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Classical models of language localize speech perception in the left superior temporal and production in the inferior frontal cortex. Nonetheless, neuropsychological, structural and functional studies have questioned such subdivision, suggesting an interwoven organization of the speech function within these cortices. We tested whether sub-regions within frontal and temporal speech-related areas retain specific phonological representations during both perception and production. Using functional magnetic resonance imaging and multivoxel pattern analysis, we showed functional and spatial segregation across the left fronto-temporal cortex during listening, imagery and production of vowels. In accordance with classical models of language and evidence from functional studies, the inferior frontal and superior temporal cortices discriminated among perceived and produced vowels respectively, also engaging in the non-classical, alternative function – i.e. perception in the inferior frontal and production in the superior temporal cortex. Crucially, though, contiguous and non-overlapping sub-regions within these hubs performed either the classical or non-classical function, the latter also representing non-linguistic sounds (i.e., pure tones). Extending previous results and in line with integration theories, our findings not only demonstrate that sensitivity to speech listening exists in production-related regions and vice versa, but they also suggest that the nature of such interwoven organisation is built upon low-level perception.

The disembedding ability (i.e., the ability to identify a simple masked figure within a complex one) depends on attentional mechanisms, executive functions and working memory. Recent cognitive models ascribed different levels of disembedding task performance to the efficiency of the subtended mental processes engaged during visuo-spatial perception. Here we aimed at assessing whether different levels of the disembedding ability were associated to the functional signatures of neural efficiency, defined as a specific modulation in response magnitude and functional connectivity strength in task-related areas. Consequently, brain activity evoked by a visual task involving the disembedding ability was acquired using functional magnetic resonance imaging (fMRI) in a sample of 23 right-handed healthy individuals. Brain activity was analyzed at different levels of information processing, from local responses to connectivity interactions between brain nodes, as far as to network topological properties. All different levels of information processing were significantly modulated by individual behavioral performance. Specifically, single voxel response magnitude, connectivity strength of the right intrahemispheric and interhemispheric edges, and graph measures (i.e., local and global efficiency) were negatively associated to behavioral performance. Altogether, these results indicate that efficiency during a disembedding task cannot be merely attributed to a reduced neural recruitment of task-specific regions, but can be better characterized as an enhanced functional hemispherical asymmetry.

Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our’s and others' laboratories. Historically, research on the ‘blind brain’ has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen.

Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.

The control of the many degrees of freedom of the hand through functional modules (hand synergies) has been proposed as a potentially useful model to describe how the hand can maintain postures while being able to rapidly change its configuration to accomplish a wide range of tasks. However, whether and to what extent synergies are actually encoded in motor cortical areas is still debated. A direct encoding of hand synergies is suggested by electrophysiological studies in nonhuman primates, but the evidence in humans resulted, so far, partial and indirect. In this chapter, we review the organization of the brain network that controls hand posture in humans and present preliminary results of a functional Magnetic Resonance Imaging (fMRI) on the encoding of synergies at a cortical level to control hand posture in humans.

How the human brain controls hand movements to carry out different tasks is still debated. The concept of synergy has been proposed to indicate functional modules that may simplify the control of hand postures by simultaneously recruiting sets of muscles and joints. However, whether and to what extent synergic hand postures are encoded as such at a cortical level remains unknown. Here, we combined kinematic, electromyography, and brain activity measures obtained by functional magnetic resonance imaging while subjects performed a variety of movements towards virtual objects. Hand postural information, encoded through kinematic synergies, were represented in cortical areas devoted to hand motor control and successfully discriminated individual grasping movements, significantly outperforming alternative somatotopic or muscle-based models. Importantly, hand postural synergies were predicted by neural activation patterns within primary motor cortex. These findings support a novel cortical organization for hand movement control and open potential applications for brain-computer interfaces and neuroprostheses. DOI: http://dx.doi.org/10.7554/eLife.13420.001, eLife digest The human hand can perform an enormous range of movements with great dexterity. Some common everyday actions, such as grasping a coffee cup, involve the coordinated movement of all four fingers and thumb. Others, such as typing, rely on the ability of individual fingers to move relatively independently of one another. This flexibility is possible in part because of the complex anatomy of the hand, with its 27 bones and their connecting joints and muscles. But with this complexity comes a huge number of possibilities. Any movement-related task – such as picking up a cup – can be achieved via many different combinations of muscle contractions and joint positions. So how does the brain decide which muscles and joints to use? One theory is that the brain simplifies this problem by encoding particularly useful patterns of joint movements as distinct units or “synergies”. A given task can then be performed by selecting from a small number of synergies, avoiding the need to choose between huge numbers of options every time movement is required. Leo et al. now provide the first direct evidence for the encoding of synergies by the human brain. Volunteers lying inside a brain scanner reached towards virtual objects – from tennis rackets to toothpicks – while activity was recorded from the area of the brain that controls hand movements. As predicted, the scans showed specific and reproducible patterns of activity. Analysing these patterns revealed that each corresponded to a particular combination of joint positions. These activity patterns, or synergies, could even be ‘decoded’ to work out which type of movement a volunteer had just performed. Future experiments should examine how the brain combines synergies with sensory feedback to allow movements to be adjusted as they occur. Such findings could help to develop brain-computer interfaces and systems for controlling the movement of artificial limbs. DOI: http://dx.doi.org/10.7554/eLife.13420.002

Previous studies in early blind individuals posited a possible role of parieto-occipital connections in conveying nonvisual information to the visual occipital cortex. As a consequence of blindness, parietal areas would thus become able to integrate a greater amount of multimodal information than in sighted individuals. To verify this hypothesis, we compared fMRI-measured BOLD signal temporal variability, an index of efficiency in functional information integration, in congenitally blind and sighted individuals during tactile spatial discrimination and motion perception tasks. In both tasks, the BOLD variability analysis revealed many cortical regions with a significantly greater variability in the blind as compared to sighted individuals, with an overlapping cluster located in the left inferior parietal/anterior intraparietal cortex. A functional connectivity analysis using this region as seed showed stronger correlations in both tasks with occipital areas in the blind as compared to sighted individuals. As BOLD variability reflects neural integration and processing efficiency, these cross-modal plastic changes in the parietal cortex, even if described in a limited sample, reinforce the hypothesis that this region may play an important role in processing nonvisual information in blind subjects and act as a hub in the cortico-cortical pathway from somatosensory cortex to the reorganized occipital areas.

How conceptual knowledge is represented in the human brain remains to be determined. To address the differential role of low-level sensory-based and high-level abstract features in semantic processing, we combined behavioral studies of linguistic production and brain activity measures by functional magnetic resonance imaging in sighted and congenitally blind individuals while they performed a property-generation task with concrete nouns from eight categories, presented through visual and/or auditory modalities.Patterns of neural activity within a large semantic cortical network that comprised parahippocampal, lateral occipital, temporo-parieto-occipital and inferior parietal cortices correlated with linguistic production and were independent both from the modality of stimulus presentation (either visual or auditory) and the (lack of) visual experience. In contrast, selected modality-dependent differences were observed only when the analysis was limited to the individual regions within the semantic cortical network.We conclude that conceptual knowledge in the human brain relies on a distributed, modality-independent cortical representation that integrates the partial category and modality specific information retained at a regional level.

Sources of noise in resting-state fMRI experiments include instrumental and physiological noises, which need to be filtered before a functional connectivity analysis of brain regions is performed. These noisy components show autocorrelated and nonstationary properties that limit the efficacy of standard techniques (i.e. time filtering and general linear model). Herein we describe a novel approach based on the combination of singular spectrum analysis and adaptive filtering, which allows a greater noise reduction and yields better connectivity estimates between regions at rest, providing a new feasible procedure to analyze fMRI data.

Enhancing cholinergic function improves performance on various cognitive tasks and alters neural responses in task specific brain regions. We have hypothesized that the changes in neural activity observed during increased cholinergic function reflect an increase in neural efficiency that leads to improved task performance. The current study tested this hypothesis by assessing neural efficiency based on cholinergically-mediated effects on regional brain connectivity and BOLD signal variability. Nine subjects participated in a double-blind, placebo-controlled crossover fMRI study. Following an infusion of physostigmine (1 mg/h) or placebo, echo-planar imaging (EPI) was conducted as participants performed a selective attention task. During the task, two images comprised of superimposed pictures of faces and houses were presented. Subjects were instructed periodically to shift their attention from one stimulus component to the other and to perform a matching task using hand held response buttons. A control condition included phase-scrambled images of superimposed faces and houses that were presented in the same temporal and spatial manner as the attention task; participants were instructed to perform a matching task. Cholinergic enhancement improved performance during the selective attention task, with no change during the control task. Functional connectivity analyses showed that the strength of connectivity between ventral visual processing areas and task-related occipital, parietal and prefrontal regions reduced significantly during cholinergic enhancement, exclusively during the selective attention task. Physostigmine administration also reduced BOLD signal temporal variability relative to placebo throughout temporal and occipital visual processing areas, again during the selective attention task only. Together with the observed behavioral improvement, the decreases in connectivity strength throughout task-relevant regions and BOLD variability within stimulus processing regions support the hypothesis that cholinergic augmentation results in enhanced neural efficiency. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.

Potentiation of cholinergic transmission influences stimulus processing by enhancing signal detection through suppression and/or filtering out of irrelevant information (bottom-up modulation) and with top-down task-oriented executive mechanisms based on the recruitment of prefrontal and parietal attentional systems. The cholinergic system also plays a critical role in working memory (WM) processes and preferentially modulates WM encoding, likely through stimulus-processing mechanisms. Previous research reported increased brain responses in visual extrastriate cortical regions during cholinergic enhancement in the encoding phase of WM, independently addressing object and spatial encoding. The current study used functional magnetic resonance imaging to determine the effects of cholinergic enhancement on encoding of key visual processing features. Subjects participated in two scanning sessions, one during an intravenous (i.v.) infusion of saline and the other during an infusion of the acetylcholinesterase inhibitor physostigmine. In each scan session, subjects alternated between a face identity recognition and a spatial location WM. Enhanced cholinergic function increased neural activity in the ventral stream during encoding of face identity and in the dorsal stream during encoding of face location. Conversely, a reduction in brain response was found for scrambled sensorimotor control images. The cholinergic effects on neural activity in the ventral stream during encoding of face identity were stronger than those observed in the dorsal stream during encoding of face location, likely as a consequence of the role of acetylcholine in establishing the inherently relevant nature of face identity. Despite the limited sample-size, the results suggest the stimulus-dependent role of cholinergic system in signal detection, as they show that cholinergic potentiation enhances neural activity in regions associated with early perceptual processing in a selective manner depending on the attended stimulus feature.

In the presence of vision, finalized motor acts can trigger spatial remapping, i.e., reference frames transformations to allow for a better interaction with targets. However, it is yet unclear how the peripersonal space is encoded and remapped depending on the availability of visual feedback and on the target position within the individual's reachable space, and which cerebral areas subserve such processes. Here, functional magnetic resonance imaging (fMRI) was used to examine neural activity while healthy young participants performed reach-to-grasp movements with and without visual feedback and at different distances of the target from the effector (near to the hand-about 15 cm from the starting position-vs. far from the hand-about 30 cm from the starting position). Brain response in the superior parietal lobule bilaterally, in the right dorsal premotor cortex, and in the anterior part of the right inferior parietal lobule was significantly greater during visually-guided grasping of targets located at the far distance compared to grasping of targets located near to the hand. In the absence of visual feedback, the inferior parietal lobule exhibited a greater activity during grasping of targets at the near compared to the far distance. Results suggest that in the presence of visual feedback, a visuo-motor circuit integrates visuo-motor information when targets are located farther away. Conversely in the absence of visual feedback, encoding of space may demand multisensory remapping processes, even in the case of more proximal targets.

The representation of actions within the action-observation network is thought to rely on a distributed functional organization. Furthermore, recent findings indicate that the action-observation network encodes not merely the observed motor act, but rather a representation that is independent from a specific sensory modality or sensory experience. In the present study, we wished to determine to what extent this distributed and 'more abstract' representation of action is truly supramodal, i.e. shares a common coding across sensory modalities. To this aim, a pattern recognition approach was employed to analyze neural responses in sighted and congenitally blind subjects during visual and/or auditory presentation of hand-made actions. Multivoxel pattern analyses-based classifiers discriminated action from non-action stimuli across sensory conditions (visual and auditory) and experimental groups (blind and sighted). Moreover, these classifiers labeled as 'action' the pattern of neural responses evoked during actual motor execution. Interestingly, discriminative information for the action/non action classification was located in a bilateral, but left-prevalent, network that strongly overlaps with brain regions known to form the action-observation network and the human mirror system. The ability to identify action features with a multivoxel pattern analyses-based classifier in both sighted and blind individuals and independently from the sensory modality conveying the stimuli clearly supports the hypothesis of a supramodal, distributed functional representation of actions, mainly within the action-observation network.

Functional magnetic resonance imaging (fMRI) is used to study brain functional connectivity (FC) after filtering the physiological noise (PN). Herein, we employ: adaptive filtering for removing nonstationary PN; random variables (RV) coefficient for FC analysis. Comparisons with standard techniques were performed by quantifying PN filtering and FC in neural vs. non-neural regions. As a result, adaptive filtering plus RV coefficient showed a greater suppression of PN and higher connectivity in neural regions, representing a novel effective approach to analyze fMRI data.

fMRI is used to investigate brain functional connectivity after removing nonneural components by General Linear Model (GLM) approach with a reference ventricle-derived signal as covariate. Ventricle signals are related to low-frequency modulations of cardiac and respiratory rhythms, which are nonstationary activities. Herein, we employed an adaptive filtering approach to improve removing physiological noise from BOLD signals. Comparisons between filtering approaches were performed by evaluating the amount of removed signal variance and the connectivity between homologous contralateral regions of interest (ROIs). The global connectivity between ROIs was estimated with a generalized correlation named RV coefficient. The mean ROI decrease of variance was •52% and •11%, for adaptive filtering and GLM, respectively. Adaptive filtering led to higher connectivity between grey matter ROIs than that obtained with GLM. Thus, adaptive filtering is a feasible method for removing the physiological noise in the low frequency band and to highlight resting state functional networks.

Mechanisms of cortical reorganization underlying the enhancement of speech processing have been poorly investigated. In the present study, we addressed changes in functional and effective connectivity induced in subjects who learned to deliberately increase activation in the right inferior frontal gyrus (rIFG), and improved their ability to identify emotional intonations by using a real-time fMRI Brain-Computer Interface. At the beginning of their training process, we observed a massive connectivity of the rIFG to a widespread network of frontal and temporal areas, which decreased and lateralized to the right hemisphere with practice. Volitional control of activation strengthened connectivity of this brain region to the right prefrontal cortex, whereas training increased its connectivity to bilateral precentral gyri. These findings suggest that changes of connectivity in a functionally specific manner play an important role in the enhancement of speech processing. Also, these findings support previous accounts suggesting that motor circuits play a role in the comprehension of speech.

Spontaneous cerebral blood oxygenation level-dependent (BOLD) fluctuations are gaining interest in the neurophysiology community. These oscillations are prominent in the low-frequency range with spatiotemporal correlations. From a healthy individual, a basal resting state BOLD fMRI acquisition has been performed by collecting 4 slices. Voxel signals from seven selected regions have been considered. We assumed a composite null-hypothesis of oscillations embedded in “red noise”. To extract oscillations from BOLD signals we applied the Monte Carlo Singular Spectrum Analysis (SSA). Phase-synchronization of the oscillatory components, in the low-frequency range 0.085-0.13Hz, have been also achieved. As results, region-dependent distributions were apparent both for the noise parameters and for the number of connections between voxels. Although further studies on population samples should confirm the result consistency, the SSA technique combined with a phase-synchronization analysis seems a feasible method to extract low frequency BOLD spontaneous oscillations and to find functional connections among cerebral areas.