Géza Gergely Ambrus

Cutaneous perception thresholds of electrical stimulation methods: comparison of tDCS and tRNS.

OBJECTIVE Controlled blinded studies using transcranial electrical stimulation (tES) paradigms need a validated sham stimulation paradigm since an itching or tingling sensation on the skin surface under the electrode can be associated with current flow. METHODS Here we investigated the skin perception thresholds of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) for current intensities ranging from 200 to 2000μA and additional non-stimulation trials using a motor cortex-contralateral orbit montage in three different healthy subject groups: subjects naïve to tES methods, subjects with previous experience with these techniques and investigators, who use these methods in their research. RESULTS Taking the whole sample into consideration the 50% perception threshold for both tDCS conditions was at 400μA while this threshold was at 1200μA in the case of tRNS. Anodal and cathodal tDCS are indistinguishable regarding sites of perception. Experienced investigators show a significantly higher anodal stimulation detection rate when compared to the naïve group, furthermore investigators performed significantly better than naïve subjects in non-stimulation discrimination. CONCLUSIONS tRNS has the advantage of higher cutaneous perception thresholds and lower response rates in when compared with tDCS. Further investigation in blinding methods (such as placebo itching) is warranted in order to improve sham control. SIGNIFICANCE As tRNS has been shown to have similar aftereffects as anodal tDCS, this finding points to the application of tRNS as a possible alternative with a better blinding control.

Both the cutaneous sensation and phosphene perception are modulated in a frequency-specific manner during transcranial alternating current stimulation

PURPOSE Transcranial alternating current stimulation (tACS) is a non-invasive stimulation technique for shaping neuroplastic processes and possibly entraining ongoing neural oscillations in humans. Despite the growing number of studies using tACS, we know little about the procedural sensations caused by stimulation. In order to fill this gap, we explored the cutaneous sensation and phosphene perception during tACS. METHODS Twenty healthy participants took part in a randomized, single-blinded, sham-controlled study, where volunteers received short duration stimulation at 1.0 mA intensity between 2 to 250 Hz using the standard left motor cortex-contralateral supraorbital montage. We recorded the perception onset latency and the strength of the sensations assessed by visual rating scale as dependent variables. RESULTS We found that tACS evoked both cutaneous sensation and phosphene perception in a frequency-dependent manner. Our results show that the most perceptible procedural sensations were induced in the beta and gamma frequency range, especially at 20 Hz, whereas minimal procedural sensations were indicated in the ripple range (140 and 250 Hz). CONCLUSIONS We believe that our results provide a relevant insight into the procedural sensations caused by oscillatory currents, and will offer a basis for developing more sophisticated stimulation protocols and study designs for future investigations.

The enhancement of cortical excitability over the DLPFC before and during training impairs categorization in the prototype distortion task.

The present study investigated the effects of transcranial weak electrical stimulation techniques applied to the right and left dorsolateral prefrontal cortex (DLPFC) on categorization learning measured using a variant of the prototype distortion task. During the training phase of this task subjects saw low- and high distortions of a prototype dot-pattern. 60 participants received 10min of either anodal or cathodal transcranial direct current (tDCS), transcranial random noise (tRNS) or sham stimulation before and during the training. We have assessed the effects of the intervention during a test phase, where the subjects had to decide whether the consecutive high- and low-distortion versions of the prototype or random patterns that were presented belonged to the category established in the training phase. Our results show that the categorization of prototypes is significantly impaired by the application of anodal tDCS and tRNS to the DLPFC. The prototype-effect, observable in the case of the sham stimulation group, was severed in all active stimulation conditions.

Comparing cutaneous perception induced by electrical stimulation using rectangular and round shaped electrodes

OBJECTIVE We have investigated the cutaneous perception differences for anodal and cathodal transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) between two electrode configurations: a standard, rectangle-shaped, and a circle-shaped, round geometry with the same surface area, and thus, same nominal current distribution. We have aimed to find whether a smaller perimeter length and the absence of corners in the case of the round configuration would lead to altered skin perception characteristics when compared to the rectangular geometry. METHODS Twelve subjects were tested for tDCS and tRNS skin perception characteristics in the intensity range of 200-2000 μA using round and rectangular electrode configurations. RESULTS We have not found any substantial differences between detection thresholds, detection rates, false positive rates or consistent alterations in the sites of perceived stimulation. CONCLUSION We conclude that there is no difference between the round and the rectangular electrode configurations regarding their blinding potentials. SIGNIFICANCE The results of this investigation indicate that the altering of the electrode geometry to a round configuration is unwarranted for better blinding purposes in future studies using tDCS and tRNS.

When Size Matters: Large Electrodes Induce Greater Stimulation-related Cutaneous Discomfort Than Smaller Electrodes at Equivalent Current Density

BACKGROUND Cutaneous discomfort is typically reported during transcranial direct current stimulation (tDCS), restricting the current intensity and duration at which tDCS can be applied. It is commonly thought that current density is associated with the intensity of perceived cutaneous perception such that larger electrodes with a lower current density results in milder cutaneous sensations. OBJECTIVE The present study examined the relationship between current density, current intensity and cutaneous sensations perceived during tDCS. METHODS Two experiments were performed. In the first control experiment, the cutaneous sensations induced by varying current intensities (0.025, 0.5, 1.0 and 1.5 mA) were examined up to 10 min. These data were used for optimizing inter-stimulation intervals in the second main experiment, where participants rated the intensity, spatial size and location of the cutaneous sensations experienced during tDCS using two electrodes sizes (16 cm2 and 35 cm2). In the equivalent current density condition, the current density was kept constant under both electrodes (0.014, 0.029 and 0.043 mA/cm2), whereas in the equal current intensity condition (0.5, 1.0 and 1.5 mA) the same intensities were used for the two electrode sizes. RESULTS Large electrodes were associated with greater cutaneous discomfort when compared to smaller electrodes at a given current density. Further, levels of cutaneous perception were similar for small and large electrodes when current intensity was kept constant. CONCLUSION Cutaneous sensations during stimulation can be minimized by reducing the electrode size from 35 cm2 to 16 cm2.

Brain-derived neurotrophic factor: its impact upon neuroplasticity and neuroplasticity inducing transcranial brain stimulation protocols

Val66Met (rs6265) is a gene variation, a single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene that codes for the protein BDNF. The substitution of Met for Val occurs at position 66 in the pro-region of the BDNF gene and is responsible for altered activity-dependent release and recruitment of BDNF in neurons. This is believed to manifest itself in an altered ability in neuroplasticity induction and an increased predisposition toward a number of neurological disorders. Many studies using neuroplasticity-inducing protocols have investigated the impact of the BDNF polymorphism on cortical modulation and plasticity; however, the results are partly contradictory and dependent on the paradigm used in a given study. The aim of this review is to summarize recent knowledge on the relationship of this BDNF SNP and neuroplasticity.

Causal evidence of the involvement of the number form area in the visual detection of numbers and letters

Recent research suggests the existence of a visual area selectively processing numbers in the human inferior temporal cortex (number form area (NFA); Abboud et al., 2015; Grotheer et al., 2016; Shum et al., 2013). The NFA is thought to be involved in the preferential encoding of numbers over false characters, letters and non-number words (Grotheer et al., 2016; Shum et al., 2013), independently of the sensory modality (Abboud et al., 2015). However, it is not yet clear if this area is mandatory for normal number processing. The present study exploited the fact that high-resolution fMRI can be applied to identify the NFA individually (Grotheer et al., 2016) and tested if transcranial magnetic stimulation (TMS) of this area interferes with stimulus processing in a selective manner. Double-pulse TMS targeted at the right NFA significantly impaired the detection of briefly presented and masked Arabic numbers in comparison to vertex stimulation. This suggests the NFA to be necessary for fluent number processing. Surprisingly, TMS of the NFA also impaired the detection of Roman letters. On the other hand, stimulation of the lateral occipital complex (LO) had neither an effect on the detection of numbers nor on letters. Our results show, for the first time, that the NFA is causally involved in the early visual processing of numbers as well as of letters.

Separating Recognition Processes of Declarative Memory via Anodal tDCS: Boosting Old Item Recognition by Temporal and New Item Detection by Parietal Stimulation

There is emerging evidence from imaging studies that parietal and temporal cortices act together to achieve successful recognition of declarative information; nevertheless, the precise role of these regions remains elusive. To evaluate the role of these brain areas in declarative memory retrieval, we applied bilateral tDCS, with anode over the left and cathode over the right parietal or temporal cortices separately, during the recognition phase of a verbal learning paradigm using a balanced old-new decision task. In a parallel group design, we tested three different groups of healthy adults, matched for demographic and neurocognitive status: two groups received bilateral active stimulation of either the parietal or the temporal cortex, while a third group received sham stimulation. Accuracy, discriminability index (d’) and reaction times of recognition memory performance were measurements of interest. The d’ sensitivity index and accuracy percentage improved in both active stimulation groups, as compared with the sham one, while reaction times remained unaffected. Moreover, the analysis of accuracy revealed a different effect of tDCS for old and new item recognition. While the temporal group showed enhanced performance for old item recognition, the parietal group was better at correctly recognising new ones. Our results support an active role of both of these areas in memory retrieval, possibly underpinning different stages of the recognition process.

Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial

Background Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. Methods We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. Results The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. Conclusion rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. Trial Registration ClinicalTrials.gov NCT01280877

The role of the putamen in cognitive functions — A case study

Abstract The role of the basal ganglia in cognition is still uncertain. This case study investigates the partial neuropsychological profile of a 20-year-old patient with a perinatal left putaminal lesion. This pathology is relatively rare and little is known of its cognitive effects. The focuses of our neuropsychological assessment were working memory, executive functions, analysis of spontaneous speech and implicit skill learning. The patients executive functions did not attain the normal range, and working memory was also partially impaired. In addition, the temporal features of her speech revealed an increased pause/signal time ratio. Finally, in an implicit skill learning task, the patient showed general motor skill learning, but no sequence specific learning. Together these findings suggest that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in higher cognitive processing such as executive functions, working memory, as well as in first-order sequence learning.