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BackgroundTranscranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex has mild to moderate antidepressant effects. Little is known about the mechanisms of action. Other antidepressant treatments have been shown to act in part by reducing negative biases, which are thought to play a causal role in the maintenance of depression. Negative biases are hypothesized to stem from aberrant reinforcement learning processes, more precisely from overestimation of the informativeness of negative outcomes. The aim of this study was to test whether bifrontal tDCS might normalise such aberrant reinforcement learning processes in depressed mood.Methods85 community volunteers with low mood received tDCS during (or before) the performance of a reinforcement learning task that manipulated the informativeness (volatility) of positive and negative outcomes. In two sessions participants received real or sham tDCS in counter-balanced order. Baseline performance (sham tDCS) was compared to a sample of healthy individuals (n = 40) to identify the effect of low mood on task performance. The impact of tDCS on task performance was assessed by contrasting real and sham tDCS.ResultsLow mood was characterised by decreased adjustment of loss relative to win learning rates in response to changes in informativeness. Bifrontal tDCS applied during task performance normalised this deficit by increasing the adjustment of loss learning rates to informativeness. Bifrontal tDCS applied before task performance had no effect indicating that the stimulation effect is cognitive state dependent.ConclusionsOur study provides preliminary evidence that bifrontal tDCS can normalise aberrant reinforcement learning processes in low mood. Crucially, this was only the case if stimulation was applied during task performance, suggesting that combining tDCS with a concurrent cognitive manipulation might increase the functional impact on cognitive functions and potentially on emotional symptoms. Future studies are needed to test if the effect on learning processes might have a beneficial effect on mood itself.

Transcranial electrical stimulation (tES) is considered effective and safe for depression, albeit modestly, and prone to logistical burdens when performed in external facilities. Investigation of portable tES (ptES), and potentiation of ptES with remote psychological interventions have shown positive, but preliminary, results.We report the rationale and design of an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES and internet-based behavioral therapy (iBT) for major depressive disorder (MDD) (NCT04889976).We will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ('double-active'), (2) active ptES + sham iBT ('ptES-only'), and (3) sham ptES + sham iBT ('double-sham'), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks. Antidepressants are allowed in stable doses during the trial.We primarily co-hypothesize changes in HDRS-17 will be greater in (1) 'double-active' compared to 'ptES-only,' (2) 'double-active' compared to 'double-sham,' and (3) 'ptES-only' compared to 'double-sham.' We aim to enroll 210 patients (70 per arm).Our results should offer new insights regarding the efficacy and scalability of combined ptES and iBT for MDD, in digital mental health.

This chapter evaluates how neuroimaging can advance non-invasive brain stimulation (NIBS) treatment for depression by addressing four questions: (1) Does neuroimaging-guided target localization improve treatment? (2) Has neuroimaging advanced understanding of NIBS treatment action? (3) Can neuroimaging help predict who will respond to treatment? (4) How can neuroimaging help personalize treatment? Since transcranial direct current stimulation (tDCS) is currently for investigational use, this chapter covers both tDCS and clinically approved treatment, transcranial magnetic stimulation, because the concepts and challenges are similar. For tDCS, the current most pressing use of imaging is to test for target engagement – to verify that stimulation is changing physiology within targeted brain circuits. Regarding treatment action, resting-state imaging suggests that stimulation normalizes aberrant fronto-limbic functional connectivity, resulting in improved regulation of negative affect. To date, the most promising predictor of treatment is strong connectivity between the cortical stimulation site and limbic regions. For treatment personalization, current imaging-guided approaches include the following: adjusting the stimulation target location per individual to maximize engagement of fronto-limbic connectivity, or categorizing patients into depression subtypes based on imaging biomarkers and tailoring the cortical target accordingly. A major future challenge will be translating group-level strategies into interventions that work for individuals.

Interacting with our ever-changing physical environment requires continual recalibration of the motor system. One mechanism by which this occurs is motor adaptation. Understanding how motor adaptation is implemented by the human brain, how different regions work in concert to retain adaptive movement accuracy, and how this function is linked to metabolic use of neurochemicals poses an important challenge in neuroscience. In humans, motor sequence learning is related to concentration of {gamma}-aminobutyric acid (GABA) in the primary motor cortex (M1). However, the role of M1 GABA in adaptation - where behaviour is acquired outside M1 but retained within M1 - is unclear. Here, we used an ultra-high field MR multimodal acquisition to address the hypothesis that M1 GABA and M1-Cerebellar functional connectivity would relate to retention of adaptation, but not acquisition of adaptation. As such, we demonstrate higher baseline M1 [GABA] relates to greater retention but does not relate to adaptation-acquisition. This relationship is mediated by change in M1-Cerebellar functional connectivity: higher M1 [GABA] relates to a decreased M1-Cerebellar connectivity, resulting in greater retention. These findings showed anatomical, neurochemical and behavioural specificity: As expected, no relationship was found between retention and a control metabolite, M1 [Glutamate], as well as retention and connectivity change between control regions and no relationship was found between M1 [GABA] and behaviour in a control condition. The implication of a mechanistic link from neurochemistry to retention significantly advances our understanding of population variability in retention behaviour and provides a crucial step towards developing therapeutic interventions to restore motor abilities.

Stroke is the largest cause of complex disability in adults. Approximately half of right-hemisphere stroke survivors suffer spatial neglect–an inability to voluntarily orient to people or objects in contralesional space. Neglect is a significant impediment to successful community reintegration. Prism adaptation (PA) is a promising behavioural intervention that can alleviate symptoms of spatial neglect. PA induces a leftward pointing bias–the prism after-effect (AE). In neglect, the prism AE generalises to improve other sensory, motor, and cognitive domains. Although the formation of an AE is a key index in neglect, we do not yet know where it is formed in the brain. Here, we used a novel computational fMRI-based approach to study, for the first time, the brain circuits that mediate the formation of PA in stroke survivors and age matched controls. Healthy individuals (n = 17) and stroke patients (n = 11) performed prism adaptation during fMRI. Temporal signatures of memory formation were extracted from the behavioural data using a state-space model and regressed against the fMRI data. This revealed that, in both groups, fMRI signal in left sensorimotor cortex correlated with the gradual formation of the prism after-effect during adaptation. This indicates that the sensorimotor cortex may be a useful target for neuromodulation that aims to improve the persistence of therapeutic prism after effects.

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex, driven by a natural decline in inhibitory tone (γ-amino butyric acid, GABA). This causes functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances adaptation memory. Therefore, using a cross-sectional design, here we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identify a form of motor memory that improves naturally with age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurore-habilitation.

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state‐level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS‐fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS‐fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS‐fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.

Importance Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) is under clinical investigation as a treatment for major depressive disorder. However, the mechanisms of action are unclear, and there is a lack of neuroimaging evidence, particularly among individuals with affective dysfunction. Furthermore, there is no direct causal evidence among humans that the prefrontal-amygdala circuit functions as described in animal models (ie, that increasing activity in prefrontal cortical control regions inhibits amygdala response to threat). Objective To determine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in individuals with trait anxiety. Design, Setting, and Participants This community-based randomized clinical trial used a double-blind, within-participants design (2 imaging sessions per participant). Eighteen women with high trait anxiety (age range, 18-42 years) who scored greater than 45 on the trait measure of State-Trait Anxiety Inventory were randomized to receive active or sham tDCS of the DLPFC during the first session and the other intervention during the next session. Each intervention was followed immediately by a functional imaging scan during which participants performed an attentional task requiring them to ignore threatening face distractors. Data were collected from May 7 to October 6, 2015. Main Outcomes and Measures Amygdala threat response, measured with functional magnetic resonance imaging. Results Data from 16 female participants (mean age, 23 years; range, 18-42 years), with 8 in each group, were analyzed. Compared with sham stimulation, active DLPFC stimulation significantly reduced bilateral amygdala threat reactivity (z = 3.30, P = .04) and simultaneously increased activity in cortical regions associated with attentional control (z = 3.28, P Conclusions and Relevance These results reveal a causal role for prefrontal regulation of amygdala function in attentional capture by threat in individuals with high trait anxiety. The finding that prefrontal stimulation acutely increases attentional control signals and reduces amygdala threat reactivity may indicate a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders.

BackgroundHuman visual cortical area hMT+, like its homologue MT in the macaque monkey, has been shown to be particularly selective to visual motion. After damage to the primary visual cortex (V1), patients often exhibit preserved ability to detect moving stimuli, which is associated with neural activity in area hMT+. As an anatomical substrate underlying residual function in the absence of V1, promoting functional plasticity in hMT+ could potentially boost visual performance despite cortical damage.ObjectiveTo establish in healthy participants whether it is possible to use transcranial direct current stimulation (tDCS) over hMT+ to potentiate learning of visual motion direction discrimination.MethodsParticipants were trained daily for five days on a visual motion direction discrimination task. Task difficulty was increased as performance improved, by decreasing the proportion of coherently moving dots, such that participants were always performing at psychophysical threshold. tDCS, either anodal or sham, was applied daily during the 20-minute training session. Task performance was assessed at baseline and at the end of the training period.ResultsAll participants showed improved task performance both during and after training. Contrary to our hypothesis, anodal tDCS did not further improve performance compared to sham stimulation. Bayesian statistics indicated significant evidence in favour of the null hypothesis.ConclusionAnodal tDCS to hMT+ does not enhance visual motion direction discrimination learning in the young healthy visual system.

Background Negative attention biases are thought to be a causal factor in the development and maintenance of depression. It has been proposed that this bias may be caused by a belief that negative events are more informative than positive events. In the present study, it was investigated whether transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, could modulate information content estimates for rewarding and aversive outcomes in healthy adults [1] , [2] . Methodology Forty healthy volunteers aged 18–45 participated in one sham and one active tDCS session in randomised order. During each session, participants completed an information bias learning task (IBLT) while receiving tDCS targeting bilateral dorsolateral prefrontal cortex (DLPFC) for 20 minutes at 2 mA. Information content estimates for positive and negative outcomes were reflected in participants’ learning rates on the IBLT, which were derived from the data with the use of computational models. Results Active bifrontal tDCS was associated with an increase in learning rates for positive but not negative outcomes on the IBLT (F = 5.47, P Conclusion These findings provide the first experimental evidence that modulating activity in the DLPFC can enhance learning from positive stimuli in healthy adults. This change in learning rates suggests an alteration in participants’ beliefs of how informative positive outcomes are compared to negative outcomes. Additional research is needed to assess whether this effect of tDCS can be harnessed to ameliorate negative attention biases associated with psychiatric disorders. The present results provide an exciting early step in the development of novel interventions for depression.

Sensorimotor cortex mediates the formation of adaptation memory. Individuals differ in the rate at which they acquire, retain, and generalize adaptation. We present a mechanistic explanation of the neurochemical and computational causes of this variation in humans. Neuroimaging identified structural, functional and neurochemical covariates of a computational parameter that determines memory persistence. To establish causality, we increased sensorimotor cortex excitability during adaptation, using transcranial direct current stimulation. As predicted, this increased retention. Inter-individual variance in the stimulation-induced E:I increase predicted the computational change, which predicted the memory gain. These relations did not hold, and memory was unchanged, with stimulation applied before adaptation. This cognitive state dependent effect was modulated by the BDNF val66met genetic polymorphism. Memory was enhanced by stimulation in Val/Val carriers only, implicating a mechanistic role for activity-dependent BDNF secretion. Sensorimotor cortex E:I causally determines the time constant of memory persistence, explaining phenotypic variation in adaptation decay.

Contains fulltext : 190289.pdf (Publisher’s version ) (Open Access) Motivational, cognitive and action goals are processed by distinct, topographically organized, corticostriatal circuits. We aimed to test whether processing in the striatum is under causal control by cortical regions in the human brain by investigating the effects of offline transcranial magnetic stimulation (TMS) over distinct frontal regions associated with motivational, cognitive and action goal processing. Using a three-session counterbalanced within-subject crossover design, continuous theta burst stimulation was applied over the anterior prefrontal cortex (aPFC), dorsolateral prefrontal cortex, or premotor cortex, immediately after which participants (N = 27) performed a paradigm assessing reward anticipation (motivation), task (cognitive) switching, and response (action) switching. Using task-related functional magnetic resonance imaging (fMRI), we assessed the effects of stimulation on processing in distinct regions of the striatum. To account for non-specific effects, each session consisted of a baseline (no-TMS) and a stimulation (post-TMS) fMRI run. Stimulation of the aPFC tended to decrease reward-related processing in the caudate nucleus, while stimulation of the other sites was unsuccessful. A follow-up analysis revealed that aPFC stimulation also decreased processing in the putamen as a function of the interaction between all factors (reward, cognition and action), suggesting stimulation modulated the transfer of motivational information to cortico-striatal circuitry associated with action control.

Prism adaptation has a long history as an experimental paradigm used to investigate the functional and neural processes that underlie sensorimotor control. In the neuropsychology literature, functional explanations of prism adaptation are typically framed within a traditional cognitive psychology ‘box-and-arrow’ framework that distinguishes putative component functions thought to give rise to behaviour (i.e. ‘strategic control’ versus ‘spatial realignment’). However, this kind of theoretical framework lacks precision and explanatory power. Here, we advocate for a computational framework that offers several advantages: 1) an algorithmic explanatory account of the computations and operations that drive behaviour; 2) expressed in quantitative mathematical terms; 3) embedded within a principled theoretical framework (Bayesian decision theory, state-space modelling); 4) that offers a means to generate and test quantitative behavioural predictions. This computational framework offers a route toward mechanistic explanations of prism adaptation behaviour. Thus it constitutes a conceptual advance compared to the traditional theoretical framework. In this paper, we illustrate how Bayesian decision theory and state-space models offer principled explanations for a range of behavioural phenomena in the field of prism adaptation (e.g. visual capture, magnitude of visual versus proprioceptive realignment, spontaneous recovery and dynamics of adaptation memory). We argue that this explanatory framework offers to advance understanding of the functional and neural mechanisms that implement prism adaptation behaviour, by enabling quantitative tests of hypotheses that go beyond mere descriptive mapping claims that ‘brain area X is (somehow) involved in psychological process Y’.

BackgroundHighly co-morbid mood and anxiety disorders are associated with aberrant fronto-limbic signalling during emotional processing. Animal models suggest that hypoactive prefrontal cortex weakens top-down control of limbic structures, causing heightened limbic and behavioural reactivity to negative information. Here we tested for this causal mechanism in human trait anxiety. We reasoned that if dorsolateral prefrontal cortex controls amygdala response to affective information, then stimulation of that brain region should reduce the hyperactive amygdala threat responsivity seen in trait anxiety.MethodsUsing a within-subjects design, sixteen high-trait anxious females received active and sham transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex, in counterbalanced order, with sessions timed to be at least one month apart. Each session was followed immediately by a functional magnetic resonance imaging (fMRI) scan during which participants performed an attentional task with threat-related distractors.ResultsAs predicted, compared to sham stimulation, active prefrontal cortex stimulation reduced amygdala threat reactivity and simultaneously increased activity in cortical regions associated with attentional control and improved task accuracy.ConclusionsThese results demonstrate a causal role for impoverished frontal regulation of amygdaloid function in attentional capture by threat in trait anxiety. The finding that prefrontal stimulation reduces amygdala threat reactivity acutely indicates a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders.

Right brain injury causes visual neglect - lost awareness of left space. During prism adaptation therapy, patients adapt to a rightward optical shift by recalibrating right arm movements leftward. This can improve left neglect, but the benefit of a single session is transient (~1 day). Here we show that tonic disinhibition of left motor cortex during prism adaptation enhances consolidation, stabilizing both sensorimotor and cognitive prism after-effects. In three longitudinal patient case series, just 20 min of combined stimulation/adaptation caused persistent cognitive after-effects (neglect improvement) that lasted throughout follow-up (18–46 days). Moreover, adaptation without stimulation was ineffective. Thus stimulation reversed treatment resistance in chronic visual neglect. These findings challenge consensus that because the left hemisphere in neglect is pathologically over-excited it ought to be suppressed. Excitation of left sensorimotor circuits, during an adaptive cognitive state, can unmask latent plastic potential that durably improves resistant visual attention deficits after brain injury.

Prism adaptation has a long history as an experimental paradigm used to investigate the functional and neural processes that underlie sensorimotor control. In the neuropsychology literature, prism adaptation behaviour is typically explained by reference to a traditional cognitive psychology framework that distinguishes putative functions, such as 'strategic control' versus 'spatial realignment'. This theoretical framework lacks conceptual clarity, quantitative precision and explanatory power. Here, we advocate for an alternative computational framework that offers several advantages: 1) an algorithmic explanatory account of the computations and operations that drive behaviour; 2) expressed in quantitative mathematical terms; 3) embedded within a principled theoretical framework (Bayesian decision theory, state-space modelling); 4) that offers a means to generate and test quantitative behavioural predictions. This computational framework offers a route towards mechanistic neurocognitive explanations of prism adaptation behaviour. Thus it constitutes a conceptual advance compared to the traditional theoretical framework. In this paper, we illustrate how Bayesian decision theory and state-space models offer principled explanations for a range of behavioural phenomena in the field of prism adaptation (e.g. visual capture, magnitude of visual versus proprioceptive realignment, spontaneous recovery and dynamics of adaptation memory). We argue that this explanatory framework can advance understanding of the functional and neural mechanisms that implement prism adaptation behaviour, by enabling quantitative tests of hypotheses that go beyond merely descriptive mapping claims that ‘brain area X is (somehow) involved in psychological process Y’., Highlights • Traditional neuropsychological models of prism adaptation lack precision. • Computational models improve explanatory and predictive power. • A range of adaptation phenomena can be explained quantitatively. • Mathematics offers a bridge between neural mechanisms and behaviour. • A neuro-computational approach will advance neuropsychology.

Psychiatric neuro-stimulation research is entering an exciting period. Big Data neuroimaging has matured to the point of identifying distinct depression ‘biotypes’-reliable covariation of symptoms and resting-state circuit dysfunction - that explain variation in response to antidepressant neurostimulation [1] . This paves the way for future personalized treatment target selection, and testifies to stable brain network configurations underlying clinical phenotypes. How should we best stimulate such networks to durably improve symptoms? The majority of brain stimulation treatment protocols are designed physiologically. The aim is re-normalize network excitability, via targeted excitation/inhibition of dysfunctional network nodes. Through repeated stimulation over weeks, these artificially-induced transient changes in excitability become stabilized. The hope is that this will also change and re-normalize function. Yet information processing–the functions these networks compute–is not in fact measured, controlled or manipulated. The most reliable way to induce long-term adaptive behaviour (brain) change is to engage endogenous neurocognitive mechanisms of learning and memory. We propose that stimulation is likely to more efficiently normalize function when applied concurrent with an adaptive learning protocol, compared to stimulation in the resting state. We illustrate this with an example from our own work developing neurostimulation therapeutics for attention deficits post-stroke [2] . We aim to highlight the value of functionally targeted stimulation, and formal computational models in particular, for designing rational intervention protocols in which stimulation is used to change information processing in a quantifiable, adaptive direction, which consequently predicts behaviour change. Model parameters enabled us to interrogate individual differences that covaried - across information processing, white matter microstructure, functional connectivity and neurochemistry - and quantify their response to stimulation [3] . We propose that computational assays of behaviour are a potentially powerful tool with which to tackle the formiddable challenges of developing and translating cognitive neurostimulation protocols into next-generation treatments in psychiatry.

Prism adaptation induces rapid recalibration of visuomotor coordination. The neural mechanisms of prism adaptation have come under scrutiny since the observations that the technique can alleviate hemispatial neglect following stroke, and can alter spatial cognition in healthy controls. Relative to non-imaging behavioral studies, fMRI investigations of prism adaptation face several challenges arising from the confined physical environment of the scanner and the supine position of the participants. Any researcher who wishes to administer prism adaptation in an fMRI environment must adjust their procedures enough to enable the experiment to be performed, but not so much that the behavioral task departs too much from true prism adaptation. Furthermore, the specific temporal dynamics of behavioral components of prism adaptation present additional challenges for measuring their neural correlates. We developed a system for measuring the key features of prism adaptation behavior within an fMRI environment. To validate our configuration, we present behavioral (pointing) and head movement data from 11 right-hemisphere lesioned patients and 17 older controls who underwent sham and real prism adaptation in an MRI scanner. Most participants could adapt to prismatic displacement with minimal head movements, and the procedure was well tolerated. We propose recommendations for fMRI studies of prism adaptation based on the design-specific constraints and our results.

“Priming of pop-out” is a form of implicit memory that facilitates detection of a recently inspected search target. Repeated presentation of a target's features or its spatial position improves detection speed (feature/spatial priming). This study investigated a role for the human frontal eye fields (FEFs) in the priming of color pop-out. To test the hypothesis that the FEFs play a role in short-term memory storage, transcranial magnetic stimulation (TMS) was applied during the intertrial interval. There was no effect of TMS on either spatial or feature priming. To test whether the FEFs are important when a saccade is being programmed to a repeated target color or location, TMS was applied during the search array. TMS over the left but not the right FEFs abolished spatial priming, but had no effect on feature priming. These findings demonstrate functional specialization of the left FEFs for spatial priming, and distinguish this role from target discrimination and saccade-related processes. The results suggest that the left FEFs integrate a spatial memory signal with an evolving saccade program, which facilitates saccades to a recently inspected location.

Unilateral neglect is a disabling syndrome frequently observed following right hemisphere brain damage. Symptoms range from visuo-motor impairments through to deficient visuo-spatial imagery, but impairment can also affect the auditory modality. A short period of adaptation to a rightward prismatic shift of the visual field is known to improve a wide range of hemispatial neglect symptoms, including visuo-manual tasks, mental imagery, postural imbalance, visuo-verbal measures and number bisection. The aim of the present study was to assess whether the beneficial effects of prism adaptation may generalize to auditory manifestations of neglect. Auditory extinction, whose clinical manifestations are independent of the sensory modalities engaged in visuo-manual adaptation, was examined in neglect patients before and after prism adaptation. Two separate groups of neglect patients (all of whom exhibited left auditory extinction) underwent prism adaptation: one group (n = 6) received a classical prism treatment ('Prism' group), the other group (n = 6) was submitted to the same procedure, but wore neutral glasses creating no optical shift (placebo 'Control' group). Auditory extinction was assessed by means of a dichotic listening task performed three times: prior to prism exposure (pre-test), upon prism removal (0 h post-test) and 2 h later (2 h post-test). The total number of correct responses, the lateralization index (detection asymmetry between the two ears) and the number of left-right fusion errors were analysed. Our results demonstrate that prism adaptation can improve left auditory extinction, thus revealing transfer of benefit to a sensory modality that is orthogonal to the visual, proprioceptive and motor modalities directly implicated in the visuo-motor adaptive process. The observed benefit was specific to the detection asymmetry between the two ears and did not affect the total number of responses. This indicates a specific effect of prism adaptation on lateralized processes rather than on general arousal. Our results suggest that the effects of prism adaptation can extend to unexposed sensory systems. The bottom-up approach of visuo-motor adaptation appears to interact with higher order brain functions related to multisensory integration and can have beneficial effects on sensory processing in different modalities. These findings should stimulate the development of therapeutic approaches aimed at bypassing the affected sensory processing modality by adapting other sensory modalities. © The Author 2010.

Les techniques de stimulations cerebrales non invasives ont fait leur entree dans les laboratoires il y a un quart de siecle. La stimulation magnetique transcrânienne s’est rapidement imposee du fait de son excellente resolution temporelle et de la possibilite de produire des effets durables. Cette derniere a ete mise a profit avec succes dans de nombreux champs cliniques, dont la modulation des processus visuospatiaux et attentionnels. Plus recente, la stimulation transcrânienne directe par courant continu (tDCS) n’a pas encore beneficie de nombreuses etudes cliniques, mais elle pourrait etre appelee a jouer un role de premier plan en matiere de reeducation des troubles de la cognition spatiale.