Visuo-spatial attention and semantic memory are supported by distinct, largely competing brain networks, yet they are frequently engaged together in daily life. How these networks interact during combined tasks remains unexplored. We conducted a factorial fMRI experiment in which 25 participants performed a novel task requiring visuo-spatial attention, semantic judgment, or both. Covert shifts of attention towards cued lateral location activated bilateral parietal (PEF), frontal eye fields (FEF), and anterior insula. Categorizing a word as referring to a living or non-living entity activated a lateral parietal region (LaP) between the dorsal tip of the angular gyrus and the lateral bank of the intraparietal sulcus, along with the left inferior frontal gyrus (IFG), superior temporal sulcus, inferior temporal lobe and bilateral anterior insula. Notably, the anterior insula was active in both conditions. Dynamic causal modeling showed excitatory-inhibitory parieto-frontal loops driving attention (PEF→FEF) and semantic processing (LaP→IFG) separately, but in the combined condition frontal-to-parietal feedback became excitatory, reflecting stronger integration, with the anterior insula driving overall connectivity. These findings identify LaP as a novel region supporting semantic processing of linguistic stimuli, and highlight the anterior insula as a key hub integrating attentional and semantic networks under concurrent cognitive demands.

The article presents the Atlantis Source Connectivity Toolbox (ASCT), a pipeline for the complete analysis of source-based directed (effective) connectivity from MEG/EEG signals. Connectivity estimation is implemented with the Directed Transfer Function, a multivariate autoregressive method grounded in the Granger causality approach. The theoretical concepts and challenges in source reconstruction and causal inferences from electrophysiological and biomagnetic recordings are introduced. Importantly, the guidelines for the custom analyses are also presented together with the toolbox user manual. By providing the complete analytic pipeline with practical recommendations, we intend to support standardization and replicability in connectivity studies. The validation of the method is further demonstrated with simulated MEG data, prepared from real resting data recording, as well as with realistic EEG data from the Eriksen flanker task. Our results highlight the importance of routine use of the leakage correction that prevents the appearance of spurious links. We also discuss potential benefits of source separation prior to their reconstruction for more accurate estimates of connectivity.

Identifying band-specific features -such as amplitude and latency/duration-from event-related desynchronization (ERD) patterns in MEG/EEG time-frequency representations can enhance our understanding of how the brain processes tasks and influences behavior. However, these features can be affected by potential noise, intrinsic instabilities, and inter-trial variability, which makes it challenging to analyze ERD dynamics accurately when multiple peaks with similar amplitudes emerge in the ERD pattern. To address these issues, we introduce SmartERD, a new pipeline designed to extract dynamic ERD features while considering ERD variability. SmartERD automatically estimates a band-specific pseudo-confidence interval around the absolute ERD peak, inspired by uncertainty propagation principles. It then identifies the first local ERD peak within this interval -representing the first component of the induced oscillatory response- and automatically extracts its features. A key advantage of this approach is that it extracts the latency of a common reference point for all subjects -the first peak response after a trigger- facilitating more consistent comparisons. We validated SmartERD through realistic simulations that mimic different trial numbers. Results showed that SmartERD's estimates are closer to the ground truth across various noise levels compared to standard methods. Additionally, when applied to experimental MEG data, SmartERD demonstrated a better ability to capture individual differences in ERD dynamics, thanks to the selection of a common reference latency. Overall, we propose SmartERD as a valuable tool for extracting meaningful features from oscillatory dynamics, with the potential to improve the analysis of brain-behavior relationships in complex cognitive tasks.

A Right Ear Advantage (REA) is well-established in perceptual tasks but it has been found also during imagery. It is ascribed to the left temporoparietal activity for language, and it can be absent/reversed in some clinical conditions including auditory hallucinations. We applied 1-Hz repetitive TMS over TP3/TP4 (left/right language areas) identified through neuronavigation in 18 healthy participants, before administering a modified white noise (WN) speech illusion paradigm: a voice was presented at one ear, at the same or lower intensities with respect to binaural WN. In some trials the voice was not presented, but participants were anyway instructed to report in which ear they believed perceiving it in all trials. Results confirmed the REA both when the voice was present (perceptual REA) and when it was absent (imaginative REA). Interestingly, results suggested that the correct localization of the voice when the stimulus was ambiguous (presented at low intensity and “masked” by WN) was better when TMS was applied over the right/left hemisphere, in male participants with a low/high proneness to unusual experiences (e.g., auditory hallucinations), respectively. This interaction must be further explored to shed light on the relationship between hemispheric asymmetries and auditory hallucinations, in healthy and clinical samples.

Neuroimaging studies conducted in the last three decades have distinguished two frontoparietal networks responsible for the control of visuospatial attention. The present review summarizes recent findings on the neurophysiological mechanisms implemented in both networks and describes the evolution from a model centered on the distinction between top-down and bottom-up attention to a model that emphasizes the dynamic interplay between the two networks based on attentional demands. The role of the dorsal attention network (DAN) in attentional orienting, by boosting behavioral performance, has been investigated with multiple experimental approaches. This research effort allowed us to trace a distinction between DAN regions involved in shifting vs. maintenance of attention, gather evidence for the modulatory influence exerted by the DAN over sensory cortices, and identify the electrophysiological correlates of the orienting function. Simultaneously, other studies have contributed to reframing our understanding of the functions of the ventral attention network (VAN) and its relevance for behavior. The VAN is not simply involved in bottom-up attentional capture but interacts with the DAN during reorienting to behaviorally relevant targets, exhibiting a general resetting function. Further studies have confirmed the selective rightward asymmetry of the VAN, proposed a functional dissociation along the anteroposterior axis, and suggested hypotheses about its emergence during the evolution of the primate brain. Finally, novel models of network interactions explain the expression of complex attentional functions and the emergence and restorations of symptoms characterizing unilateral spatial neglect. These latter studies emphasize the importance of considering patterns of network interactions for understanding the consequences of brain lesions.

Neuroimaging studies associate specific functional roles to distinct brain regions investigating separate cognitive processes using dedicated tasks. For example, using both correlative (i.e., fMRI) and causal (i.e., TMS) approaches it has been shown the involvement of intra-parietal sulcus (IPS), as part of the dorsal attention network, in spatial attentional tasks as well as the importance of the angular gyrus (AG), as part of the default mode network, during the selection of relevant information in semantic memory. Nonetheless, in our daily life attention and semantic memory are rarely needed in isolation. In the present TMS study we investigate how the brain combines attentional and semantic memory demands in a single task. Results showed that, compared to a pseudo-TMS, stimulation of IPS, but not AG, affects behavioral performance, thus suggesting its preponderant role in such a combined task. Moreover, the lack of difference between the effect of IPS and AG stimulations seems to suggest that the two regions may be coactivated or that a third-party source might indirectly mediate the interaction between the two networks.

Background/Purpose: To investigate the association between the degree of spatial neglect and the changes of brain system segregation (SyS; i.e., the ratio of the extent to which brain networks interact internally and with each other) after stroke. Methods: A cohort of 20 patients with right hemisphere lesion was submitted to neuropsychological assessment as well as to resting-state functional magnetic resonance imaging session at acute stage after stroke. The severity of spatial neglect was quantified using the Center of Cancellation (CoC) scores of the Bells cancellation test. For each patient, resting-state functional connectivity (FC) matrices were assessed by implementing a brain parcellation of nine networks that included the visual network, dorsal attention network (DAN), ventral attention network (VAN), sensorimotor network (SMN), auditory network, cingulo-opercular network, language network, frontoparietal network, and default mode network (DMN). For each patient and each network, we then computed the SyS derived by subtracting the between-network FC from the within-network FC (normalized by the within-network FC). Finally, for each network, the CoC scores were correlated with the SyS. Results: The correlational analyses indicated a negative association between CoC and SyS in the DAN, VAN, SMN, and DMN (q < 0.05 false discovery rate [FDR]-corrected). Patients with more severe spatial neglect exhibited lower SyS and vice versa. Conclusion: The loss of segregation in multiple and specific networks provides a functional framework for the deficits in spatial and nonspatial attention and motor/exploratory ability observed in neglect patients.

Microstate analysis applied to electroencephalographic signals (EEG) allows both temporal and spatial imaging exploration and represents the activity across the scalp. Despite its potential usefulness in understanding brain activity during a specific task, it has been mostly exploited at rest. We extracted EEG microstates during the presentation of emotional expressions, presented either unilaterally (a face in one visual hemifield) or bilaterally (two faces, one in each hemifield). Results revealed four specific microstate’s topographies: (i) M1 involves the temporal areas, mainly in the right hemisphere, with a higher occurrence for stimuli presented in the left than in the right visual field; (ii) M2 is localized in the left temporal cortex, with higher occurrence and coverage for unilateral than bilateral presentations; (iii) M3, with a bilateral temporo-parietal localization, shows higher coverage for bilateral than unilateral presentation; (iv) M4, mainly localized in the right fronto-parietal areas and possibly representing the hemispheric specialization for the peculiar stimulus category, shows higher occurrence and coverage for unilateral stimuli presented in the left than in the right visual field. These results suggest that microstate analysis is a valid tool to explore the cerebral response to emotions and can add new insights on the cerebral functioning, with respect to other EEG markers.

In the present case report, we investigated the cortical networks of a patient (DDA) affected by right parietal stroke who showed a constructional phenomenon, in which when coping and recalling from memory a complex figure, the model was reproduced rotated of 90° along the vertical axis. Previous studies suggested that rotation on copy is associated with visuospatial impairments and abnormalities in parietal cortex, whereas rotation on recall might be related to executive deficits and dysfunction of frontal regions. Here, we computed the DDA's resting-state functional connectivity (FC) derived from cortical regions of the dorsal attention (DAN) and the frontal portion of the executive-control network (fECN), which are involved in the control of visuospatial attention and multiple executive functions, respectively. We observed that, as compared to a control group of right stroke patients without drawing rotation, DDA exhibited selective increased FC of the DAN and fECN, but not of task-irrelevant language network, within the undamaged hemisphere. These patterns might reflect a pathological communication in such networks leading to impaired attentional and executive operations required to reproduce the model in the correct orientation. Notably, such enhancement of FC was not detected in a patient with a comparable neuropsychological profile as DDA, yet without rotated drawing, suggesting that network-specific modulations in DDA might be ascribed to the constructional phenomenon of rotated drawing.

Background/Purpose: To identify brain hubs that are behaviorally relevant for neglect after stroke as well as to characterize their functional architecture of communication. Methods: Twenty acute right hemisphere damaged patients underwent neuropsychological and resting-state functional magnetic resonance imaging sessions. Spatial neglect was assessed by means of the Center of Cancellation on the Bells Cancellation Test. For each patient, resting-state functional connectivity matrices were derived by adopting a brain parcellation scheme consisting of 153 nodes. For every node, we extracted its betweenness centrality (BC) defined as the portion of all shortest paths in the connectome involving such node. Then, neglect hubs were identified as those regions showing a high correlation between their BC and neglect scores. Results: A first set of neglect hubs was identified in multiple systems including dorsal attention and ventral attention, default mode, and frontoparietal executive-control networks within the damaged hemisphere as well as in the posterior and anterior cingulate cortex. Such cortical regions exhibited a loss of BC and increased (i.e., less efficient) weighted shortest path length (WSPL) related to severe neglect. Conversely, a second group of neglect hubs found in visual and motor networks, in the undamaged hemisphere, exhibited a pathological increase of BC and reduction of WSPL associated with severe neglect. Conclusion: The topological reorganization of the brain in neglect patients might reflect a maladaptive shift in processing spatial information from higher level associative-control systems to lower level visual and sensory-motor processing areas after a right hemisphere lesion.

Background: The endogenous allocation of spatial attention to selected environmental stimuli is controlled by prefrontal (frontal eye fields [FEFs]) and parietal (superior parietal lobe [SPL] and intraparietal sulcus [IPS]) regions belonging to the dorsal attention network (DAN) with a subdivision in subsystems devoted to reorienting (or shifting) of attention between locations (SPL) or maintaining attention at contralateral versus ipsilateral locations (ventral IPS [vIPS]). Although previous studies suggested a leading role of prefrontal regions over parietal sites in orienting attention, the spectral signature of communication flow within the DAN for different attention processes is still debated.Methods: We used the directed transfer function (DTF) on magnetoencephalography (MEG) data to examine the causal interaction between prefrontal and parietal regions of the DAN when subjects shifted versus maintained attention to a stream of cued visual stimuli.Results: In the beta band, we found that shift versus stay cues induced stronger connectivity (DTF values) from right FEF to right SPL, in the early phase of reorienting. Conversely, when considering stay versus shift cues, an increase of DTF values and stronger directionality was observed between bilateral vIPS and from right vIPS to FEF. Similar analyses carried out in theta, alpha, and gamma showed no significant frontoparietal increases of DTF for shift versus stay cues, whereas the stay-related increase of DTF observed in beta between ventral parietal areas was preserved in the alpha band.Conclusions: These findings suggest that control processes in DAN regions (in particular between FEF and SPL) can be associated to a beta frequency channel during shift of attention. Impact statementIn the present study, we compared the reorienting response to novel stimuli with respect to maintaining response. Results provided new insights into understanding the neural mechanisms of control attention processes by identifying the frequency-specific causal interactions between frontal and parietal regions belonging to the dorsal attention network supporting spatial reorienting response.

Electrophysiological (EEG) correlates both at time (i.e., event-related potentials, ERP) and frequency (i.e., event-related desynchronization, ERD) domains have been shown to be modulated by external magnetic interference. Parallel studies reported a similar interference also for the EEG microstate at rest and in the period that anticipates a task. Here we investigated whether such interference was prolonged during the evoked activity in the framework of the semantic decision task. To this aim, rTMS was delivered over a core region of both the Default mode network and the language network (i.e., left angular gyrus, AG), previously associated to the current task, and as active control we stimulated the left IPS. When subjects received a non-active stimulation (i.e., Sham), in the period that follows the target onset (i.e., 2 sec after the rTMS) we found an interesting alternation of two dominant microstates (MS1, MS3), previously associated to the phonological network and the Cingulo-Opercular Network (CON), respectively. This dynamic was not altered when TMS was delivered over the left IPS. On the contrary, rTMS over left AG selectively suppressed the phonological-related microstate. These findings provide the first causal evidence of region specificity of the EEG microstates topography during the evoked activity corroborating the idea of a crucial role of AG in the semantic memory. Moreover, the present results might provide insight for understanding the neurophysiological correlates of language disorders e.g., aphasia as well as for planning non-invasive brain stimulation protocols for the rehabilitation.

In the last decades, several electrophysiological markers have been investigated to better understand how humans precede a signaled event. Among others, the pre-stimulus microstates' topography, representing the whole brain activity, has been proposed as a promising index of the anticipatory period in several cognitive tasks. However, to date, a clear relationship between the metrics of the pre-stimulus microstates [i.e., the global explained variance (GEV) and the frequency of occurrence (FOO)] and well-known electroencephalography marker of the anticipation (i.e., the alpha power reduction) has not been investigated. Here, after extracting the microstates during the expectancy of the semantic memory task, we investigate the correlations between the microstate features and the anticipatory alpha (8-12 Hz) power reduction (i.e., the event-related de-synchronization of the alpha rhythms; ERD) that is widely interpreted as a functional correlate of brain activation. We report a positive correlation between the occurrence of the dominant, but not non-dominant, microstate and both the mean amplitude of high-alpha ERD and the magnitude of the alpha ERD peak so that the stronger the decrease (percentage) in the alpha power, the higher the FOO of the dominant microstate. Moreover, we find a positive correlation between the occurrence of the dominant microstate and the latency of the alpha ERD peak, suggesting that subjects with higher FOO present the stronger alpha ERD closely to the target. These correlations are not significant between the GEV and all anticipatory alpha ERD indices. Our results suggest that only the occurrence of the dominant, but not non-dominant, microstate should be considered as a useful electrophysiological correlate of the cortical activation.

We have recently described a facilitation effect for the execution of a walking-related action in response to distant objects/locations in the extrapersonal space. Based on the parallelism with the well-known effect of "micro-affordance", observed during the execution of functionally appropriate hand-related actions towards manipulable objects, we have referred to this effect in terms of "macro-affordance". Here we used transcranical magnetic stimulation (TMS) to investigate whether a foot-related region located in the human dorsal precuneate cortex plays a causal role in the generation and maintenance of such behavioral effect. This question was addressed by comparing the magnitude of the facilitation effect during an incidental go/no-go task, i.e. advantage for walking-related actions to pictures framing an environment from a far vs. near distance, during three different TMS conditions. The three TMS conditions were collected in all subjects in a randomized order and included stimulation of: i. a foot-related region in the anterior precuneus, ii. a control region in the middle intraparietal sulcus (mIPS), and iii. a sham condition. Enrollment in the TMS protocol was based on analysis of individual performance during a preliminary session conducted using a sham stimulation. TMS was administered at a low frequency range before the beginning of each condition. The results showed that stimulation of the foot-related region in the anterior precuneus produced a significant reduction of the walking-related facilitation effect as compared to both stimulation of the active-control region and the non-active sham stimulation. These findings suggest that the foot-related sensory-motor system directly participates in the process of extraction of the spatial features (i.e. distance) from an environmental scene that are useful for locomotion. More in general, these findings support an automatic coding of environmental affordance or "macro-affordances" in the walking-related sensory-motor system.

Individuals are able to improve their visual skill with practice, a phenomenon called Visual Perceptual Learning (VPL). We previously observed that after training on a difficult shape identification task, the dorsal visual regions (i.e. right V2d/V3 and right lateral occipital, LO) corresponding to the trained visual quadrant, and their homologous in the opposite hemisphere, exhibited a selective activation at the end of the learning. By contrast, such modulation was not observed in the ventral visual regions, corresponding to the untrained quadrants. The causal role of the trained visual cortex was previously showed in a TMS study as its inactivation impaired behavioral performance to learned stimuli. Here, using the same experimental design, we employed TMS over the homologous of the trained area (i.e. left V2d/V3) as well as over the untrained region (i.e. right V4) to causally map the visual network during the perceptual learning. We report a decrease of accuracy after TMS over left V2d/V3 as compared to both right V4 and Sham (inactive stimulation) conditions. Importantly, TMS effect was correlated with the degree of learning, such that subjects with lower accuracy at the end of the training exhibited stronger TMS impairment. These results provide evidence that segregated regions within the visual network are causally involved in visual perceptual learning.

Deutsch’s octave illusion is produced by a sequence of two specular dichotic stimuli presented in alternation to the left and right ear causing an illusory segregation of pitch (frequency) and side (ear of origin). Previous studies have indicated that illusory perception of pitch takes place in temporo-frontal areas, whereas illusory perception of side is primarily associated to neural activity in parietal cortex and in particular in the inferior parietal lobule (IPL). Here we investigated the causal role of left IPL in the perception of side (ear of origin) during the octave illusion by following its inhibition through continuous theta-burst stimulation (cTBS), as compared to the left posterior intraparietal sulcus (pIPS), whose activity is thought to be unrelated to side perception during the illusion. We observed a prolonged modification in the side of the illusory perceived tone during the first 10 minutes following the stimulation. Specifically, while after cTBS over the left IPS subjects reported to perceive the last tone more often at the right compared to the left ear, cTBS over left IPL significantly reverted this distribution, as the number of last perceived tones at the right ear was smaller than at the left ear. Such alteration was not maintained in the successive 10 minutes. These results provide the first evidence of the causal involvement of the left IPL in the perception of side during the octave illusion.

Different electrophysiological (EEG) correlates may provide specific important assessment of the period that anticipates an imperative stimulus. Previous study of our group showed that a local (i.e. parietal) anticipatory EEG marker (i.e. the event related de-synchronization of the alpha rhythms; ERD) is selectively affected when transcranial magnetic stimulation (TMS) is delivered over crucial nodes belonging to well-known human networks involved in different cognitive domains. Here, we investigated whether such distinction is also present in the whole brain activity as seen through the pre-stimulus microstate's topography, representing a global and reference-free measure of the neural activity. First, when subjects received a pseudo-stimulation (sham), we found two distinct pre-stimulus topographies during perceptual or memory task, respectively. Second, we reported that, during the visuo-spatial attention task, stimulation of left intraparietal sulcus (IPS), but not left angular gyrus (AG), significantly modifies the topography observed in the Sham condition. Conversely, stimulation of AG, but not IPS, changes the topography observed in the Sham condition during a semantic memory task. These findings provide the first causal evidence for the task and region specificity of the pre-stimulus EEG microstates, thus proposing this EEG index as of particular interest for the assessment of the period that precedes a predictable event.

The Right Hemisphere Hypothesis (RHH) posits that the right hemisphere is specialized in processing all emotions; the Valence Hypothesis (VH) suggests a left/right-hemispheric specialization for positive/negative emotions, respectively. Behavioural, neuroimaging and physiological investigations alternatively support either the RHH or the VH, but connectivity analyses have been hardly exploited in this field. In the present study, unilateral and bilateral presentations of positive (happy) and negative (angry) emotional faces were used during electroencephalographic (EEG) recordings, and estimation of effective connectivity was performed using the Directed Transfer Function, to estimate causal influences between brain regions (Granger causality approach). The results show a strong pattern of connectivity among different frontal areas (orbitofrontal and dorsolateral prefrontal cortex), attentional network (frontal eye field, intraparietal sulcus), visual occipital areas and temporal sites, mainly lateralized in the right hemisphere for all emotions, in accordance with the RHH. Moreover, a stronger pattern of connectivity is evident when stimuli are presented in accordance with the VH (positive/negative emotions to the left/right hemisphere, respectively). Finally, the results suggest a crucial role of the right dorsolateral prefrontal cortex in a top-down regulation toward different areas involved in emotional processing. We conclude that the RHH and the VH are not mutually exclusive, but they seem to coexist during affective perception.