Emiliano Macaluso

Several methods are available for the identification of functional networks of brain areas using functional magnetic resonance imaging (fMRI) time-series. These typically assume a fixed relationship between the signal of the areas belonging to the same network during the entire time-series (e.g., positive correlation between the areas belonging to the same network), or require a priori information about when this relationship may change (task-dependent changes of connectivity). We present a fully data-driven method that identifies transient network configurations that are triggered by the external input and that, therefore, include only regions involved in stimulus/task processing. Intersubject synchronization with short sliding time-windows was used to identify if/when any area showed stimulus/task-related responses. Next, a first clustering step grouped together areas that became engaged concurrently and repetitively during the time-series (stimulus/task-related networks). Finally, for each network, a second clustering step grouped together all the time-windows with the same BOLD signal. The final output consists of a set of network configurations that show stimulus/task-related activity at specific time-points during the fMRI time-series. We label these configurations: "brain modes" (bModes). The method was validated using simulated datasets and a real fMRI experiment with multiple tasks and conditions. Future applications include the investigation of brain functions using complex and naturalistic stimuli. Hum Brain Mapp 36:3404-3425, 2015. © 2015 Wiley Periodicals, Inc.

The fractionation view holds that distinct cognitive operations are mediated by subregions of the inferior parietal lobule (IPL). Within IPL, we hypothesised that retrieval-related activity in different parts of the right supramarginal gyrus (rSMG) may be modulated differentially by information acquired via different combinations of attention signals at encoding. We had two groups of participants watch a 42-min TV episode and, after a 24-hr delay, perform a temporal-order judgment task during fMRI. Each retrieval trial comprised three images presented sequentially, requiring participants to judge the temporal order between the first and last images while ignoring the second image ("distractor"). We manipulated the bottom-up factor by presenting distractors that were extracted from either an event-boundary or a non-boundary of the movie. The top-down factor was manipulated by instructing one group perform a segmentation task reporting the event-boundaries at encoding, while the other group watched the movie passively. Across groups, we found that the stimulus-related factor modulated retrieval activation in the anterior rSMG (areas PFt and PFop), whereas the goal-related influence of prior segmentation interacted with this effect in the middle rSMG (area PF), demonstrating IPL segregation during retrieval as a function of prior bottom-up vs. top-down attention signals.

In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (...

ABSTRACT We present a new method for the analysis of fMRI time series. The aim is to identify functionally-relevant transient "bursts" of inter-regional coupling between brain areas, using a fully data-driven approach. We use inter-subjects synchronization (i.e. correlation between time series of different subjects who are presented with the same sensory input) to isolate relevant transients in the fMRI time series. Next, we apply a first cluster analysis to group together areas that show such synchronized activity in a concurrent manner. Finally, a second cluster analysis identifies patterns of the fMRI signal that repeat consistently across the different transients. The final output of the analysis is a set of networks that show transient patterns of functionally relevant fMRI signal, consistently over specific windows of the time series. Importantly, the fMRI signal can differ between different areas belonging to the same network. This new approach is particularly suited to investigate multi-components control processes using naturalistic stimuli during fMRI.

ABSTRACT Our sensory organs continuously receive a large amount of input from the external world; some of these are important for a successful interaction with the environment, whereas others can be ignored. The operation of selecting relevant signals and filtering out irrelevant information is a key task of the attentional system (Desimone and Duncan 1995; Kastner and Ungerleider 2001). Attentional selection can occur on the basis of many different criteria, with a main distinction between endogenous control (i.e., selection based on voluntary attention, current aims, and knowledge) and stimulus-driven control (i.e., selection based on the intrinsic features of the sensory input). Accordingly, we can decide to pay attention to the face of one person in a crowded room (i.e., attending to subtle details in a rich and complex environment), or attention can be captured by a loud sound in a quiet room (i.e., attention captured by a salient stimulus). Many different constraints can guide endogenous and stimulus-driven attention. We can voluntarily decide to attend to a specific visual feature, such as color or motion, but the very same features can guide stimulus-driven attention if they stand out from the surrounding environment (“pop-out” item, e.g., a single red stimulus presented among many green stimuli). Here, I will focus on processes related to attentional selection based on spatial location. The investigation of mechanisms of spatial attention control is appealing for many reasons. Spatial selectivity is one of the most important characteristics of single neurons (i.e., the neuron’s receptive field) and well-organized maps of space can be found throughout the brain (Gross and Graziano 1995). These include sensory areas (e.g., striate and extrastriate occipital regions, for retinotopic representations of the visual world; Tootell et al. 1982), subcortical regions [e.g., the superior colliculus (SC); Wallace et al. 1997], and higher-level associative areas in frontal and parietal cortex (e.g., Ben Hamed et al. 2001; Sommer and Wurtz 2000). This widespread selectivity for spatial locations opens the question about how/ whether these anatomically segregated representations contribute to the formation of an integrated representation of external space. Indeed, from a subjective point of view, signals about different visual features (e.g., shape/color) as well as motor commands seem to all merge effortlessly, giving rise to a coherent and unified perception–action system that allows us to interact spatially with the external environment.

Recent demonstrations of scale invariance in cognitive domains prompted us to investigate whether a scale-free pattern might exist in retrieving the temporal order of events from episodic memory. We present four experiments using an encoding-retrieval paradigm with naturalistic stimuli (movies or video clips). Our studies show that temporal order judgement retrieval times were negatively correlated with the temporal separation between two events in the movie. This relation held, irrespective of whether temporal distances were on the order of tens of minutes (Exp 1-2) or just a few seconds (Exp 3-4). Using the SIMPLE model, we factored in the retention delays between encoding and retrieval (delays of 24h, 15min, 1.5-2.5s, and 0.5s for Exp 1-4, respectively) and computed a temporal similarity score for each trial. We found a positive relation between similarity and retrieval times; that is, the more temporally similar two events, the slower the retrieval of their temporal order. Using Bayesian analysis, we confirmed the equivalence of the RT/similarity relation across all experiments, which included a vast range of temporal distances and retention delays. These results provide evidence for scale invariance during the retrieval of temporal order of episodic memories.

We investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1.5-2.5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip ("scene-chronology"), or with a correct spatial arrangement ("scene-layout"), or that had been shown ("scene-recognition"). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal-order retrieval, the superior parietal cortex was activated bilaterally for spat...

The ability to detect changes in the environment is necessary for appropriate interactions with the external world. Changes in the background go more unnoticed than foreground changes, possibly because attention prioritizes processing of foreground/near stimuli. Here, we investigated the detectability of foreground and background changes within natural scenes and the influence of stereoscopic depth cues on this. Using a flicker paradigm, we alternated a pair of images that were exactly same or differed for one single element (i.e., a color change of one object in the scene). The participants were asked to find the change that occurred either in a foreground or background object, while viewing the stimuli either with binocular and monocular cues (bmC) or monocular cues only (mC). The behavioral results showed faster and more accurate detections for foreground changes and overall better performance in bmC than mC conditions. The imaging results highlighted the involvement of fronto-pa...

The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computati...

The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments...

This review discusses how visual and the tactile signals are combined in the brain to ensure appropriate interactions with the space around the body. Visual and tactile signals converge in many regions of the brain (e.g. parietal and premotor cortices) where multisensory input can interact on the basis of specific spatial constraints. Crossmodal interactions can modulate also unisensory visual and somatosensory cortices, possibly via feed-back projections from fronto-parietal areas. These processes enable attentional selection of relevant locations in near body space, as demonstrated by studies of spatial attention in healthy volunteers and in neuropsychological patients with crossmodal extinction. These crossmodal spatial effects can be flexibly updated taking into account the position of the eyes and the limbs, thus reflecting the spatial alignment of visuo-tactile stimuli in external space. Further, studies that manipulated vision of body parts (alien, real or fake limbs) have de...

Speech perception can use not only auditory signals, but also visual information from seeing the speaker's mouth. The relative timing and relative location of auditory and visual inputs are both known to influence crossmodal integration psychologically, but previous imaging studies of audiovisual speech focused primarily on just temporal aspects. Here we used Positron Emission Tomography (PET) during audiovisual speech processing to study how temporal and spatial factors might jointly affect brain activations. In agreement with previous work, synchronous versus asynchronous audiovisual speech yielded increased activity in multisensory association areas (e.g., superior temporal sulcus [STS]), plus in some unimodal visual areas. Our orthogonal manipulation of relative stimulus position (auditory and visual stimuli presented at same location vs. opposite sides) and stimulus synchrony showed that (i) ventral occipital areas and superior temporal sulcus were unaffected by relative lo...

When two identical stimuli, such as a pair of clicks, are presented with a sufficiently long time-interval between them they are readily perceived as two separate events. However, as they are presented progressively closer together, there comes a point when the two separate stimuli are perceived as one. This phenomenon applies not only to hearing but also to other sensory

Functional asymmetries between hemispheres have been reported in relation to spatial and temporal information processing. Here we used functional magnetic resonance imaging to investigate the influence of task on activity in extrastriate areas during selective spatial attention. During bilateral visual stimulation, subjects attended either the left or the right hemifield. Within the attended side, the task was either to discriminate

The anatomical organization of the brain is such that incoming signals from different sensory modalities are initially processed in anatomically separate regions of the cortex. When these signals originate from a single event or object in the external world, it is essential that the inputs are integrated to form a coherent representation of the multisensory event. This review discusses recent data indicating that the integration of multisensory signals relies not only on anatomical convergence from sensory-specific cortices to multi-sensory brain areas but also on reciprocal influences between cortical regions that are traditionally considered as sensory-specific. These findings highlight integration mechanisms that go beyond traditional models based on a hierarchical convergence of sensory processing.

Two positron-emission tomography (PET) experiments explored the neural basis of selective spatial attention in vision and touch, testing for modality-specific versus multimodal activations due to attended side. In the first study, either light flashes or finger vibrations were presented bilaterally. Twelve healthy volunteers were scanned while sustaining covert attention on the left or right hemifield within each modality. The main effect for attending right minus left, across both modalities, revealed bimodal spatial attention effects in the left intraparietal sulcus and left occipitotemporal junction. Modality-specific attentional effects (again, for attending right vs. left) were found in the left superior occipital gyrus for vision, and left superior postcentral gyrus for touch. No significant activations were seen for attending left minus right. The second study presented only tactile stimuli, manipulating whether the eyes were open or closed, and including passive stimulation and rest baselines. The unimodal activation for tactile spatial attention in the left superior postcentral gyrus was replicated. The bimodal activation of the left intraparietal sulcus observed in the first study was now found for touch, but only when the eyes were open (hands visible), apparently confirming its multimodal nature. These results reveal mechanisms of sustained spatial attention operating at both modality-specific and multimodal levels.

Simultaneous EEG–fMRI is a powerful tool to study spontaneous and evoked brain activity because of the complementary advantages of the two techniques in terms of temporal and spatial resolution. In recent years, a significant number of scientific works have been published on this subject. However, many technical problems related to the intrinsic incompatibility of EEG and MRI methods are still

ABSTRACT In everyday life short-term memory involves processing of complex and unrepeated environments, which is in striking contrast with standard experimental paradigms typically utilizing highly stereotyped, simple and repeated stimuli. Remembering of complex visual stimuli demands a tight interplay between memory functions and attentional selection. Here, we examined this interplay during free-viewing of complex and dynamic visual scenes (8 videos, approx. 5 min each). Each video was characterized by 8 different actors/actresses who entered twice into the scene, at unpredictable times: the first appearance corresponded to the memory “encoding” phase, while the second presentation represented the memory “retrieval” phase. Participants were asked to watch the videos without any specific task-requirement. During fMRI scanning, we monitored gaze-direction and we used the tendency of the subjects to look towards each actor/actress as an index of attentional selection. Accordingly, we categorised each actors/actresses as: “high probability of selection/encoding”, when subjects fixated the actor more during the first than the second presentation; versus “low probability of selection/encoding”, when subjects fixated the actor more during the second than the first presentation. The fMRI analyses considered the second presentation of the actors/actresses (i.e. the memory retrieval phase) and compared activity for actors with “high versus low” indexes of selection. This revealed activation of fronto-parietal regions, including the inferior frontal gyrus and the intra-parietal sulcus, plus the middle temporal complex (MT+). We conclude that differential patterns of eye-movements can predict retrieval-related activation in fronto-parietal regions during passive viewing of complex and dynamic visual environments.

This study investigates abnormalities of grey (GM) and white matter (WM) in Alzheimer's disease (AD), by modeling the AD pathological process as a continuous course between normal aging and fully developed dementia, with amnesic mild cognitive impairment (aMCI) as an intermediate stage. All subjects (9 AD, 16 aMCI patients, and 13 healthy controls) underwent a full neuropsychological assessment and an MRI examination at 3 Tesla, including a volumetric scan and diffusion tensor (DT)-MRI. The volumes were processed to perform a voxel-based morphometric analysis of GM and WM volume, while DT-MRI data were analyzed using tract based spatial statistics, to estimate changes in fractional anisotropy and mean diffusivity data. GM and WM volume and mean diffusivity and fractional anisotropy were compared across the three groups, and their correlation with cognitive functions was investigated. While AD presented a pattern of widespread GM atrophy, tissue loss was more subtle in patients w...

Event-related functional magnetic resonance imaging was used to identify brain areas involved in spatial attention and determine whether these operate unimodally or supramodally for vision and touch. On a trial-by-trial basis, a symbolic auditory cue indicated the most likely side for the subsequent target, thus directing covert attention to one side. A subsequent target appeared in vision or touch on the cued or uncued side. Invalidly cued trials (as compared with valid trials) activated the temporo-parietal junction and regions of inferior frontal cortex, regardless of target modality. These brain areas have been associated with multimodal spatial coding in physiological studies of the monkey brain and were linked to a change in the location that must be attended to in the present study. The intraparietal sulcus and superior frontal cortex were also activated in our task, again, regardless of target modality, but did not show any specificity for invalidly cued trials. These results identify a supramodal network for spatial attention and reveal differential activity for inferior circuits involving the temporo-parietal junction and inferior frontal cortex (specific to invalid trials) versus more superior intraparietal-frontal circuits (common to valid and invalid trials).

In this MRI study, diffusional kurtosis imaging (DKI) and T2 * multiecho relaxometry were measured from the white matter (WM) of human brains and correlated with each other, with the aim of investigating the influence of magnetic-susceptibility (Δχ (H2O-TISSUE) ) on the contrast. We focused our in vivo analysis on assessing the dependence of mean, axial, and radial kurtosis (MK, K‖ , K⊥ ), as well as DTI indices on Δχ (H2O-TISSUE) (quantified by T2 *) between extracellular water and WM tissue molecules. Moreover, Monte Carlo (MC) simulations were used to elucidate experimental data. A significant positive correlation was observed between K⊥ , MK and R2 * = 1/T2 *, suggesting that Δχ (H2O-TISSUE) could be a source of DKI contrast. In this view, K⊥ and MK-map contrasts in human WM would not just be due to different restricted diffusion processes of compartmentalized water but also to local Δχ (H2O-TISSUE) . However, MC simulations show a strong dependence on microstructure rearrangement and a feeble dependence on Δχ (H2O-TISSUE) of DKI signal. Our results suggests a concomitant and complementary existence of multi-compartmentalized diffusion process and Δχ (H2O-TISSUE) in DKI contrast that might explain why kurtosis contrast is more sensitive than DTI in discriminating between different tissues. However, more realistic numerical simulations are needed to confirm this statement. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.