Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS-EEG study.

Major depressive disorder affects over 300 million people globally, with approximately 30% experiencing treatment-resistant depression (TRD). Given that impaired neuroplasticity underlies depression, the present study focused on neuroplasticity in the dorsolateral prefrontal cortex (DLPFC). Here, we aimed to investigate the differences in neuroplasticity between 60 individuals with TRD and 30 age- and sex-matched healthy controls (HCs). To induce neuroplasticity, participants underwent a paired associative stimulation (PAS) paradigm involving peripheral median nerve stimulation and transcranial magnetic stimulation (TMS) targeting the left DLPFC. Neuroplasticity was assessed by using measurements combining TMS with EEG before and after PAS. Both groups exhibited significant increases in the early component of TMS-evoked potentials (TEP) after PAS (P < 0.05, paired t-tests with the bootstrapping method). However, the HC group demonstrated a greater increase in TEPs than the TRD group (P = 0.045, paired t-tests). Additionally, event-related spectral perturbation analysis highlighted that the gamma power significantly increased after PAS in the HC group, whereas it was decreased in the TRD group (P < 0.05, paired t-tests with the bootstrapping method). This gamma power modulation revealed a significant group difference (P = 0.006, paired t-tests), indicating an inverse relationship for gamma power modulation. Our findings underscore the impaired neuroplasticity of the DLPFC in individuals with TRD.

Motor point stimulation activates fewer Ia-sensory nerves than peripheral nerve stimulation in human soleus muscle.

Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) are noninvasive techniques used to induce muscle contraction, aiding motor function restoration in individuals with neurological disorders. Understanding sensory inputs from PNS and MPS is crucial for facilitating neuroplasticity and restoring impaired motor function. Although previous studies suggest that MPS could induce Ia-sensory inputs less than PNS, experimental evidence supporting this claim is insufficient. Here, we implemented a conditioning paradigm combining transcutaneous spinal cord stimulation (tSCS) with PNS or MPS to investigate their Ia-sensory inputs. This paradigm induces postactivation depression of spinal reflexes associated with transient decreases in neurotransmitter release from Ia-afferent terminals, allowing us to examine the Ia-sensory input amount from PNS and MPS based on the depression degree. We hypothesized that MPS would induce less postactivation depression than PNS. Thirteen individuals underwent MPS and PNS on the soleus muscle as conditioning stimuli, with tSCS applied to the skin between the spinous processes (L1-L2) as test stimuli. PNS- and MPS-conditioned spinal reflexes were recorded at five interstimulus intervals (ISIs) and four intensities. Results revealed that all PNS conditioning showed significant decreases in spinal reflex amplitudes, indicating postactivation depression. Furthermore, PNS conditioning exhibited greater depression for shorter ISIs and higher conditioning intensities. In contrast, MPS conditioning demonstrated intensity-dependent depression, but without all-conditioning depression and clear ISI dependency as seen in PNS conditioning. In addition, PNS induced significantly greater depression than MPS across most conditions. Our findings provide experimental evidence supporting the conclusion that MPS activates Ia-sensory nerves less than PNS.NEW & NOTEWORTHY Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) induce neuroplasticity, but differences in their effects on Ia-sensory inputs are unclear. We investigated their Ia-sensory inputs using a conditioning paradigm with spinal reflexes. Results showed that PNS conditioning significantly inhibited spinal reflexes than MPS conditioning, indicating greater postactivation depression due to Ia-sensory nerve activation. These findings provide experimental evidence that MPS activates Ia-sensory nerves to a lesser extent than PNS, enhancing our understanding of neuroplasticity.

Distinct locomotor adaptation between conventional walking and walking with a walker.

Rolling walkers are common walking aids for individuals with poor physical fitness or balance impairments. There is no doubt that rolling walkers are useful in assisting locomotion. On the other hand, it is arguable that walking with rolling walkers (WW) is effective for maintaining or restoring the nervous systems that are recruited during conventional walking (CW). This is because the differences and similarities of the neural control of these locomotion forms remain unknown. The purpose of the present study was to compare the neural control of WW and CW from the perspective of a split-belt adaptation paradigm and reveal how the adaptations that take place in WW and CW would affect each other. The anterior component of the ground reaction (braking) forces was measured during and after walking on a split-belt treadmill by 10 healthy subjects, and differences in the peak braking forces between the left and right sides were calculated as the index of the split-belt adaptation (the degree of asymmetry). The results demonstrated that (1) WW enabled subjects to respond to the split-belt condition immediately after its start as compared to CW; (2) the asymmetry movement pattern acquired by the split-belt adaptation in one gait mode (i.e., CW or WW) was less transferable to the other gait mode; (3) the asymmetry movement pattern acquired by the split-belt adaptation in CW was not completely washed out by subsequent execution in WW and vice versa. The results suggest unique control of WW and the specificity of neural control between WW and CW; use of the walkers is not necessarily appropriate as training for CW from the perspective of neural control.

F-waves induced by motor point stimulation are facilitated during handgrip and motor imagery tasks.

The F-wave is a motor response elicited via the antidromic firings of motor nerves by the electrical stimulation of peripheral nerves, which reflects the motoneuron pool excitability. However, the F-wave generally has low robustness i.e., low persistence and small amplitude. We recently found that motor point stimulation (MPS), which provides the muscle belly with electrical stimulation, shows different neural responses compared to nerve stimulation, e.g., MPS elicits F-waves more robustly than nerve stimulation. Here, we investigated whether F-waves induced by MPS can identify changes in motoneuron pool excitability during handgrip and motor imagery. Twelve participants participated in the present study. We applied MPS on their soleus muscle and recorded F-waves during eyes-open (EO), eyes-closed (EC), handgrip (HG), and motor imagery (MI) conditions. In the EO and EC conditions, participants relaxed with their eyes open and closed, respectively. In the HG, participants matched the handgrip force level to 30% of the maximum voluntary force with visual feedback. In the MI, they performed kinesthetic MI of plantarflexion at the maximal strength with closed eyes. In the HG and MI, the amplitudes of the F-waves induced by MPS were increased compared with those in the EO and EC, respectively. These results indicate that the motoneuron pool excitability was facilitated during the HG and MI conditions, consistent with findings in previous studies. Our findings suggest that F-waves elicited by MPS can be a good tool in human neurophysiology to assess the motoneuron pool excitability during cognitive and motor tasks.

Motor point stimulation induces more robust F-waves than peripheral nerve stimulation.

The F-wave is a motor response induced by electrical stimulation of peripheral nerves via the antidromic firing of motor nerves, which reflects the motoneuron excitability. To induce F-waves, transcutaneous peripheral nerve stimulation (PNS) is used, which activates nerve branches via transcutaneous electrodes over the nerve branches. An alternative method to activate peripheral nerves, that is, motor point stimulation (MPS), which delivers electrical stimulation over the muscle belly, has not been used to induce F-waves. In our previous studies, we observed that MPS induced F-wave-like responses, that is, motor responses at the latency of F-waves at a supramaximal stimulation. Here, we further investigated the F-wave-like responses induced by MPS in comparison with PNS in the soleus muscle. Thirteen individuals participated in this study. We applied MPS and PNS on the participant's left soleus muscle. Using a monopolar double-pulse stimulation, the amplitude of the second H-reflex induced by PNS decreased, whereas the amplitude of the motor response at the F-wave latency induced by MPS did not decrease. These results suggest that the motor response at the F-wave latency induced by MPS was not an H-reflex but an F-wave. We also found that the F-wave induced by MPS had a greater amplitude and higher persistence and caused less pain when compared with the F-waves induced using PNS. We conclude that MPS evokes antidromic firing inducing F-waves more consistently compared with PNS.

Corticospinal excitability and somatosensory information processing of the lower limb muscle during upper limb voluntary or electrically induced muscle contractions.

Neural interactions between upper and lower limbs underlie motor coordination in humans. Specifically, upper limb voluntary muscle contraction can facilitate spinal and corticospinal excitability of the lower limb muscles. However, little remains known on the involvement of somatosensory information in arm-leg neural interactions. Here, we investigated effects of voluntary and electrically induced wrist flexion on corticospinal excitability and somatosensory information processing of the lower limbs. In Experiment 1, we measured transcranial magnetic stimulation (TMS)-evoked motor evoked potentials (MEPs) of the resting soleus (SOL) muscle at rest or during voluntary or neuromuscular electrical stimulation (NMES)-induced wrist flexion. The wrist flexion force was matched to 10% of the maximum voluntary contraction (MVC). We found that SOL MEPs were significantly increased during voluntary, but not NMES-induced, wrist flexion, compared to the rest (P < .001). In Experiment 2, we examined somatosensory evoked potentials (SEPs) following tibial nerve stimulation under the same conditions. The results showed that SEPs were unchanged during both voluntary and NMES-induced wrist flexion. In Experiment 3, we examined the modulation of SEPs during 10%, 20% and 30% MVC voluntary wrist flexion. During 30% MVC voluntary wrist flexion, P50-N70 SEP component was significantly attenuated compared to the rest (P = .003). Our results propose that the somatosensory information generated by NMES-induced upper limb muscle contractions may have a limited effect on corticospinal excitability and somatosensory information processing of the lower limbs. However, voluntary wrist flexion modulated corticospinal excitability and somatosensory information processing of the lower limbs via motor areas.

Phase dependent modulation of cortical activity during action observation and motor imagery of walking: An EEG study.

Action observation (AO) and motor imagery (MI) are motor simulations which induce cortical activity related to execution of observed and imagined movements. Neuroimaging studies have mainly investigated where the cortical activities during AO and MI of movements are activated and if they match those activated during execution of the movements. However, it remains unclear how cortical activity is modulated; in particular, whether activity depends on observed or imagined phases of movements. We have previously examined the neural mechanisms underlying AO and MI of walking, focusing on the combined effect of AO with MI (AO+MI) and phase dependent modulation of corticospinal and spinal reflex excitability. Here, as a continuation of our previous studies, we investigated cortical activity depending on gait phases during AO and AO+MI of walking by using electroencephalography (EEG); 64-channel EEG signals were recorded in which participants observed walking with or without imagining it, respectively. EEG source and spectral analyses showed that, in the sensorimotor cortex during AO+MI and AO, the alpha and beta power were decreased, and power spectral modulations depended on walking phases. The phase dependent modulations during AO+MI, but not during AO, were like those which occur during actual walking as reported by previous walking studies. These results suggest that combinatory effects of AO+MI could induce parts of the phase dependent activation of the sensorimotor cortex during walking even without any movements. These findings would extend understanding of the neural mechanisms underlying walking and cognitive motor processes and provide clinically beneficial information towards rehabilitation for patients with neurological gait dysfunctions.

Gait-phase-dependent and gait-phase-independent cortical activity across multiple regions involved in voluntary gait modifications in humans.

Modification of ongoing walking movement to fit changes in external environments requires accurate voluntary control. In cats, the motor and posterior parietal cortices have crucial roles for precisely adjusting limb trajectory during walking. In human walking, however, it remains unclear which cortical information contributes to voluntary gait modification. In this study, we investigated cortical activity changes associated with visually guided precision stepping using electroencephalography source analysis. Our results demonstrated frequency- and gait-event-dependent changes in the cortical power spectrum elicited by voluntary gait modification. The main differences between normal walking and precision stepping were as follows: (a) the alpha, beta or gamma power decrease during the swing phases in the sensorimotor, anterior cingulate and parieto-occipital cortices, and (b) a power decrease in the theta, alpha and beta bands and increase in the gamma band throughout the gait cycle in the parieto-occipital cortex. Based on the previous knowledge of brain functions, the former change was considered to be related to execution and planning of leg movement, while the latter change was considered to be related to multisensory integration and motor awareness. Therefore, our results suggest that the gait modification is achieved by higher cortical involvements associated with different sensorimotor-related functions across multiple cortical regions including the sensorimotor, anterior cingulate and parieto-occipital cortices. The results imply the critical importance of the cortical contribution to voluntary modification in human locomotion. Further, the observed cortical information related to voluntary gait modification would contribute to developing volitional control systems of brain-machine interfaces for walking rehabilitation.

Interlimb neural interactions in corticospinal and spinal reflex circuits during preparation and execution of isometric elbow flexion.

Although coordinated and simultaneous movement of upper and lower limb muscles is required for activities of daily living, interlimb neural interaction mechanisms and their nature are yet to be fully elucidated. The purpose of this study was to investigate effects of motor preparation and execution of ipsilateral, contralateral, and bilateral upper limb muscle contractions on the excitability of corticospinal and spinal reflex circuits of the lower limb muscles. Fourteen able-bodied individuals were recruited in each study. Experiments were conducted to investigate 1) corticospinal excitability with transcranial magnetic stimulation applied on the primary motor cortex to evoke motor evoked potentials (MEPs) and 2) spinal reflex excitability with transcutaneous spinal cord stimulation applied at the lumbothoracic level to evoke spinal reflexes. Measurements were recorded from multiple right lower limb muscles simultaneously during 1) ipsilateral (right), 2) contralateral (left), and 3) bilateral (right and left) elbow flexion. The results indicate that MEPs in lower limb muscles were facilitated during both preparation and execution of elbow flexion, whereas spinal reflexes were facilitated only during motor execution. Moreover, the extent of facilitation did not differ between right, left, and bilateral contractions. In conclusion, motor preparation for upper limb muscle contractions did not affect spinal circuits but seemed to affect the supraspinal networks controlling lower limb muscles. However, actual contraction (motor execution) of upper limb muscles is required to facilitate spinal reflex circuits controlling the lower limb muscles. Moreover, interlimb remote facilitation in corticospinal and spinal reflex circuits did not depend on whether contralateral or ipsilateral hands were contracted or if they were contracted bilaterally.NEW & NOTEWORTHY We found that upper limb muscle contractions facilitated corticospinal circuits controlling lower limb muscles even during motor preparation, whereas motor execution of the task was required to facilitate spinal circuits. We also found that facilitation did not depend on whether contralateral or ipsilateral hands were contracted or if they were contracted bilaterally. Overall, these findings suggest that training of unaffected upper limbs may be useful to enhance facilitation of affected lower limbs in paraplegic individuals.

Spatiotemporal characteristics of locomotor adaptation of walking with two handheld poles.

Pole walking (PW) has received attention not only as a whole-body exercise that can be adapted for elderly people with poor physical fitness but also as a possible intervention for the restoration of gait function in normal walking without the use of poles (i.e., conventional walking CW). However, the characteristics of PW, especially how and why PW training affects CW, remain unclear. The purpose of this study was to examine the characteristics of locomotor adaptation in PW from the perspective of kinematic variables. For this purpose, we compared the locomotor adaptation in PW and CW to that when walking on a split-belt treadmill in terms of spatial and temporal coordination. The result showed that adaptations to the split-belt treadmill in PW and CW were found only in interlimb parameters (step length and double support time ratios (fast/slow limb)), not in intralimb parameters (stride length and stance time ratios). In these interlimb parameters, the movement patterns acquired through split-belt locomotor adaptations (i.e., the aftereffects) were transferred between CW and PW regardless of whether the novel movement patterns were learned in CW or PW. The aftereffects of double support time and step length learned in CW were completely washed out by the subsequent execution in PW. On the other hand, the aftereffect of double support time learned in PW was not completely washed out by the subsequent execution in CW, whereas the aftereffect of step length learned in PW was completely washed out by the subsequent execution in CW. These results suggest that the neural mechanisms related to controlling interlimb parameters are shared between CW and PW, and it is possible that, in interlimb coordination, temporal coordination is preferentially stored in adaptation during PW.

Remote muscle contraction enhances spinal reflexes in multiple lower-limb muscles elicited by transcutaneous spinal cord stimulation.

Transcutaneous spinal cord stimulation (tSCS) is a useful technique for the clinical assessment of neurological disorders. However, the characteristics of the spinal cord circuits activated by tSCS are not yet fully understood. In this study, we examined whether remote muscle contraction enhances the spinal reflexes evoked by tSCS in multiple lower-limb muscles. Eight healthy men participated in the current experiment, which required them to grip a dynamometer as fast as possible after the presentation of an auditory cue. Spinal reflexes were evoked in multiple lower-limb muscles with different time intervals (50-400 ms) after the auditory signals. The amplitudes of the spinal reflexes in all the recorded leg muscles significantly increased at 50-250 ms after remote muscle activation onset. This suggests that remote muscle contraction simultaneously facilitates the spinal reflexes in multiple lower-limb muscles. In addition, eight healthy men performed five different tasks (i.e., rest, hand grip, pinch grip, elbow flexion, and shoulder flexion). Compared to control values recorded just before each task, the spinal reflexes evoked at 250 ms after the auditory signals were significantly enhanced by the above tasks except for the rest task. This indicates that such facilitatory effects are also induced by remote muscle contractions in different upper-limb areas. The present results demonstrate the existence of a neural interaction between remote upper-limb muscles and spinal reflex circuits activated by tSCS in multiple lower-limb muscles. The combination of tSCS and remote muscle contraction may be useful for the neurological examination of spinal cord circuits.

Accurate digitization of EEG electrode locations by electromagnetic tracking system: The proposed head rotation method and comparison against optical system.

Electroencephalogram (EEG) electrode digitization is crucial for accurate EEG source estimation, and several commercial systems are available for this purpose. The present study aimed to evaluate the digitizing accuracy of electromagnetic and optical systems. Additionally, we introduced a novel rotation method for the electromagnetic system and compared its accuracy with the conventional method of electromagnetic and optical systems. In the conventional method, the operator moves around a stationary participant to digitize, while the participant does not move their head or body. In contrast, in our proposed rotation method with an electromagnetic system, the operator rotates the participant sitting on a swivel chair to digitize in a consistent position. We showed high localization accuracy in both the optical and electromagnetic systems, with an average localization error of less than 3.6 mm. Comparisons of the digitization methods revealed that the electromagnetic system demonstrates superior digitizing accuracy compared to the optical system. Notably, the proposed rotational method is the most accurate among the three methods, which can be attributed to the consistent positioning of EEG electrode digitization within the electromagnetic field. Considering the affordability of the electromagnetic system, our findings provide valuable insights for researchers aiming for precise EEG source estimation.•The study compares the accuracy of electromagnetic and optical systems for EEG electrode digitization, introducing a novel rotation method for improved consistency and precision.•The electromagnetic system, especially with the proposed rotation method, achieves superior digitizing accuracy over the optical system.•Highlighting the cost-effectiveness and precision of the electromagnetic system with the rotation method, this research offers significant insights for achieving precise EEG source estimation.

High-skilled first-person shooting game players have specific frontal lobe activity: Power spectrum analysis in an electroencephalogram study.

First-person shooting (FPS) games are among the most famous video games worldwide. However, cortical activities in environments related to real FPS games have not been studied. This study aimed to determine differences in cortical activity between low- and high-skilled FPS game players using 160-channel electroencephalography. Nine high-skilled FPS game players (official ranks: above the top 10%) and eight low-skilled FPS game players (official ranks: lower than the top 20%) were recruited for the experiment. The task was set for five different conditions using the AimLab program, which was used for the FPS game players' training. Additionally, we recorded the brain activity in the resting condition before and after the task, in which the participants closed their eyes and relaxed. The reaction time and accuracy (the number of hit-and-miss targets) were calculated to evaluate the task performance. The results showed that high-skilled FPS game players have fast reaction times and high accuracy during tasks. High-skilled FPS game players had higher cortical activity in the frontal cortex than low-skilled FPS game players during each task. In low-skilled players, cortical activity level and performance level were associated. These results suggest that high cortical activity levels were critical to achieving high performance in FPS games.

Modulation of lower limb muscle corticospinal excitability during various types of motor imagery.

Motor imagery (MI) is used for rehabilitation and sports training. Previous studies focusing on the upper limb have investigated the effects of MI on corticospinal excitability in the muscles involved in the imagined movement (i.e., the agonist muscles). The present study focused on several lower-limb movements and investigated the influences of MI on corticospinal excitability in the lower limb muscles. Twelve healthy individuals (ten male and two female individuals) participated in this study. Motor-evoked potentials (MEP) from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles were elicited through transcranial magnetic stimulation (TMS) to the primary motor cortex during MI of knee extension, knee flexion, ankle dorsiflexion, and ankle plantarflexion and at rest. The results showed that the RF MEPs were significantly increased during MI in knee extension, ankle dorsiflexion, and ankle plantarflexion but not in knee flexion, compared with those at rest. The TA MEPs were significantly increased during MI in knee extension and foot dorsiflexion, while MEPs were not significantly different during MI in knee flexion and foot dorsiflexion than those at rest. For the BF and SOL muscles, there was no significant MEP modulation in either MI. These results demonstrated that corticospinal excitability of the RF and TA muscles was facilitated during MI of movements in which they are active and during MI of lower-limb movements in which they are not involved. On the contrary, corticospinal excitability of the BF and SOL muscles was not facilitated by MI of lower-limb movements. These results suggest that facilitation of corticospinal excitability depends on the muscle and the type of lower-limb MI.

Effects of finger pinch motor imagery on short-latency afferent inhibition and corticospinal excitability.

Motor imagery is a cognitive process involving the simulation of motor actions without actual movements. Despite the reported positive effects of motor imagery training on motor function, the underlying neurophysiological mechanisms have yet to be fully elucidated. Therefore, the purpose of the present study was to investigate how sustained tonic finger-pinching motor imagery modulates sensorimotor integration and corticospinal excitability using short-latency afferent inhibition (SAI) and single-pulse transcranial magnetic stimulation (TMS) assessments, respectively. Able-bodied individuals participated in the study and assessments were conducted under two experimental conditions in a randomized order between participants: (1) participants performed motor imagery of a pinch task while observing a visual image displayed on a monitor (Motor Imagery), and (2) participants remained at rest with their eyes fixed on the monitor displaying a cross mark (Control). For each condition, sensorimotor integration and corticospinal excitability were evaluated during sustained tonic motor imagery in separate sessions. Sensorimotor integration was assessed by SAI responses, representing inhibition of motor-evoked potentials (MEPs) in the first dorsal interosseous muscle elicited by TMS following median nerve stimulation. Corticospinal excitability was assessed by MEP responses elicited by single-pulse TMS. There was no significant difference in the magnitude of SAI responses between motor imagery and Control conditions, while MEP responses were significantly facilitated during the Motor Imagery condition compared to the Control condition. These findings suggest that motor imagery facilitates corticospinal excitability, without altering sensorimotor integration, possibly due to insufficient activation of the somatosensory circuits or lack of afferent feedback during sustained tonic motor imagery.

Effects of arousal and valence on center of pressure and ankle muscle activity during quiet standing.

Emotion affects postural control during quiet standing. Emotional states can be defined as two-dimensional models comprising valence (pleasant/unpleasant) and arousal (aroused/calm). Most previous studies have investigated the effects of valence on postural control without considering arousal. In addition, studies have focused on the center of pressure (COP) trajectory to examine emotional effects on the quiet standing control; however, the relationship between neuromuscular mechanisms and the emotionally affected quiet standing control is largely unknown. This study aimed to investigate the effects of arousal and valence on the COP trajectory and ankle muscle activity during quiet standing. Twenty-two participants were instructed to stand on a force platform and look at affective pictures for 72 seconds. The tasks were repeated six times, according to the picture conditions composed of arousal (High and Low) and valence (Pleasant, Neutral, and Unpleasant). During the task, the COP, electromyogram (EMG) of the tibialis anterior and soleus muscles, and electrocardiogram (ECG) were recorded. The heart rate calculated from the ECG was significantly affected by valence; the value was lower in Unpleasant than that in Neutral and Pleasant. The 95% confidence ellipse area and standard deviation of COP in the anterior-posterior direction were lower, and the mean power frequency of COP in the anterior-posterior direction was higher in Unpleasant than in Pleasant. Although the mean velocity of the COP in the medio-lateral direction was significantly lower in Unpleasant than in Pleasant, the effect was observed only when arousal was low. Although the EMG variables were not significantly affected by emotional conditions, some EMG variables were significantly correlated with the COP variables that were affected by emotional conditions. Therefore, ankle muscle activity may be partially associated with postural changes triggered by emotional intervention. In conclusion, both valence and arousal affect the COP variables, and ankle muscle activity may be partially associated with these COP changes.

Neurophysiological profiles of patients with bipolar disorders as probed with transcranial magnetic stimulation: A systematic review.

AIM: Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations, highlighting the need for a better understanding of the neurophysiology of BD for early diagnosis and novel therapeutic strategies. DESIGN: Employing a systematic review approach of the PRISMA guidelines, this study assessed the usefulness and validity of transcranial magnetic stimulation (TMS) neurophysiology in patients with BD. METHODS: Databases searched included PubMed, MEDLINE, Embase, and PsycINFO, covering studies from January 1985 to January 2024. RESULTS: Out of 6597 articles screened, nine studies met the inclusion criteria, providing neurophysiological insights into the pathophysiological basis of BD using TMS-electromyography and TMS-electroencephalography methods. Findings revealed significant neurophysiological impairments in patients with BD compared to healthy controls, specifically in cortical inhibition and excitability. In particular, short-interval cortical inhibition (SICI) was consistently diminished in BD across the studies, which suggests a fundamental impairment of cortical inhibitory function in BD. This systematic review corroborates the potential utility of TMS neurophysiology in elucidating the pathophysiological basis of BD. Specifically, the reduced cortical inhibition in the SICI paradigm observed in patients with BD suggests gamma-aminobutyric acid (GABA)-A receptor-mediated dysfunction, but results from other TMS paradigms have been inconsistent. Thus, complex neurophysiological processes may be involved in the pathological basis underlying BD. This study demonstrated that BD has a neural basis involving impaired GABAergic function, and it is highly expected that further research on TMS neurophysiology will further elucidate the pathophysiological basis of BD.

Reciprocal inhibition of the thigh muscles in humans: A study using transcutaneous spinal cord stimulation.

Evaluating reciprocal inhibition of the thigh muscles is important to investigate the neural circuits of locomotor behaviors. However, measurements of reciprocal inhibition of thigh muscles using spinal reflex, such as H-reflex, have never been systematically established owing to methodological limitations. The present study aimed to clarify the existence of reciprocal inhibition in the thigh muscles using transcutaneous spinal cord stimulation (tSCS). Twenty able-bodied male individuals were enrolled. We evoked spinal reflex from the biceps femoris muscle (BF) by tSCS on the lumber posterior root. We examined whether the tSCS-evoked BF reflex was reciprocally inhibited by the following conditionings: (1) single-pulse electrical stimulation on the femoral nerve innervating the rectus femoris muscle (RF) at various inter-stimulus intervals in the resting condition; (2) voluntary contraction of the RF; and (3) vibration stimulus on the RF. The BF reflex was significantly inhibited when the conditioning electrical stimulation was delivered at 10 and 20 ms prior to tSCS, during voluntary contraction of the RF, and during vibration on the RF. These data suggested a piece of evidence of the existence of reciprocal inhibition from the RF to the BF muscle in humans and highlighted the utility of methods for evaluating reciprocal inhibition of the thigh muscles using tSCS.

Fear in action: Fear conditioning and alleviation through body movements.

Fear memories enhance survival especially when the memories guide defensive movements to minimize harm. Accordingly, fear memories and body movements have tight relationships in animals: Fear memory acquisition results in adapting reactive defense movements, while training active defense movements reduces fear memory. However, evidence in humans is scarce because their movements are typically suppressed in experiments. Here, we tracked adult participants' body motions while they underwent ecologically valid fear conditioning in a 3D virtual space. First, with body motion tracking, we revealed that distinct spatiotemporal body movement patterns emerge through fear conditioning. Second, subsequent training to actively avoid threats with naturalistic defensive actions led to a long-term (24 h) reduction of physiological and embodied conditioned responses, while extinction or vicarious training only transiently reduced the responses. Together, our results highlight the role of body movements in human fear memory and its intervention.

Paired associative stimulation on the soleus H-Reflex using motor point and peripheral nerve stimulation.

Paired associative stimulation (PAS) has been shown to modulate the corticospinal excitability via spike timing dependent plasticity (STDP). In this study, we aimed to suppress the spinal H-Reflex using PAS. We paired two stimulation modalities, i.e., peripheral nerve stimulation (PNS) and motor point stimulation (MPS). We used PNS to dominantly activate the Ia sensory axon, and we used MPS to dominantly activate the α-motoneuron cell body antidromically. Thus, we applied both PNS and MPS such that the α-motoneuron cell body was activated 5 ms before the activation of the Ia sensory axon ending at the Ia-α motoneuron synapse. If the spinal reflexes can be modulated by STDP, and a combination of MPS and PNS is timed appropriately, then the H-Reflex amplitude will decrease while no change in H-Reflex amplitude is expected for MPS or PNS only. To test this hypothesis, six young healthy participants (5M/1F: 26.8 ± 4.1 yrs) received one of the three following conditions on days separated by at least 24 hr: 1) PAS, 2) MPS only or 3) PNS only. The H-Reflex and M-wave recruitment curves of the soleus were measured immediately prior to, immediately after, 30 min and 60 min after the intervention. The normalized H-Reflex amplitudes were then compared across conditions and times using a two-way ANOVA (3 conditions × 4 times). No main effects of condition or time, or interaction effect were found. These results suggest that relying solely on STDP may be insufficient to inhibit the soleus H-Reflex.