One Definition to Join Them All: The N-Spherical Solution for the EEG Lead Field.

Albeit its simplicity, the concentric spheres head model is widely used in EEG. The reason behind this is its simple mathematical definition, which allows for the calculation of lead fields with negligible computational cost, for example, for iterative approaches. Nevertheless, the literature shows contradictory formulations for the electrical solution of this head model. In this work, we study several different definitions for the electrical lead field of a four concentric spheres conduction model, finding that their results are contradictory. A thorough exploration of the mathematics used to build these formulations, provided in the original works, allowed for the identification of errors in some of the formulae, which proved to be the reason for the discrepancies. Moreover, this mathematical review revealed the iterative nature of some of these formulations, which allowed us to develop a formulation to solve the lead field in a head model built from an arbitrary number of concentric, homogeneous, and isotropic spheres.

Offset-related brain activity in the left ventrolateral prefrontal cortex promotes long-term memory formation of verbal events.

BACKGROUND: Recent evidence suggests that brain activity following the offset of a stimulus during encoding contributes to long-term memory formation, however the exact mechanisms underlying offset-related encoding are still unclear. OBJECTIVES: Here, in three repetitive transcranial magnetic stimulation studies (rTMS) we investigated offset-related activity in the left ventrolateral prefrontal cortex (VLPFC). rTMS was administered at different points in time around stimulus offset while participants encoded visually-presented words or pairs of words. The analyses focused on the effects of the stimulation on subsequent memory performance. RESULTS: rTMS administered at the offset of the stimuli, but not during online encoding, disrupted subsequent memory performance. In Experiment 1 we found that rTMS specifically disrupted encoding mechanisms initiated by the offset of the stimuli rather than general, post-stimulus processes. Experiment 2 showed that this effect was not dependent upon rTMS-induced somatosensory effects. In a third rTMS experiment we further demonstrated a robust decline in associative memory performance when the stimulation was delivered at the offset of the word pairs, suggesting that offset-related encoding may contribute to the binding of information into an episodic memory trace. CONCLUSIONS: The offset of the stimulus may represent an event boundary that promotes the reinstatement of the previously experienced event and episodic binding.

Enhancing links between visual short term memory, visual attention and cognitive control processes through practice: An electrophysiological insight.

The operation of attention on visible objects involves a sequence of cognitive processes. The current study firstly aimed to elucidate the effects of practice on neural mechanisms underlying attentional processes as measured with both behavioural and electrophysiological measures. Secondly, it aimed to identify any pattern in the relationship between Event-Related Potential (ERP) components which play a role in the operation of attention in vision. Twenty-seven participants took part in two recording sessions one week apart, performing an experimental paradigm which combined a match-to-sample task with a memory-guided efficient visual-search task within one trial sequence. Overall, practice decreased behavioural response times, increased accuracy, and modulated several ERP components that represent cognitive and neural processing stages. This neuromodulation through practice was also associated with an enhanced link between behavioural measures and ERP components and with an enhanced cortico-cortical interaction of functionally interconnected ERP components. Principal component analysis (PCA) of the ERP amplitude data revealed three components, having different rostro-caudal topographic representations. The first component included both the centro-parietal and parieto-occipital mismatch triggered negativity - involved in integration of visual representations of the target with current task-relevant representations stored in visual working memory - loaded with second negative posterior-bilateral (N2pb) component, involved in categorising specific pop-out target features. The second component comprised the amplitude of bilateral anterior P2 - related to detection of a specific pop-out feature - loaded with bilateral anterior N2, related to detection of conflicting features, and fronto-central mismatch triggered negativity. The third component included the parieto-occipital N1 - related to early neural responses to the stimulus array - which loaded with the second negative posterior-contralateral (N2pc) component, mediating the process of orienting and focusing covert attention on peripheral target features. We discussed these three components as representing different neurocognitive systems modulated with practice within which the input selection process operates.

Beliefs in being unlucky and deficits in executive functioning: an ERP study.

There has been initial evidence to support the Dysexecutive Luck hypothesis, which proposes that beliefs in being unlucky are associated with deficits in executive functioning (Maltby et al., 2013). The present study tested the Dysexecutive Luck hypothesis by examining whether deficits in the early stage of top down attentional control led to an increase of neural activity in later stages of response related selection process among those who thought themselves to be unlucky. Individuals with these beliefs were compared to a control group using an Event-Related Potential (ERP) measure assessing underlying neural activity of semantic inhibition while completing a Stroop test. Results showed stronger main interference effects in the former group, via greater reaction times and a more negative distributed scalp late ERP component during incongruent trials in the time window of 450-780 ms post stimulus onset. Further, less efficient maintenance of task set among the former group was associated with greater late ERP response-related activation to compensate for the lack of top-down attentional control. These findings provide electrophysiological evidence to support the Dysexecutive Luck hypothesis.

An electrophysiological insight into visual attention mechanisms underlying schizotypy.

A theoretical framework has been put forward to understand attention deficits in schizophrenia (Luck SJ & Gold JM. Biological Psychiatry. 2008; 64:34-39). We adopted this framework to evaluate any deficits in attentional processes in schizotypy. Sixteen low schizotypal (LoS) and 16 high schizotypal (HiS) individuals performed a novel paradigm combining a match-to-sample task, with inhibition of return (using spatially uninformative cues) and memory-guided efficient visual-search within one trial sequence. Behavioural measures and event-related potentials (ERPs) were recorded. Behaviourally, HiS individuals exhibited a spatial cueing effect while LoS individuals showed the more typical inhibition of return effect. These results suggest HiS individuals have a relative deficit in rule selection - the endogenous control process involved in disengaging attention from the uninformative location cue. ERP results showed that the late-phase of N2pc evoked by the target stimulus had greater peak latency and amplitude in HiS individuals. This suggests a relative deficit in the implementation of selection - the process of focusing attention onto target features that enhances relevant/suppresses irrelevant inputs. This is a different conclusion than when the same theoretical framework has been applied to schizophrenia, which argues little or no deficit in implementation of selection amongst patients. Also, HiS individuals exhibited earlier onset and greater amplitude of the mismatch-triggered negativity component. In summary, our results indicate deficits of both control and implementation of selection in HiS individuals.

Theta-burst Transcranial Magnetic Stimulation Alters the Functional Topography of the Cortical Motor Network.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive tool that is able to modulate the electrical activity of the brain depending upon its protocol of stimulation. Theta burst stimulation (TBS) is a high-frequency TMS protocol that is able to induce prolonged plasticity changes in the brain. The induction of plasticity-like effects by TBS is useful in both experimental and therapeutic settings; however, the underlying neural mechanisms of this modulation remain unclear. The aim of this study was to investigate the effects of continuous TBS (cTBS) on the intrahemispheric and interhemispheric functional connectivity of the resting and active brain. METHODS: A total of 26 healthy humans were randomly divided into two groups that received either real cTBS or sham (control) over the left primary motor cortex. Surface electroencephalogram (EEG) was used to quantify the changes of neural oscillations after cTBS at rest and after a choice reaction time test. The cTBS-induced EEG oscillations were computed using spectral analysis of event-related coherence (ERCoh) of theta (4-7.5 Hz), low alpha (8-9.5 Hz), high alpha (10-12.5 Hz), low beta (13-19.5 Hz), and high beta (20-30 Hz) brain rhythms. RESULTS: We observed a global decrease in functional connectivity of the brain in the cTBS group when compared to sham in the low beta brain rhythm at rest and high beta brain rhythm during the active state. In particular, EEG spectral analysis revealed that high-frequency beta, a cortically generated brain rhythm, was the most sensitive band that was modulated by cTBS. CONCLUSION: Overall, our findings suggest that cTBS, a TMS protocol that mimics the mechanism of long-term depression of synaptic plasticity, modulates motor network oscillations primarily at the cortical level and might interfere with cortical information coding.

Event-related potential N270 delayed and enhanced by the conjunction of relevant and irrelevant perceptual mismatch.

Event-related potential studies using delayed match-to-sample tasks have demonstrated the presence of two components, N270 and N400, possibly reflecting the sequential processing of multiple sources of endogenous mismatch. To date, studies have only investigated mismatch between a single cue and target. In this study, we used distractor stimuli to investigate the effect of a secondary source of mismatch distinct from the task-relevant stimulus. Subjects performed two paradigms in which the cue and target could match or mismatch. In one paradigm, task-irrelevant distractors were added--producing a source of task-irrelevant perceptual mismatch. A mismatch-triggered negativity was elicited in both paradigms, but was delayed and enhanced in magnitude in the distractors present paradigm. It is suggested that the distractors may differentially affect mismatch responses through the generation of a task-irrelevant mismatch response.

Quantitative electroencephalography as a biomarker for proneness toward developing psychosis.

The fully dimensional approach to the relationship between schizotypal personality traits and schizophrenia describes schizotypy as a continuum throughout the general population ranging from low schizotypy (LoS) and psychological health to high schizotypy (HiS) and psychosis-proneness. However, no biological markers have yet been discovered that reliably quantify an individual's degree of schizotypy and/or psychosis. This study aimed to evaluate quantitative electroencephalographic (qEEG) measures of power spectra as potential biomarkers of the proneness towards the development of psychosis in schizotypal individuals. The resting-state oscillatory brain dynamics under eyes-closed condition from 16 LoS and 16 HiS individuals were analysed for qEEG measures of background rhythm frequency, relative power in δ, θ, low-α, high-α, low-ß, high-ß and low-γ frequency bands, and the high-temporal cross-correlation of power spectra between low- and high-frequency bands observed by averaging signals from whole-head EEG electrodes. HiS individuals at rest locked the thalamocortical loop in the low-α band at a lower-frequency oscillation and displayed an abnormally high level of neural synchronisation. In addition, the high-α band was found to be positively correlated with both the high-ß and low-γ bands unlike LoS individuals, indicating widespread thalamocortical resonance in HiS individuals. The increase of regional alpha oscillations in HiS individuals suggests abnormal high-level attention, whereas the pattern of correlation between frequency bands resembles the thalamocortical dysrhythmia phenomenon which underlies the symptomatology of a variety of neuropsychiatric disorders including schizophrenia. These qEEG biomarkers may aid clinicians in identifying HiS individuals with a high-risk of developing psychosis.

A neurophysiological insight into the potential link between transcranial magnetic stimulation, thalamocortical dysrhythmia and neuropsychiatric disorders.

Altered neural oscillations and their abnormal synchronization are crucial factors in the pathophysiology of several neuropsychiatric disorders. There is increasing evidence that the perturbation with an abnormal increase of spontaneous thalamocortical neural oscillations lead to a phenomenon termed Thalamocortical dysrhythmia (TCD) which underlies the symptomatology of a variety of neurological and psychiatric disorders including Parkinson's disease, schizophrenia, epilepsy, neuropathic pain, tinnitus, major depression and obsessive-compulsive disorder. In addition, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurophysiological tool that has been shown to both induce a modulation of neural oscillations and alleviate a wide range of human neuropsychiatric pathologies. However, little is known about the precise electrophysiological mechanisms behind the therapeutic effect of rTMS and its potential to improve abnormal oscillations across diverse neuropsychiatric disorders. Here we show, using combined rTMS and surface electroencephalography (EEG), a short lasting frequency-dependent rTMS after-effect on thalamocortical rhythmic interplay of low-frequency oscillations in healthy humans at rest. In particular, high-frequency rTMS (10 Hz) induces a transient synchronised activity for delta (δ) and theta (θ) rhythms thus mimicking the pathological TCD-like oscillations. In contrast, rTMS 1 and 5 Hz have the opposite outcome of de-synchronising low-frequency brain rhythms. These results lead to a new neurophysiological insight of basic mechanisms underlying neurological and psychiatric disorders and a probable electrophysiological mechanism underlying the therapeutic effects of rTMS. Thus, we propose the use of rTMS and EEG as a platform to test possible treatments of TCD phenotypes by restoring proper neural oscillations across various neuropsychiatric disorders.

Long lasting modulation of cortical oscillations after continuous theta burst transcranial magnetic stimulation.

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4-7.5 Hz), low α (8-9.5 Hz), µ (10-12.5 Hz), low ß (13-19.5 Hz), and high ß (20-30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of ß frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans.

Human cortical theta reactivity to high-frequency repetitive transcranial magnetic stimulation.

Electroencephalography (EEG) can directly monitor the temporal progression of cortical changes induced by repetitive Transcranial Magnetic Stimulation (rTMS) and facilitate the understanding of cortical and subcortical influences in the genesis of oscillations. In this combined rTMS/EEG study, we aimed to investigate changes in oscillatory activity after high-frequency (∼11 Hz) rTMS relative to the number of applied pulses. Twenty intermittent trains of 20 or 60 rTMS pulses were delivered over the human primary motor cortex at rest and tuned to individual mu frequency. The regional and interregional oscillatory neural activity after stimulation were evaluated using event-related power (ERPow) and event-related coherence (ERCoh) transformations. The most prominent changes for ERPow were observed in the theta band (4-7 Hz), as an increase in ERPow up to 20 s following 60 rTMS pulses, whereas ERPow increases were smaller in mu (10-12 Hz) and beta (13-30 Hz). ERCoh revealed that rTMS 60 modulated the connectivity in the theta band for up to 20 s. The topography of mu and theta changes were not identical; mu was more focal and theta was more global. Our data suggested the presence of independent cortical theta and mu generators with different reactivity to rTMS but could not rule out possible thalamocortical contributions in generating theta and mu over the motor network.

Lateral head turning affects temporal memory.

Spatial attention is a key factor in the exploration and processing of the surrounding environment, and plays a role in linking magnitudes such as space, time, and numbers. The present work evaluates whether shifting the coordinates of spatial attention through rotational head movements may affect the ability to estimate the duration of different time intervals. A computer-based implicit timing task was employed, in which participants were asked to concentrate and report verbally on colour changes of sequential stimuli displayed on a computer screen; subsequently, they were required to reproduce the temporal duration (ranging between 5 and 80 sec.) of the perceived stimuli using the computer keyboard. There was statistically significant overestimation of the 80-sec. intervals exclusively on the rightward rotation head posture, whereas head posture did not affect timing performances on shorter intervals. These findings support the hypothesis that the coordinates of spatial attention influence the ability to process time, consistent with the existence of common cortical metrics of space and time in healthy humans.

An ERP assessment of hemispheric projections in foveal and extrafoveal word recognition.

BACKGROUND: The existence and function of unilateral hemispheric projections within foveal vision may substantially affect foveal word recognition. The purpose of this research was to reveal these projections and determine their functionality. METHODOLOGY: Single words (and pseudowords) were presented to the left or right of fixation, entirely within either foveal or extrafoveal vision. To maximize the likelihood of unilateral projections for foveal displays, stimuli in foveal vision were presented away from the midline. The processing of stimuli in each location was assessed by combining behavioural measures (reaction times, accuracy) with on-line monitoring of hemispheric activity using event-related potentials recorded over each hemisphere, and carefully-controlled presentation procedures using an eye-tracker linked to a fixation-contingent display. PRINCIPAL FINDINGS: Event-related potentials 100-150 ms and 150-200 ms after stimulus onset indicated that stimuli in extrafoveal and foveal locations were projected unilaterally to the hemisphere contralateral to the presentation hemifield with no concurrent projection to the ipsilateral hemisphere. These effects were similar for words and pseudowords, suggesting this early division occurred before word recognition. Indeed, event-related potentials revealed differences between words and pseudowords 300-350 ms after stimulus onset, for foveal and extrafoveal locations, indicating that word recognition had now occurred. However, these later event-related potentials also revealed that the hemispheric division observed previously was no longer present for foveal locations but remained for extrafoveal locations. These findings closely matched the behavioural finding that foveal locations produced similar performance each side of fixation but extrafoveal locations produced left-right asymmetries. CONCLUSIONS: These findings indicate that an initial division in unilateral hemispheric projections occurs in foveal vision away from the midline but is not apparent, or functional, when foveal word recognition actually occurs. In contrast, the division in unilateral hemispheric projections that occurs in extrafoveal locations is still apparent, and is functional, when extrafoveal word recognition takes place.

The role of the left inferior frontal gyrus in episodic encoding of faces: An interference study by repetitive transcranial magnetic stimulation.

Despite extensive research on face recognition, only a few studies have examined the integration of perceptual features with semantic, biographical, and episodic information. In order to address this issue, we used repetitive transcranial magnetic stimulation (rTMS) to target the left inferior frontal gyrus (IFG) and the left occipital face area (OFA) during a face recognition task. rTMS was delivered during the encoding of "context" faces (i.e., linked to an occupation, e.g., "lawyer") and "no-context" faces (i.e., linked to a nonword pattern, e.g., "xxxx"). Subjects were then asked to perform a recognition memory task. Accuracy at retrieval showed a mild decrease after left OFA stimulation, whereas rTMS over the left IFG drastically compromised memory performance selectively for no-context faces. On the other hand, absence of rTMS interference on context faces might be due either to the fact that pairing an occupation to a face makes the memory trace stronger, therefore less susceptible to rTMS interference, or to a different functional specificity of the left IFG subregions.

Attention has memory: priming for the size of the attentional focus.

Repeating the same target's features or spatial position, as well as repeating the same context (e.g. distractor sets) in visual search leads to a decrease of reaction times. This modulation can occur on a trial by trial basis (the previous trial primes the following one), but can also occur across multiple trials (i.e. performance in the current trial can benefit from features, position or context seen several trials earlier), and includes inhibition of different features, position or contexts besides facilitation of the same ones. Here we asked whether a similar implicit memory mechanism exists for the size of the attentional focus. By manipulating the size of the attentional focus with the repetition of search arrays with the same vs. different size, we found both facilitation for the same array size and inhibition for a different array size, as well as a progressive improvement in performance with increasing the number of repetition of search arrays with the same size. These results show that implicit memory for the size of the attentional focus can guide visual search even in the absence of feature or position priming, or distractor's contextual effects.

Functional representation of living and nonliving domains across the cerebral hemispheres: a combined event-related potential/transcranial magnetic stimulation study.

Transcranial magnetic stimulation (TMS) over the left hemisphere has been shown to disrupt semantic processing but, to date, there has been no direct demonstration of the electrophysiological correlates of this interference. To gain insight into the neural basis of semantic systems, and in particular, study the temporal and functional organization of object categorization processing, we combined repetitive TMS (rTMS) and ERPs. Healthy volunteers performed a picture-word matching task in which Snodgrass drawings of natural (e.g., animal) and artifactual (e.g., tool) categories were associated with a word. When short trains of high-frequency rTMS were applied over Wernicke's area (in the region of the CP5 electrode) immediately before the stimulus onset, we observed delayed response times to artifactual items, and thus, an increased dissociation between natural and artifactual domains. This behavioral effect had a direct ERP correlate. In the response period, the stimuli from the natural domain elicited a significant larger late positivity complex than those from the artifactual domain. These differences were significant over the centro-parietal region of the right hemisphere. These findings demonstrate that rTMS interferes with post-perceptual categorization processing of natural and artifactual stimuli that involve separate subsystems in distinct cortical areas.

Corticospinal excitability in human subjects during nonrapid eye movement sleep: single and paired-pulse transcranial magnetic stimulation study.

The mechanisms responsible for changes in brain function during normal sleep are poorly understood. In this study, we aimed to investigate the effects of sleep on human corticospinal excitability by estimating resting motor threshold (RMT), and latency and amplitude of motor-evoked potentials (MEPs) after delivering transcranial magnetic stimulation (TMS) in ten healthy subjects. We also aimed to study short-interval intracortical inhibition (SICI) during sleep with paired-pulse TMS (pp-TMS). Ten healthy volunteers were studied. They were monitored immediately before, during and after a 3-h sleep (from 1 p.m. to 4 p.m., immediately after the mid-day meal). EEG was continuously recorded during sleep and the various sleep stages were identified off line. Every 10 min, subjects received ten single stimuli (to estimate RMT, MEP latency and amplitude) and six paired stimuli (to estimate SICI). MEP amplitude decreased and latency and RMT increased during the various sleep stages and returned to baseline values on awakening. Post hoc comparisons showed a significant difference in pp-TMS MEP amplitudes between the sleep and all the other conditions. The changes in TMS evoked variables during the different sleep stages indicate that during nonrapid eye movement sleep, cortical pyramidal neuron excitability (as measured by RMT, MEP latency and amplitude) progressively diminishes and the efficiency of the intracortical GABA-ergic network (as assessed by three pp-TMS) increases. On awakening, these sleep-induced changes in corticospinal excitability return rapidly to values observed during wakefulness.

Acute modulation of cortical oscillatory activities during short trains of high-frequency repetitive transcranial magnetic stimulation of the human motor cortex: a combined EEG and TMS study.

In this study, a combined repetitive transcranial magnetic stimulation/electroencephalography (rTMS/EEG) method was used to explore the acute changes of cortical oscillatory activity induced by intermittent short trains of high-frequency (5-Hz) rTMS delivered over the left primary motor cortex (M1). We evaluated the electrophysiological reaction to magnetic stimulation during and 2-4 s after 20 trains of 20-pulses rTMS, using event-related power (ERPow) that reflects the regional oscillatory activity of neural assemblies, and event-related coherence (ERCoh) that reflects the interregional functional connectivity of oscillatory neural activity. These event-related transformations were for the upper alpha (10-12 Hz) and beta (18-22 Hz) frequency ranges, respectively. For the alpha band, threshold rTMS and subthreshold rTMS induced an ERPow increase during the trains of stimulation mainly in frontal and central regions ipsilateral to stimulation. For the beta band, a similar synchronization of cortical oscillations for both rTMS intensities was seen. Moreover, subthreshold rTMS affected alpha-band activity more than threshold rTMS, inducing a specific ERCoh decrease over the posterior regions during the trains of stimulation. For beta band, the decrease in functional coupling was observed mainly during threshold rTMS. These findings provide a better understanding of the cortical effects of high-frequency rTMS, whereby the induction of oscillations reflects the capacity of electromagnetic pulses to alter regional and interregional synaptic transmissions of neural populations.

Long-lasting effects of high frequency repetitive transcranial magnetic stimulation in major depressed patients.

The majority of previous clinical studies have indicated that repetitive transcranial magnetic stimulation (rTMS) may have antidepressant effects. Herein, we investigated the longitudinal, long-term antidepressant efficacy of daily left prefrontal cortex (PFC) rTMS for a 1-week period. Nineteen patients were randomly assigned to two treatment groups at 90% of individual motor threshold (MT): Twelve received active repetitive transcranial magnetic stimulation and seven received sham treatment. Each patient underwent five sessions of twenty 2-s trains of 20 Hz rTMS with 800 stimuli/day. The Beck Depression Inventory and the Hamilton Depression Rating Scale were used to assess severity of depression at 1, 4 and 12 weeks post-therapy. A significant reduction of baseline depression scores was observed after 1 week of active treatment that lasted for 1 month, indicating improvement of depressive symptoms. No significant effects were observed in patients receiving sham treatment. The results of this controlled study are in agreement with the findings of previous studies suggesting that daily left PFC rTMS has an antidepressant effect.