Dementia prevention in memory clinics: recommendations from the European task force for brain health services.

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.

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.

TMS combined with EEG: Recommendations and open issues for data collection and analysis.

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS-EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS-EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS-EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS-EEG covered all aspects that should be considered in TMS-EEG experiments, providing methodological recommendations (when possible) for effective TMS-EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS-EEG methodology and thus may promote standardization of experimental and computational procedures across groups.

Opposite pattern of transcranial direct current stimulation effects in middle-aged and older adults: Behavioral and neurophysiological evidence.

Introduction: Episodic memory (EM) exhibits an age-related decline, with overall increased impairment after the age of 65. The application of transcranial direct current stimulation (tDCS) to ameliorate cognitive decline in ageing has been extensively investigated, but its efficacy has been reported with mixed results. In this study, we aimed to assess whether age contributes to interindividual variability in tDCS efficacy. Methods: Thirty-eight healthy adults between 50 and 81 years old received anodal tDCS over the left prefrontal cortex during images encoding and then performed an EM recognition task while event-related potentials (ERPs) were recorded. Results: Our results showed an opposite pattern of effect between middle-aged (50-64 years) and older (65-81 years) adults. Specifically, performance in the recognition task after tDCS was enhanced in older adults and was worsened in middle-aged adults. Moreover, ERPs acquired during the recognition task showed that two EM components related to familiarity and post-retrieval monitoring, i.e., Early Frontal and Late Frontal Old-New effects, respectively, were significantly reduced in middle-aged adults after anodal tDCS. Discussion: These results support an age-dependent effect of prefrontal tDCS on EM processes and its underlying electrophysiological substrate, with opposing modulatory trajectories along the aging lifespan.

Digitalized transcranial electrical stimulation: A consensus statement.

OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.

The hand motor hotspot for seed-based functional connectivity of hand motor networks at rest.

In the seed-based method for studying functional connectivity (FC), seed selection is relevant. Here, we propose a new methodological approach for resting-state FC analysis of hand motor networks using the individual hand motor hotspot (hMHS) as seed. Nineteen right-handed healthy volunteers underwent a transcranial magnetic stimulation (TMS) session and resting-state fMRI. For each subject, the hMHS in both hemispheres was identified by TMS with the contralateral abductor pollicis brevis muscle as the target, the site eliciting the highest and most reliable motor-evoked potentials. Seed regions were built on coordinates on the cortex corresponding to the individual left and right hMHSs. For comparison, the left and right Brodmann's area 4 (BA4) masks extracted from a standard atlas were used as seed. The left and right hMHSs showed FC patterns at rest mainly including sensorimotor regions, with a bilateral connectivity only for the left hMHS. The statistical contrast BA4 > hMHS for both hemispheres showed different extension and lateralization of the functionally connected cortical regions. On the contrary, no voxels survived the opposite contrast (hMHS > BA4). This suggests that detection of individual hand motor seeds by TMS allows to identify functionally connected motor networks that are more specific with respect to those obtained starting from the a priori atlas-based identification of the primary motor cortex.

Early response competition over the motor cortex underlies proactive control of error correction.

Response inhibition is a fundamental brain function that must be flexible enough to incorporate proactive goal-directed demands, along with reactive, automatic and well consolidated behaviors. However, whether proactive inhibitory processes can be explained by response competition, rather than by active top-down inhibitory control, remains still unclear. Using a modified version of the Eriksen flanker task, we examined the behavioral and electrophysiological correlates elicited by manipulating the degree of inhibitory control in a task that involved the fast amendment of errors. We observed that restraining or encouraging the correction of errors did not affect the behavioral and neural correlates associated to reactive inhibition. We rather found that an early, sustained and bilateral activation, of both the correct and the incorrect response, was required for an effective proactive inhibitory control. Selective unilateral patterns of response preparation were instead associated with defective response suppression. Our results provide behavioral and electrophysiological evidence of a simultaneous dual pre-activation of two motor commands, likely underlying a global operating mechanism suggesting competition or lateral inhibition to govern the amendment of errors. These findings are consistent with the response inhibitory processes already observed in speed-accuracy tradeoff studies, and hint at a decisive role of early response competition to determine the success of multiple-choice action selection.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper.

Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.

Age-related Changes in Cortical Excitability Linked to Decreased Attentional and Inhibitory Control.

Understanding age-related changes in cortical excitability and their relation to cognitive functions will help to improve interventions based on non-invasive brain stimulation that aim to support cognitive function in older adults. Here, we investigate the relationship between cortical excitability, executive function, and underlying neural activity in samples of healthy young and older adults. These participants performed a Simon task during electroencephalogram (EEG) recording. During the task, participants had to respond to the colour of a lateralized stimulus while ignoring its spatial location. We studied event-related brain potential correlates of attentional and inhibitory control [i.e., the posterior contralateral negativity (N2pc) and central contralateral negativity (N2cc), respectively] related to the Simon task performance. We also used transcranial magnetic stimulation (TMS) EEG coregistration. In detail, we applied single-pulse TMS during EEG recording in order to analyse global mean field power (GMFP) and TMS-evoked potentials (TEPs) as correlates of cortical excitability. We found lower GMFP amplitude within 101-200 ms in older compared to young adults. Moreover, older adults showed smaller N45 amplitude and slower P180 latency. These findings suggest cortical excitability alterations related to ageing. Older adults also exhibited longer reaction times and N2pc and N2cc latencies, indicating that it took them longer to allocate attention to the target stimulus and inhibit the tendency to respond to the attended location. Finally, in older adults, cortical excitability alterations correlated with longer reaction times and N2pc latencies. These results suggest that age-related alterations in cortical excitability represent a dysfunctional change associated with physiological ageing.

An integrated TMS-EEG and MRI approach to explore the interregional connectivity of the default mode network.

Explorations of the relation between brain anatomy and functional connections in the brain are crucial for shedding more light on network connectivity that sustains brain communication. In this study, by means of an integrative approach, we examined both the structural and functional connections of the default mode network (DMN) in a group of sixteen healthy subjects. For each subject, the DMN was extracted from the structural and functional resonance imaging data; the areas that were part of the DMN were defined as the regions of interest. Then, the target network was structurally explored by diffusion-weighted imaging, tested by neurophysiological means, and retested by means of concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG). A series of correlational analyses were performed to explore the relationship between the amplitude of early-latency TMS-evoked potentials and the indexes of structural connectivity (weighted number of fibres and fractional anisotropy). Stimulation of the left or right parietal nodes of the DMN-induced activation in the contralateral parietal and frontocentral electrodes within 60 ms; this activation correlated with fractional anisotropy measures of the corpus callosum. These results showed that distant secondary activations after target stimulation can be predicted based on the target's anatomical connections. Interestingly, structural features of the corpus callosum predicted the activation of the directly connected nodes, i.e., parietal-parietal nodes, and of the broader DMN network, i.e., parietal-frontal nodes, as identified with functional magnetic resonance imaging. Our results suggested that the proposed integrated approach would allow us to describe the contributory causal relationship between structural connectivity and functional connectivity of the DMN.

Responsiveness to left-prefrontal tDCS varies according to arousal levels.

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.

Transcranial electric stimulation as a neural interface to gain insight on human brain functions: current knowledge and future perspective.

The use of brain stimulation approaches in social and affective science has greatly increased over the last two decades. The interest in social factors has grown along with technological advances in brain research. Transcranial electric stimulation (tES) is a research tool that allows scientists to establish contributory causality between brain functioning and social behaviour, therefore deepening our understanding of the social mind. Preliminary evidence is also starting to demonstrate that tES, either alone or in combination with pharmacological or behavioural interventions, can alleviate the symptomatology of individuals with affective or social cognition disorders. This review offers an overview of the application of tES in the field of social and affective neuroscience. We discuss the issues and challenges related to this application and suggest an avenue for future basic and translational research.

Protocols for cognitive enhancement. A user manual for Brain Health Services-part 5 of 6.

Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs ("smart drugs", acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.

Alpha-band cortico-cortical phase synchronization is associated with effective connectivity in the motor network.

OBJECTIVE: Communication-through-coherence proposes that the phase synchronization (PS) of neural oscillations between cortical areas supports neural communication. In this study, we exploited transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) to test this hypothesis at the macroscale level, i.e., whether PS between cortical areas supports interarea communication. TEPs are electroencephalographic (EEG) responses time-locked to TMS pulses reflecting interarea communication, as they are generated by the transmission of neural activity from the stimulated area to connected regions. If interarea PS is important for communication, it should be associated with the TEP amplitude in the connected areas. METHODS: TMS was delivered over the left primary motor cortex (M1) of fourteen healthy volunteers, and 70-channel EEG was recorded. Early TEP components were source-localized to identify their generators, i.e., distant brain regions activated by M1 through effective connections. Next, linear regressions were used to test the relationship between the TEP amplitude and the pre-stimulus PS between the M1 and the connected regions in four frequency bands (range 4-45 Hz). RESULTS: Pre-stimulus interarea PS in the alpha-band was positively associated with the amplitude of early TEP components, namely, the N15 (ipsilateral supplementary motor area), P25 (contralateral M1) and P60 (ipsilateral parietal cortex). CONCLUSIONS: Alpha-band PS predicts the response amplitude of the distant brain regions effectively connected to M1. SIGNIFICANCE: Our study supports the role of EEG-PS in interarea communication, as theorized by communication-through-coherence.

Baseline levels of alertness influence tES effects along different age-related directions.

Normal aging is usually accompanied by several structural and functional physiological changes of the brain, which are closely related to alterations of cognitive functions (e.g., visual short-term memory). As the average age of the population increases, it has become crucial to identify cognitive-behavioural interventions to maintain a healthy level of cognitive performance. Among a variety of approaches, the targeting of specific intrinsic alertness mechanisms has shown a solid rationale and beneficial effects in both healthy and pathological ageing. In a similar vein, the use of non-invasive transcranial electrical stimulation (tES) represents another promising approach to induce an alerting state that can produce advantages in the information processing in the brain and therefore behaviour. Here, we investigated whether time-locked bursts of tES (i.e., transcranial random noise stimulation) were effective in inducing behavioural and physiological changes, consistently with an alertness increase, in both young and older healthy adults. Namely, we expected to find a beneficial alerting effect on visual short-term memory performance as a function of stimulus perceptual salience and tES. The initial results showed that the performance of younger adults was not affected by tES, while older adults scored lower correct responses for high-salience stimuli during real tES with respect to sham stimulation. However, after including a baseline measure of subjective level of alertness in the analyses, a tES-induced memory improvement did emerge in the less alerted younger adults, while only the more alerted older adults were subject to the worsening effect by tES. We discuss these results in consideration of the evidence on critical age-related differences as well as the interaction between neurostimulation and baseline alerting mechanisms.

The impact of artifact removal approaches on TMS-EEG signal.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) allow one to assess cortical excitability and effective connectivity in clinical and basic research. However, obtaining clean TEPs is challenging due to the various TMS-related artifacts that contaminate the electroencephalographic (EEG) signal when the TMS pulse is delivered. Different preprocessing approaches have been employed to remove the artifacts, but the degree of artifact reduction or signal distortion introduced in this phase of analysis is still unknown. Knowing and controlling this potential source of uncertainty will increase the inter-rater reliability of TEPs and improve the comparability between TMS-EEG studies. The goal of this study was to assess the variability in TEP waveforms due to of the use of different preprocessing pipelines. To accomplish this aim, we preprocessed the same TMS-EEG data with four different pipelines and compared the results. The dataset was obtained from 16 subjects in two identical recording sessions, each session consisting of both left dorsolateral prefrontal cortex and left inferior parietal lobule stimulation at 100% of the resting motor threshold. Considerable differences in TEP amplitudes and global mean field power (GMFP) were found between the preprocessing pipelines. Topographies of TEPs from the different pipelines were all highly correlated (ρ>0.8) at latencies over 100 ms. By contrast, waveforms at latencies under 100 ms showed a variable level of correlation, with ρ ranging between 0.2 and 0.9. Moreover, the test-retest reliability of TEPs depended on the preprocessing pipeline. Taken together, these results take us to suggest that the choice of the preprocessing approach has a marked impact on the final TEP, and that further studies are needed to understand advantages and disadvantages of the different approaches.

Remember as we empathize. Do brain mechanisms engaged in autobiographical memory retrieval causally affect empathy awareness? A combined TMS and EEG registered report.

Social interactions are partly driven by our ability to empathize-the capacity to share and understand others' inner states. While a growing body of evidence suggests a link between past experiences and empathy, to what degree empathy is dependent on our own previous experiences (autobiographical memories, AMs) is still unclear. Whereas neuroimaging studies have shown wide overlapping brain networks underpinning AM and empathic processes, studies on clinical populations with memory loss have not always shown empathy is impaired. The current transcranial magnetic stimulation (TMS) and electroencephalography study will seek to shed light on this neuropsychological puzzle by testing whether self-perceived empathy is causally linked to AM retrieval. Cortical activity, together with self-rating of empathy, will be recorded for scenarios that echo personal experiences while a brain region critical for AM retrieval will be transiently inhibited using TMS before task performance.

Asymmetric transcallosal conduction delay leads to finer bimanual coordination.

It has been theorized that hemispheric dominance and more segregated information processing have evolved to overcome long conduction delays through the corpus callosum (transcallosal conduction delay - TCD) but that this may still impact behavioral performance, mostly in tasks requiring high timing accuracy. Nevertheless, a thorough understanding of the temporal features of interhemispheric communication is lacking. Here, we aimed to assess the relationship between TCD and behavioral performance with a noninvasive directional cortical measure of TCD obtained from transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) in the motor system. Twenty-one healthy right-handed subjects were tested. TEPs were recorded during an ipsilateral silent period (iSP) paradigm and integrated with diffusion tensor imaging (DTI) and an in-phase bimanual thumb-opposition task. Linear mixed models were applied to test relationships between measures. We found TEP indexes of transcallosal communication at ∼15 ms both after primary motor cortex stimulation (M1-P15) and after dorsal premotor cortex stimulation (dPMC-P15). Both M1-and dPMC-P15 were predicted by mean diffusivity in the callosal body. Moreover, M1-P15 was positively related to iSP. Importantly, M1-P15 latency was linked to bimanual coordination with direction-dependent effects, so that asymmetric TCD was the best predictor of bimanual coordination. Our findings support the idea that transcallosal timing in signal transmission is essential for interhemispheric communication and can impact the final behavioral outcome. However, they challenge the view that a short conduction delay is always beneficial. Rather, they suggest that the effect of the conduction delay may depend on the direction of information flow.

tDCS over posterior parietal cortex increases cortical excitability but decreases learning: An ERPs and TMS-EEG study.

The application of anodal transcranial direct current stimulation (AtDCS) is generally associated with increased neuronal excitability and enhanced cognitive functioning. Nevertheless, previous work showed that applying this straight reasoning does not always lead to the desired results at behavioural level. Here, we investigated electrophysiological markers of AtDCS-mediated effects on visuo-spatial contextual learning (VSCL). In order to assess cortical excitability changes after 3 mA AtDCS applied over posterior parietal cortex, event-related potentials (ERPs) were collected during task performance. Additionally, AtDCS-induced effects on cortical excitability were explored by measuring TMS-evoked potentials (TEPs) collected before AtDCS, after AtDCS and after AtDCS and VSCL interaction. Behavioural results revealed that the application of AtDCS induced a reduction of VSCL. At the electrophysiological level, ERPs showed enhanced cortical response (P2 component) in the group receiving Real-AtDCS as compared to Sham-AtDCS. Cortical responsiveness at rest as measured by TEP, did not indicate any significant difference between Real- and Sham-tDCS groups, albeit a trend was present. Overall, our results suggest that AtDCS increases cortical response to incoming visuo-spatial stimuli, but with no concurrent increase in learning. Detrimental effects on behaviour could result from the interaction between AtDCS- and task-mediated cortical activation. This interaction might enhance cortical excitability and hinder normal task-related neuroplastic phenomena subtending learning.