Increased short latency afferent inhibition after anodal transcranial direct current stimulation

Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21-37) before and after anodal tDCS (primary motor cortex, 13min, 1mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.     

Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a non-invasive powerful method to modulate brain activity. It can enhance motor learning and working memory in healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the dominant and non-dominant primary motor cortex (M1) on hand motor performance in healthy right-handed volunteers, healthy subjects underwent one session of both sham and active anodal stimulation of the non-dominant or dominant primary motor cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand Function Test. For the non-dominant hand, active tDCS was able to improve motor function significantly-there was a significant interaction between time and condition of stimulation (p = 0.003). Post hoc tests showed a significant enhancement of JTT performance after 1 mA anodal tDCS of M1 (mean improvement of 9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84). For the dominant hand, however, neither active nor sham tDCS resulted in a significant change in motor performance. Our findings show that anodal tDCS of the non-dominant primary motor cortex results in motor function enhancement and thus confirm and extend the notion that tDCS can change behavior. We speculate that the under-use of the non-dominant hand with its associated consequences in cortical plasticity might be one of the reasons to explain motor performance enhancement in the non-dominant hand only.     

Enhancement of pinch force in the lower leg by anodal transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a procedure to polarize human brain. It has been reported that tDCS over the hand motor cortex transiently improves the performance of hand motor tasks. Here, we investigated whether tDCS could also improve leg motor functions. Ten healthy subjects performed pinch force (PF) and reaction time (RT) tasks using the left leg before, during and after anodal, cathodal or sham tDCS over the leg motor cortex. The anodal tDCS transiently enhanced the maximal leg PF but not RT during its application. Neither cathodal nor sham stimulation changed the performance. None of the interventions affected hand PF or RT, showing the spatial specificity of the effect of tDCS. These results indicate that motor performance of not only the hands but also the legs can be enhanced by anodal tDCS. tDCS may be applicable to the neuro-rehabilitation of patients with leg motor disability.     

一种可实现动物清醒状态下施加经颅直流电刺激的方法

目的:建立一种适用于小型实验动物,特别是啮齿类动物清醒状态下施加经颅直流电刺激(transcranial direct currentstimulation,t DCS)的方法以满足实验室研究的需要。方法:根据实验需要自行设计并制备杯状电极及配套电极-电路连接装置;通过骨水泥和颅钉联合固定的方法将刺激电极固定于目标脑区对应的颅骨表面;连接刺激通路、调节刺激参数,并开始对实验动物施加清醒t DCS刺激,在刺激过程中检测电流和电压变化并观察实验动物的反应;通过与传统金属电极比较证明该方法在长期饲养和多次刺激时的可靠性。结果:成功制备符合实验要求且规格一致的杯状电极与电极-电路连接装置;成功通过骨水泥及颅钉联合固定的方法将刺激电极长期固定于目标脑区对应的颅骨表面;实现动物清醒状态下t DCS刺激,刺激期间电流稳定,动物未出现神经精神行为异常;比较该杯状电极与传统电极发现,为了达到预订刺激电流强度,传统金属电极组需要更高的输出电压(P0.01),并且杯状电极在固定牢固性、刺激电流稳定性和操作简易性等方面明显高于传统金属电极,同时杯状电极重复利用度明显高于金属电极。结论:本方法制备的杯状电极可以满足小型实验动物长期、多次清醒t DCS刺激的需要,与传统金属电极相比具有明显优势。     

Norepinephrine-elicited accumulation of cyclic AMP in slices of rat cerebral cortex polarized with a weak anodal current

Cyclic AMP accumulation in response to norepinephrine was examined in slices of rat cerebral cortex the day after a unilateral application of anodal current of 0.3, 3.0 or 30 microA to the surface of the sensorimotor cortex. When 3.0 microA was applied, the norepinephrine-elicited accumulation of cyclic AMP was greater in the cortical area including the application point than in either the contralateral cortical area or non-polarized control cortical slices. The changes in cyclic AMP accumulation are discussed in relation to the role of the direct current in producing functional changes in the cortex.     

Slow-oscillatory transcranial direct current stimulation can induce bidirectional shifts in motor cortical excitability in awake humans

Constant transcranial direct stimulation (c-tDCS) of the primary motor hand area (M1_HAND) can induce bidirectional shifts in motor cortical excitability depending on the polarity of tDCS. Recently, anodal slow oscillation stimulation at a frequency of 0.75 Hz has been shown to augment intrinsic slow oscillations during sleep and theta oscillations during wakefulness. To embed this new type of stimulation into the existing tDCS literature, we aimed to characterize the after effects of slowly oscillating stimulation (so-tDCS) on M1_HAND excitability and to compare them to those of c-tDCS. Here we show that so-tDCS at 0.8 Hz can also induce lasting changes in corticospinal excitability during wakefulness. Experiment 1. In 10 healthy awake individuals, we applied c-tDCS or so-tDCS to left M1_HAND on separate days. Each tDCS protocol lasted for 10 min. Measurements of motor evoked potentials (MEPs) confirmed previous work showing that anodal c-tDCS at an intensity of 0.75 mA (maximal current density 0.0625 mA/cm2) enhanced corticospinal excitability, while cathodal c-tDCS at 0.75 mA reduced it. The polarity-specific shifts in excitability persisted for at least 20 min after c-tDCS. Using a peak current intensity of 0.75 mA, neither anodal nor cathodal so-tDCS had consistent effects on corticospinal excitability. Experiment 2. In a separate group of ten individuals, peak current intensity of so-tDCS was raised to 1.5 mA (maximal current density 0.125 mA/cm2) to match the total amount of current applied with so-tDCS to the amount of current that had been applied with c-tDCS at 0.75 mA in Experiment 1. At peak intensity of 1.5 mA, anodal and cathodal so-tDCS produced bidirectional changes in corticospinal excitability comparable to the after effects that had been observed after c-tDCS at 0.75 mA in Experiment 1. The results show that so-tDCS can induce bidirectional shifts in corticospinal excitability in a similar fashion as c-tDCS if the total amount of applied current during the tDCS session is matched.     

Enhancement of pain inhibition by working memory with anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex

The aim of this study was to examine whether transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) enhances pain inhibition by improving working memory (WM). Forty healthy volunteers participated in two tDCS sessions. Pain was evoked by electrical stimulation at the ankle. Participants performed an n-back task (0-back and 2-back). The experimental protocol comprised five counterbalanced conditions (0-back, 2-back, pain, 0-back with pain and 2-back with pain) that were performed twice (pre-tDCS baseline and during tDCS). Compared with the pre-tDCS baseline values, anodal tDCS decreased response times for the 2-back condition (p < 0.01) but not for the 0-back condition (p > 0.5). Anodal tDCS also decreased pain ratings marginally in the 2-back with pain condition, but not the 0-back with pain condition (p = 0.052 and p > 0.2, respectively). No effect was produced by sham tDCS for any condition (p > 0.2). These results indicate that tDCS of the left DLPFC may enhance pain inhibition by improving WM.     

Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortex

Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot-induced velocity-dependent force fields. Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity-dependent force field (adaptation; 25 N s m⁻¹) and once again in a null force field (de-adaptation). Active or sham tDCS was directed to the motor cortex representation of biceps brachii muscle during the adaptation phase of the motor learning protocol. During the adaptation phase, the global error in arm reaching (summed error from an ideal trajectory) was similar in both tDCS conditions. However, active tDCS induced a significantly greater global reaching (overshoot) error during the early stage of de-adaptation compared to the sham tDCS condition. The overshoot error may be representative of the development of a greater predictive movement to overcome the expected imposed force. An estimate of the predictive, initial movement trajectory (signed error in the first 150 ms of movement) was significantly augmented during the adaptation phase with active tDCS compared to sham tDCS. Furthermore, this increase was linearly related to the change of the overshoot summed error in the de-adaptation process. Together the results suggest that anodal tDCS augments the development of an internal model of the novel adapted movement and suggests that the primary motor cortex is involved in adaptation of reaching movements of healthy human subjects.     

Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human

Training of a thumb movement in the opposite direction of a twitch in response to transcranial magnetic stimulation (TMS) induces a transient directional change of post-training TMS-evoked movements towards the trained direction. Functional synaptic mechanisms seem to underlie this rapid training-induced plasticity. Transcranial direct current stimulation (tDCS) induces outlasting changes of cerebral excitability, thus presenting as promising tool for neuroplasticity research. We studied the influence of tDCS, applied over the motorcortex during training, on angular deviation of post-training to pre-training TMS-evoked thumb movements. With tDCS of anodal and cathodal polarity the training-induced directional change of thumb movements was significantly reduced during a 10 min post-training interval, indicating an interference of tDCS with mechanisms of rapid training-induced plasticity.     

Effects of arylaminobenzoate-type chloride channel blockers on equivalent short-circuit current in rabbit colon

Arylaminobenzoates were examined in rabbit colon mounted in an Ussing chamber. The open-circuit transepithelial voltage (V _te) and resistance (R _te) were measured and the equivalent short-circuit current (I _SC=V _te/ R _te) was calculated. After serosal (s) and mucosal (m) addition of indomethacin (1 mol/l) I _SC was –71±11 (n = 118) A/cm². Amiloride (0.1 mmol/l, m) inhibited this current and reversed the polarity to + 32±4 (n=118) A/cm². In the presence of amiloride and indomethacin, prostaglandin E₂ (1 mol/l, s), known to induce Cl^– secretion, generated an I _SC of -143 ± 8 (n = 92) A/cm². The arylaminobenzoate and Cl^– channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) reduced I _SC reversibly with a half-maximal inhibition (IC₅₀) at approximately 0.35 mmol/l and 0.2 mmol/l for mucosal and serosal application respectively. To test whether the poor effect was caused by mucus covering the luminal surface, dose/response curves of the mucosal effect were repeated after several pretreatments. Acidic pH on the mucosal side reduced IC₅₀ to approximately 0.1 mmol/l. A similar effect was observed after N-acetyl-l-cysteine (m) preincubation. Pretreatment with N-acetyl-l-cysteine (m) and carbachol (s), in order to exhaust mucus secretion, and l-homocysteine (m) were more effective and reduced IC₅₀ to approximately 50 mol/l. To test whether this effect of NPPB was caused by non-specific effects, the two enantiomers of 5-nitro-2-(+/–1-phenylethylamino)-benzoate were tested of which only the (+) form inhibited the Cl^– conductance in the thick ascending limb of the loop of Henle (TAL). In the present study the (+) enantiomer inhibited significantly more strongly than the (–) form. This suggests that the inhibitory effect of NPPB, even though it requires rather high concentrations, is probably due to Cl^– channel inhibition. For other arylaminobenzoates the sequence of potencies was different from that determined for the TAL. The present data indicate that substances that have been designed to block the Cl^– conductance of the TAL segment also inhibit reversibly but with much lower affinity the PGE₂-induced Cl^– secretion in rabbit colon.Supported by DFG Gr 480/10     

Vasodilatation in response to repeated anodal current application in the human skin relies on aspirin-sensitive mechanisms

The vasodilatation resulting from prolonged square-wave monopolar current application as used in iontophoresis is assumed to rely on an axon reflex. Involvement of prostaglandins in the anodal current-induced vasodilatation remains unclear. We tested the hypothesis that prostaglandins participate in a sensitisation mechanism to current application rather than as direct vasodilators. In healthy volunteers, laser Doppler flowmetry (LDF) was recorded in the forearm during and following isolated or repeated 0.1 mA transcutaneous anodal current applications, using deionised water as a vehicle. Segmented current applications of 6 or 12 mC resulted in an LDF increase twice that observed following current applications of comparable total charge delivered all at once (   P < 0.05  ). Following a 1 min anodal application, a slow and prolonged LDF drift occurred (slope: 0.3 ± 0.5 arbitrary units min⁻¹). When the same current application was repeated after intervals of 5 and 20 min, an abrupt vasodilatation occurred, with maximal LDF amplitude of 53.5 ± 34.0 and 48.2 ± 19.1 arbitrary units, respectively. Pretreatment with 1 g oral aspirin abolished the abrupt vasodilatation to repeated current application but not the initial slow drift. We suggest that vasodilatation occurs through two parallel pathways: (1) a slow progressive drift of LDF of limited amplitude insensitive to aspirin pretreatment, and (2) an abrupt vasodilatation probably resulting from afferent fibre activation, appearing if a preliminary sensitisation by current application is performed. Sensitisation lasts for at least 20 min, and is blocked by aspirin, suggesting participation of prostanoids.     

Opposite effects of weak transcranial direct current stimulation on different phases of short interval intracortical inhibition (SICI)

Short interval intracortical inhibition (SICI) is a common paired-pulse TMS technique that is used to measure GABAa-ergic inhibition in the cerebral motor cortex. However, inhibition evaluated with an interstimulus interval (ISI) between the TMS pulses of 2.5 ms has quite different properties from that seen at 1 ms. It is thought that the latter may represent either (or both) a different type of synaptic inhibition or refractoriness of neural membranes. The present experiments provide further evidence about the early and late components of SICI using transcranial direct current stimulation (tDCS), a technique thought to change neural excitability by polarising the nerve membranes. We assessed SICI using a threshold tracking method at a range of ISIs during concurrent application of tDCS in 11 healthy volunteers (8 males, 27–43 years old). Each subject underwent both anodal and cathodal tDCS with two different intensities of stimulation (1 and 2 mA). Because there was no significant difference between the results at the two intensities, the data were combined. Principal component analysis was used to separate the contributions of early and late SICI to the time course of inhibition from 1 to 5 ms tDCS had opposite effects on early and late SICI. Anodal tDCS reduced late SICI but enhanced early SICI, whereas cathodal tDCS had the opposite effect. This is further evidence that the two phases of SICI are produced by different mechanisms, perhaps involving different sets of neurones or different locations on the same neurone that respond oppositely to tDCS.     

花生四烯酸对家兔心室肌细胞动作电位和L-型钙电流的影响

目的：研究花生四烯酸(AA)对家兔单个心室肌细胞动作电位和L-型钙电流的影响。方法：酶解法分离家兔单个心室肌细胞，用全细胞膜片钳技术记录其动作电位和L-型钙电流。结果：①AA明显缩短动作电位时程（APD），而对静息电位（RP）和动作电位幅值（APA）无明显影响。②AA使L- 型钙电流峰电流密度从(10.21±3.15) PA/PF减少到（6.53±2.17）PA/PF(n=6,P＜0.05）,I-V关系曲线上移，其形状和峰值电压保持不变。结论：花生四烯酸能抑制L-型钙电流，缩短动作电位时程，这可能是其心血管作用的重要机制之一。     

Long-lasting post-tetanic potentiation in the sensorimotor cortex of the awake rabbit

Neuroscience and Behavioral Physiology -