Giorgio Fuggetta

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 β (13–19.5 Hz), and high β (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 β 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.

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 Parkinsons 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.

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 Wernickes 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 postperceptual categorization processing of natural and artifactual stimuli that involve separate subsystems in distinct cortical areas.

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.

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 individuals 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-β, high-β 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-β 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.

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.

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. Hum Brain Mapp 33:2224–2237, 2012.

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

Repeating the same targets 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 distractors contextual effects.