Noise in the brain: Transcranial random noise stimulation and perceptual noise act on a stochastic resonance-like mechanism.

Stochastic resonance (SR) is a phenomenon in which a certain amount of random noise added to a weak subthreshold stimulus can enhance signal detectability. It is unknown how external noise interacts with neural noise in producing an SR-like phenomenon and whether this interaction results in a modulation of either network efficiency or the efficiency of single neurons. Using random dot motion stimuli and noninvasive brain stimulation, we attempted to unveil the specific mechanism of action of the SR-like phenomenon in motion perception, if present. We aimed to determine whether signal integration efficiency changes with external noise (random dot numerosity) and how electrical transcranial random noise stimulation (tRNS) can affect the peak performance. The participants performed a coherent motion detection task in which the random dot numerosity varied, whereas the signal-to-noise ratio (SNR) remained constant. We applied placebo or tRNS with an amplitude of either 1 or 2 mA during task execution. We found peaks in participants' performance both in the case of placebo stimulation and in the case of 1-mA tRNS. In the latter case (i.e., with an additional noise source), the peak emerged at lower random dot numerosity levels than when no additional noise was added (placebo). No clear peak was observed with 2-mA tRNS. An equivalent noise (EN) analysis confirmed that SR arises from a modulation of the network efficiency underlying motion signal integration. These results indicate a joint contribution of external and neural noise (modulated by tRNS) in eliciting an SR-like phenomenon.

State-dependent TMS reveals the differential contribution of ATL and IPS to the representation of abstract concepts related to social and quantity knowledge.

The neural representation of abstract concepts is a current matter of debate. While social concepts have been associated to superior anterior temporal lobe (sATL), the neural correlates of quantity-related concepts have seldom been investigated. The right intraparietal sulcus (IPS) is known to be involved in the processing of numerical information and of quantifiers. In the present study, we investigated the causal role of right sATL and right IPS in representing social and quantity-related concepts, using a state-dependent transcranial magnetic stimulation (TMS)-priming paradigm. We modulated the neural activation by priming to a category label (either SOCIAL or QUANTITY), before applying TMS and presenting the target (i.e., an exemplar of one of the two abstract classes). When the target word belonged to the quantity category, TMS applied over the IPS (but not sATL) abolished the expected priming effect by speeding up reaction times (RTs) in incongruent trials. For the social category, both IPS and sATL stimulation abolished the priming effect, by reducing RTs in incongruent trials. Our results suggest a specialization of distinct brain areas in processing different classes of abstract concepts. The right IPS contains neuronal representations tuned to quantity-related concepts, in line with its well-known role in numerical and magnitude representation. Social concepts, in contrast, are represented in both the right sATL and the right IPS, known to be involved in social cognition and person-related knowledge.

Age-related changes in cortical connectivity influence the neuromodulatory effects of transcranial electrical stimulation.

Transcranial electrical stimulation (tES) is a potentially viable tool for boosting cognitive performance in aging. However, most knowledge on tES effects is based on studies involving young adults. Here, we applied tES (transcranial random noise stimulation [tRNS] as an effective stimulation and anodal transcranial direct current stimulation [atDCS] as a "control" stimulation) to the visual cortex during visual perceptual learning (VPL) in healthy young and older individuals. Moreover, we measured transcranial magnetic stimulation-evoked potentials to investigate the neurophysiological underpinnings of tES effects. We found that only the tRNS in the young, but not in the older, subjects modulated VPL, by decreasing performance. Transcranial magnetic stimulation-evoked potentials revealed age-related changes in connectivity, that is, a stronger activation of the prefrontal cortex after visual cortex stimulation, and a stronger modulation of the prefrontal cortex after VPL in the older subjects. These results may indicate that task performance in older adults relies on the recruitment of a wider network and a crucial contribution of the anterior portion of the brain, which may dramatically influence tES effects in aging.

Transcranial Electrical Stimulation: What We Know and Do Not Know About Mechanisms.

In recent years, there has been remarkable progress in the understanding and practical use of transcranial electrical stimulation (tES) techniques. Nevertheless, to date, this experimental effort has not been accompanied by substantial reflections on the models and mechanisms that could explain the stimulation effects. Given these premises, the aim of this article is to provide an updated picture of what we know about the theoretical models of tES that have been proposed to date, contextualized in a more specific and unitary framework. We demonstrate that these models can explain the tES behavioral effects as distributed along a continuum from stimulation dependent to network activity dependent. In this framework, we also propose that stochastic resonance is a useful mechanism to explain the general online neuromodulation effects of tES. Moreover, we highlight the aspects that should be considered in future research. We emphasize that tES is not an "easy-to-use" technique; however, it may represent a very fruitful approach if applied within rigorous protocols, with deep knowledge of both the behavioral and cognitive aspects and the more recent advances in the application of stimulation.

Acute effects of aerobic exercise promote learning.

The benefits that physical exercise confers on cardiovascular health are well known, whereas the notion that physical exercise can also improve cognitive performance has only recently begun to be explored and has thus far yielded only controversial results. In the present study, we used a sample of young male subjects to test the effects that a single bout of aerobic exercise has on learning. Two tasks were run: the first was an orientation discrimination task involving the primary visual cortex, and the second was a simple thumb abduction motor task that relies on the primary motor cortex. Forty-four and forty volunteers participated in the first and second experiments, respectively. We found that a single bout of aerobic exercise can significantly facilitate learning mechanisms within visual and motor domains and that these positive effects can persist for at least 30 minutes following exercise. This finding suggests that physical activity, at least of moderate intensity, might promote brain plasticity. By combining physical activity-induced plasticity with specific cognitive training-induced plasticity, we favour a gradual up-regulation of a functional network due to a steady increase in synaptic strength, promoting associative Hebbian-like plasticity.

What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects.

OBJECTIVE: The goals of this work are to report data regarding a large number of stimulation sessions and to use model analyses to explain the similarities or differences in the sensations induced by different parameters of tES application. METHODS: We analysed sensation data relative to 693 different tES sessions. In particular, we studied the effects on sensations induced by different types of current, categories of polarity and frequency, different timing, levels of current density and intensity, different electrode sizes and different electrode locations (areas). RESULTS: The application of random or fixed alternating current stimulation (i.e., tRNS and tACS) over the scalp induced less sensation compared with transcranial direct current stimulation (tDCS), regardless of the application parameters. Moreover, anodal tDCS induced more annoyance in comparison to other tES. Additionally, larger electrodes induced stronger sensations compared with smaller electrodes, and higher intensities were more strongly perceived. Timing of stimulation, montage and current density did not influence sensations perception. The analyses demonstrated that the induced sensations could be clustered on the basis of the type of somatosensory system activated. Finally and most important no adverse events were reported. CONCLUSION: Induced sensations are modulated by electrode size and intensity and mainly pertain to the cutaneous receptor activity of the somatosensory system. Moreover, the procedure currently used to perform placebo stimulation may not be totally effective when compared with anodal tDCS. SIGNIFICANCE: The reported observations enrich the literature regarding the safety aspects of tES, confirming that it is a painless and safe technique.

Is neural hyperpolarization by cathodal stimulation always detrimental at the behavioral level?

Cathodal transcranial direct current stimulation (c-tDCS) is usually considered an inhibitory stimulation. From a physiological perspective, c-tDCS induces hyperpolarization at the neural level. However, from a behavioral perspective, c-tDCS application does not always result in performance deterioration. In this work, we investigated the role of several important stimulation parameters (i.e., timing, presence of pauses, duration, and intensity) in shaping the behavioral effects of c-tDCS over the primary visual cortex. In Experiment 1, we applied c-tDCS at two different times (before or during an orientation discrimination task). We also studied the effects of pauses during the stimulation. In Experiments 2 and 3, we compared different durations (9 vs. 22 min) and intensities (0.75 vs. 1.5 mA) of stimulation. c-tDCS applied before task execution induced an improvement of performance, highlighting the importance of the activation state of the cortex. However, this result depended on the duration and intensity of stimulation. We suggest that the application of c-tDCS induces depression of cortical activity over a specific stimulated area; but to keep reactivity within given limits, the brain react in order to restore the equilibrium and this might result in increased sensitivity in visual performance. This is a further example of how the nervous system dynamically maintains a condition that permits adequate performance in different environments.

The timing of cognitive plasticity in physiological aging: a tDCS study of naming.

This study aimed to explore the effects of transcranial direct current stimulation (tDCS) on physiologically aging adults performing a naming task. tDCS is a method that modulates human cortical excitability. Neuroplasticity is considered to have its foundation in cortical excitability as a property that adjusts the connection strength between neurons in the brain. Language efficiency, as all functions, relies on integration of information (i.e., effectiveness of connectivity) through neurons in the brain. So the use of tDCS, to modulate cortical excitability, can help to define the state of cognitive plasticity in the aging brain. Based on Hebb's rule, an increase in synaptic efficacy does not rely only on the increase of excitability but also on the timing of activation. Therefore, a key issue in this study is the timing of tDCS application in relation to a task: When to deliver tDCS to induce modulatory effects on task execution to facilitate naming. Anodal tDCS was applied to the left dorsolateral prefrontal cortex of older and young adults before and during a naming task. In older adults, tDCS improved naming performance and decreased the verbal reaction times only if it was applied during the task execution, whereas in young subjects both stimulation conditions improved naming performance. These findings highlight that in healthy aging adults, the cerebral network dedicated to lexical retrieval processing may be facilitated only if stimulation is applied to an "active" neural network. We hypothesize that this change is due to the neuronal synaptic changes, in the aging brain, which reduce the window of when cortical excitability can facilitate synaptic efficacy and therefore plasticity.

The role of timing in the induction of neuromodulation in perceptual learning by transcranial electric stimulation.

BACKGROUND: Transcranial electric stimulation (tES) protocols are able to induce neuromodulation, offering important insights to focus and constrain theories of the relationship between brain and behavior. Previous studies have shown that different types of tES (i.e., direct current stimulation - tDCS, and random noise stimulation - tRNS) induce different facilitatory behavioral effects. However to date is not clear which is the optimal timing to apply tES in relation to the induction of robust facilitatory effects. OBJECTIVE/HYPOTHESIS: The goal of this work was to investigate how different types of tES (tDCS and tRNS) can modulate behavioral performance in the healthy adult brain in relation to their timing of application. We applied tES protocols before (offline) or during (online) the execution of a visual perceptual learning (PL) task. PL is a form of implicit memory that is characterized by an improvement in sensory discrimination after repeated exposure to a particular type of stimulus and is considered a manifestation of neural plasticity. Our aim was to understand if the timing of tES is critical for the induction of differential neuromodulatory effects in the primary visual cortex (V1). METHODS: We applied high-frequency tRNS, anodal tDCS and sham tDCS on V1 before or during the execution of an orientation discrimination task. The experimental design was between subjects and performance was measured in terms of d' values. RESULTS: The ideal timing of application varied depending on the stimulation type. tRNS facilitated task performance only when it was applied during task execution, whereas anodal tDCS induced a larger facilitation if it was applied before task execution. CONCLUSION: The main result of this study is the finding that the timing of identical tES protocols yields opposite effects on performance. These results provide important guidelines for designing neuromodulation induction protocols and highlight the different optimal timing of the two excitatory techniques.

Double dissociation of working memory load effects induced by bilateral parietal modulation.

Transcranial magnetic stimulation and neuroimaging data have revealed bilateral posterior parietal cortex (PPC) involvement during verbal n-back working memory (WM). In this task as n (i.e., WM load) increases, subjects show poorer behavioral performance as well as greater activation of this brain area. Moreover, there is evidence that a brief period of practice or even increased familiarity with the task can improve WM performance and lead to activation changes in the PPC. The aim of this study was to investigate, using transcranial direct current stimulation (tDCS), the effects on WM load performance induced by different PPC modulation after increased familiarity with the task. After a short practice, we tested verbal WM using an n-back task (1-back vs. 2-back) before and after the application of bilateral tDCS over PPCs (left anodal-right cathodal, left cathodal-right anodal or sham). ANOVA showed a significant interaction between tDCS and task. In the 1-back task, left anodal-right cathodal modulation abolished improvement in reaction times observed in the other two modulation conditions. Conversely, in the 2-back task the same effect was observed after left cathodal-right anodal modulation relative to the other two modulation conditions. This double dissociation demonstrates either a differential engagement of each PPC or changes in the interhemispheric balance of activity across this brain region. Neuroimaging studies show parametric activation of the PPC as difficulty increases, but activation does not switch sides. Thus, our observed effects cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we suggest that these findings reflect the use of different processing strategies to perform these two tasks. In conclusion, after increased familiarity with the task, different tDCS modulations lead to changes in a task-related region depending on differences in processing strategies in 1-back vs. 2-back.

Random noise stimulation improves neuroplasticity in perceptual learning.

Perceptual learning is considered a manifestation of neural plasticity in the human brain. We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation (tES). We hypothesized that different types of tES would have varying actions on the nervous system, which would result in different efficacies of neural plasticity modulation. Thus, the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [i.e., direct current stimulation (tDCS) and random noise stimulation (tRNS)] during the execution of a visual perceptual learning task.

Anomia training and brain stimulation in chronic aphasia.

Recent studies have reported enhanced performance on language tasks induced by non-invasive brain stimulation, i.e., repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), in patients with aphasia due to stroke or Alzheimer's disease (AD). The first part of this article reviews brain stimulation studies related to language recovery in aphasic patients. The second part reports results from a pilot study with three chronic stroke patients who had non-fluent aphasia, where real or placebo rTMS was immediately followed by 25 minutes of individualised speech therapy. Real rTMS consisted of high-frequency rTMS over the left dorsolateral prefrontal cortex (BA 8/9) for 25 minutes. Each patient underwent a total of four weeks of intervention. P1 underwent four weeks of real rTMS (5 days/week) where individualised speech therapy was provided for 25 minutes immediately following each rTMS session. P2 and P3 each underwent two weeks of placebo rTMS, followed immediately by individualised speech therapy; then two weeks of real rTMS, followed immediately by individualised speech therapy. Assessments took place at 2, 4, 12, 24 and 48 weeks post-entry/baseline testing. Relative to entry/baseline testing, a significant improvement in object naming was observed at all testing times, from two weeks post-intervention in real rTMS plus speech therapy, or placebo rTMS plus speech therapy. Our findings suggest beneficial effects of targeted behavioural training in combination with brain stimulation in chronic aphasic patients. However, further work is required in order to verify whether optimal combination parameters (rTMS alone or speech therapy alone) and length of rTMS treatment may be found.

Naming facilitation induced by transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is able to generate a long-term increase or decrease in the neuronal excitability that can modulate cognitive tasks, similar to repetitive transcranial magnetic stimulation. The aim of this study was to explore the effects of tDCS on a language task in young healthy subjects. Anodal, cathodal and sham tDCS were applied to the left dorsolateral prefrontal cortex (DLPFC) before two picture naming experiments, a preliminary study (i.e., experiment 1) and a main study (i.e., experiment 2). The results show that anodal tDCS of the left DLPFC improves naming performance, speeding up verbal reaction times after the end of the stimulation, whereas cathodal stimulation had no effect. We hypothesize that the cerebral network dedicated to lexical retrieval processing is facilitated by anodal tDCS to the left DLPFC. Although the mechanisms responsible for facilitation are not yet clear, the results presented herein implicate a facilitation lasting beyond the end of the stimulation that imply cortical plasticity mechanisms. The opportunity to non-invasively interact with the functioning of these plasticity mechanisms will surely open new and promising scenarios in language studies in basic and clinical neuroscience fields.