Papers by Debora Brignani
Journal of Cognitive Neuroscience, Dec 1, 2009
& We developed a new experimental task to investigate the relative timing of neural activity duri... more & We developed a new experimental task to investigate the relative timing of neural activity during shifts of spatial attention with event-related potentials. The task enabled the investigation of nonlateralized as well as lateralized neural activity associated with spatial shifts. Participants detected target stimuli within one of two peripheral streams of visual letters. Colored letters embedded within the streams indicated which stream was to be used for target detection, signaling that participants should ''hold'' or ''shift'' their current focus of spatial attention. A behavioral experiment comparing performance in these focused-attention conditions with performance in a divided-attention condition confirmed the efficacy of the spatial cues. Another behavioral experiment showed that overt shifts of spatial attention were mainly complete by around 400 msec, placing an upper boundary for isolating neural activity that was instrumental in controlling spatial shifts. Event-related potentials recorded during a covert version of the focused-attention task showed a large amount of nonlateralized neural activity associated with spatial shifts, with significant effects starting around 330 msec. The effects started over posterior scalp regions, where they remained pronounced. Transient effects were also observed over frontal scalp regions. The results are compatible with a pivotal role of posterior parietal areas in initiating shifts of spatial attention. &
NeuroImage, 2010
Attention can be focused voluntarily and effectively on spatial locations in order to enhance the... more Attention can be focused voluntarily and effectively on spatial locations in order to enhance the processing of task-relevant events. However, work on 'attentional capture' has demonstrated that spatial biases can be temporarily reset by transient and salient stimuli, especially if they share defining characteristics with the targets of a task goal. In the current study, we investigated whether the appearance of stimuli containing task-defining features at an unattended location was sufficient to capture attention, even when these were not perceptually salient. We used event-related-potential (ERP) markers to test whether the selection of task-defining features was modulated by top-down spatial attention, and to test whether the appearance of 'unattended targets' transiently disrupted the spatial bias. Surprisingly, the results revealed that ERP markers of selection of task-defining features were equivalent for stimuli appearing at spatially attended and unattended locations. In addition, the presentation of task-defining stimuli at the spatially unattended location induced a short-lived redistribution of the pre-established spatial attention bias toward the 'capture' side. These findings show that task-defining features of a stimulus are automatically processed independently from spatial attention, and suggest the coexistence of multiple sources of top-down biasing signals, which might in part sustain the capture mechanism.
European Journal of Neuroscience, Feb 1, 2022
Over the past two decades, the postulated modulatory effects of transcranial direct current stimu... more Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.
Frontiers in Neuroscience, 2021
A growing number of studies is using fMRI-based connectivity to guide transcranial magnetic stimu... more A growing number of studies is using fMRI-based connectivity to guide transcranial magnetic stimulation (TMS) target identification in both normal and clinical populations. TMS has gained increasing attention as a potential therapeutic strategy also in Alzheimer’s disease (AD), but an endorsed target localization strategy in this population is still lacking. In this proof of concept study, we prove the feasibility of a tailored TMS targeting approach for AD, which stems from a network-based perspective. Based on functional imaging, the procedure allows to extract individual optimal targets meanwhile accounting for functional variability. Single-subject resting-state fMRI was used to extract individual target coordinates of two networks primarily affected in AD, the default mode and the fronto-parietal network. The localization of these targets was compared to that of traditional group-level approaches and tested against varying degrees of TMS focality. The distance between individua...
Targeting Default Mode Network Dysfunction in Persons at Risk of Alzheimer’s Disease with Transcranial Magnetic Stimulation (NEST4AD): Rationale and Study Design
Journal of Alzheimer's Disease, 2021
Background: Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD... more Background: Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. Objective: This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. Methods: We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS w...
Clinical Neurophysiology, 2020
Recently, transcranial magnetic stimulation and electroencephalography (TMS-EEG) coregistration h... more Recently, transcranial magnetic stimulation and electroencephalography (TMS-EEG) coregistration has gained popularity among the techniques used in neuroscience. In this combination, TMS allows for a causal and non-invasive interaction with brain dynamics, which can be tracked and recorded with a millisecond e84 Abstracts / Clinical Neurophysiology 131 (2020) e11-e178
Neuropsychologia, 2018
Neurologically healthy young adults display a behavioral bias, called pseudoneglect, which favors... more Neurologically healthy young adults display a behavioral bias, called pseudoneglect, which favors the processing of stimuli appearing in the left visual field. Pseudoneglect arises from the right hemisphere dominance for visuospatial attention. Previous studies investigating the effects of normal aging on pseudoneglect in line bisection and greyscale tasks have produced divergent results. In addition, scarce systematic investigations of visual biases in dementia have been reported. The aim of the present study was to evaluate whether the leftward bias appearing during an enumeration task in young adults would be preserved in normal aging and at different stages of severity of Alzheimer's disease. In Experiment 1, young and older healthy adults showed a comparable pseudoneglect, performing better when targets appeared in the left visual field. In Experiment 2, the leftward bias was maintained in amnesic mild cognitive impairment patients (aMCI), but it vanished in mild Alzheimer's disease patients (AD). The maintenance of pseudoneglect in normal aging and in aMCI patients is consistent with compensatory phenomena involving the right fronto-parietal network, which allow maintaining the right hemisphere dominance. Conversely, the lack of pseudoneglect in the sample of AD patients likely results from a loss of the right hemisphere dominance, caused by the selective degeneration of the right fronto-parietal network. These results highlight the need of further systematic investigations of visuospatial biases along the continuum of normal and pathological aging, both for a better understanding of the changes characterizing cognitive aging and for improvements in the evaluation of neglect in Alzheimer's disease.
Journal of Alzheimer's Disease, 2017
The aim of this study was to investigate the behavioral and electrophysiological dynamics of mult... more The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.
Neurobiology of Aging, 2016
Theories on neural compensation suggest that aged participants overactivate the brain areas invol... more Theories on neural compensation suggest that aged participants overactivate the brain areas involved in a task to compensate for the age-related decline. In this electrophysiological study, we investigated the temporal locus of neural overactivation in aging during multiple target processing. We measured performance and three event-related brain potential responses (N1, N2pc, and contralateral delay activity) in young and old adults, while they enumerated a variable number (1e4) of targets presented in an easy (distractor absent) or difficult (distractor present) condition. The main results indicated that although N2pc (w200 ms) increased in amplitude in the distractor-present condition in the young group, no modulation occurred for the old group. Old participants were associated with larger N2pc amplitudes than young participants in the distractor-absent condition, where both groups had comparable levels of accuracy. These effects were not present for N1 and contralateral delay activity. Overall, the data suggest that in enumeration, aging is associated with compensatory effects that rely on the selection mechanism responsible for target individuation.
PLOS ONE, 2015
To understand the nature of age-related changes in enumeration abilities we measured two ERP resp... more To understand the nature of age-related changes in enumeration abilities we measured two ERP responses-N2pc and CDA, associated respectively to attentive individuation and VWM-and posterior alpha band (8-15 Hz) event-related desynchronization (ERD), traditionally linked to enhanced target processing. Two groups of old and young participants enumerated a variable number (1-6) of targets presented among distractors. Older participants were less accurate in enumerating targets. ERP results in old participants showed a suppression of N2pc amplitudes for all numerosities, and a decrease in CDA only for the largest set (4-6 targets). In contrast with the pattern for young adults, time/frequency results on older adults revealed neither a modulation of alpha oscillations as a function of target numerosity, nor an effect of ERD lateralization. These patterns indicate that both attention and working memory contribute to the age-related decline in enumeration, and point to an overall decrease in the activity of the visual areas responsible for the processing of the hemifield where the relevant objects are presented.
Neuropsychologia, Jan 9, 2015
Spatial neglect is traditionally explained as an imbalance of the interhemispheric reciprocal inh... more Spatial neglect is traditionally explained as an imbalance of the interhemispheric reciprocal inhibition exerted by the two hemispheres: after a right lesion, the contralesional hemisphere becomes disinhibited and its enhanced activity suppresses the activity in the lesioned one. Even though the hyperexcitability of the left hemisphere is the theoretical framework of several rehabilitation interventions using non-invasive brain stimulation protocols in neglect, no study has yet investigated directly the actual state of cortical excitability of the contralesional hemisphere immediately after the brain lesion. The present study represents the first attempt to directly assess the interhemispheric rivalry model adopting a novel approach based on the induction of neglect-like biases in healthy participants. Applying repetitive transcranial magnetic stimulation (rTMS) over the right posterior parietal cortex while concurrently recording the EEG activity allows to measure specific neurophy...
rs-fMRI network-based TMS targeting
The present data are collected from 8 Alzheimer's disease patients to prove the feasibility o... more The present data are collected from 8 Alzheimer's disease patients to prove the feasibility of a tailored network-based transcranial magnetic stimulation (TMS) targeting approach. Based on resting state functional imaging, the procedure allows to extract individual optimal targets of two networks affected by Alzheimer's disease: the default mode (DMN) and the fronto-parietal network (FPN). The dataset includes: - The raw independent components maps (melodic_IC.nii.gz) in native space extracted from individual rs-fMRI with Melodic independent component analysis (Beckman and Smith 2004) - A table with the demographic and clinical characteristics of the sample (n=8) together with the individual coordinates of the target in native space.
Baseline levels of alertness influence tES effects along different age-related directions
Neuropsychologia
Normal aging is usually accompanied by several structural and functional physiological changes of... more Normal aging is usually accompanied by several structural and functional physiological changes of the brain, which are closely related to alterations of cognitive functions (e.g., visual short-term memory). As the average age of the population increases, it has become crucial to identify cognitive-behavioural interventions to maintain a healthy level of cognitive performance. Among a variety of approaches, the targeting of specific intrinsic alertness mechanisms has shown a solid rationale and beneficial effects in both healthy and pathological ageing. In a similar vein, the use of non-invasive transcranial electrical stimulation (tES) represents another promising approach to induce an alerting state that can produce advantages in the information processing in the brain and therefore behaviour. Here, we investigated whether time-locked bursts of tES (i.e., transcranial random noise stimulation) were effective in inducing behavioural and physiological changes, consistently with an alertness increase, in both young and older healthy adults. Namely, we expected to find a beneficial alerting effect on visual short-term memory performance as a function of stimulus perceptual salience and tES. The initial results showed that the performance of younger adults was not affected by tES, while older adults scored lower correct responses for high-salience stimuli during real tES with respect to sham stimulation. However, after including a baseline measure of subjective level of alertness in the analyses, a tES-induced memory improvement did emerge in the less alerted younger adults, while only the more alerted older adults were subject to the worsening effect by tES. We discuss these results in consideration of the evidence on critical age-related differences as well as the interaction between neurostimulation and baseline alerting mechanisms.
Author response for "Responsiveness to left‐prefrontal tDCS varies according to arousal levels
Arousal levels can be used to predict the ongoing effects of neuromodulation
In this study, we aimed to verify whether the behavioural effects induced by a common prefrontal ... more In this study, we aimed to verify whether the behavioural effects induced by a common prefrontal tDCS montage were dependent on the participants' arousal levels. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects on reaction times and pupil dilation were evaluated as a function of subjective (STAI-Y State scores) and physiological (pre-target pupil size) arousal predictors. We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil dilation was affected according to the ongoing levels of arousal. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, and thus encourage a more caref...
Brain Stimulation, 2020
The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a ... more The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning. The present study provides important hints on the promising therapeutic use of rTMS in AD.
Over the past two decades, the postulated modulatory effects of transcranial direct current stimu... more Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated, with attractive real-world applications. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to the great interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted individual state-dependent factors. On these grounds, we aimed to verify whether the behavioural effects induced by a common prefrontal tDCS montage were dependent on the participants’ arousal levels. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects on reaction times and pupil dilation were evaluated as a function of subjective and physiological arousal predictors. Both predictors significantly explained perf...
Scientific Reports, 2016
Evidence suggests that Alzheimer’s disease (AD) is part of a continuum, characterized by long pre... more Evidence suggests that Alzheimer’s disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to hea...
NeuroImage, 2016
Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cort... more Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCSinduced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p b 0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p b 0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner.
NeuroImage, 2016
In any given common situation, when an individual controls him/herself or obeys and stops a curre... more In any given common situation, when an individual controls him/herself or obeys and stops a current action when asked to do, it is because the brain executes an inhibitory process. This ability is essential for adaptive behaviour, and it is also a requirement for accurate performance in daily life. It has been suggested that there are two main inhibitory functions related to behaviour, as inhibition is observed to affect behaviour at different time intervals. Proactive inhibition permits the subject to control his behavioural response over time by creating a response tendency, while reactive inhibition is considered to be a process that usually inhibits an already initiated response. In this context, it has been established that inhibitory function is implemented by specific frontobasal-ganglia circuits. In the present study, we investigated the role of the right inferior frontal cortex (rIFC) in response inhibition by combining into a single task the Go-NoGo task and the Stop-Signal task. Concurrently, we applied transcranial direct current stimulation (tDCS) over the IFC and recorded electroencephalography (EEG). Thus, we obtained online EEG measurements of the tDCS-induced modifications in the IFC together with the participant's performance in a response inhibition task. We found that applying bilateral tDCS on the IFC (right anodal/left cathodal) significantly increased proactive inhibition, although the behavioural parameters indicative of reactive inhibition were unaffected by the stimulation. Finally, the inhibitory-P3 component reflected a similar modulation under both inhibitory conditions induced by the stimulation. Our data indicates that an online tDCS-ERP approach is achievable, but that a tDCS bilateral montage may not be the most efficient one for modulating the rIFC.
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Papers by Debora Brignani