Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia.

BACKGROUND AND PURPOSE: Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer's disease. PURPOSE: To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA. METHODS: Ten patients with a diagnosis of PNFA were enrolled. High-frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. RESULTS: A repeated-measure anova with stimulus site (sham, left and right rTMS) showed significant effects. Action-naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. CONCLUSIONS: Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

The neural bases of word encoding and retrieval: A fMRI-guided transcranial magnetic stimulation study.

There is evidence that the human prefrontal cortex is asymmetrically involved in long-term episodic memory processing. Moreover, abstract and concrete words processing has been reported to differentially involve prefrontal and parietal areas. We implemented a two-stages functional magnetic resonance imaging (fMRI)-repetitive transcranial magnetic stimulation (rTMS) paradigm to investigate the role of the dorsolateral prefrontal cortices (DLPFCs) and parietal cortices (PARCs) in encoding and retrieval of abstract and concrete words. Using this paradigm we could select areas to be stimulated on the basis of single-subject (SS) anatomical and functional data, investigating the usefulness of this integration approach. With respect to fMRI, abstract and concrete words differed only for a greater left fusiform gyrus activation for concrete words. In turn, significant rTMS effects were found, but only for the retrieval of abstract words. Consistent with previous findings, repetitive stimulation of the right DLPFC had a specific impact on episodic retrieval. Memory retrieval performance was also disrupted when rTMS was applied to the left PARC. Finally, we found a significant positive correlation between the effect sizes of SS right PARC activations for abstract word retrieval and the consequent rTMS interference effects. Taken together these data provide for the first time evidence that also the PARC has a necessary role in episodic retrieval of abstract words. Importantly, from a methodological perspective, our data demonstrate that fMRI-guided rTMS with a SS approach provides a powerful tool to investigate the neural underpinnings of cognitive functions.

Attentional orienting induced by arrows and eye-gaze compared with an endogenous cue.

Exogenous orienting has been widely studied by using peripheral cues whereas endogenous orienting has been studied with directional central cues. However, recent evidence has shown that centrally presented eye-gaze and arrows may produce an automatic rather than voluntary orienting of attention. Therefore, the aim of the present study was to investigate the behavioural and electrophysiological (event-related potentials-ERP) correlates of the attentional shift induced by arrows and eye-gaze. In order to have a control condition, we compared arrows and eye-gaze with a purely endogenous cue, i.e., a texture arbitrarily coding one direction. We analyzed the ERP components (P1, N1, P2a, P2p, P3) elicited by the cue stimuli and the early lateralised attentional effect (early directing attention negativity-EDAN). In addition, in order to investigate the topography of the neural mechanisms underlying the cortical activity in each cueing condition, we applied a temporal segmentation procedure. The results showed that the three cueing conditions induced a different strength of activation within the same cortical network. Occipito-parietal regions were involved in the early processing of visual information, followed by an involvement of frontal areas, likely implicated in learning associations. These data confirm the assumption that, in contrast to purely endogenous cues, arrows and eye-gaze induce a very fast attentional shift. However, the similarity of the ERP components and of the topographical cortical maps among conditions suggest that this early orienting of attention is more likely related to an overlearned association mechanism rather than to a real exogenous attentional process.

Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study.

OBJECTIVE: To investigate whether anodal and cathodal transcranial direct current stimulation (tDCS) can modify cognitive performance and neural activity in healthy elderly and Alzheimer's disease (AD) patients. METHODS: Fourteen healthy elderly and twelve AD patients performed a working memory task during an electroencephalogram recording before and after receiving anodal, cathodal, and sham tDCS over the left dorsolateral prefrontal cortex. Behavioural performance, event-related potentials (P200, P300) and evoked cortical oscillations were studied as correlates of working memory. RESULTS: Anodal tDCS increased P200 and P300 amplitudes in healthy elderly. Cathodal tDCS increased P200 amplitude and frontal theta activity between 150 and 300 ms in AD patients. Improved working memory after anodal tDCS correlated with increased P300 in healthy elderly. In AD patients, slight tendencies between enhanced working memory and increased P200 after cathodal tDCS were observed. CONCLUSIONS: Functional neural modulations were promoted by anodal tDCS in healthy elderly and by cathodal tDCS in AD patients. SIGNIFICANCE: Interaction between tDCS polarity and the neural state (e.g., hyper-excitability exhibited by AD patients) suggests that appropriate tDCS parameters (in terms of tDCS polarity) to induce behavioural improvements should be chosen based on the participant's characteristics. Future studies using higher sample sizes should confirm and extend the present findings.

Excitatory and inhibitory lateral interactions effects on contrast detection are modulated by tRNS.

Contrast sensitivity for a Gabor signal is affected by collinear high-contrast Gabor flankers. The flankers reduce (inhibitory effect) or increase (facilitatory effect) sensitivity, at short (2λ) and intermediate (6λ) target-to-flanker separation respectively. We investigated whether these inhibitory/facilitatory sensitivity effects are modulated by transcranial random noise stimulation (tRNS) applied to the occipital and frontal cortex of human observers during task performance. Signal detection theory was used to measure sensitivity (d') and the Criterion (C) in a contrast detection task, performed with sham or tRNS applied over the occipital or the frontal cortex. After occipital stimulation results show a tRNS-dependent increased sensitivity for the single Gabor signal of low but not high contrast. Moreover, results suggest a dissociation of the tRNS effect when the Gabor signal is presented with the flankers, consisting in a general increased sensitivity at 2λ where the flankers had an inhibitory effect (reduction of inhibition) and a decreased sensitivity at 6λ where the flankers had a facilitatory effect on the Gabor signal (reduction of facilitation). After a frontal stimulation, no specific effect of the tRNS was found. We account for these complex interactions between tRNS and flankers by assuming that tRNS not only enhances feedforward input from the Gabor signal to the cortex, but also enhances the excitatory or inhibitory lateral intracortical input from the flankers. The boosted lateral input depends on the excitation-inhibition (E/I) ratio, namely when the lateral input is weak, it is boosted by tRNS with consequent modification of the contrast-dependent E/I ratio.

Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline.

OBJECTIVE: Word-finding difficulty (anomia) is commonly observed in Alzheimer's dementia (AD). The aim of this study was to assess the effect of repetitive transcranial magnetic stimulation (rTMS) applied to the dorso-lateral prefrontal cortex (dlPFC) on picture naming in 24 probable AD patients with different degrees of cognitive decline. METHODS: High-frequency rTMS was applied to the left and right dlPFC during object and action naming in AD patients. A sham stimulation was used as a control condition. RESULTS: Whilst, as previously reported, stimulation to both the left and the right dlPFC improved action, but not object naming in the mild AD group; an improved naming accuracy for both classes of stimuli was found in the moderate to severe group. CONCLUSIONS: Repetitive transcranial magnetic stimulation applied to the dlPFC improves naming performance also in the advanced stages of AD. Moreover, in the severe group the effect is not specific for action naming, as in the case of the mild AD group. These findings suggest that rTMS can affect the intrinsic ability of the brain to restore or compensate for damaged function and may represent an useful new tool for cognitive rehabilitation.

The contribution of TMS to frontotemporal dementia variants.

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions mainly characterized by personality changes and cognitive deficits in language and executive functions; movement disorders have also been associated with FTLD. The present study aimed to measure the primary motor cortex (M1) inhibitory and facilitatory functions in patients affected by FTLD. MATERIALS AND METHODS: The study included 17 FTLD patients, 8 age-matched healthy controls and 8 Alzheimer's disease (AD) patients. Transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (ICI) and facilitation (ICF) by using a double-pulse paradigm. RESULTS: FTLD patients were comparable with controls and AD patients for ICI and ICF. Corticobasal degeneration (CBD) patients presented significant reduced inhibition at ISI3; moreover two out of seven CBD patients had only ipsilateral responses. DISCUSSION: The present study reveals a selective impairment of M1 ICI inhibitory response in CBD, which may help in distinguishing among the FTLD clinical spectrum.

Prefrontal [correction of Prefontal] cortex in long-term memory: an "interference" approach using magnetic stimulation.

Neuroimaging has consistently shown engagement of the prefrontal cortex during episodic memory tasks, but the functional relevance of this metabolic/hemodynamic activation in memory processing is still to be determined. We used repetitive transcranial magnetic stimulation (rTMS) to transiently interfere with either left or right prefrontal brain activity during the encoding or retrieval of pictures showing complex scenes. We found that the right dorsolateral prefrontal cortex (DLPFC) was crucial for the retrieval of the encoded pictorial information, whereas the left DLPFC was involved in encoding operations. This 'interference' approach allowed us to establish whether a cortical area activated by a memory task actually contributes to behavioral performance.

How brain response and eating habits modulate food energy estimation.

The estimates we do of the energy content of different foods tend to be inaccurate, depending on several factors. The elements influencing such evaluation are related to the differences in the portion size of the foods shown, their energy density (kcal/g), but also to individual differences of the estimators, such as their body-mass index (BMI) or eating habits. Within this context the contribution of brain regions involved in food-related decisions to the energy estimation process is still poorly understood. Here, normal-weight and overweight/obese women with restrained or non-restrained eating habits, received anodal transcranial direct current stimulation (AtDCS) to modulate the activity of the left dorsolateral prefrontal cortex (dlPFC) while they performed a food energy estimation task. Participants were asked to judge the energy content of food images, unaware that all foods, for the quantity presented, shared the same energy content. Results showed that food energy density was a reliable predictor of their energy content estimates, suggesting that participants relied on their knowledge about the food energy density as a proxy for estimating food energy content. The neuromodulation of the dlPFC interacted with individual differences in restrained eating, increasing the precision of the energy content estimates in participants with higher scores in the restrained eating scale. Our study highlights the importance of eating habits, such as restrained eating, in modulating the activity of the left dlPFC during food appraisal.

The time course of idiom processing.

Recent neuropsychological and neurophysiological studies have suggested that the neural correlates of idiom processing are predominantly located in the left Brodmann's area (BA) 22 and, to some extent, in the prefrontal cortex. The present study explores the temporal dynamics of left prefrontal and temporal cortex in idiom processing by using repetitive transcranial magnetic stimulation (rTMS) in normal subjects. Forty-five opaque highly familiar idioms and 45 literal sentences were used. Forty-three subjects completed 5 blocks of 18 trials (9 idioms, 9 literal sentences) corresponding to 4 stimulation conditions (left prefrontal, left temporal, vertex, no-stimulation baseline). Each subject was assigned to one of three groups, which differed in the timing of stimulation delivery. A selective impairment in accuracy for idioms was found when rTMS was applied to the prefrontal and temporal cortex 80ms after picture presentation, confirming the role of these regions in this task. Moreover, rTMS to the prefrontal cortex, but not to the temporal cortex, continued to affect the performance with idiomatic sentences at the later time of 120ms. The results seem to suggest that the prefrontal region is involved in both the retrieval of the figurative meaning from semantic memory and the monitoring of the response by inhibiting alternative interpretations when a picture-matching task is used.

Vascular damage and EEG markers in subjects with mild cognitive impairment.

OBJECTIVE: We evaluated the changes induced by cerebrovascular (CV) damage on brain rhythmicity recorded by electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). METHODS: We enrolled 99 MCI subjects (Mini-Mental State Examination [MMSE] mean score 26.6). All subjects underwent EEG recording and magnetic resonance imaging (MRI). EEGs were recorded at rest. Individual EEG frequencies were indexed by the theta/alpha transition frequency (TF) and by the individual alpha frequency (IAF) with power peak in the extended alpha range (5-14 Hz). Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands on the basis of the TF and IAF values. Subsequently, we divided the cohort in four sub-groups based on subcortical CV damage as scored by the age-related white matter changes scale (ARWMC). RESULTS: CV damage was associated with 'slowing' of TF proportional to its severity. In the spectral bandpower the severity of vascular damage was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with IAF and alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. CONCLUSIONS: EEG analysis may show physiological markers sensitive to CV damage. The appropriate use of this EEG index may help the differential diagnosis of different forms of cognitive decline, namely primary degenerative and secondary to CV damage. SIGNIFICANCE: The EEG neurophysiological approach, together with anatomical features from imaging, could be helpful in the understanding of the functional substrate of dementing disorders.

Hippocampal atrophy and EEG markers in subjects with mild cognitive impairment.

OBJECTIVE: The present study evaluates the potential relationship between hippocampal atrophy and EEG brain rhythmicity, as assessed by relative band power and alpha frequency indices in a cohort of subjects with mild cognitive impairment (MCI). METHODS: Eighty-eight subjects falling within the definition of MCI patients were enrolled. All subjects underwent EEG recording and magnetic resonance imaging (MRI). Volumetric morphometry estimates of the hippocampal region were computed. Individual EEG frequencies were indexed by the theta/alpha transition frequency (TF) and the individual alpha frequency (IAF). The relative power was separately computed for delta, theta, alpha1, alpha2 and alpha3 frequency bands. The MCI cohort was classified into four subgroups, based on the mean and standard deviations of the hippocampal volume of a normal elderly control sample. RESULTS: The group with moderate hippocampal atrophy showed the highest increase in the theta power on frontal regions, and of the alpha2 and alpha3 powers on frontal and temporo-parietal areas. The analysis of the individual alpha frequency markers showed that the values for the alpha markers were highest in the group with the smallest hippocampal volume, whereas in the group with moderate hippocampal atrophy, these values were lower than in the group with severe atrophy. CONCLUSIONS: The relationship between hippocampal atrophy and EEG activity changes in MCI subjects is not proportional to the hippocampal atrophy. Therefore, EEG markers could represent a new tool for differential diagnosis. SIGNIFICANCE: The hippocampal atrophy induces different brain synchronization/desynchronization patterns. EEG changes model the brain activity induced by a discrete change of the hippocampal volume. The changes in the EEG rhythmicity differ greatly from those in MCI patients with subcortical vascular damage.

Persistent autobiographical amnesia: a case report.

We describe a 47-year-old man who referred to the Emergency Department for sudden global amnesia and left mild motor impairment in the setting of increased arterial blood pressure. The acute episode resolved within 24 hours. Despite general recovery and the apparent transitory nature of the event, a persistent selective impairment in recollecting events from some specific topics of his personal life became apparent. Complete neuropsychological tests one week after the acute onset and 2 months later demonstrated a clear retrograde memory deficit contrasting with the preservation of anterograde memory and learning abilities. One year later, the autobiographical memory deficit was unmodified, except for what had been re-learnt. Brain MRI was normal while H20 brain PET scans demonstrated hypometabolism in the right globus pallidus and putamen after 2 weeks from onset, which was no longer present one year later. The absence of a clear pathomechanism underlying focal amnesia lead us to consider this case as an example of functional retrograde amnesia.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms.

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Transcranial magnetic stimulation and cortical evoked potentials: a TMS/EEG co-registration study.

OBJECTIVE: In recent years, a promising tool has been introduced which allows the co-registration of electroencephalographic (EEG) activity during brain transcranial magnetic stimulation (TMS). The aims of the present study are to identify eventual stimulus-related artefacts, and to confirm and extend previous EEG/TMS findings about the possible networks generating EEG responses evoked by TMS. METHODS: Focal TMS was delivered to the left primary motor cortex (MI), with different coils (real and sham) and orientations (45 and 135 degrees in respect to the sagittal plane), in six healthy subjects. EEG and motor evoked potentials (MEPs) were simultaneously recorded from 19 scalp electrodes. RESULTS: TMS, with coil oriented at 45 degrees , induced EEG responses characterized by a sequence of positive deflections peaking at approximately 14, 30, 60 and 190 ms and negative deflections peaking at approximately 10, 18, 40 and 100 ms post-TMS. The negative components were recorded at the recording electrode corresponding with the stimulation site (N10, N18), as well as at recording electrodes over the frontal region of the contralateral, unstimulated, hemisphere (N40) and bilaterally over the central hemispheres with its maximal representation at the stimulation site (N100). The positive components were instead detected at the frontal region of the right, unstimulated, hemisphere (P14), over the central electrodes Cz, Fz and the frontal region of the right hemisphere (P30), at the stimulation site (P60), and over the frontal regions of both hemispheres. When TMS was delivered with the coil oriented at 135 degrees , no MEPs were recorded from the right target muscle. Nonetheless, all the TMS-induced EEG components were still evoked apart from the N20-P30. Finally, TMS with the sham coil over left MI did not induce either significant EEG responses or MEPs. CONCLUSIONS: In conclusion, the TMS evoked components we have obtained by recording in continuous mode strikingly fit with those already described by other authors for both their latencies and the spatio-temporal pattern of scalp distribution. SIGNIFICANCE: This experiment is a farther validation of the combined EEG/TMS recording technique as a promising tool for experimental and clinical purposes.

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES).

OBJECTIVE: We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. METHODS: To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. RESULTS: MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CONCLUSIONS: CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches.

A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

Modulation of brain activity by selective task sets observed using event-related potentials.

We investigated the ability of subjects to shift dynamically between selective task sets, using informative trial-by-trial cues. Two tasks were used which involved non-overlapping neural systems and different hemispheric specialization. In a verbal task, subjects decided whether a letter string was a real word or a non-word. In a spatial task, subjects decided whether an angle was acute or obtuse. A behavioural experiment showed that performance improved when cues predicted the upcoming task (80% validity), compared to when neutral cues did not afford selective task sets. Event-related potentials (ERPs) revealed brain activity related to forming selective task expectations, to switching tasks, and to the modulation of target processing as a function of such expectations and switches. Activity predicting the probable task started over parietal electrodes 160 ms after cue presentation, while activity related to task switching started at frontal electrodes around 280 ms. Both types of activities developed before target onset. Target processing was significantly influenced by the validity of the cue prediction, including strong modulation of language-related potentials. These results show that it is possible to switch dynamically between task sets involving distinct neural systems, even before the appearance of an imperative target stimulus, and that the nature of the task sets can influence neural activity related to task-set reconfiguration. Selective task sets can in turn modulate the processing of target stimuli. The effects also apply to the case of foveally presented words, whose processing has often been hypothesized to be automatic and outside the influence of selective attention.