH did not modify either corticospinal excitability or excitability of intracortical facilitatory and inhibitory circuits within the primary motor cortex. Future research should explore whether a more severe or individualised AIH dose would induce consistent, measurable changes in corticospinal excitability.

Modulations of corticospinal excitability following rapid ankle dorsiflexion in skill- and endurance-trained athletes

PurposeLong-term sports training, such as skill and endurance training, leads to specific neuroplasticity. However, it remains unclear if muscle stretch-induced proprioceptive feedback influences corticospinal facilitation/inhibition differently between skill- and endurance-trained athletes. This study investigated modulation of corticospinal excitability following rapid ankle dorsiflexion between well-trained skill and endurance athletes.MethodsTen skill- and ten endurance-trained athletes participated in the study. Corticospinal excitability was tested by single- and paired-pulse transcranial magnetic stimulations (TMS) at three different latencies following passive rapid ankle dorsiflexion. Motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), and long-latency intracortical inhibition (LICI) were recorded by surface electromyography from the soleus muscle.ResultsCompared to immediately before ankle dorsiflexion (Onset), TMS induced significantly greater MEPs during the supraspinal reaction period (~ 120 ms after short-latency reflex, SLR) in the skill group only (from 1.7 ± 1.0 to 2.7 ± 1.8%M-max, P = 0.005) despite both conditions being passive. ICF was significantly greater over all latencies in skill than endurance athletes (F(3, 45) = 4.64, P = 0.007), although no between-group differences for stimulations at specific latencies (e.g., at SLR) were observed.ConclusionThe skill group showed higher corticospinal excitability during the supraspinal reaction phase, which may indicate a “priming” of corticospinal excitability following rapid ankle dorsiflexion for a supraspinal reaction post-stretch, which appears absent in endurance-trained athletes.

Inhibitory Control of Short-Term Plasticity during Paired Pulse Stimulation Depends on Actin Polymerization

Inhibitory Control of Short-Term Plasticity during Paired Pulse Stimulation Depends on Actin Polymerization

The influence of experimental low back pain on neural networks involved in the control of lumbar erector spinae muscles.

Low back pain (LBP) often modifies spine motor control, but the neural origin of these motor control changes remains largely unexplored. This study aimed to determine the impact of experimental low back pain on the excitability of cortical, subcortical, and spinal networks involved in the control of back muscles. Thirty healthy subjects were recruited and allocated to pain (capsaicin and heat) or control (heat) groups. Corticospinal excitability (motor-evoked potential; MEP) and intracortical networks were assessed by single- and paired-pulse transcranial magnetic stimulation, respectively. Electrical vestibular stimulation was applied to assess vestibulospinal excitability (vestibular MEP; VMEP) and the stretch reflex for excitability of the spinal or supraspinal loop (R1 and R2, respectively). Evoked back motor responses were measured before, during, and after pain induction. Nonparametric rank-based ANOVA determined if pain modulated motor neural networks. A decrease of R1 amplitude was present after the pain disappearance (P = 0.01) whereas an increase was observed in the control group (P = 0.03) compared with the R1 amplitude measured at prepain and preheat period, respectively (group × time interaction, P < 0.001). No difference in MEP and VMEP amplitude was present during and after pain (P > 0.05). During experimental LBP, no change in cortical, subcortical, or spinal networks was observed. After pain disappearance, the reduction of the R1 amplitude without modification of MEP and VMEP amplitude suggests a reduction in spinal excitability potentially combined with an increase in descending drives. The absence of effect during pain needs to be further explored.NEW & NOTEWORTHY In the presence of experimental low back pain, spinal, subcortical, and cortical motor networks involved in the control of back muscles were not modified. However, once the pain disappeared, a reduction in motoneuronal excitability was observed without change in corticospinal and vestibulospinal excitability, suggesting a reduction in descending drive. Experimental low back pain may elicit long-term plasticity even after pain extinction.

Can training of a skilled pelvic movement change corticomotor control of back muscles? Comparison of single and paired-pulse transcranial magnetic stimulation.

Evidence suggests excitability of the motor cortex (M1) changes in response to motor skill learning of the upper limb. Few studies have examined immediate changes in corticospinal excitability and intra‐cortical mechanisms following motor learning in the lower back. Further, it is unknown which transcranial magnetic stimulation (TMS) paradigms are likely to reveal changes in cortical function in this region. This study aimed to (1) compare corticospinal excitability and intra‐cortical mechanisms in the lower back region of M1 before and after a single session of lumbopelvic tilt motor learning task in healthy people and (2) compare these measures between two TMS coils and two methods of recruitment curve (RC) acquisition. Twenty‐eight young participants (23.6 ± 4.6 years) completed a lumbopelvic tilting task involving three 5‐min blocks. Single‐pulse (RC from 70% to 150% of active motor threshold) and paired‐pulse TMS measures (ICF, SICF and SICI) were undertaken before (using 2 coils: figure‐of‐8 and double cone) and after (using double cone coil only) training. RCs were also acquired using a traditional and rapid method. A significant increase in corticospinal excitability was found after training as measured by RC intensities, but this was not related to the RC slope. No significant differences were found for paired‐pulse measures after training. Finally, there was good agreement between RC parameters when measured with the two different TMS coils or different acquisition methods (traditional vs. rapid). Changes in corticospinal excitability after a single session of lumbopelvic motor learning task are seen, but these changes are not explained by changes in intra‐cortical mechanisms.

Cerebellar Transcranial Direct Current Stimulation in Spinocerebellar Ataxia Type 3: a Randomized, Double-Blind, Sham-Controlled Trial

Repeated sessions of cerebellar anodal transcranial direct current stimulation (tDCS) have been suggested to modulate cerebellar-motor cortex (M1) connectivity and decrease ataxia severity. However, therapeutic trials involving etiologically homogeneous groups of ataxia patients are lacking. The objective of this study was to investigate if a two-week regimen of daily cerebellar tDCS sessions diminishes ataxia and non-motor symptom severity and alters cerebellar-M1 connectivity in individuals with spinocerebellar ataxia type 3 (SCA3). We conducted a randomized, double-blind, sham-controlled trial in which twenty mildly to moderately affected SCA3 patients received ten sessions of real or sham cerebellar tDCS (i.e., five days per week for two consecutive weeks). Effects were evaluated after two weeks, three months, six months, and twelve months. Change in Scale for the Assessment and Rating of Ataxia (SARA) score after two weeks was defined as the primary endpoint. Static posturography, SCA Functional Index tests, various patient-reported outcome measures, the cerebellar cognitive affective syndrome scale, and paired-pulse transcranial magnetic stimulation to examine cerebellar brain inhibition (CBI) served as secondary endpoints. Absolute change in SARA score did not differ between both trial arms at any of the time points. We observed significant short-term improvements in several motor, cognitive, and patient-reported outcomes after the last stimulation session in both groups but no treatment effects in favor of real tDCS. Nonetheless, some of the patients in the intervention arm showed a sustained reduction in SARA score lasting six or even twelve months, indicating interindividual variability in treatment response. CBI, which reflects the functional integrity of the cerebellothalamocortical tract, remained unchanged after ten tDCS sessions. Albeit exploratory, there was some indication for between-group differences in SARA speech score after six and twelve months and in the number of extracerebellar signs after three and six months. Taken together, our study does not provide evidence that a two-week treatment with daily cerebellar tDCS sessions reduces ataxia severity or restores cerebellar-M1 connectivity in early-to-middle-stage SCA3 patients at the group level. In order to potentially increase therapeutic efficacy, further research is warranted to identify individual predictors of symptomatic improvement.

Morphine Consumption During Lactation Impairs Short-Term Neuronal Plasticity in Rat Offspring CA1 Neurons

Background: Facing environmental factors during early postnatal life, directly or indirectly via mother-infant relationships, profoundly affects the structure and function of the mammals’ Central Nervous System (CNS). Objectives: This study aimed to evaluate the effect of morphine consumption during the lactation period on short-term synaptic plasticity of the hippocampal Cornu Ammonis 1 (CA1) neurons in rat offspring. Materials &amp; Methods: In addition to a group of control mother rats (CO), three groups subcutaneously received 5 (M5), 10 (M10), or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, following the stimulation of the Schaffers’ collaterals, basic field Excitatory Post-Synaptic Potentials (fEPSPs) were recorded in their offspring’s hippocampal CA1 neuronal circuits. After the construction input/output curve, paired-pulse stimulations with the inter-stimulus intervals of 20, 80, and 200 ms were applied to determine the short-term synaptic plasticity, and the paired-pulse ratio was evaluated. Results: The baseline synaptic responses of the rats CA1 neurons whose mothers received 10 and 20 mg/kg morphine twice daily during the lactation period decreased compared to the CO animals (P&lt;0.01 &amp; P&lt;0.001, respectively). Furthermore, compared to the controls, the Paired-Pulse Ratio (PPR) of the CA1 neural circuits of M10 and M20 rats at 20 and 80 ms Inter-Stimulus Intervals (ISI) decreased (P&lt;0.01). Conclusion: Morphine exposure during the lactation period has a detrimental impact on the primary synaptic activity and short-term synaptic plasticity of the hippocampal CA1 neuronal circuits of rats’ offspring.

The use of surface EMG in neurorehabilitation following traumatic spinal cord injury: A scoping review

ObjectiveSurface electromyography (sEMG) is a common electrophysiological assessment used in clinical trials in individuals with spinal cord injury (SCI). This scoping review summarizes the most common sEMG techniques used to address clinically relevant neurorehabilitation questions. We focused on the role of sEMG assessments in the clinical practice and research studies on neurorehabilitation after SCI, and how sEMG reflects the changes observed with rehabilitation. Additionally, this review emphasizes the limitations and pitfalls of the sEMG assessments in the field of neurorehabilitation after SCI. MethodsA comprehensive search of Medline (Ovid), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, Emcare, Cumulative Index to Nursing & Allied Health Literature, and PubMed was conducted to find peer-reviewed journal articles that included individuals post-SCI that participated in neurorehabilitation interventions using sEMG assessments. This is a scoping review using a systematic search (hybrid review). ResultsOf 4522 references captured in the primary database searches, 100 references were selected and included in the scoping review. The main focus of the studies was on neurorehabilitation using sEMG biofeedback, brain stimulation, locomotor training, neuromuscular electrical stimulation (NMES), paired-pulse stimulation, pharmacology, posture and balance training, spinal cord stimulation, upper limb training, vibration, and photobiomodulation. ConclusionsMost studies employed sEMG amplitude to understand the effects of neurorehabilitation on muscle activation during volitional efforts or reduction of spontaneous muscle activity (e.g., spasms, spasticity, and hypertonia). Further studies are needed to understand the long-term reliability of sEMG amplitude, to circumvent normalization issues, and to provide a deeper physiological background to the different sEMG analyses. SignificanceThis scoping review reveals the potential of sEMG in exploring promising neurorehabilitation strategies following SCI and discusses the barriers limiting its widespread use in the clinic.

Altered Visual Cortical Excitability Is Associated With Psychopathological Symptoms in Major Depressive Disorder.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.

Morphine Consumption During Lactation Impairs Short-Term Neuronal Plasticity in Rat Offspring CA1 Neurons

Background: Facing environmental factors during early postnatal life, directly or indirectly via mother-infant relationships, profoundly affects the structure and function of the mammals’ Central Nervous System (CNS). Objectives: This study aimed to evaluate the effect of morphine consumption during the lactation period on short-term synaptic plasticity of the hippocampal Cornu Ammonis 1 (CA1) neurons in rat offspring. Methods: In addition to a group of control mother rats (CO), three groups subcutaneously received 5 (M5), 10 (M10), or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, following the stimulation of the Schaffers’ collaterals, basic field Excitatory Post-Synaptic Potentials (fEPSPs) were recorded in their offspring's hippocampal CA1 neuronal circuits. After the construction input/output curve, paired-pulse stimulations with the inter-stimulus intervals of 20, 80, and 200 ms were applied to determine the short-term synaptic plasticity, and the paired-pulse ratio was evaluated. Results: The baseline synaptic responses of the rats CA1 neurons whose mothers received 10 and 20 mg/kg morphine twice daily during the lactation period decreased compared to the CO animals (P&lt;0.01 &amp; P&lt;0.001, respectively). Furthermore, compared to the controls, the Paired-Pulse Ratio (PPR) of the CA1 neural circuits of M10 and M20 rats at 20 and 80 ms Inter-Stimulus Intervals (ISI) decreased (P&lt;0.01). Conclusions: Morphine exposure during the lactation period has a detrimental impact on the primary synaptic activity and short-term synaptic plasticity of the hippocampal CA1 neuronal circuits of rats’ offspring.

Strengthening the GABAergic System Through Neurofeedback Training Suppresses Implicit Motor Learning

Gamma-aminobutyric acid (GABA) activity within the primary motor cortex (M1) is essential for motor learning in cortical plasticity, and a recent study has suggested that real-time neurofeedback training (NFT) can self-regulate GABA activity. Therefore, this study aimed to investigate the effect of GABA activity strengthening via NFT on subsequent motor learning. Thirty-six healthy participants were randomly assigned to either an NFT group or control group, which received sham feedback. GABA activity was assessed for short intracortical inhibition (SICI) within the right M1 using paired-pulse transcranial magnetic stimulation. During the NFT intervention period, the participants tried to modulate the size of a circle, which was altered according to the degree of SICI in the NFT group. However, the size was altered independently of the degree of SICI in the control group. We measured the reaction time before, after (online learning), and 24 h after (offline learning) the finger-tapping task. Results showed the strengthening of GABA activity induced by the NFT intervention, and the suppression of the online but not the offline learning. These findings suggest that prior GABA activity modulation may affect online motor learning.

Transsynaptic Long-Term Potentiation in the Hippocampus of Behaving Mice.

Long-term potentiation (LTP) is an experimental procedure that shares certain mechanisms with neuronal learning and memory processes and represents a well-known example of synaptic plasticity. LTP consists of an increase of the synaptic response to a control stimulus following the presentation of a high-frequency stimulation (HFS) train to an afferent pathway. This technique is studied mostly in the hippocampus due to the latter’s high susceptibility and its laminar nature which facilitates the location of defined synapses. Although most preceding studies have been performed in vitro, we have developed an experimental approach to carry out these experiments in alert behaving animals. The main goal of this study was to confirm the existence of synaptic changes in strength in synapses that are post-synaptic to the one presented with the HFS. We recorded field excitatory post-synaptic potentials (fEPSPs) evoked in five hippocampal synapses, from both hemispheres, of adult male mice. HFS was presented to the perforant pathway (PP). We characterized input/output curves, paired-pulse stimulation, and LTP of these synapses. We also performed depth-profile recordings to determine differences in fEPSP latencies. Collected data indicate that the five selected synapses have similar basic electrophysiological properties, a fact that enables an easier comparison of LTP characteristics. Importantly, we observed the presence of significant LTP in the contralateral CA1 (cCA1) area following the control stimulation of non-HFS-activated pathways. These results indicate that LTP appears as a physiological process present in synapses located far away from the HFS-stimulated afferent pathway.

Impact of interhemispheric inhibition on bimanual movement control in young and old

Interhemispheric interactions demonstrate a crucial role for directing bimanual movement control. In humans, a well-established paired-pulse transcranial magnetic stimulation paradigm enables to assess these interactions by means of interhemispheric inhibition (IHI). Previous studies have examined changes in IHI from the active to the resting primary motor cortex during unilateral muscle contractions; however, behavioral relevance of such changes is still inconclusive. In the present study, we evaluated two bimanual tasks, i.e., mirror activity and bimanual anti-phase tapping, to examine behavioral relevance of IHI for bimanual movement control within this behavioral framework. Two age groups (young and older) were evaluated as bimanual movement control demonstrates evident behavioral decline in older adults. Two types of IHI with differential underlying mechanisms were measured; IHI was tested at rest and during a motor task from the active to the resting primary motor cortex. Results demonstrate an association between behavior and short-latency IHI in the young group: larger short-latency IHI correlated with better bimanual movement control (i.e., less mirror activity and better bimanual anti-phase tapping). These results support the view that short-latency IHI represents a neurophysiological marker for the ability to suppress activity of the contralateral side, likely contributing to efficient bimanual movement control. This association was not observed in the older group, suggesting age-related functional changes of IHI. To determine underlying mechanisms of impaired bimanual movement control due to neurological disorders, it is crucial to have an in-depth understanding of age-related mechanisms to disentangle disorder-related mechanisms of impaired bimanual movement control from age-related ones.

Abnormal sensorimotor cortex and thalamo-cortical networks in familial adult myoclonic epilepsy type 2: pathophysiology and diagnostic implications.

Familial adult myoclonic epilepsy type 2 is a hereditary condition characterized by cortical tremor, myoclonus and epilepsy. It belongs to the spectrum of cortical myoclonus and the sensorimotor cortex hyperexcitability represents an important pathogenic mechanism underlying this condition. Besides pericentral cortical structures, the impairment of subcortical networks seems also to play a pathogenetic role, mainly via the thalamo-cortical pathway. However, the mechanisms underlying cortical–subcortical circuits dysfunction, as well as their impact on clinical manifestations, are still unknown. Therefore, the main aims of our study were to systematically study with an extensive electrophysiological battery, the cortical sensorimotor, as well as thalamo-cortical networks in genetically confirmed familial adult myoclonic epilepsy patients and to establish reliable neurophysiological biomarkers for the diagnosis.In 26 familial myoclonic epilepsy subjects, harbouring the intronic ATTTC repeat expansion in the StAR-related lipid transfer domain-containing 7 gene, 17 juvenile myoclonic epilepsy patients and 22 healthy controls, we evaluated the facilitatory and inhibitory circuits within the primary motor cortex using single and paired-pulse transcranial magnetic stimulation paradigms. We also probed the excitability of the somatosensory, as well as the thalamo-somatosensory cortex connection by using ad hoc somatosensory evoked potential protocols. The sensitivity and specificity of transcranial magnetic stimulation and somatosensory evoked potential metrics were derived from receiver operating curve analysis. Familial adult myoclonic epilepsy patients displayed increased facilitation and decreased inhibition within the sensorimotor cortex compared with juvenile myoclonic epilepsy patients (all P < 0.05) and healthy controls (all P < 0.05). Somatosensory evoked potential protocols also displayed a significant reduction of early high-frequency oscillations and less inhibition at paired-pulse protocol, suggesting a concomitant failure of thalamo-somatosensory cortex circuits. Disease onset and duration and myoclonus severity did not correlate either with sensorimotor hyperexcitability or thalamo-cortical measures (all P > 0.05). Patients with a longer disease duration had more severe myoclonus (r = 0.467, P = 0.02) associated with a lower frequency (r = −0.607, P = 0.001) and higher power of tremor (r = 0.479, P = 0.02). Finally, familial adult myoclonic epilepsy was reliably diagnosed using transcranial magnetic stimulation, demonstrating its superiority as a diagnostic factor compared to somatosensory evoked potential measures. In conclusion, deficits of sensorimotor cortical and thalamo-cortical circuits are involved in the pathophysiology of familial adult myoclonic epilepsy even if these alterations are not associated with clinical severity. Transcranial magnetic stimulation-based measurements display an overall higher accuracy than somatosensory evoked potential parameters to reliably distinguish familial adult myoclonic epilepsy from juvenile myoclonic epilepsy and healthy controls.