Polarity-dependent Manner Research Articles

Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

Contrasting MEG effects of anodal and cathodal high-definition TDCS on sensorimotor activity during voluntary finger movements.

Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation. To characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands. Anodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either. MRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs-increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

Online monitoring of epithelial barrier kinetics and cell detachment during cisplatin-induced toxicity of renal proximal tubule cells.

Real-time and non-invasive assessment of tissue health is crucial for maximizing the potential of microphysiological systems (MPS) for drug-induced nephrotoxicity screening. Although impedance has been widely considered as a measure of the barrier function, it has not been incorporated to detect cell detachment in MPS with top and bottom microfluidic channels separated by a porous membrane. During cell delamination from the porous membrane, the resistance between both channels decreases, while capacitance increases, allowing the detection of such detachment. Previously reported concepts have solely attributed the decrease in the resistance to the distortion of the barrier function, ignoring the resistance and capacitance changes due to cell detachment. Here, we report a two-channel MPS with integrated indium tin oxide (ITO) electrodes capable of measuring impedance in real time. The trans-epithelial electrical resistance (TEER) and tissue reactance (capacitance) were extracted from the impedance profiles. We attributed the anomalous initial increase observed in TEER, upon cisplatin administration, to the distortion of tight junctions. Cell detachment was captured by sudden jumps in capacitance. TEER profiles illuminated the effects of cisplatin and cimetidine treatments in a dose-dependent and polarity-dependent manner. The correspondence between TEER and barrier function was validated for a continuous tissue using the capacitance profiles. These results demonstrate that capacitance can be used as a real-time and non-invasive indicator of confluence and will support the accuracy of the drug-induced cytotoxicity assessed by TEER profiles in the two-channel MPS for the barrier function of a cell monolayer.

Polarity-Specific and Pyrimidine-over-Purine Adaptive Triplex DNA Recognition by a Near-Infrared Fluorogenic Molecular Rotor.

Triplex DNA structures have displayed a wide range of applications including nanosensing, molecule switching, and drug delivering. Therefore, it is of great importance to effectively recognize triplex DNA structures by a simple and highly selective manner. Herein, we found that a near-infrared fluorogenic probe of NIAD-4 with a molecular rotor (MR) merit can selectively recognize triplex DNA structures over G-quadruplex, i-motif, and duplex structures (Tri-over-QID selectivity), which is competent over the widely used MR probe of thioflavin T (ThT). Furthermore, NIAD-4 exhibits as well a high selectivity toward the 'pyrimidine-type' triplex structures (Y:R-Y type) with respect to the 'purine-type' triplex structures (R:R-Y type) (a Y-over-R selectivity). Interestingly, NIAD-4 recognizes the Y:R-Y triplex structures by a polarity-dependent manner. The 3' end triplet is the preferential binding field of NIAD-4 with respect to the 5' end one (a 3'-over-5' selectivity) as the 3' end triplet is more stable than the 5' end one in the Hoogsteen hydrogen bond. It is expected that the adaptive stacking interaction between NIAD-4 and the 3' end triplet favors the Tri-over-QID, Y-over-R, and 3'-over-5' selectivities since this MR probe has three rotating shafts matching well with the triplet in topology. Such a high selectivity of NIAD-4 opens a new route in designing sensors with DNA structures switching between triplex, i-motif, and G-quadruplex structures.

Epicranial Direct Current Stimulation Suppresses Harmaline Tremor in Rats

IntroductionEssential tremor (ET) is the most common neurologic movement disorder worldwide. It is characterized by a postural tremor, mostly in the upper extremities, causing difficulties in daily activities that may lead to social exclusion. Some patients with ET do not respond well to or do not tolerate medication. Thus, deep brain stimulation can be offered. In a recent study, we proposed a novel neuromodulation technique called epicranial current stimulation (ECS) that works in a minimally invasive way by placing the electrodes subcutaneously under the skin and directly over the skull. In this study, we investigated the feasibility of using epicranial direct current stimulation (EDCS) to suppress tremor in a rat harmaline ET model. Materials and MethodsIn experiment 1, seven Sprague Dawley rats were implanted with ECS electrodes placed over the motor cortex (MC) and the cerebellum to investigate whether stimulating between them could suppress tremor. In experiments 2 and 3, eight rats were implanted with ECS electrodes placed over the MC, cerebellum, and the rostral skull to separate the effects on tremor caused by stimulating each target. During each experiment, the rats were injected with harmaline, which induced tremor that was quantified using an accelerometer. EDCS was then applied through the different electrode configurations to evaluate their tremor suppression effectiveness. ResultsResults from experiment 1 showed that MCcathode-Cerebellaranode suppressed tremor compared with stimulation-OFF but MCanode-Cerebellarcathode did not. Furthermore, experiments 2 and 3 showed that it was the cerebellar anodal electrode that was driving tremor suppression. ConclusionCerebellar EDCS suppressed harmaline tremor in rats in a polarity-dependent manner. EDCS could be a promising neuromodulation method for patients with ET.

Phytochemical, Proximate, in-vitro Anti-malarial, Anti-inflammatory and Antimicrobial Screening of Leaf Extracts of Combretum platypterum (Welw) Hutch & Dalziel

Background: Combretum platypterum is used ethno-medically in the treatment many diseases in Africa, such as; helminthiasis, sexually transmitted diseases, conjunctivitis, malaria, lumps, fever, eye problems, diarrhea, lower backache, coughs, swellings, as febrifuge, tonic, and to stop post-partum bleeding.
 Aim: This work was aimed at investigating the phytochemical, proximate, anti malarial, anti inflammatory, anti bacterial and anti fungal activities of leaf extracts of Combretum platypterum.
 Methods: Leaves of C. platypterum were cold extracted with methanol, ethyl acetate and n-hexane. The extracts were subjected to preliminary phytochemical analyses, proximate, anti malarial, anti inflammatory and antimicrobial tests.
 Results: The results revealed that, alkaloids, terpenoids, flavonoids, cardiac glycosides, carbohydrates, resins and reducing sugars were found in all the extracts. It was also observed that the presence of the metabolites in each extract was in polarity-dependent manner. The percentage composition of carbohydrates was also the highest followed by the composition of proteins. The suppressions of the extracts against P. falciparum at half-maximal inhibitory concentration (IC50 mg/ml) were found to be higher than that of chloroquine at IC50 µg/ml. It was also found that methanol extract had the highest inhibition against Gram positive, Gram negative bacteria and C. albicans in a dose-dependent manner. K. pneumonia was resistant to the inhibition of the extracts. The anti inflammatory assays showed that methanol extracts at 500 mg/ml exhibited higher lipoxygenase Inhibition than diclofenac at 500 µg/ml. Ethyl acetate extract showed highest inhibition of heat-induced hemolysis, protein denaturation and proteinase among all the extracts.
 Conclusion: The therapeutic use of the leaves of C. platypterum against malaria and swelling was confirmed by the activities of the extracts against inflammation and P. falciparum. It is also necessary that the bioactive compounds responsible for these activities be isolated.

Molecular mechanisms of ion conduction and ion selectivity in TMEM16 lipid scramblases

TMEM16 lipid scramblases transport lipids and also operate as ion channels with highly variable ion selectivities and various physiological functions. However, their molecular mechanisms of ion conduction and selectivity remain largely unknown. Using computational electrophysiology simulations at atomistic resolution, we identified the main ion-conductive state of TMEM16 lipid scramblases, in which an ion permeation pathway is lined by lipid headgroups that directly interact with permeating ions in a voltage polarity-dependent manner. We found that lipid headgroups modulate the ion-permeability state and regulate ion selectivity to varying degrees in different scramblase isoforms, depending on the amino-acid composition of the pores. Our work has defined the structural basis of ion conduction and selectivity in TMEM16 lipid scramblases and uncovered the mechanisms responsible for the direct effects of membrane lipids on the conduction properties of ion channels.

Position-Sensing Established During Compaction Dictates Cell Fate in the Mammalian Embryo

Precise patterning within the 3-dimensional context of tissues, organs and embryos implies that cells can sense their relative position. We still understand relatively little about how cells sense their relative position within small groups of cells. During preimplantation development, outside and inside cells rely on apicobasal polarity and the Hippo pathway to choose their fate. Despite recent findings suggesting that mechanosensing may be central to this process, the relationship between blastomere geometry (i.e. shape and position) and the Hippo pathway effector YAP remains unknown. To address this, we used a highly quantitative approach to collect and analyse information on the geometry and YAP localisation of individual blastomeres of mouse and human embryos. We find that the fraction of YAP in the nucleus responds to the proportion of exposed cell surface area rather than blastomere shape. To directly test the influence of blastomere position on YAP localisation we developed an approach using hydrogel based cylindrical cavities to alter blastomere arrangement in cultured embryos. Unbiased clustering analyses of blastomeres from such embryos reveal that the ability to respond to position emerges as early as the 8-cell stage during compaction and that altering the relative position of a blastomere within an embryo can alter its fate. Finally, we demonstrate that this response is lost upon inhibiting PKC signalling, linking it to the cell polarity. Our results pinpoint when during early embryogenesis cell specification decisions are initiated and show how blastomeres can sense their position in a polarity dependent manner to alter YAP localisation.

Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation.

Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.

Differential effects of high-definition transcranial direct current stimulation on verbal working memory performance according to sensory modality

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability in a polarity-dependent manner. The diffuse nature of tDCS makes it difficult to investigate the optimal stimulation parameters for more effective and specific cognitive enhancement; to address this deficit, a more focalized stimulation technique, high-definition tDCS (HD-tDCS), has been developed. To date, only a few studies have examined the effects of HD-tDCS on cognitive functions; and none has investigated the effects of HD-tDCS on different sensory modalities of verbal working memory. Therefore, the present study compared the effects of prefrontal HD-tDCS on visual and auditory working memory tasks. Twenty healthy participants completed three sessions of each modality task, and additionally a sustained attention task. Anodal or sham HD-tDCS was administered to the dorsolateral prefrontal cortex (DLPFC) during the second session of the task in a parallel, single-blind design. Anodal stimulation to the DLPFC significantly enhanced the visual verbal working memory accuracy during and 20 min after the stimulation. In contrast, auditory verbal working memory performance was not modulated by anodal stimulation. Anodal stimulation to the DLPFC showed no effect on any other cognitive functions. The present study revealed the differential effects of HD-tDCS on two different modalities (visual vs. auditory) of working memory performance: important preliminary findings for the establishment of a more effective and specific use of tDCS.

Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division

The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus-ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle-pulling forces. Our results document a physical basis for the attenuation of spindle-pulling force, which may be generally used in asymmetric cell division and, when disrupted, potentially contributes to division defects in cancer.

P129 Prefrontal cortical excitability enhancement after cathodal tDCS: A multimodal study

Introduction Transcranial direct current stimulation (tDCS) is a non-invasive technique that is increasingly used in neuroscience, as it has the potential to induce cortical excitability changes (Nitsche et al., 2008; Woods et al., 2016). Specifically, tDCS has been widely applied to study cognition. Nevertheless, differently from motor system, applying tDCS in cognitive domains does not allow to have a direct physiological measure able to monitor polarity-dependent effects on cortical excitability. Event related potentials (ERPs) and TMS-evoked potentials (TEPs) could represent valuable surrogate markers of cortical excitability changes (Kesser et al., 2011; Miniussi and Thut, 2010). Objective The purpose of the present study was verifying the capability of tDCS to modulate cortical reactivity (using TEPs) of prefrontal cortex and characterizing the electrophysiological correlates (using ERPs) of cognitive processes underlying a working memory task. Materials & methods A sample of healthy young participants performed a 3-back task while EEG was recording before and after applying 13 min of tDCS (anodal, cathodal and sham sessions) over the left dorsolateral prefrontal cortex (DLPFC). TEPs were also collected before and after the tDCS. Results Results showed no tDCS polarity-dependent differences in task performance. However, increased prefrontal activity was observed at 150–200 ms over the stimulated region after cathodal tDCS. Furthermore, parietal activity underlying P3 component, which was typically related to working memory processes (Kesser et al., 2011), was larger after cathodal tDCS. Surprisingly, differences were found only after cathodal tDCS. These results were consistent with TEPs, which were modulated by tDCS in a polarity-dependent manner. Conclusion Our findings demonstrate that tDCS is able to induce prefrontal cortical activity and reactivity changes, which can be assessed by EEG and TMS-EEG measures, even when behavioral data are not sensitive enough to reveal functional modifications. Overall, these results suggest potential clinical application of tDCS and utility of ERPs and TEPs to monitor cortical excitability modifications induced by the stimulation protocols.

Cerebellar tDCS Effects on Conditioned Eyeblinks using Different Electrode Placements and Stimulation Protocols.

There is good evidence that the human cerebellum is involved in the acquisition and timing of classically conditioned eyeblink responses (CRs). Animal studies suggest that the cerebellum is also important in CR extinction and savings. Cerebellar transcranial direct current stimulation (tDCS) was reported to modulate CR acquisition and timing in a polarity dependent manner. To extent previous findings three experiments were conducted using standard delay eyeblink conditioning. In a between-group design, effects of tDCS were assessed with stimulation over the right cerebellar hemisphere ipsilaterally to the unconditioned stimulus (US). An extracephalic reference electrode was used in Experiment 1 and a cephalic reference in Experiment 2. In both parts the influence on unconditioned eyeblink responses (UR) was investigated by starting stimulation in the second half of the pseudoconditioning phase lasting throughout the first half of paired trials. In a third experiment, effects of cerebellar tDCS during 40 extinction trials were assessed on extinction and reacquisition on the next day. In each experiment, 30 subjects received anodal, cathodal or sham stimulation in a double-blinded fashion. Using the extracephalic reference electrode, no significant effects on CR incidences comparing stimulation groups were observed. Using the cephalic reference anodal as well as cathodal cerebellar tDCS increased CR acquisition compared to sham only on a trend level. Analysis of timing parameters did not reveal significant effects on CR onset and peaktime latencies nor on UR timing. In the third experiment, cerebellar tDCS during extinction trials had no significant effect on extinction and savings on the next day. The present study did not reveal clear polarity dependent effects of cerebellar tDCS on CR acquisition and timing as previously described. Weaker effects may be explained by start of tDCS before the learning phase i.e., offline, individual thresholds and current flow based on individual anatomy may also play role. Likewise cerebellar tDCS during extinction did not modulate extinction or reacquisition. Further studies are needed in larger subject populations to determine parameters of stimulation and learning paradigms yielding robust cerebellar tDCS effects.

EP 129. The effect of tDCS over M1 prior to and during implicit motor sequence learning

Motor learning is an essential skill allowing the acquisition of new movement patterns. Transcranial direct current stimulation (tDCS) has been shown to modulate neuronal excitability along with behavioural performance in a polarity-dependent manner. Besides polarity, the effects of tDCS on motor learning also vary with the timing of stimulation. In order to gain a better understanding regarding the optimal timing of tDCS application to modulate implicit motor sequence learning, motor-cortical tDCS was applied prior to and during training on a serial reaction time task (SRTT). The SRTT employs a fixed sequential pattern of button presses allowing the assessment of implicit motor sequence learning. A random pattern served as control condition. 36 healthy subjects were assigned to one of two experiments: tDCS was applied prior to (experiment 1) or during (experiment 2) SRTT training. Anodal vs. cathodal vs. sham tDCS was applied to the left primary motor cortex (M1) for ten minutes in a counterbalanced order. Reaction times of the right hand were measured at Baseline and after SRTT training (End of Acquisition (EoA)). Anodal tDCS prior to SRTT training yielded a beneficial effect on the acquisition of the motor sequence, i.e. reaction times decreased significantly from Baseline to EoA in the sequential pattern. Moreover, at EoA, reaction times were significantly faster following anodal as compared to cathodal tDCS. Reaction times of the random pattern were not differentially modulated by stimulation polarity indicating a sequence-specific effect. In contrast, tDCS applied during SRTT training did not differentially modulate the acquisition of the motor sequence. These results indicate that the timing of tDCS is a crucial parameter yielding distinct effects on implicit motor sequence learning. Anodal tDCS prior to SRTT training resulted in a facilitation emphasising a beneficial effect of increased left M1 excitability for the subsequent acquisition of a new motor sequence. In contrast, modulation of motor-cortical excitability by tDCS during SRTT training yielded no differential effects. This finding implies that tDCS effects may vary with the activation level during stimulation (rest vs. movement).

Polarity-Specific Cortical Effects of Transcranial Direct Current Stimulation in Primary Somatosensory Cortex of Healthy Humans.

Transcranial direct current stimulation (tDCS) is a non-invasive stimulation method that has been shown to modulate the excitability of the motor and visual cortices in human subjects in a polarity dependent manner in previous studies. The aim of our study was to investigate whether anodal and cathodal tDCS can also be used to modulate the excitability of the human primary somatosensory cortex (S1). We measured paired-pulse suppression (PPS) of somatosensory evoked potentials in 36 right-handed volunteers before and after anodal, cathodal, or sham stimulation over the right non-dominant S1. Paired-pulse stimulation of the median nerve was performed at the dominant and non-dominant hand. After anodal tDCS, PPS was reduced in the ipsilateral S1 compared to sham stimulation, indicating an excitatory effect of anodal tDCS. In contrast, PPS in the stimulated left hemisphere was increased after cathodal tDCS, indicating an inhibitory effect of cathodal tDCS. Sham stimulation induced no pre–post differences. Thus, tDCS can be used to modulate the excitability of S1 in polarity-dependent manner, which can be assessed by PPS. An interesting topic for further studies could be the investigation of direct correlations between sensory changes and excitability changes induced by tDCS.

Neurophysiological and behavioural effects of dual-hemisphere transcranial direct current stimulation on the proximal upper limb.

Dual-hemisphere transcranial direct current stimulation over the primary motor cortex (M1-M1 tDCS) is assumed to modulate neural excitability in a polarity-dependent manner and improve motor performance of the hand. In the proximal upper limb, the neurophysiological and behavioural after-effects of M1-M1 tDCS are not well known. This study investigated the after-effects of M1-M1 tDCS on contralateral, ipsilateral and transcallosal excitability to the proximal upper limb muscle biceps brachii (BB). Circle tracing was used to assess motor performance before and after tDCS as this task requires coordination of proximal and distal musculature. Sixteen healthy right-handed adults participated in the study, each receiving M1-M1 tDCS (1mA, 15min) or sham tDCS in separate sessions. The anode was positioned over right M1 and cathode over left M1. M1-M1 tDCS suppressed transcallosal inhibition from the M1 under the cathode (P<0.045). No other neurophysiologic or behavioural effects were observed (P>0.6). The study provides important information regarding inconsistent neurophysiological and behavioural changes following tDCS that have implications for future tDCS research on the motor system.

The effect of oppositional parietal transcranial direct current stimulation on lateralized brain functions.

Cognitive functions such as numerical processing and spatial attention show varying degrees of lateralization. Transcranial direct current stimulation (tDCS) can be used to investigate how modulating cortical excitability affects performance of these tasks. This study investigated the effect of bi‐parietal tDCS on numerical processing, spatial and sustained attention. It was hypothesized that tDCS would have distinct effects on these tasks because of varying lateralization (numerical processing left, spatial attention right) and that these effects are partly mediated by modulation of sustained attention. A single‐blinded, crossover, sham‐controlled study was performed. Eighteen healthy right‐handed participants performed cognitive tasks during three sessions of oppositional parietal tDCS stimulation: sham; right anodal with left cathodal (RA/LC); and right cathodal with left anodal (RC/LA). Participants performed a number comparison task, a modified Posner task, a choice reaction task (CRT) and the rapid visual processing task (RVP). RA/LC tDCS impaired number comparison performance compared with sham, with slower responses to numerically close numbers pairs. RA/LC and RC/LA tDCS had distinct effects on CRT performance, specifically affecting vigilance level during the final block of the task. No effect of stimulation on the Posner task or RVP was found. It was demonstrated that oppositional parietal tDCS affected both numerical performance and vigilance level in a polarity‐dependent manner. The effect of tDCS on numerical processing may partly be due to attentional effects. The behavioural effects of tDCS were specifically observed under high task demands, demonstrating the consequences of an interaction between stimulation type and cognitive load.

P75. Transcranial direct current stimulation (tDCS) of the midline cerebellum does not facilitate learning of a complex whole body dynamic balance task

The purpose of this study was to investigate if cerebellar tDCS facilitates learning of a complex whole body motor skill. 36 young and healthy subjects participated in 2 days of balance training on a Lafayette Instrument 16030 stability platform®. Training consisted of 15 trials, 30 s each, on day 1 and 7 trials on day 2. On day 1, twelve subjects received anodal, 12 subjects cathodal and 12 subjects sham tDCS over the midline cerebellum (electrode size 7 × 5 cm 2 , center of the upper end 2.5 cm above the inion; current intensity 2.8 mA; Neuroconn® DC Stimulator). As measures of balance performance mean platform angle deviation and mean balance time were assessed in each trial. Balance time was defined as the time, in which subjects were able to hold the platform between −5° and 5° relative to earth horizontal (0°). All groups exhibited significant improvement of balance over the course of the two training days which, however, was not significantly modulated by stimulation (trial effect: p p > 0.64; ANOVA with repeated measures). Yet, a main effect of stimulation with worse performance during cathodal compared to anodal stimulation was found ( p p p > 0.42) and not in females. On average, males were taller than females and performance measures correlated negatively with body height. In conclusion, tDCS of the midline cerebellum did not facilitate learning of a complex whole body dynamic balance task in young and healthy subjects. This negative finding disappoints expectations somewhat, yet does not exclude the possibility, that tDCS might facilitate balance training of cerebellar patients. However, baseline performance was modulated by tDCS in males in a polarity-dependent manner. The gender difference might be a consequence of larger body size, arguably rendering taller subjects more sensitive to a modulatory influence of tDCS in the examined task. Acknowledgement Supported by the Bernd-Fink Foundation .

Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity.

Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans.

Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS.

Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex. The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS. A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality. CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset. Acquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.