Comparing the effects of anodal and cathodal transcranial direct current stimulation of primary motor cortex at varying intensities on motor learning in healthy young adults.

Inconsistent results are observed in the effects of transcranial direct current stimulation (tDCS) with different montages on motor learning. This study aimed to compare the effects of anodal and cathodal tDCS (c-tDCS) over primary motor cortex (M1) at different intensities on motor learning in healthy young adults. The participants were randomly divided into: (1) 1 mA M1 c-tDCS, (2) 1 mA M1 anodal tDCS (a-tDCS), (3) 2 mA M1 c-tDCS, (4) 2 mA M1 a-tDCS and (5) M1 sham tDCS groups. The groups received 20-min stimulation with serial reaction time task (SRTT) incidentally, while the tDCS was turned off after 30 s in the sham tDCS group. Response time (RT) and error rate (ER) during SRTT were assessed prior, during and 72 h after the intervention. The results of the paired t-test indicated that online learning occurred in all groups (p < 0.05), except in M1 c-tDCS (1 mA) (p > 0.05). One-way ANOVA analysis also indicated that there were differences in offline learning (RT (F(DF) = 5.19(4); p < 0.001; and ER (F(DF) = 9(4), p < 0.0001) among groups, with more offline learning in 1 mA M1 a-tDCS, 2 mA M1 c-tDCS and 2 mA M1 a-tDCS groups (p < 0.05). On the other hand, the 1 mA M1 c-tDCS group did not indicate any consolidation effect or even a trend toward negative offline learning. M1 a-tDCS with different intensities and also 2 mA M1 c-tDCS may be helpful for the enhancement of motor learning in young healthy adults. This study enhances our understanding of tDCS intensity and polarity effects on motor learning, with potential for optimizing therapeutic protocols.

Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway.

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.

Kinesiophysiological analysis associated with changes in subjective intensities in belt electrode-skeletal muscle electrical stimulation: a prospective exploratory study.

[Purpose] Belt electrode-skeletal muscle electrical stimulation (B-SES) is a novel electrical muscle stimulation treatment that causes less pain and discomfort and induces contraction in a wider skeletal muscle area than conventional electrodes. However, the stimulation intensity depends on patients' subjectivity. In the present study, B-SES and an expiratory gas device were combined to analyze the kinesiophysiological data associated with changes in subjective intensity. [Participants and Methods] Seventeen healthy participants were recruited. The subjective intensities were set to four conditions (weak, normal, strong, and maximum tolerated intensity), and the stimulation was performed in each condition in the "metabolic mode" (frequency, 4 Hz; pulse width, 250 µs). The primary outcome was metabolic equivalents (METs), and this data were compared for each condition. [Results] METs generated by B-SES were 2.0 (1.0) for weak intensity, 2.7 (1.2) for normal intensity, 3.9 (1.3) for strong intensity, and 5.0 (1.3) for the tolerance limit intensity; differences detected between all subjective intensities were statistically significant. [Conclusion] These findings show that objective intensities of >3 METs, as recommended in rehabilitation prescriptions, can be achieved when the subjective intensity is set at strong or maximum tolerated. Treatment with B-SES may provide a viable alternative to therapeutic exercise.

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

Isometric agonist and antagonist muscle activation interacts differently with 140-Hz transcranial alternating current stimulation aftereffects at different intensities.

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca2+ increase, and their role in the aftereffects of tACS.NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.

Selecting stimulation intensity in repetitive transcranial magnetic stimulation studies: A systematic review between 1991 and 2020.

Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used, non-invasive brain stimulation technique in neuroscience research and clinical practice with a broad spectrum of suggested applications. Among other parameters, the choice of stimulus intensity and intracranial electric field strength substantially impacts rTMS outcome. This review provides a systematic overview of the intensity selection approaches and stimulation intensities used in human rTMS studies. We also examined whether studies report sufficient information to reproduce stimulus intensities for basic science research models. We performed a systematic review by focusing on original studies published between 1991 and 2020. We included conventional (e.g., 1 or 10 Hz) and patterned protocols (e.g., continuous or intermittent theta burst stimulation). We identified 3,784 articles in total, and we manually processed a representative portion (20%) of randomly selected articles. The majority of the analyzed studies (90% of entries) used the motor threshold (MT) approach and stimulation intensities from 80% to 120% of the MT. For continuous and intermittent theta burst stimulation, the most frequent stimulation intensity was 80% of the active MT. Most studies (92% of entries) did not report sufficient information to reproduce the stimulation intensity. Only a minority of studies (1.03% of entries) estimated the rTMS-induced electric field strengths. We formulate easy-to-follow recommendations to help scientists and clinicians report relevant information on stimulation intensity. Future standardized reporting guidelines may facilitate the use of basic science approaches aiming at better understanding the molecular, cellular, and neuronal mechanisms of rTMS.

Objective pain stimulation intensity and pain sensation assessment using machine learning classification and regression based on electrodermal activity.

An objective measure of pain remains an unmet need of people with chronic pain, estimated to be 1/3 of the adult population in the United States. The current gold standard to quantify pain is highly subjective, based upon self-reporting with numerical or visual analog scale (VAS). This subjectivity complicates pain management and exacerbates the epidemic of opioid abuse. We have tested classification and regression machine learning models to objectively estimate pain sensation in healthy subjects using electrodermal activity (EDA). Twenty-three volunteers underwent pain stimulation using thermal grills. Three different "pain stimulation intensities" were induced for each subject, who reported the "pain sensation" right after each stimulus using a VAS (0-10). EDA data were collected throughout the experiment. For machine learning, we computed validated features of EDA based on time-domain decomposition, spectral analysis, and differential features. Models for estimation of pain stimulation intensity and pain sensation achieved maximum macroaveraged geometric mean scores of 69.7% and 69.2%, respectively, when three classes were considered ("No," "Low," and "High"). Regression of levels of stimulation intensity and pain sensation achieved R2 values of 0.357 and 0.47, respectively. Overall, the high variance and inconsistency of VAS scores led to lower performance of pain sensation classification, but regression was better for pain sensation than stimulation intensity. Our results provide that three levels of pain can be quantified with good accuracy and physiological evidence that sympathetic responses recorded by EDA are more correlated to the applied stimuli's intensity than to the pain sensation reported by the subject.

Effects of 1 mA and 2 mA transcranial direct current stimulation on working memory performance in healthy participants.

Anodal transcranial current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) has been shown to enhance working memory (WM) in neuropsychiatric patients. In healthy populations, however, tDCS obtains inconclusive results, mostly due to heterogeneous study and stimulation protocols. Here, we approached these issues by investigating effects of tDCS intensity on simultaneous WM performance with three cognitive loads by directly comparing findings of two double-blind, cross-over, sham-controlled experiments. TDCS was administrated to the left DLPFC at intensity of 1 mA (Experiment 1) or 2 mA (Experiment 2), while participants completed a verbal n-back paradigm (1-, 2-, 3-back). Analysis showed no overall effects of tDCS on WM, but a significant interaction with cognitive load. The present study suggests that cognitive load rather than tDCS intensity could be a decisive factor for effects on WM. Moreover, it emphasizes the need of thorough investigation on study parameters to develop more efficient stimulation protocols.

The TMS Map Scales with Increased Stimulation Intensity and Muscle Activation.

One way to study cortical organisation, or its reorganisation, is to use transcranial magnetic stimulation (TMS) to construct a map of corticospinal excitability. TMS maps are reported to be acquired with a wide variety of stimulation intensities and levels of muscle activation. Whilst MEPs are known to increase both with stimulation intensity and muscle activation, it remains to be established what the effect of these factors is on the map's centre of gravity (COG), area, volume and shape. Therefore, the objective of this study was to systematically examine the effect of stimulation intensity and muscle activation on these four key map outcome measures. In a first experiment, maps were acquired with a stimulation intensity of 110, 120 and 130% of resting threshold. In a second experiment, maps were acquired at rest and at 5, 10, 20 and 40% of maximum voluntary contraction. Map area and map volume increased with both stimulation intensity (P < 0.01) and muscle activation (P < 0.01). Neither the COG nor the map shape changed with either stimulation intensity or muscle activation (P > 0.09 in all cases). This result indicates the map simply scales with stimulation intensity and muscle activation.

Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats. / ä¸åŒå¼ºåº¦ç”µé’ˆå¯¹å¤§é¼ è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒä¼¤å®³æ€§æ”¾ç”µçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Near-threshold recruitment characteristics of motor evoked potentials in transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can induce motor evoked potentials (MEPs). In TMS applications, near-threshold stimulation intensities (SIs) are often used for characterizing corticospinal excitability using MEPs. We aimed to characterize the individual near-threshold recruitment of MEPs and to test the assumptions related to selection of the suprathreshold SI. We utilized MEP data from a right-hand muscle induced at variable SIs. The single-pulse TMS (spTMS) data from previous studies (27 healthy volunteers), as well as data from new measurements (10 healthy volunteers) that included also MEPs modulated by paired-pulse TMS (ppTMS), were included. The probability of MEP (pMEP) was represented with individually fitted cumulative distribution function (CDF) with two parameters: resting motor threshold (rMT) and spread relative to rMT. MEPs were recorded with 110% and 120% of rMT as well as with Mills-Nithi upper threshold (UT). The individual near-threshold characteristics varied with CDF parameters: the rMT and the relative spread (median: 0.052). The rMT was lower with ppTMS than with spTMS (p < 0.001), while the relative spread remained similar (p = 0.812). At suprathreshold SIs, the probability of MEP was similar between UT and 110% of rMT (pMEP > 0.88), and higher for 120% of rMT (pMEP > 0.98). The individual near-threshold characteristics determine how probably MEPs are produced at common suprathreshold SIs. At the population level, the used SIs UT and 110% of rMT produced MEPs at similar probability. The individual variability in the relative spread parameter was large; therefore, the method of determining the proper suprathreshold SI for TMS applications is of crucial importance.

Identifying Dose Components of Manual Acupuncture to Determine the Dose-Response Relationship of Acupuncture Treatment: A Systematic Review.

The dose-response relationship is a hallmark of pharmacological studies. However, this relationship has not been fully established in acupuncture research. This systematic review aims to provide the characteristics of the dose-response relationship in acupuncture research. We further summarized the differences in acupuncture effects according to dose components. Dose components of acupuncture were categorized into three groups: number of needles, stimulation intensity, and total number/frequency of treatments. The PubMed database was used to identify studies examining the effects of different doses of acupuncture from the establishment of the database to August 13, 2020. Dose components and responses were extracted from each study, and the results of low- and high-dose conditions were compared. Fourteen studies were included in this study. Of the included studies, 37.5% showed statistically significant enhanced responses to acupuncture treatment under high-dose conditions compared to low-dose conditions. Significant differences between high- and low-dose conditions were observed most frequently in studies that used various stimulation intensities (four out of six studies), followed in order by studies that used various numbers of needles (two out of seven studies), and those that used various numbers or frequencies of treatment (none of the three studies). Responses were categorized into symptom changes, physiological changes, experimentally induced pain/stimuli perception, and needling sensation. Stimulation intensity, which is considered one of the most important needling components, might indeed have a great impact on clinical responses to acupuncture.

Dose-response relationship between iTBS and prefrontal activation during executive functioning: A fNIRS study.

Introduction: Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation paradigm that has demonstrated promising therapeutic benefits for a variety of neuropsychiatric disorders. It has recently garnered widespread favor among researchers and clinicians, owing to its comparable potentiation effects as conventional high-frequency repetitive transcranial magnetic stimulation (rTMS), but administered in a much shorter time frame. However, there is still a lack of agreement over the optimal stimulation intensity, particularly when targeting the prefrontal regions. The objective of this study was to systematically investigate the influence of different stimulation intensities of iTBS, applied over the left dorsolateral prefrontal cortex (DLPFC), on brain activity and executive function in healthy adults. Methods: Twenty young healthy adults were enrolled in this randomized cross-over experiment. All participants received a single session iTBS over the left DLPFC at intensities of 50, 70, or 100% of their individual resting motor threshold (RMT), each on separate visits. Functional near-infrared spectroscopy (fNIRS) was used to measure changes of hemoglobin concentrations in prefrontal areas during the verbal fluency task (VFT) before and after stimulation. Results: After stimulation, iTBS to the left DLPFC with 70% RMT maintained the concentration change of oxyhemoglobin (HbO) in the target area during the VFT. In contrast, 50% [t (17) = 2.203, P = 0.042, d = 0.523] and 100% iTBS [t (17) = 2.947, P = 0.009, d = 0.547] significantly decreased change of HbO concentration, indicating an inverse U-shape relationship between stimulation intensity and prefrontal hemodynamic response in healthy young adults. Notably, improved VFT performance was only observed after 70% RMT stimulation [t (17) = 2.511, P = 0.022, d = 0.592]. Moreover, a significant positive correlation was observed between task performance and the difference in HbO concentration change in the targeted area after 70% RMT stimulation (r = 0.496, P = 0.036) but not after 50 or 100% RMT stimulation. Conclusion: The linear relationship between stimulation intensity and behavioral outcomes reported in previous conventional rTMS studies may not be translated to iTBS. Instead, iTBS at 70% RMT may be more efficacious than 100% RMT.

Effects of acoustic stimulation intensity on air-conducted vestibular evoked myogenic potential in children.

Objective: To investigate the effects of acoustic stimulation intensity on ocular and cervical vestibular evoked myogenic potential (oVEMP and cVEMP) responses elicited by air-conducted sound (ACS) in healthy children. Methods: Thirteen healthy children aged 4-10 years and 20 healthy adults aged 20-40 years with normal hearing and tympanometry were enrolled in this study. All subjects received oVEMP and cVEMP tests under different acoustic stimulation intensities (131, 126, 121, 116, 111 and 106 dB SPL). Mean n1 latency, p1 latency, interpeak latency, amplitude and response rate were investigated and analyzed. Results: As the acoustic stimulation intensity decreased, for oVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 57.69% (116 dB SPL), 26.92% (111 dB SPL) and 11.54% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 55% (116 dB SPL), 12.5% (111 dB SPL) and 2.5% (106 dB SPL). There were lower n1 latency, p1 latency and higher amplitude in children when comparing by acoustic stimulation intensities (p < 0.05). Regarding cVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 88.46% (116 dB SPL), 53.85% (111 dB SPL) and 26.92% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 85% (116 dB SPL), 37.5% (111 dB SPL) and 7.5% (106 dB SPL). A statistically significant difference was found in amplitude at different acoustic stimulation intensities in both children and adults (p < 0.05). When stimulated by 131 dB SPL acoustic stimulation, there were lower n1 latency, p1 latency and higher amplitude in children in oVEMP and cVEMP compared with adults (p < 0.05). Conclusion: The response rate and amplitude of oVEMP and cVEMP in children and adults presented significant differences with a decrease in acoustic stimulation intensity. In this study, using 121 dB SPL for children and 126 dB SPL for adults during VEMP test could be regarded as safer stimulation intensities and thus reduced sound exposure.

Fast acquisition of resting motor threshold with a stimulus-response curve - Possibility or hazard for transcranial magnetic stimulation applications?

OBJECTIVE: Previous research has suggested that transcranial magnetic stimulation (TMS) related cortical excitability measures could be estimated quickly using stimulus-response curves with short interstimulus intervals (ISIs). Here we evaluated the resting motor threshold (rMT) estimated with these curves. METHODS: Stimulus-response curves were measured with three ISIs: 1.2-2 s, 2-3 s, and 3-4 s. Each curve was formed with 108 stimuli using stimulation intensities ranging from 0.75 to 1.25 times the rMTguess, which was estimated based on motor evoked potential (MEP) amplitudes of three scout responses. RESULTS: The ISI did not affect the rMT estimated from the curves (F = 0.235, p = 0.683) or single-trial MEP amplitudes at the group level (F = 0.90, p = 0.405), but a significant subject by ISI interaction (F = 3.64; p < 0.001) was detected in MEP amplitudes. No trend was observed which ISI was most excitable, as it varied between subjects. CONCLUSIONS: At the group level, the stimulus-response curves are unaffected by the short ISI. At the individual level, these curves are highly affected by the ISI. SIGNIFICANCE: Estimating rMT using stimulus-response curves with short ISIs impacts the rMT estimate and should be avoided in clinical and research TMS applications.

Successful Motor Evoked Potential Monitoring in Cervical Myelopathy : Related Factors and the Effect of Increased Stimulation Intensity.

OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) has been widely used during spine surgery to reduce or prevent neurologic deficits, however, its application to the surgical management for cervical myelopathy remains controversial. This study aimed to assess the success rate of IONM in patients with cervical myelopathy and to investigate the factors associated with successful baseline monitoring and the effect of increasing the stimulation intensity by focusing on motor evoked potentials (MEPs). METHODS: The data of 88 patients who underwent surgery for cervical myelopathy with IONM between January 2016 and June 2018 were retrospectively reviewed. The success rate of baseline MEP monitoring at the initial stimulation of 400 V was investigated. In unmonitorable cases, the stimulation intensity was increased to 999 V, and the success rate final MEP monitoring was reinvestigated. In addition, factors related to the success rate of baseline MEP monitoring were investigated using independent t-test, Wilcoxon rank-sum test, chi-squared test, and Fisher's exact probability test for statistical analysis. The factors included age, sex, body mass index, diabetes mellitus, smoking history, symptom duration, Torg-Pavlov ratio, space available for the cord (SAC), cord compression ratio (CCR), intramedullary increased signal intensity (SI) on magnetic resonance imaging, SI length, SI ratio, the Medical Research Council (MRC) grade, the preoperative modified Nurick grade and Japanese Orthopedic Association (JOA) score. RESULTS: The overall success rate for reliable MEP response was 52.3% after increasing the stimulation intensity. No complications were observed to be associated with increased intensity. The factors related to the success rate of final MEP monitoring were found to be SAC (p<0.001), CCR (p<0.001), MRC grade (p<0.001), preoperative modified Nurick grade (p<0.001), and JOA score (p<0.001). The cut-off score for successful MEP monitoring was 5.67 mm for SAC, 47.33% for the CCR, 3 points for MRC grade, 2 points for the modified Nurick grade, and 12 points for the JOA score. CONCLUSION: Increasing the stimulation intensity could significantly improve the success rate of baseline MEP monitoring for unmonitorable cases at the initial stimulation in cervical myelopathy. In particular, the SAC, CCR, MRC grade, preoperative Nurick grade and JOA score may be considered as the more important related factors associated with the success rate of MEP monitoring. Therefore, the degree of preoperative neurological functional deficits and the presence of spinal cord compression on imaging could be used as new detailed criteria for the application of IONM in patients with cervical myelopathy.

Long-term changes of stimulation intensities in hypoglossal nerve stimulation.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HNS) is a novel therapy in the treatment of obstructive sleep apnea. Previous studies have focused on the effectiveness of HNS, but there are no studies specifically investigating the long-term changes of the stimulation intensities in HNS. Increasing stimulation intensity requirements have been reported in the past in other peripheral nerve stimulation therapies. The aim of this study was to investigate the development of stimulation intensities over the observation period of 4 years. METHODS: All patients who were implanted with an HNS system since December 2013 and maintained a bipolar configuration over the observation period were included. Sensation threshold (ST), functional threshold, the titrated stimulation intensity (SI), and the apnea-hypopnea index (AHI) were recorded. RESULTS: A total of 82 patients were enrolled (sex: 69 men, 13 women, age: 60 ± 11 years, body mass index: 29. 8 ± 4.0 kg/m²). Two months after surgery, the median ST was 0.8 ± 0.5 V. During the observation period of 48 months, no significant change of ST was observed. The median ST was 1.0 ± 0.4 V (P = 0.93) at 48 months. Similar results were found for functional threshold and the titrated stimulation intensity. There was a significant reduction of the baseline median AHI when compared with the median AHI at 1, 12, 24, 36 and 48 months after surgery (P < 0.05). CONCLUSIONS: The stimulation intensities in HNS show no significant changes over 4 years. Despite the constant stimulation intensity, AHI was significantly reduced. This indicates that the stimulation threshold of the hypoglossal nerve does not change over time with this therapy.

Optimal stimulation intensity for Br(E)-MsEP waveform derivation at baseline in pediatric spinal surgery.

OBJECTIVES: Br(E)-MsEP monitoring is widely used in spinal surgery for detection of spinal cord injury. However, Br(E)-MsEP waveform derivation requires high-intensity stimulation, and this raises a concern of adverse effects due to the immature corticospinal tract in pediatric patients. The purpose of this study is to determine the optimal stimulation intensity required for derivation of Br(E)-MsEP waveforms at baseline in pediatric spinal surgery. PATIENTS AND METHODS: The subjects were 85 pediatric patients (4-15 years old, mean age at surgery: 11.1 years old) who were treated with spinal surgery using a posterior only approach under Br(E)-MsEP monitoring. The main diagnoses were adolescent idiopathic scoliosis (n = 44), syndromic and neuromuscular scoliosis (n = 23), and congenital scoliosis (n = 12). A total of 1513 muscles in the lower extremities were chosen for monitoring. RESULTS: A baseline waveform was obtained in all 85 cases and baseline Br(E)-MsEP responses were obtained from 1437/1513 muscles (95%). The mean stimulation intensity for baseline waveform derivation was 156.4 mA (range: 100-200 mA), and the stimulation intensity was significantly correlated with age (p < 0.05). The mean stimulation intensities were 129 ± 12, 138 ± 20, and 167 ± 25 mA for children <5, 6 to 10, and 11 to 15 years old, respectively. CONCLUSION: There are no criteria for derivation of Br(E)-MsEP waveforms in pediatric patients undergoing spinal surgery. The stimulation intensity increased with age, and starting at a lower stimulation strength than that used in adults is appropriate for younger children.

Improving working memory in schizophrenia: Effects of 1 mA and 2 mA transcranial direct current stimulation to the left DLPFC.

Deficits in various cognitive processes, such as working memory, are characteristic for schizophrenia, lowering patients' functioning and quality of life. Recent research suggests that transcranial direct stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) may be a potential therapeutic intervention for cognitive deficits in schizophrenia. Here, we examined the effects of online tDCS to the DLPFC on working memory (WM) performance in 40 schizophrenia patients in two separate experiments with a double blind, sham-controlled, cross-over design. Patients underwent single sessions of active and sham tDCS in a randomized order. Stimulation parameters were anode F3, cathode right deltoid muscle, 21 min tDCS duration, 1 mA tDCS in Experiment 1 (N = 20) and 2 mA tDCS in Experiment 2 (N = 20). Primary outcome was the change in WM performance as measured by a verbal n-back paradigm (1- to 3-back). Irrespective of the stimulation intensity, data analysis showed a significant higher WM accuracy during active tDCS than during sham tDCS (p = 0.019), but no main effect of stimulation intensity (p = 0.392). Subsequent separate analyses revealed a significantly improved WM performance only during 1 mA (p = 0.048). TDCS facilitated WM functioning in schizophrenia, with an advantage of 1 mA over 2 mA. Our results support the notion that tDCS may be a potential treatment for cognitive deficits in schizophrenia and emphasize the need for future research on the specific stimulation parameters.