Posterior parietal cortex is causally involved in reward valuation but not in probability weighting during risky choice.

This study provides evidence that the posterior parietal cortex is causally involved in risky decision making via the processing of reward values but not reward probabilities. In the within-group experimental design, participants performed a binary lottery choice task following transcranial magnetic stimulation of the right posterior parietal cortex, left posterior parietal cortex, and a right posterior parietal cortex sham (placebo) stimulation. The continuous theta-burst stimulation protocol supposedly downregulating the cortical excitability was used. Both, mean-variance and the prospect theory approach to risky choice showed that the posterior parietal cortex stimulation shifted participants toward greater risk aversion compared with sham. On the behavioral level, after the posterior parietal cortex stimulation, the likelihood of choosing a safer option became more sensitive to the difference in standard deviations between lotteries, compared with sham, indicating greater risk avoidance within the mean-variance framework. We also estimated the shift in prospect theory parameters of risk preferences after posterior parietal cortex stimulation. The hierarchical Bayesian approach showed moderate evidence for a credible change in risk aversion parameter toward lower marginal reward value (and, hence, lower risk tolerance), while no credible change in probability weighting was observed. In addition, we observed anecdotal evidence for a credible increase in the consistency of responses after the left posterior parietal cortex stimulation compared with sham.

Midfrontal theta transcranial alternating current stimulation modulates behavioural adjustment after error execution.

Cognitive control during conflict monitoring, error processing, and post-error adjustment appear to be associated with the occurrence of midfrontal theta (MFÏ´). While this association is supported by correlational EEG studies, much less is known about the possible causal link between MFÏ´ and error and conflict processing. In the present study, we aimed to explore the role of band-specific effects in modulating the error system during a conflict resolution. In turn, we delivered transcranial alternating current stimulation (tACS) at different frequency bands (delta δ, theta θ, alpha α, beta ß, gamma γ) and sham stimulation over the medial frontal cortex (MFC) in 36 healthy participants performing a modified version of the Flanker task. Task performance and reports about the sensations (e.g. visual flickering, cutaneous burning) induced by the different frequency bands, were also recorded. We found that online θ-tACS increased the response speed to congruent stimuli after error execution with respect to sham stimulation. Importantly, the accuracy following the errors did not decrease because of speed-accuracy trade off. Moreover, tACS evoked visual and somatosensory sensations were significantly stronger at α-tACS and ß-tACS compared to other frequencies. Our findings suggest that theta activity plays a causative role in modulating behavioural adjustments during perceptual choices in a stimulus-response conflict task.

Frequency-specific insight into short-term memory capacity.

The digit span is one of the most widely used memory tests in clinical and experimental neuropsychology for reliably measuring short-term memory capacity. In the forward version, sequences of digits of increasing length have to be reproduced in the order in which they are presented, whereas in the backward version items must be reproduced in the reversed order. Here, we assessed whether transcranial alternating current stimulation (tACS) increases the memory span for digits of young and midlife adults. Imperceptibly weak electrical currents in the alpha (10 Hz), beta (20 Hz), theta (5 Hz), and gamma (40 Hz) range, as well as a sham stimulation, were delivered over the left posterior parietal cortex, a cortical region thought to sustain maintenance processes in short-term memory through oscillatory brain activity in the beta range. We showed a frequency-specific effect of beta-tACS that robustly increased the forward memory span of young, but not middle-aged, healthy individuals. The effect correlated with age: the younger the subjects, the greater the benefit arising from parietal beta stimulation. Our results provide evidence of a short-term memory capacity improvement in young adults by online frequency-specific tACS application.

Individual and sex-related differences in pain and relief responsiveness are associated with differences in resting-state functional networks in healthy volunteers.

Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex-related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting-state network. In men, pain measures correlated with increased connectivity within the visual resting-state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions.

Role of brain hemispheric dominance in anticipatory postural control strategies.

Most of the cerebral functions are asymmetrically represented in the two hemispheres. Moreover, dexterity and coordination of the distal segment of the dominant limbs depend on cortico-motor lateralization. In this study, we investigated whether postural control may be also considered a lateralized hemispheric brain function. To this aim, 15 young subjects were tested in standing position by measuring center of pressure (COP) shifts along the anteroposterior axis (COP-Y) during dynamic posturography before and after continuous Theta Burst Stimulation (cTBS) intervention applied to the dominant or non-dominant M1 hand area as well as to the vertex. We show that when subjects were expecting a forward platform translation, the COP-Y was positioned significantly backward or forward after dominant or non-dominant M1 stimulation, respectively. We postulate that cTBS applied on M1 may have disrupted the functional connectivity between intra- and interhemispheric areas implicated in the anticipatory control of postural stability. This study suggests a functional asymmetry between the two homologous primary motor areas, with the dominant hemisphere playing a critical role in the selection of the appropriate postural control strategy.

State-dependent effects of transcranial oscillatory currents on the motor system: what you think matters.

Imperceptible transcranial alternating current stimulation (tACS) changes the endogenous cortical oscillatory activity in a frequency-specific manner. In the human motor system, tACS coincident with the idling beta rhythm of the quiescent motor cortex increased the corticospinal output. We reasoned that changing the initial state of the brain (i.e., from quiescence to a motor imagery task that desynchronizes the local beta rhythm) might also change the susceptibility of the corticospinal system to resonance effects induced by beta-tACS. We tested this hypothesis by delivering tACS at different frequencies (theta, alpha, beta, and gamma) on the primary motor cortex at rest and during motor imagery. Motor-evoked potentials (MEPs) were obtained by transcranial magnetic stimulation (TMS) on the primary motor cortex with an online-navigated TMS-tACS setting. During motor imagery, the increase of corticospinal excitability was maximal with theta-tACS, likely reflecting a reinforcement of working memory processes required to mentally process and "execute" the cognitive task. As expected, the maximal MEPs increase with subjects at rest was instead obtained with beta-tACS, substantiating previous evidence. This dissociation provides new evidence of state and frequency dependency of tACS effects on the motor system and helps discern the functional role of different oscillatory frequencies of this brain region. These findings may be relevant for rehabilitative neuromodulatory interventions.

Differential effects of acute cortisol administration on deep and shallow episodic memory traces: a study on healthy males.

We aimed at investigating rapid effects of plasma cortisol elevations on the episodic memory phase of encoding or retrieval, and on the strength of the memory trace. Participants were asked either to select a word containing the letter "e" (shallow encoding task) or to judge if a word referred to a living entity (deep encoding task). We intravenously administered a bolus of 20mg of cortisol either 5 min before encoding or 5 min before retrieval, in a between-subjects design. The study included only male participants tested in the late afternoon, and neutral words as stimuli. When cortisol administration occurred prior to retrieval, a main effect of group emerged. Recognition accuracy was higher for individuals who received cortisol compared to placebo. The higher discrimination accuracy for the cortisol group was significant for words encoded during deep but not shallow task. Cortisol administration before encoding did not affect subsequent retrieval performance (either for deep or shallow stimuli) despite a facilitatory trend. Because genomic mechanisms take some time to develop, such a mechanism cannot apply to our findings where the memory task was performed shortly after the enhancement of glucocorticoid levels. Therefore, glucocorticoids, through non-genomic fast effects, determine an enhancement in episodic memory if administered immediately prior to retrieval. This effect is more evident if the memory trace is laid down through deep encoding operations involving the recruitment of specific neural networks.

TMS interference with primacy and recency mechanisms reveals bimodal episodic encoding in the human brain.

A classic finding of the psychology of memory is the "serial position effect." Immediate free recall of a word list is more efficient for items presented early (primacy effect) or late (recency effect), with respect to those in the middle. In an event-related, randomized block design, we interfered with the encoding of unrelated words lists with brief trains of repetitive TMS (rTMS), applied coincidently with the acoustic presentation of each word to the left dorsolateral pFC, the left intraparietal lobe, and a control site (vertex). Interference of rTMS with encoding produced a clear-cut double dissociation on accuracy during immediate free recall. The primacy effect was selectively worsened by rTMS of the dorsolateral pFC, whereas recency was selectively worsened by rTMS of the intraparietal lobe. These results are in agreement with the double dissociation between short-term and long-term memory observed in neuropsychological patients and provide direct evidence of distinct cortical mechanisms of encoding in the human brain.

Transcranial magnetic stimulation of the left middle frontal gyrus modulates the information people communicate in different social contexts.

Neocortical structures of the left frontal lobe, middle frontal gyrus (MFG) in particular, have been suggested to be linked to the processing of punishing and unpleasant outcomes in decision tasks. To assess the role of left MFG (lMFG) in communicative decisions, we used repetitive transcranial magnetic stimulation (rTMS) to inhibit its function during communicational exchanges under two types of social contexts: formal and informal. Three groups of participants received an offline 1-Hz inhibitory rTMS of lMFG, right MFG as an active control site, or lMFG sham/placebo TMS as a passive control condition. Participants' task included answering difficult general-knowledge questions, rating their confidence in their answers' correctness, and, finally, deciding if they would report or withhold these answers in formal and informal social contexts. There were significantly more reported than withheld answers in the informal context in all groups. The formal context showed no differences between reported and withheld answers in both control conditions, while, crucially, real rTMS of lMFG produced a different pattern, with more withheld than reported answers. Thus, lMFG inhibition seems to result in more rational decisions made only in formal communication contexts, where there is a perception of a certain pressure or possible negative outcomes. In informal social contexts and in the absence of negative consequences the pattern of answers did not change, regardless of the reporting strategy or the TMS protocol used. These results suggest selective context-dependent involvement of the lMFG in decision-making processes during communicational exchanges taking place under social pressure.

Frequency-dependent tuning of the human motor system induced by transcranial oscillatory potentials.

Different corticothalamic brain modules intrinsically oscillate at a "natural frequency" in a topographically organized manner. In "quiescent" human sensorimotor regions, the main detectable oscillatory activity peaks at ∼20 Hz, and partly contributes to determine the state of corticospinal excitability. Here, we showed that the transcranial application of an imperceptible, short-lasting (90 s) electric field oscillating at a physiological range increases corticospinal excitability online, with well defined frequency dependence and regional specificity. Indeed, the size of motor evoked potentials (MEPs) induced by navigated single-pulse TMS over the motor cortex significantly increased only during the local application of transcranial alternating current stimulation (tACS) at 20 Hz (ß range). Other tACS frequencies (5, 10, and 40 Hz) applied on the motor cortex did not impact MEPs' size. Moreover, tACS applied on a control site (parietal cortex) and on a peripheral site (ulnar nerve) also failed to modulate MEPs. These results help clarifying the functional significance of the 20 Hz idling ß rhythm of sensorimotor regions and suggest potential clinical applications of this approach.

Temporal dynamics of memory trace formation in the human prefrontal cortex.

Event-related repetitive transcranial magnetic stimulation (rTMS) can dynamically interfere with the memory encoding of complex visual scenes. Here, we investigated the critical time elapsing from stimulus presentation to the formation of an effective memory trace by delivering rTMS (900 ms at 20 Hz) during the encoding of visual scenes at different poststimulus delays (from 100 to 500 ms) in 28 healthy volunteers. The stimulation delay showed a robust inverse correlation with the correct retrieval of encoded images. In particular, rTMS stimulation delivered with a delay of 500 ms and lasting for 400 ms after stimulus offset resulted in a huge drop in retrieval accuracy. Such a timing suggests that rTMS affects the formation of long-term memory through interference with postperceptual executive processes, rather than with perceptual analysis of the stimuli. The effect was specific for stimulation of the left dorsolateral prefrontal cortex (DLPFC), whereas rTMS applied to the right DLPFC, vertex (active control site), as well as sham stimulation (placebo) did not affect accuracy. These results confirm the crucial role of the left DLPFC in encoding and provide novel information about the critical timing of its engagement in the formation, consolidation, and maintenance of the memory trace.

Noninvasive brain stimulation and brain oscillations.

Recent technological advances in the field of noninvasive brain stimulation (NIBS) have allowed to interact with endogenous brain oscillatory activity, the main neural communication code of our brain, opening new scenarios for transient modifications of cognitive and behavioral performances: such a possibility can be capitalized both for research purposes in healthy subjects, as well as in the context of therapeutic and rehabilitative settings. Among NiBS methodologies, transcranial magnetic stimulation (TMS) has been the first used to this purpose, and also thanks to the technical development of TMS-EEG co-registering systems, the mechanistic knowledge regarding the role of brain oscillations has been improved. Another approach to brain oscillations considers electric stimulation methods, such as transcranial direct current stimulation (tDCS), and especially transcranial alternating current stimulation (tACS), for which -however- some technical and conceptual caveats have emerged. In this chapter, we briefly review the uses of NiBS in this field up to now, by providing an update on the current status of research applications as well as of its attempts of exploitation in translational clinical applications, especially regarding motor disorders and for understanding and reducing some psychiatric symptoms.

Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

In this study, we provide causal evidence that the dorsolateral prefrontal cortex (DLPFC) supports the computation of subjective value in choices under risk via its involvement in probability weighting. Following offline continuous theta-burst transcranial magnetic stimulation (cTBS) of the DLPFC subjects (N = 30, mean age 23.6, 56% females) completed a computerized task consisting of 96 binary lottery choice questions presented in random order. Using the hierarchical Bayesian modeling approach, we then estimated the structural parameters of risk preferences (the degree of risk aversion and the curvature of the probability weighting function) and analyzed the obtained posterior distributions to determine the effect of stimulation on model parameters. On a behavioral level, temporary downregulation of the left DLPFC excitability through cTBS decreased the likelihood of choosing an option with higher expected reward while the probability of choosing a riskier lottery did not significantly change. Modeling the stimulation effects on risk preference parameters showed anecdotal evidence as assessed by Bayes factors that probability weighting parameter increased after the left DLPFC TMS compared to sham.

Repetitive transcranial magnetic stimulation modulates action naming over the left but not right inferior frontal gyrus.

fMRI language mapping studies report right-hemispheric contribution to language in healthy individuals. However, it remains unclear whether these right-hemispheric patterns of activity are critical for language, which is highly relevant for clinical preoperative language mapping. The available findings are controversial. In this study, we first measured individual patterns of language lateralization with an fMRI language localizer in healthy participants with different handedness (N = 31). Then, the same participants received rTMS over the individual coordinates of peak fMRI-based activation in the left and right inferior frontal gyri. During rTMS, participants performed a picture naming task. It included both objects and actions to test whether naming of nouns and verbs would be equally modulated by rTMS. Stimulation of the left inferior frontal gyrus resulted in accuracy facilitation of verb production regardless of individual language lateralization. No modulation of object naming was found at any stimulation site in terms of accuracy nor reaction time. This study causally confirmed the critical contribution of the left, but not the right hemisphere to verb production regardless of the language lateralization patterns observed with fMRI. Also, the results stress that action rather than object naming is the task of choice for mapping language in the frontal lobe.

Impact of ß-range-induced oscillatory activity on human input-output relationship of the corticospinal pathway.

Objective: The aim of the study was to show that short-lasting (90 s) transcranial alternating current stimulation (tACS) at 20 Hz delivered over the left primary motor cortex (M1) is able to change the shape of recruitment curve of the corticospinal pathway.Methods: The corticospinal pathway was studied during tACS by means of the relationship between the intensity of transcranial magnetic stimulation (TMS) delivered over the left M1 and corresponding motor evoked potentials (MEPs) recorded from the right first dorsal interosseus muscle (FDI), in nine healthy subjects. In order to extract characteristics of the input-output relationship that have particular physiological relevance, data were fitted to the Boltzmann sigmoidal function by the Levenberg-Marquardt nonlinear, least mean squares algorithm.Results: The ß-rhythm tACS influenced the shape and parameters of the input-output relation, so that the initial segment of the conditioned curve (from threshold to 30% of maximum muscle size) diverged, while the subsequent segment converged to overlap the unconditioned control curve.Discussion: ß-rhythm tACS conditions only a definite subset of corticospinal elements influencing less than 30% of the entire motoneuronal pool. The fact that ß-rhythm tACS mainly affects the most excitable motoneurons could explain the observed antikinetic effect of the tACS at ß-rhythm applied in the motor regions.

Online and offline effects of transcranial alternating current stimulation of the primary motor cortex.

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms by means of external sinusoidal potentials. The physiological mechanisms underlying tACS effects are still under debate. Whereas online (e.g., ongoing) tACS over the motor cortex induces robust state-, phase- and frequency-dependent effects on cortical excitability, the offline effects (i.e. after-effects) of tACS are less clear. Here, we explored online and offline effects of tACS in two single-blind, sham-controlled experiments. In both experiments we used neuronavigated transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) as a probe to index changes of cortical excitability and delivered M1 tACS at 10 Hz (alpha), 20 Hz (beta) and sham (30 s of low-frequency transcranial random noise stimulation; tRNS). Corticospinal excitability was measured by single pulse TMS-induced motor evoked potentials (MEPs). tACS was delivered online in Experiment 1 and offline in Experiment 2. In Experiment 1, the increase of MEPs size was maximal with the 20 Hz stimulation, however in Experiment 2 neither the 10 Hz nor the 20 Hz stimulation induced tACS offline effects. These findings support the idea that tACS affects cortical excitability only during online application, at least when delivered on the scalp overlying M1, thereby contributing to the development of effective protocols that can be applied to clinical populations.

Event-related rTMS at encoding affects differently deep and shallow memory traces.

The "level of processing" effect is a classical finding of the experimental psychology of memory. Actually, the depth of information processing at encoding predicts the accuracy of the subsequent episodic memory performance. When the incoming stimuli are analyzed in terms of their meaning (semantic, or deep, encoding), the memory performance is superior with respect to the case in which the same stimuli are analyzed in terms of their perceptual features (shallow encoding). As suggested by previous neuroimaging studies and by some preliminary findings with transcranial magnetic stimulation (TMS), the left prefrontal cortex may play a role in semantic processing requiring the allocation of working memory resources. However, it still remains unclear whether deep and shallow encoding share or not the same cortical networks, as well as how these networks contribute to the "level of processing" effect. To investigate the brain areas casually involved in this phenomenon, we applied event-related repetitive TMS (rTMS) during deep (semantic) and shallow (perceptual) encoding of words. Retrieval was subsequently tested without rTMS interference. RTMS applied to the left dorsolateral prefrontal cortex (DLPFC) abolished the beneficial effect of deep encoding on memory performance, both in terms of accuracy (decrease) and reaction times (increase). Neither accuracy nor reaction times were instead affected by rTMS to the right DLPFC or to an additional control site excluded by the memory process (vertex). The fact that online measures of semantic processing at encoding were unaffected suggests that the detrimental effect on memory performance for semantically encoded items took place in the subsequent consolidation phase. These results highlight the specific causal role of the left DLPFC among the wide left-lateralized cortical network engaged by long-term memory, suggesting that it probably represents a crucial node responsible for the improved memory performance induced by semantic processing.

The role of the right temporoparietal junction in intersensory conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict.