Increased Transcranial Direct Current Stimulation After Effects During Concurrent Peripheral Electrical Nerve Stimulation

In this study we tested the hypothesis whether a lasting change in the excitability of cortical output circuits can be obtained in healthy humans by combining a peripheral nerve stimulation during a concomitant depolarization and/or hyperpolarization of motor cortex. To reach this aim we combined two different neurophysiological techniques each of them able to induce a lasting increase of cortical excitability by them self: namely median nerve repetitive electrical stimulation (rEPNS) and transcranial direct current stimulation (tDCS). Ten normal young volunteers were enrolled in the present study. All subjects underwent five different protocols of stimulation: (1, 2) tDCS alone (anodal or cathodal); (3) Sham tDCS plus rEPNS; (4, 5) anodal or cathodal tDCS plus rEPNS. The baseline MEP amplitude from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscle, the FCR H-reflex were compared with that obtained immediately after and 10, 20, 30, 60 min after the stimulation protocol. Anodal tDCS alone induced a significant transient increase of MEP amplitude immediately after the end of stimulation while anodal tDCS + rEPNS determined MEP changes which persisted for up 60 min. Cathodal tDCS alone induced a significant reduction of MEP amplitude immediately after the end of stimulation while cathodal tDCS + rEPNS prolonged the effects for up to 60 min. Sham tDCS + rEPNS did not induce significant changes in corticospinal excitability. Anodal or cathodal tDCS + rEPNS and sham tDCS + rEPNS caused a lasting facilitation of H-reflex. These findings suggest that by providing afferent input to the motor cortex while its excitability level is increased or decreased by tDCS may be a highly effective means for inducing an enduring bi-directional plasticity. The mechanism of this protocol may be complex, involving either cortical and spinal after effects.     

Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat

Objective

Transcranial direct current stimulation (tDCS) induces changes in cortical excitability and improves hand-motor function in chronic stroke. These effects depend on polarity, duration of stimulation and current intensity applied. Towards evaluating the therapeutic potential of tDCS in acute stroke, we investigated tDCS-effects on cerebral blood flow (CBF) in a tDCS rat model adapted for this purpose.

Methods

In a randomised crossover design eight Sprague–Dawley rats received three single cathodal and anodal tDCS for 15 min every other day. At each polarity, current intensities of 25, 50 and 100 μA were applied. CBF was measured prior and after tDCS for at least 30 min with laser Doppler flowmetry (LDF).

Results

At higher intensities (50 and 100 μA) anodal tDCS increased CBF up to 30 min. At 100 μA CBF was increased by about 25%, at 50 μA by about 18%. In contrast, cathodal tDCS led to a decrease of CBF, likewise depending on the current intensity applied. At 100 μA the effects were about 25% of baseline levels and persisted for at least 30 min. At 25 and 50 μA, baseline-levels were mostly re-established within 30 min.

Conclusions

tDCS modulates CBF in a polarity specific way, the extent of modulation depending on the stimulation parameters applied. Because of its polarity-specificity, we assume that CBF-alterations are causally related to tDCS-induced alterations in cortical excitability via neuro-vascular coupling. tDCS may constitute a therapeutic option in acute stroke patients or in patients at risk for vasospasm-induced ischemia after subarachnoid hemorrhage.     

Transcranial Direct Current Stimulation (tDCS) of the Cortical Motor Areas in Three Cases of Cerebellar Ataxia

The excitability of the motor areas of the cerebral cortex is reduced in ataxia. Since transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique able to increase the cortical excitability, we assessed the effect of anodal tDCS over the motor cortex in three patients with ataxia. A clinical evaluation, a video-taped SARA rating scale and a gait analysis with cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle. The full cycle was composed by five consecutive constant current sessions of stimulation. Anodal tDCS (2.0 mA, 20 min, max current density: 0.0278 mA/cm², max total charge: 0.033 C/cm²) was performed on the M1 area of the most affected side. The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20 min, max current density: 0.0278 mA/cm², max total charge: 0.033 C/cm²). After anodal tDCS, gait analysis revealed an improvement of the symmetry of step execution and reduction of base-width lasting 30 days associated to patients’ perception of amelioration. No relevant changes were found after sham stimulation. Our results suggest tDCS can improve gait symmetry in patients with ataxia for a short-term period. Future researches are needed in order to standardize time, amplitude, and area of stimulation in order to reach a long lasting effect on cerebellar ataxia.     

Current intensity‐ and polarity‐specific online and aftereffects of transcranial direct current stimulation: An fMRI study

Transcranial direct current stimulation (tDCS) induces polarity‐ and dose‐dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation‐induced changes in cortical excitability obtained from TMS, and cortical neurovascular activity obtained from fMRI, prevent the extrapolation of respective physiological and mechanistic bases. We investigated polarity‐ and intensity‐dependent effects of tDCS on cerebral blood flow (CBF) using resting‐state arterial spin labeling (ASL‐MRI), and compared the respective changes to TMS‐induced cortical excitability (amplitudes of motor evoked potentials, MEP) in separate sessions within the same subjects (n = 29). Fifteen minutes of sham, 0.5, 1.0, 1.5, and 2.0‐mA anodal or cathodal tDCS was applied over the left primary motor cortex (M1) in a randomized repeated‐measure design. Time‐course changes were measured before, during and intermittently up to 120‐min after stimulation. ROI analyses indicated linear intensity‐ and polarity‐dependent tDCS after‐effects: all anodal‐M1 intensities increased CBF under the M1 electrode, with 2.0‐mA increasing CBF the greatest (15.3%) compared to sham, while all cathodal‐M1 intensities decreased left M1 CBF from baseline, with 2.0‐mA decreasing the greatest (?9.3%) from sham after 120‐min. The spatial distribution of perfusion changes correlated with the predicted electric field, as simulated with finite element modeling. Moreover, tDCS‐induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand‐knob region. Our findings reveal lasting tDCS‐induced alterations in cerebral perfusion, which are dose‐dependent with tDCS parameters, but only partially account for excitability changes.     

Noninvasive transcranial direct current stimulation in a genetic absence model

The proposed area of onset for absence epilepsy characteristic of spontaneously occurring spike and slow-wave discharges (SWDs) in the genetic absence rat model is the subgranular layer of the somatosensory cortex. Modulation of the hyperexcitable cortical foci by bilateral transcranial direct current stimulation (tDCS) might change the expression of SWDs. The effects of cathodal and anodal tDCS as well as cumulative effects of different intensities of repeated cathodal stimulation on EEG and behavior were examined. Cathodal tDCS reduced the number of SWDs during stimulation and affected the mean duration after stimulation both in an intensity-dependent manner. Behavior was changed after the highest stimulation intensity. Spectral analyses of the EEG during stimulation revealed an increase in sub-delta and delta frequency ranges, suggesting that cortical cells were hyperpolarized. Cathodal tDCS might be an effective non-invasive tool to decrease cortical excitability, presumably in focal zone in this genetic model.     

Transcranial direct current stimulation disrupts tactile perception

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.     

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.     

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.     

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.