Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap.

A recent hypothesis characterizes difficulties in multitasking as being the price humans pay for our ability to generalize learning across tasks. The mitigation of these costs through training has been associated with reduced overlap of constituent task representations within frontal, parietal, and subcortical regions. Transcranial direct current stimulation, which can modulate functional brain activity, has shown promise in generalizing performance gains when combined with multitasking training. However, the relationship between combined transcranial direct current stimulation and training protocols with task-associated representational overlap in the brain remains unexplored. Here, we paired prefrontal cortex transcranial direct current stimulation with multitasking training in 178 individuals and collected functional magnetic resonance imaging data pre- and post-training. We found that 1 mA transcranial direct current stimulation applied to the prefrontal cortex paired with multitasking training enhanced training transfer to spatial attention, as assessed via a visual search task. Using machine learning to assess the overlap of neural activity related to the training task in task-relevant brain regions, we found that visual search gains were predicted by changes in classification accuracy in frontal, parietal, and cerebellar regions for participants that received left prefrontal cortex stimulation. These findings demonstrate that prefrontal cortex transcranial direct current stimulation may interact with training-related changes to task representations, facilitating the generalization of learning.

Dopamine Alters the Effect of Brain Stimulation on Decision-Making.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating a range of psychiatric and neurologic conditions. However, optimization of such applications requires a better understanding of how tDCS alters cognition and behavior. Existing evidence implicates dopamine in tDCS alterations of brain activity and plasticity; however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behavior. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed-accuracy trade-off, which taps ubiquitous strategic operations. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants (N = 62, 24 males, 38 females) completed a dot-motion task, making judgments on the direction of a field of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modeling to uncover how our interventions altered latent decisional processes driving the speed-accuracy trade-off. We show that dopamine in combination with tDCS (but not tDCS alone nor dopamine alone) not only impaired decision accuracy but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behavior.SIGNIFICANCE STATEMENT tDCS can improve cognitive and behavioral impairments in clinical conditions; however, a better understanding of its mechanisms is required to optimize future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed-accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behavior.

Individual Differences in Decision Strategy Relate to Neurochemical Excitability and Cortical Thickness.

The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.SIGNIFICANCE STATEMENT The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.

Neural substrates of individual differences in learning generalization via combined brain stimulation and multitasking training.

A pervasive limitation in cognition is reflected by the performance costs we experience when attempting to undertake two tasks simultaneously. While training can overcome these multitasking costs, the more elusive objective of training interventions is to induce persistent gains that transfer across tasks. Combined brain stimulation and cognitive training protocols have been employed to improve a range of psychological processes and facilitate such transfer, with consistent gains demonstrated in multitasking and decision-making. Neural activity in frontal, parietal, and subcortical regions has been implicated in multitasking training gains, but how the brain supports training transfer is poorly understood. To investigate this, we combined transcranial direct current stimulation of the prefrontal cortex and multitasking training, with functional magnetic resonance imaging in 178 participants. We observed transfer to a visual search task, following 1 mA left or right prefrontal cortex transcranial direct current stimulation and multitasking training. These gains persisted for 1-month post-training. Notably, improvements in visual search performance for the right hemisphere stimulation group were associated with activity changes in the right hemisphere dorsolateral prefrontal cortex, intraparietal sulcus, and cerebellum. Thus, functional dynamics in these task-general regions determine how individuals respond to paired stimulation and training, resulting in enhanced performance on an untrained task.

On the relationship between GABA+ and glutamate across the brain.

Equilibrium between excitation and inhibition (E/I balance) is key to healthy brain function. Conversely, disruption of normal E/I balance has been implicated in a range of central neurological pathologies. Magnetic resonance spectroscopy (MRS) provides a non-invasive means of quantifying in vivo concentrations of excitatory and inhibitory neurotransmitters, which could be used as diagnostic biomarkers. Using the ratio of excitatory and inhibitory neurotransmitters as an index of E/I balance is common practice in MRS work, but recent studies have shown inconsistent evidence for the validity of this proxy. This is underscored by the fact that different measures are often used in calculating E/I balance such as glutamate and Glx (glutamate and glutamine). Here we used a large MRS dataset obtained at ultra-high field (7 T) measured from 193 healthy young adults and focused on two brain regions - prefrontal and occipital cortex - to resolve this inconsistency. We find evidence that there is an inter-individual common ratio between GABA+ (γ-aminobutyric acid and macromolecules) and Glx in the occipital, but not prefrontal cortex. We further replicate the prefrontal result in a legacy dataset (n = 78) measured at high-field (3 T) strength. By contrast, with ultra-high field MRS data, we find extreme evidence that there is a common ratio between GABA+ and glutamate in both prefrontal and occipital cortices, which cannot be explained by participant demographics, signal quality, fractional tissue volume, or other metabolite concentrations. These results are consistent with previous electrophysiological and theoretical work supporting E/I balance. Our findings indicate that MRS-detected GABA+ and glutamate (but not Glx), are a reliable measure of E/I balance .

The influence of tDCS intensity on decision-making training and transfer outcomes.

Transcranial direct current stimulation (tDCS) has been shown to improve single- and dual-task performance in healthy participants and enhance transferable training gains following multiple sessions of combined stimulation and task practice. However, it has yet to be determined what the optimal stimulation dose is for facilitating such outcomes. We aimed to test the effects of different tDCS intensities, with a commonly used electrode montage, on performance outcomes in a multisession single/dual-task training and transfer protocol. In a preregistered study, 123 participants, who were pseudorandomized across four groups, each completed six sessions (pre- and posttraining sessions and four combined tDCS and training sessions) and received 20 min of prefrontal anodal tDCS at 0.7, 1.0, or 2.0 mA or 15-s sham stimulation. Response time and accuracy were assessed in trained and untrained tasks. The 1.0-mA group showed substantial improvements in single-task reaction time and dual-task accuracy, with additional evidence for improvements in dual-task reaction times, relative to sham performance. This group also showed near transfer to the single-task component of an untrained multitasking paradigm. The 0.7- and 2.0-mA intensities varied in which performance measures they improved on the trained task, but in sum, the effects were less robust than for the 1.0-mA group, and there was no evidence for the transfer of performance. Our study highlights that training performance gains are augmented by tDCS, but their magnitude and nature are not uniform across stimulation intensity.NEW & NOTEWORTHY Using techniques such as transcranial direct current stimulation to modulate cognitive performance is an alluring endeavor. However, the optimal parameters to augment performance are unknown. Here, in a preregistered study with a large sample (123 subjects), three different stimulation dosages (0.7, 1.0, and 2.0 mA) were applied during multitasking training. Different cognitive training performance outcomes occurred across the dosage conditions, with only one of the doses (1.0 mA) leading to training transfer.

Causal evidence of right temporal parietal junction involvement in implicit Theory of Mind processing.

The ability to represent the internal thoughts, beliefs and desires of others, and recognise that these might be distinct from one's own, is crucial for adaptive social interaction. Such operations are thought to tap Theory of Mind (ToM), with its importance underscored by the link between ToM impairment and a range of neurodevelopmental disorders (e.g., Autism and Schizophrenia). Extensive investigations into the neural substrates of ToM, when individuals have to make overt/explicit judgments concerning others, have highlighted a link with a network of regions including the temporal parietal junction (TPJ), particularly in the right hemisphere. Recently, evidence has emerged that ToM can also operate implicitly and that this may be particularly impaired in Autism. However, very few studies have examined the neural basis of implicit ToM and none have employed methods allowing casual inferences to be made. Here, using brain stimulation, a Sally-Anne false-belief task, and eye-tracking we show that right TPJ is causally involved in ToM judgments that are made implicitly. These findings have implications for characterising the neural substrates of a key executive function, determining the extent to which implicit and explicit ToM draw on overlapping neural architecture and, potentially, better understanding of disorders tied to ToM impairment.

The efficacy of transcranial direct current stimulation to prefrontal areas is related to underlying cortical morphology.

Applying a weak electrical current to the cortex can have effects on a range of behaviours. Techniques such as transcranial direct current stimulation (tDCS) have been widely used in both research and clinical settings. However, there is significant variability across individuals in terms of their responsiveness to stimulation, which poses practical challenges to the application of tDCS, but also provides a unique opportunity to study the link between the brain and behaviour. Here, we assessed the role of individual differences in cortical morphology - specifically in prefrontal cortical regions of interest - for determining the influence of tDCS on decision-making performance. Specifically, we employed magnetic resonance imaging (MRI) and a previously replicated paradigm in which we modulated learning in a simple decision-making task by applying tDCS to the left prefrontal cortex in human subjects of both sexes. Cortical thickness of the left (but not right) prefrontal cortex accounted for almost 35% of the variance in stimulation efficacy across subjects. This is the first demonstration that variations in cortical architecture are associated with reliable differences in the effects of tDCS on cognition. Our findings have important implications for predicting the likely efficacy of different non-invasive brain stimulation treatments on a case by case basis.

Improvements in Attention and Decision-Making Following Combined Behavioral Training and Brain Stimulation.

In recent years there has been a significant commercial interest in 'brain training' - massed or spaced practice on a small set of tasks to boost cognitive performance. Recently, researchers have combined cognitive training regimes with brain stimulation to try and maximize training benefits, leading to task-specific cognitive enhancement. It remains unclear, however, whether the performance gains afforded by such regimes can transfer to untrained tasks, or how training and stimulation affect the brain's latent information processing dynamics. To examine these issues, we applied transcranial direct current stimulation (tDCS) over the prefrontal cortex while participants undertook decision-making training over several days. Anodal, relative to cathodal/sham tDCS, increased performance gains from training. Critically, these gains were reliable for both trained and untrained tasks. The benefit of anodal tDCS occurred for left, but not right, prefrontal stimulation, and was absent for stimulation delivered without concurrent training. Modeling revealed left anodal stimulation combined with training caused an increase in the brain's rate of evidence accumulation for both tasks. Thus tDCS applied during training has the potential to modulate training gains and give rise to transferable performance benefits for distinct cognitive operations through an increase in the rate at which the brain acquires information.

Transcranial direct current stimulation of superior medial frontal cortex disrupts response selection during proactive response inhibition.

Cognitive control is a vital executive process that is involved in selecting, generating, and maintaining appropriate, goal-directed behaviour. One operation that draws heavily on this resource is the mapping of sensory information to appropriate motor responses (i.e., response selection). Recently, a transcranial direct current stimulation (tDCS) study demonstrated that the left posterior lateral prefrontal cortex (pLPFC) is casually involved in response selection and response selection training. Correlational brain imaging evidence has also implicated the superior medial frontal cortex (SMFC) in response selection, and there is causal evidence that this brain region is involved in the proactive modulation of response tendencies when occasional stopping is required (response inhibition). However, to date there is only limited causal evidence that implicates the SMFC in response selection. Here, we investigated the role of SMFC in response selection, response selection training (Experiment 1) and response selection when occasional response inhibition is anticipated (Experiments 2 and 3) by employing anodal, cathodal, and sham tDCS. Cathodal stimulation of the SMFC modulated response selection by increasing reaction times in the context of proactive response inhibition. Our results suggest a context dependent role of the SMFC in response selection and hint that task set can influence the interaction between the brain and behaviour.

Disrupting prefrontal cortex prevents performance gains from sensory-motor training.

Humans show large and reliable performance impairments when required to make more than one simple decision simultaneously. Such multitasking costs are thought to largely reflect capacity limits in response selection (Welford, 1952; Pashler, 1984, 1994), the information processing stage at which sensory input is mapped to a motor response. Neuroimaging has implicated the left posterior lateral prefrontal cortex (pLPFC) as a key neural substrate of response selection (Dux et al., 2006, 2009; Ivanoff et al., 2009). For example, activity in left pLPFC tracks improvements in response selection efficiency typically observed following training (Dux et al., 2009). To date, however, there has been no causal evidence that pLPFC contributes directly to sensory-motor training effects, or the operations through which training occurs. Moreover, the left hemisphere lateralization of this operation remains controversial (Jiang and Kanwisher, 2003; Sigman and Dehaene, 2008; Verbruggen et al., 2010). We used anodal (excitatory), cathodal (inhibitory), and sham transcranial direct current stimulation (tDCS) to left and right pLPFC and measured participants' performance on high and low response selection load tasks after different amounts of training. Both anodal and cathodal stimulation of the left pLPFC disrupted training effects for the high load condition relative to sham. No disruption was found for the low load and right pLPFC stimulation conditions. The findings implicate the left pLPFC in both response selection and training effects. They also suggest that training improves response selection efficiency by fine-tuning activity in pLPFC relating to sensory-motor translations.

Exploring the intra-individual reliability of tDCS: A registered report.

Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has become an important tool for the study of in-vivo brain function due to its modulatory effects. Over the past two decades, interest in the influence of tDCS on behaviour has increased markedly, resulting in a large body of literature spanning multiple domains. However, the effect of tDCS on human performance often varies, bringing into question the reliability of this approach. While reviews and meta-analyses highlight the contributions of methodological inconsistencies and individual differences, no published studies have directly tested the intra-individual reliability of tDCS effects on behaviour. Here, we conducted a large scale, double-blinded, sham-controlled registered report to assess the reliability of two single-session low-dose tDCS montages, previously found to impact response selection and motor learning operations, across two separate time periods. Our planned analysis found no evidence for either protocol being effective nor reliable. Post-hoc explorative analyses found evidence that tDCS influenced motor learning, but not response selection learning. In addition, the reliability of motor learning performance across trials was shown to be disrupted by tDCS. These findings are amongst the first to shed light specifically on the intra-individual reliability of tDCS effects on behaviour and provide valuable information to the field.

Intensity-dependent effects of tDCS on motor learning are related to dopamine.

Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are popular methods for inducing neuroplastic changes to alter cognition and behaviour. One challenge for the field is to optimise stimulation protocols to maximise benefits. For this to happen, we need a better understanding of how stimulation modulates cortical functioning/behaviour. To date, there is increasing evidence for a dose-response relationship between tDCS and brain excitability, however how this relates to behaviour is not well understood. Even less is known about the neurochemical mechanisms which may drive the dose-response relationship between stimulation intensities and behaviour. Here, we examine the effect of three different tDCS stimulation intensities (1 mA, 2 mA, 4 mA anodal motor cortex tDCS) administered during the explicit learning of motor sequences. Further, to assess the role of dopamine in the dose-response relationship between tDCS intensities and behaviour, we examined how pharmacologically increasing dopamine availability, via 100 mg of levodopa, modulated the effect of stimulation on learning. In the absence of levodopa, we found that 4 mA tDCS improved and 1 mA tDCS impaired acquisition of motor sequences relative to sham stimulation. Conversely, levodopa reversed the beneficial effect of 4 mA tDCS. This effect of levodopa was no longer evident at the 48-h follow-up, consistent with previous work characterising the persistence of neuroplastic changes in the motor cortex resulting from combining levodopa with tDCS. These results provide the first direct evidence for a role of dopamine in the intensity-dependent effects of tDCS on behaviour.

Dopamine Increases Accuracy and Lengthens Deliberation Time in Explicit Motor Skill Learning.

Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females; 11 males; aged 18-29 years) first consumed either 100 mg of levodopa (n = 19), a dopamine precursor that increases dopamine availability, or placebo (n = 19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets jumped mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy and not speed. The effect of the dopamine manipulations on skill learning was assessed during training and after an overnight follow-up. Increasing dopamine availability at training improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training and, importantly, at follow-up, despite prominent session-by-session performance improvements in both accuracy and speed. Exogenous dopamine thus seems to result in a learnt, persistent propensity to better adhere to task goals. Results support the proposal that dopamine is important in engagement of instrumental motivation to optimize adherence to task goals, particularly when learning to execute goal-directed strategies in motor skill learning.

The causal role of the prefrontal and superior medial frontal cortices in the incidental manipulation of decision strategies.

A key strategic decision one must make in virtually every task context concerns the speed accuracy trade-off (SAT). Experimentally, this ubiquitous phenomenon, whereby response speed and task accuracy are inversely related, is typically studied by explicitly instructing participants to adjust their strategy: by either focusing on speed, or on accuracy. Computational modelling has been applied to deconvolve the latent decision processes involved in the SAT, with considerable evidence suggesting that response caution (the amount of evidence needed for a decision to be reached) is a key variable in the setting of SAT strategy. Neuroimaging has implicated the prefrontal cortex, the pre-supplementary motor area (preSMA), and the striatum in the setting of response caution. In addition, brain stimulation has provided causal evidence for the involvement of the left prefrontal cortex and superior medial frontal cortex (SMFC, which includes the preSMA) in adjustments of response caution following explicit instructions, although stimulation of the two regions has dissociable effects. Here, in a double-blind and preregistered study we investigated the role of these two regions using an incidental manipulation of SAT strategy - via stimulus signal variability - which has previously been shown to influence decision confidence. We again found tDCS applied to both regions modulated response caution, and there was a dissociation: stimulating prefrontal cortex increased, and stimulating SMFC decreased, response caution. These findings provide further support for key, but dissociable, roles of these brain regions in decision strategies whether they are implemented explicitly or incidentally.

The influence of self-reported history of mild traumatic brain injury on cognitive performance.

The long-term cognitive consequences of mild traumatic brain injury (mTBI) are poorly understood. Studies investigating cognitive performance in the chronic stage of injury in both hospital-based and population-based samples have revealed inconsistent findings. Importantly, population-based mTBI samples remain under-studied in the literature. This study investigated cognitive performance among individuals with a history of self-reported mTBI using a battery of cognitively demanding behavioural tasks. Importantly, more than half of the mTBI participants had experienced multiple mild head injuries. Compared to control participants (n = 49), participants with a history of mTBI (n = 30) did not demonstrate deficits in working memory, multitasking ability, cognitive flexibility, visuospatial ability, response inhibition, information processing speed or social cognition. There was moderate evidence that the mTBI group performed better than control participants on the visual working memory measure. Overall, these findings suggest that even multiple instances of mTBI do not necessarily lead to long-term cognitive impairment at the group level. Thus, we provide important evidence of the impact of chronic mTBI across a number of cognitive processes in a population-based sample. Further studies are necessary to determine the impact that individual differences in injury-related variables have on cognitive performance in the chronic stage of injury.

tDCS augments decision-making efficiency in an intensity dependent manner: A training study.

The application of transcranial direct current stimulation (tDCS) to the prefrontal cortex has the potential to improve performance more than cognitive training alone. Such stimulation-induced performance enhancements can generalize beyond trained tasks, leading to benefits for untrained tasks/processes. We have shown evidence that stimulation intensity has non-linear effects on augmenting cognitive training outcomes. However, it is currently unclear how stimulation intensity augments cognitive processing to impact training and transfer effects. Here, we applied decision-making modelling via the linear ballistic accumulator framework to understand what aspects of cognitive processes underlying speeded single-/dual-task decision-making performance change with tDCS intensity. One hundred and twenty-three participants were split into four groups: sham, 0.7 mA, 1.0 mA and 2.0 mA stimulation intensities. Participants completed four training sessions whilst tDCS was delivered. The 0.7 mA & 1.0 mA intensities provided the greatest benefit for performance (increased decision-making efficiency as measured by drift rates) on the trained task - more than sham or 2.0 mA stimulation. The latent decision components integrated both accuracy and reaction times to estimate performance more broadly. We see an inverted u-shaped function of stimulation intensity and cognitive performance in the trained-on task, where either no stimulation or too much stimulation is sub-optimal for performance. By contrast, 1.0 mA and 2.0 mA intensities led to increased drift rates in an untrained (transfer) single task. In sum, tDCS intensity non-linearly modulates cognitive processes related to decision-making efficiency.

Intervention is a better predictor of tDCS mind-wandering effects than subjective beliefs about experimental results.

Blinding in non-invasive brain stimulation research is a topic of intense debate, especially regarding the efficacy of sham-controlled methods for transcranial direct current stimulation (tDCS). A common approach to assess blinding success is the inclusion of correct guess rate. However, this method cannot provide insight into the effect of unblinding on observed stimulation outcomes. Thus, the implementation of measures to systematically evaluate subjective expectation regarding stimulation is needed. Previous work evaluated subjective effects in an earlier study which reported a mind-wandering and tDCS data set and concluded that subjective belief drove the pattern of results observed. Here we consider the subjective and objective intervention effects in a key contrast from that data set-2 mA vs. sham-which was not examined in the reanalysis. In addition, we examine another key contrast from a different tDCS mind-wandering study that employed similar methodology. Our findings support objective intervention as the strongest predictor of the observed effects of mind-wandering in both re-analyses, over and above that of subjective intervention. However, it is important to control for and understand the possible inadequacies of sham-controlled methods.

Age-related differences in the role of the prefrontal cortex in sensory-motor training gains: A tDCS study.

The ability to process multiple sources of information concurrently is particularly impaired as individuals age and such age-related increases in multitasking costs have been linked to impairments in response selection. Previous neuroimaging studies with young adults have implicated the left hemisphere prefrontal cortex (PFC) as a key neural substrate of response selection. In addition, several transcranial direct current stimulation (tDCS) studies have provided causal evidence implicating this region in response selection and multitasking operations. For example, Filmer et al. (2013b) demonstrated that typically observed response selection learning/training gains in young adults were disrupted via offline tDCS of left, but not right, PFC. Here, considering evidence of age-related structural and functional changes in the brains of older adults, we assessed if this pattern of response selection learning disruption via tDCS to the left PFC is observed in older adults, testing if this region remains a key response selection node as individuals age. In a pre-registered study with 58 older adults, we applied anodal, cathodal, and sham stimulation to left and right PFC, and measured performance as participants trained on low- and high-response selection load tasks. Active stimulation did not disrupt training in older adults as compared to younger adults from our previous study. The results highlight age-related differences in the casual neural substrates that subserve response selection and learning.