The neuronal and synaptic dynamics underlying post-inhibitory rebound burst related to major depressive disorder in the lateral habenula neuron model.

A burst behavior observed in the lateral habenula (LHb) neuron related to major depressive disorder has attracted much attention. The burst is induced from silence by the excitatory N-methyl-D-aspartate (NMDA) synapse or by the inhibitory stimulation, i.e., a post-inhibitory rebound (PIR) burst, which has not been explained clearly. In the present paper, the neuronal and synaptic dynamics for the PIR burst are acquired in a theoretical neuron model. At first, dynamic cooperations between the fast rise of inhibitory γ-aminobutyric acid (GABA) synapse, slow rise of NMDA synapse, and T-type calcium current to evoke the PIR burst are obtained. Similar to the inhibitory pulse stimulation, fast rising GABA current can reduce the membrane potential to a level low enough to de-inactivate the low threshold T-type calcium current to evoke a PIR spike, which can enhance the slow rising NMDA current activated at a time before or after the PIR spike. The NMDA current following the PIR spike exhibits slow decay to induce multiple spikes to form the PIR burst. Such results present a theoretical explanation and a candidate for the PIR burst in real LHb neurons. Then, the dynamical mechanism for the PIR spike mediated by the T-type calcium channel is obtained. At large conductance of T-type calcium channel, the resting state corresponds to a stable focus near Hopf bifurcation and exhibits an "uncommon" threshold curve with membrane potential much lower than the resting membrane potential. Inhibitory modulation induces membrane potential decreased to run across the threshold curve to evoke the PIR spike. At small conductance of the T-type calcium channel, a stable node appears and manifests a common threshold curve with higher membrane potential, resulting in non-PIR phenomenon. The results present the dynamic cooperations between neuronal dynamics and fast/slow dynamics of different synapses for the PIR burst observed in the LHb neuron, which is helpful for the modulations to major depressive disorder.

Sex differences of signal complexity at resting-state functional magnetic resonance imaging and their associations with the estrogen-signaling pathway in the brain.

Sex differences in the brain have been widely reported and may hold the key to elucidating sex differences in many medical conditions and drug response. However, the molecular correlates of these sex differences in structural and functional brain measures in the human brain remain unclear. Herein, we used sample entropy (SampEn) to quantify the signal complexity of resting-state functional magnetic resonance imaging (rsfMRI) in a large neuroimaging cohort (N = 1,642). The frontoparietal control network and the cingulo-opercular network had high signal complexity while the cerebellar and sensory motor networks had low signal complexity in both men and women. Compared with those in male brains, we found greater signal complexity in all functional brain networks in female brains with the default mode network exhibiting the largest sex difference. Using the gene expression data in brain tissues, we identified genes that were significantly associated with sex differences in brain signal complexity. The significant genes were enriched in the gene sets that were differentially expressed between the brain cortex and other tissues, the estrogen-signaling pathway, and the biological function of neural plasticity. In particular, the G-protein-coupled estrogen receptor 1 gene in the estrogen-signaling pathway was expressed more in brain regions with greater sex differences in SampEn. In conclusion, greater complexity in female brains may reflect the interactions between sex hormone fluctuations and neuromodulation of estrogen in women. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09954-y.

Influence of inhibitory autapses on synchronization of inhibitory network gamma oscillations.

A recent experimental study showed that inhibitory autapses favor firing synchronization of parvalbumin interneurons in the neocortex during gamma oscillations. In the present paper, to provide a comprehensive and deep understanding to the experimental observation, the influence of inhibitory autapses on synchronization of interneuronal network gamma oscillations is theoretically investigated. Weak, middle, and strong synchronizations of a globally inhibitory coupled network composed of Wang-Buzsáki model without autapses appear at the bottom-left, middle, and top-right of the parameter plane with the conductance (gsyn) and the decay constant (τsyn) of inhibitory synapses taken as the x-axis and y-axis, respectively. After introducing inhibitory autapses, the border between the strong and middle synchronizations in the (gsyn, τsyn) plane moves to the top-right with increasing the conductance (gaut) and the decay constant (τaut) of autapses, due to that interspike interval of the single neuron becomes longer, leading to that larger τsyn is needed to ensure the strong synchronization. Then, the synchronization degree of middle and strong synchronizations around the border in the (gsyn, τsyn) plane decreases, while of strong synchronization in the remaining region remains unchanged. The synchronization degree of weak synchronization increases with increasing τaut and gaut, due to that the inhibitory autaptic current becomes strong and long to facilitate synchronization. The enhancement of weak synchronization modulated by inhibitory autapses is also simulated in the random, small-world, and scale-free networks, which may provide explanations to the experimental observation. These results present complex dynamics of synchronization modulated by inhibitory autapses, which needs future experimental demonstrations.

Effects of repetitive peripheral magnetic stimulation on spasticity evaluated with modified Ashworth scale/Ashworth scale in patients with spastic paralysis: A systematic review and meta-analysis.

Background: Spasticity is a common motor disorder resulting from upper motor neuron lesions. It has a serious influence on an individual's motor function and daily activity. Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive and painless approach developed for therapeutic intervention in clinical rehabilitation. However, the effectiveness of this intervention on spasticity in patients with spastic paralysis remains uncertain. Objective: This study aimed to investigate the effectiveness of rPMS on spasticity, motor function, and activities of daily living in individuals with spastic paralysis. Methods: PubMed, PEDro, Embase, Cochrane Library, and Web of Science were searched for eligible papers with date up to March 31, 2022. Two independent researchers conducted study screening, data extraction, and methodological quality assessment. RCTs that explored the effects of rPMS on spasticity, motor function, and activities of daily living in patients with spastic paralysis were included for review. The Cochrane collaboration tool was used to assess methodological quality. The cumulative effects of available data were processed for a meta-analysis using Reedman software. Results: Eight studies with 297 participants were included. Most of the studies presented low to moderate risk of bias. Compared with the control group, the results showed that rPMS had a significant effect on spasticity (all spasticity outcomes: standardized mean difference [SMD] = -0.55, 95% confidence interval [CI]: -0.94 to -0.16, I 2 = 40%, and P = 0.006, Modified Ashworth Scale: mean difference [MD] = -0.48, 95% CI: -0.82 to -0.14, I 2 = 0%, and P = 0.006), motor function (Fugl-Meyer Assessment: MD = 4.17, 95% CI: 0.89 to 7.46, I 2 = 28%, and P = 0.01), and activities of daily living (Barthel Index: MD = 5.12, 95% CI: 2.58 to 7.67, I 2 = 0%, and P < 0.0001). No side effect was reported. Conclusion: The meta-analysis demonstrated that the evidence supported rPMS in improving spasticity especially for passive muscle properties evaluated with Modified Ashworth Scale/Ashworth Scale, as well as motor function and daily activity of living in individuals with spastic paralysis. Study registration: The reviewed protocol of this study is registered in the international prospective register of systematic reviews (PROSPERO) (CRD42022322395). Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022322395.

Reliability of TMS measurements using conventional hand-hold method with different numbers of stimuli for tibialis anterior muscle in healthy adults.

Objective: The objective of this study was to determine the reliability of corticomotor excitability measurements using the conventional hand-hold transcranial magnetic stimulation (TMS) method for the tibialis anterior (TA) muscle in healthy adults and the number of stimuli required for reliable assessment. Methods: Forty healthy adults participated in three repeated sessions of corticomotor excitability assessment in terms of resting motor threshold (rMT), slope of recruitment curve (RC), peak motor evoked potential amplitude (pMEP), and MEP latency using conventional TMS method. The first two sessions were conducted with a rest interval of 1 h, and the last session was conducted 7-10 days afterward. With the exception of rMT, the other three outcomes measure elicited with the block of first 3-10 stimuli were analyzed respectively. The within-day (session 1 vs. 2) and between-day (session 1 vs. 3) reliability for all four outcome measures were assessed using intraclass correlation coefficient (ICC), standard error of measurement, and minimum detectable difference at 95% confidence interval. Results: Good to excellent within-day and between-day reliability was found for TMS-induced outcome measures examined using 10 stimuli (ICC ≥ 0.823), except in pMEP, which showed between-day reliability at moderate level (ICC = 0.730). The number of three stimuli was adequate to achieve minimum acceptable within-day reliability for all TMS-induced parameters and between-day reliability for MEP latency. With regard to between-day reliability of RC slope and pMEP, at least seven and nine stimuli were recommended respectively. Conclusion: Our findings indicated the high reliability of corticomotor excitability measurement by TMS with adequate number of stimuli for the TA muscle in healthy adults. This result should be interpreted with caveats for the specific methodological choices, equipment setting, and the characteristics of the sample in the current study. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100045141.

Psychometric Properties of Four Common Clinical Tests for Assessing Hamstring Flexibility in Young Adults.

Objective: To examine the psychometric properties of four common hamstring muscle flexibility tests involving the straight leg raise (SLR), passive knee extension (PKE), sit and reach test (SRT) and toe touch test (TTT) in young adults. Methods: Forty-three young healthy adults (mean age 27.4 years) were recruited for 3 repeated sessions of hamstring flexibility assessments using the 4 tests mentioned above and the subsequent isokinetic examinations. The first two sessions (S1 and S2) were conducted by two different raters randomly on the first day (D1), and the third session (S3) was conducted by the same rater as S1 3 days later (D4). The next day (D5), the isokinetic performances of knee extensors and flexors of the dominant leg were assessed. To evaluate the interrater (S1 vs. S2) and test-retest (S1 vs. S3) reliability of hamstring flexibility tests, intraclass correlation coefficients (ICCs), standard errors of measurement, and the minimum detectable differences were calculated. Correlation analyses were performed to study the association of each hamstring flexibility test with the isokinetic muscle function of the knee flexors (H) and extensors (Q), including the peak torque (PT), total amount of work (TW) and average power (AP). Results: Excellent interrater and test-retest reliability of hamstring flexibility tests involving the SLR, PKE, SRT and TTT were confirmed with ICCs ranging from 0.923 to 0.986. Fair correlations were found between the 4 hamstring flexibility tests and the H/Q for the PT at angular speeds of 180°/s (Pearson's r at 0.330-0.449). In addition, the PKE was fairly correlated with the AP of the hamstring (Pearson's r = 0.320) and the H/Q for the TW (Pearson's r = 0.345) and AP (Pearson's r = 0.386) at angular speeds of 180°/s. Conclusions: This study confirmed that the SLR, PKE, SRT and TTT were reliable flexibility tests for hamstring muscles in young healthy adults, and the PKE might be a more valid outcome measure to predict hamstring injury.

Preconditioning with Cathodal High-Definition Transcranial Direct Current Stimulation Sensitizes the Primary Motor Cortex to Subsequent Intermittent Theta Burst Stimulation.

Noninvasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can induce long-term potentiation-like facilitation, but whether the combination of TMS and tDCS has additive effects is unclear. To address this issue, in this randomized crossover study, we investigated the effect of preconditioning with cathodal high-definition (HD) tDCS on intermittent theta burst stimulation- (iTBS-) induced plasticity in the left motor cortex. A total of 24 healthy volunteers received preconditioning with cathodal HD-tDCS or sham intervention prior to iTBS in a random order with a washout period of 1 week. The amplitude of motor evoked potentials (MEPs) was measured at baseline and at several time points (5, 10, 15, and 30 min) after iTBS to determine the effects of the intervention on cortical plasticity. Preconditioning with cathodal HD-tDCS followed by iTBS showed a greater increase in MEP amplitude than sham cathodal HD-tDCS preconditioning and iTBS at each time postintervention point, with longer-lasting after-effects on cortical excitability. These results demonstrate that preintervention with cathodal HD-tDCS primes the motor cortex for long-term potentiation induced by iTBS and is a potential strategy for improving the clinical outcome to guide therapeutic decisions.

Modulation of the Corticomotor Excitability by Repetitive Peripheral Magnetic Stimulation on the Median Nerve in Healthy Subjects.

Objective: We aimed to examine the effects of repetitive peripheral nerve magnetic stimulation (rPNMS) on the excitability of the contralateral motor cortex and motor function of the upper limb in healthy subjects. Methods: Forty-six healthy subjects were randomly assigned to either a repetitive peripheral nerve magnetic stimulation group (n = 23) or a sham group (n = 23). The repetitive peripheral nerve magnetic stimulation group received stimulation using magnetic pulses at 20 Hz, which were applied on the median nerve of the non-dominant hand, whereas the sham group underwent the same protocol without the stimulation output. The primary outcome was contralateral transcranial magnetic stimulation (TMS)-induced corticomotor excitability for the abductor pollicis brevis of the stimulated hand in terms of resting motor threshold (rMT), the slope of recruitment curve, and peak amplitude of motor evoked potential (MEP), which were measured at baseline and immediately after each session. The secondary outcomes were motor hand function including dexterity and grip strength of the non-dominant hand assessed at baseline, immediately after stimulation, and 24 h post-stimulation. Results: Compared with the sham stimulation, repetitive peripheral nerve magnetic stimulation increased the peak motor evoked potential amplitude immediately after the intervention. The repetitive peripheral nerve magnetic stimulation also increased the slope of the recruitment curve immediately after intervention and enhanced hand dexterity after 24 h. However, the between-group difference for the changes was not significant. The significant changes in hand dexterity and peak amplitude of motor evoked potential after repetitive peripheral nerve magnetic stimulation were associated with their baseline value. Conclusions: Repetitive peripheral nerve magnetic stimulation may modulate the corticomotor excitability together with a possible lasting improvement in hand dexterity, indicating that it might be helpful for clinical rehabilitation.

Functional follow-up after endoscopic calcaneoplasty for Haglund's deformity using the biodex isokinetic muscle testing system: A case series.

Isokinetic muscle strength test implemented by the Biodex system is a method used for evaluating muscle function that has been applied clinically in the field of sports and rehabilitation medicine. However, information on its application on Haglund's deformity remain insufficient. Therefore, the present study examined the effectiveness of the muscle strength test using the Biodex system in evaluating the recovery of athletic capacity in patients with Haglund's deformity following endoscopic surgery. In total, 34 patients treated by the authors from June 2012 to November 2018 at Peking University Third Hospital (Beijing, China) were included. To compare muscle strength before surgery, then 3 and 6 months after surgery, using the uninjured side as the control, the Biodex system test was conducted in parallel to the collection of the American Orthopaedic Foot and Ankle Score values and visual analog scale scores. The Biodex system test results showed that Haglund's deformity mainly hinders plantar flexion strength. Patients recovered daily living capacity within 3 months and athletic capacity within 6 months following surgery, which matched the AOFAS values, VAS scores and the self-assessments of the patients. These findings suggest that the Biodex system can dynamically reflect the degree of postoperative recovery in Haglund's deformity.

Sample entropy reveals an age-related reduction in the complexity of dynamic brain.

Dynamic reconfiguration of the human brain is characterized by the nature of complexity. The purpose of this study was to measure such complexity and also analyze its association with age. We modeled the dynamic reconfiguration process by dynamic functional connectivity, which was established by resting-state functional magnetic resonance imaging (fMRI) data, and we measured complexity within the dynamic functional connectivity by sample entropy (SampEn). A brainwide map of SampEn in healthy subjects shows larger values in the caudate, the olfactory gyrus, the amygdala, and the hippocampus, and lower values in primary sensorimotor and visual areas. Association analysis in healthy subjects indicated that SampEn of the amygdala-cortical connectivity decreases with advancing age. Such age-related loss of SampEn, however, disappears in patients with schizophrenia. These findings suggest that SampEn of the dynamic functional connectivity is a promising indicator of normal aging.

Transition from double coherence resonances to single coherence resonance in a neuronal network with phase noise.

The effect of phase noise on the coherence dynamics of a neuronal network composed of FitzHugh-Nagumo (FHN) neurons is investigated. Phase noise can induce dissimilar coherence resonance (CR) effects for different coupling strength regimes. When the coupling strength is small, phase noise can induce double CRs. One corresponds to the average frequency of phase noise, and the other corresponds to the intrinsic firing frequency of the FHN neuron. When the coupling strength is large enough, phase noise can only induce single CR, and the CR corresponds to the intrinsic firing frequency of the FHN neuron. The results show a transition from double CRs to single CR with the increase in the coupling strength. The transition can be well interpreted based on the dynamics of a single neuron stimulated by both phase noise and the coupling current. When the coupling strength is small, the coupling current is weak, and phase noise mainly determines the dynamics of the neuron. Moreover, the phase-noise-induced double CRs in the neuronal network are similar to the phase-noise-induced double CRs in an isolated FHN neuron. When the coupling strength is large enough, the coupling current is strong and plays a key role in the occurrence of the single CR in the network. The results provide a novel phenomenon and may have important implications in understanding the dynamics of neuronal networks.