The Role of Cognitive Reserve in Protecting Cerebellar Volumes of Older Adults with mild Cognitive Impairment.

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.

The effect of emotion intensity on time perception: a study with transcranial random noise stimulation.

Emotional facial expressions provide cues for social interactions and emotional events can distort our sense of time. The present study investigates the effect of facial emotional stimuli of anger and sadness on time perception. Moreover, to investigate the causal role of the orbitofrontal cortex (OFC) in emotional recognition, we employed transcranial random noise stimulation (tRNS) over OFC and tested the effect on participants' emotional recognition as well as on time processing. Participants performed a timing task in which they were asked to categorize as "short" or "long" temporal intervals marked by images of people expressing anger, sad or neutral emotional facial expressions. In addition, they were asked to judge if the image presented was of a person expressing anger or sadness. The visual stimuli were facial emotional stimuli indicating anger or sadness with different degrees of intensity at high (80%), medium (60%) and low (40%) intensity, along with neutral emotional face stimuli. In the emotional recognition task, results showed that participants were faster and more accurate when emotional intensity was higher. Moreover, tRNS over OFC interfered with emotion recognition, which is in line with its proposed role in emotion recognition. In the timing task, participants overestimated the duration of angry facial expressions, although neither emotional intensity not OFC stimulation significantly modulated this effect. Conversely, as the emotional intensity increased, participants exhibited a greater tendency to overestimate the duration of sad faces in the sham condition. However, this tendency disappeared with tRNS. Taken together, our results are partially consistent with previous findings showing an overestimation effect of emotionally arousing stimuli, revealing the involvement of OFC in emotional distortions of time, which needs further investigation.

When Corticospinal Inhibition Favors an Efficient Motor Response.

Many daily activities involve responding to the actions of other people. However, the functional relationship between the motor preparation and execution phases still needs to be clarified. With the combination of different and complementary experimental techniques (i.e., motor excitability measures, reaction times, electromyography, and dyadic 3-D kinematics), we investigated the behavioral and neurophysiological signatures characterizing different stages of a motor response in contexts calling for an interactive action. Participants were requested to perform an action (i.e., stirring coffee or lifting a coffee cup) following a co-experimenter's request gesture. Another condition, in which a non-interactive gesture was used, was also included. Greater corticospinal inhibition was found when participants prepared their motor response after observing an interactive request, compared to a non-interactive gesture. This, in turn, was associated with faster and more efficient action execution in kinematic terms (i.e., a social motor priming effect). Our results provide new insights on the inhibitory and facilitatory drives guiding social motor response generation. Altogether, the integration of behavioral and neurophysiological indexes allowed us to demonstrate that a more efficient action execution followed a greater corticospinal inhibition. These indexes provide a full picture of motor activity at both planning and execution stages.

Structure of the Motor Descending Pathways Correlates with the Temporal Kinematics of Hand Movements.

The projection system, a complex organization of ascending and descending white matter pathways, is the principal system for conveying sensory and motor information, connecting frontal and sensorimotor regions with ventral regions of the central nervous system. The corticospinal tract (CST), one of the principal projection pathways, carries distal movement-related information from the cortex to the spinal cord, and whether its microstructure is linked to the kinematics of hand movements is still an open question. The aim of the present study was to explore how microstructure of descending branches of the projection system, namely the hand motor tract (HMT), the corticospinal tract (CST) and its sector within the internal capsule (IC), can relate to the temporal profile of reaching and reach-to-grasp movements. Projection pathways of 31 healthy subjects were virtually dissected by means of diffusion tractography and the kinematics of reaching and reach-to-grasp movements were also analyzed. A positive association between Hindrance Modulated Orientation Anisotropy (HMOA) and kinematics was observed, suggesting that anisotropy of the considered tract can influence the temporal unfolding of motor performance. We highlight, for the first time, that hand kinematics and the visuomotor transformation processes underlying reaching and reach-to-grasp movements relate to the microstructure of specific projection fibers subserving these movements.

Neuroanatomical Correlates of Binge-Eating Behavior: At the Roots of Unstoppable Eating.

Binge-eating refers to episodes of uncontrolled eating accompanied by a perceived loss of control, which can be common in the general population. Given the profound negative consequences of persistent binge-eating such as weight and eating disorders, it is vital to determine what makes someone more vulnerable than others to engage in such a conduct. A total of 42 normal-weight individuals (21 with binge-eating episodes and 21 without binge-eating episodes) underwent a structural magnetic resonance imaging measurement and Voxel-based morphometry (VBM) was used to assess between-group differences in terms of gray matter volume (GMV), together with self-report impulsivity and binge-eating measures. The results showed binge-eating individuals as characterized by higher trait impulsivity and greater regional GMV in the left middle frontal gyrus: however, the GMV in this region appeared to be positively correlated only with measures of binge-eating but not with trait impulsivity measures. These findings provide novel insights on the neurobiological roots of BE in normal-weight individuals and highlight how this behavior can be associated with brain morphometric changes within prefrontal regions also in a non-clinical population. Overall, this study provides a further characterization of the neural correlates of binge-eating and novel insights into the treatment of its more severe pathological forms.

Reach-to-Grasp: A Multisensory Experience.

The reach-to-grasp movement is ordinarily performed in everyday living activities and it represents a key behavior that allows humans to interact with their environment. Remarkably, it serves as an experimental test case for probing the multisensory architecture of goal-oriented actions. This review focuses on experimental evidence that enhances or modifies how we might conceptualize the "multisensory" substrates of prehension. We will review evidence suggesting that how reach-to-grasp movements are planned and executed is influenced by information coming from different sensory modalities such as vision, proprioception, audition, taste, and olfaction. The review closes with some considerations about the predominant role of the multisensory constituents in shaping prehensile behavior and how this might be important for future research developments, especially in the rehabilitative domain.

Handedness and White Matter Networks.

The development and persistence of laterality is a key feature of human motor behavior, with the asymmetry of hand use being the most prominent. The idea that asymmetrical functions of the hands reflect asymmetries in terms of structural and functional brain organization has been tested many times. However, despite advances in laterality research and increased understanding of this population-level bias, the neural basis of handedness remains elusive. Recent developments in diffusion magnetic resonance imaging enabled the exploration of lateralized motor behavior also in terms of white matter and connectional neuroanatomy. Despite incomplete and partly inconsistent evidence, structural connectivity of both intrahemispheric and interhemispheric white matter seems to differ between left and right-handers. Handedness was related to asymmetry of intrahemispheric pathways important for visuomotor and visuospatial processing (superior longitudinal fasciculus), but not to projection tracts supporting motor execution (corticospinal tract). Moreover, the interindividual variability of the main commissural pathway corpus callosum seems to be associated with handedness. The review highlights the importance of exploring new avenues for the study of handedness and presents the latest state of knowledge that can be used to guide future neuroscientific and genetic research.

Metacognition in individuals recovered from anorexia nervosa: a voxel-based morphometry study.

Recent evidence shows that individuals with Anorexia Nervosa (AN) can be characterized by dysfunctional metacognition as well as reductions of gray matter volumes (GMV) in prefrontal brain regions involved in cognitive processes. However, whether these differences are reversible or stable markers has yet to be understood. Thus, we aimed at characterizing metacognition and brain morphometry in individuals recovered from AN (rec-AN). A combined psychometric-brain morphometry investigation on metacognitive functioning in rec-AN individuals was conducted. Fifteen healthy controls (HC) and fifteen rec-AN women underwent a psychometric assessment for metacognitive functioning and a high-resolution T1-weighted Magnetic Resonance Imaging measurement to assess global and regional brain volumes, using Voxel-Based Morphometry. The two groups did not differ for metacognitive functioning and GMV, while regional GMV reductions were observed in rec-AN compared to HC in the left Inferior Frontal Gyrus (IFG). While changes in metacognitive abilities may not represent a stable trait of AN, regional GMV reductions in brain regions devoted to specific cognitive functions, such as inhibitory/top-down control processes, can act as a neurobiological fingerprint for such condition. These findings can represent a promising hint for future investigations on the maintaining factors of AN.

Characterizing impulsivity and resting-state functional connectivity in normal-weight binge eaters.

OBJECTIVE: Binge eating is characterized by episodes of uncontrolled eating, within discrete periods of time. Although it is usually described in obese individuals or as a symptom of Binge Eating Disorder (BED), this behavior can also occur in the normal-weight (NW) population. An interesting premise suggests that impulsivity might contribute to the onset of binge eating and the progression toward weight gain. Drawing upon this evidence, here we explored impulsivity in NW individuals reporting binge-eating episodes through a functional connectivity approach. We hypothesized that, even in the absence of an eating disorder, NW binge eaters would be characterized by connectivity pattern changes in corticostriatal regions implicated in impulsivity, similarly to the results described in BED individuals. METHODS: A resting-state functional magnetic resonance imaging study tested 39 NW men and women, with and without binge eating (binge eaters, BE and non-BE). Brain functional connectivity was explored by means of graph theoretic centrality measures and traditional seed-based analysis; trait impulsivity was assessed with self-report questionnaires. RESULTS: The BE group was characterized by a higher degree of trait impulsivity. Brain functional connectivity measures revealed lower degree centrality within the right middle frontal gyrus, left insula/putamen and left temporoparietal regions and a lower functional connectivity between the right middle frontal gyrus and right insula in the BE group. DISCUSSION: The results support previous evidence on BED of altered functional connectivity and higher impulsivity at the roots of overeating behavior, but further extend this concept excluding any potential confounding effect exerted by the weight status.

The effect of mental countermeasures on neuroimaging-based concealed information tests.

During the last decade and a half, functional magnetic resonance imaging (fMRI) has been used to determine whether it is possible to detect concealed knowledge by examining brain activation patterns, with mixed results. Concealed information tests rely on the logic that a familiar item (probe) elicits a stronger response than unfamiliar, but otherwise comparable items (irrelevants). Previous work has shown that physical countermeasures can artificially modulate neural responses in concealed information tests, decreasing the accuracy of these methods. However, the question remains as to whether purely mental countermeasures, which are much more difficult to detect than physical ones, can also be effective. An fMRI study was conducted to address this question by assessing the effect of attentional countermeasures on the accuracy of the classification between knowledge and no-knowledge cases using both univariate and multivariate analyses. Results replicate previous work and show reliable group activation differences between the probe and the irrelevants in fronto-parietal networks. Critically, classification accuracy was generally reduced by the mental countermeasures, but only significantly so with region of interest analyses (both univariate and multivariate). For whole-brain analyses, classification accuracy was relatively low, but it was not significantly reduced by the countermeasures. These results indicate that mental countermeasure need to be addressed before these paradigms can be used in applied settings and that methods to defeat countermeasures, or at least to detect their use, need to be developed. HIGHLIGHTS: FMRI-based concealed information tests are vulnerable to mental countermeasures Measures based on regions of interest are affected by mental countermeasures Whole-brain analyses may be more robust than region of interest ones Methods to detect mental countermeasure use are needed for forensic applications.

The Neural Correlates of Grasping in Left-Handers: When Handedness Does Not Matter.

Neurophysiological studies showed that in macaques, grasp-related visuomotor transformations are supported by a circuit involving the anterior part of the intraparietal sulcus, the ventral and the dorsal region of the premotor area. In humans, a similar grasp-related circuit has been revealed by means of neuroimaging techniques. However, the majority of "human" studies considered movements performed by right-handers only, leaving open the question of whether the dynamics underlying motor control during grasping is simply reversed in left-handers with respect to right-handers or not. To address this question, a group of left-handed participants has been scanned with functional magnetic resonance imaging while performing a precision grasping task with the left or the right hand. Dynamic causal modeling was used to assess how brain regions of the two hemispheres contribute to grasping execution and whether the intra- and inter-hemispheric connectivity is modulated by the choice of the performing hand. Results showed enhanced inter-hemispheric connectivity between anterior intraparietal and dorsal premotor cortices during grasping execution with the left dominant hand (LDH) (e.g., right hemisphere) compared to the right (e.g., left hemisphere). These findings suggest that that the left hand, although dominant and theoretically more skilled in left handers, might need additional resources in terms of the visuomotor control and on-line monitoring to accomplish a precision grasping movement. The results are discussed in light of theories on the modulation of parieto-frontal networks during the execution of prehensile movements, providing novel evidence supporting the hypothesis of a handedness-independent specialization of the left hemisphere in visuomotor control.

Effects of intentionality and subliminal information in free-choices to inhibit.

Stopping an action at the very last moment is an important feature of human behavioural flexibility. Intentional inhibition has been defined as the ability to inhibit an action on the basis of an internal decision process. Without this ability, actions would be impulsive and would leave little space to correct misguided decisions. Previous research suggests that making a choice between action alternatives activates a specific "choice network" that includes the rostral cingulate zone (RCZ), the anterior insula (AI), the dorsolateral prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). The activity of this network has shown to be influenced by non-conscious (subliminal) stimuli. In this study, we tested whether the same regions are recruited by free-choices to inhibit and modulated by unconscious information as reported in the case of free-choices to act. Using functional magnetic resonance imaging (fMRI) we manipulated the degree of 'freedom' of the choice between acting and inhibiting an action by introducing explicit cues or leaving the participants free to choose between action alternatives. We included subliminal masked primes to test whether responses to targets were facilitated and/or obstructed by conditions of congruency and incongruency between primes and targets. Our findings confirmed higher activation of the "choice network" in free-choice trials when compared to cued choices. However subliminal priming failed to significantly influence participants' responses, in free-choice conditions.

Potential for social involvement modulates activity within the mirror and the mentalizing systems.

Processing biological motion is fundamental for everyday life activities, such as social interaction, motor learning and nonverbal communication. The ability to detect the nature of a motor pattern has been investigated by means of point-light displays (PLD), sets of moving light points reproducing human kinematics, easily recognizable as meaningful once in motion. Although PLD are rudimentary, the human brain can decipher their content including social intentions. Neuroimaging studies suggest that inferring the social meaning conveyed by PLD could rely on both the Mirror Neuron System (MNS) and the Mentalizing System (MS), but their specific role to this endeavor remains uncertain. We describe a functional magnetic resonance imaging experiment in which participants had to judge whether visually presented PLD and videoclips of human-like walkers (HL) were facing towards or away from them. Results show that coding for stimulus direction specifically engages the MNS when considering PLD moving away from the observer, while the nature of the stimulus reveals a dissociation between MNS -mainly involved in coding for PLD- and MS, recruited by HL moving away. These results suggest that the contribution of the two systems can be modulated by the nature of the observed stimulus and its potential for social involvement.

Decoding social intentions in human prehensile actions: Insights from a combined kinematics-fMRI study.

Consistent evidence suggests that the way we reach and grasp an object is modulated not only by object properties (e.g., size, shape, texture, fragility and weight), but also by the types of intention driving the action, among which the intention to interact with another agent (i.e., social intention). Action observation studies ascribe the neural substrate of this 'intentional' component to the putative mirror neuron (pMNS) and the mentalizing (MS) systems. How social intentions are translated into executed actions, however, has yet to be addressed. We conducted a kinematic and a functional Magnetic Resonance Imaging (fMRI) study considering a reach-to-grasp movement performed towards the same object positioned at the same location but with different intentions: passing it to another person (social condition) or putting it on a concave base (individual condition). Kinematics showed that individual and social intentions are characterized by different profiles, with a slower movement at the level of both the reaching (i.e., arm movement) and the grasping (i.e., hand aperture) components. fMRI results showed that: (i) distinct voxel pattern activity for the social and the individual condition are present within the pMNS and the MS during action execution; (ii) decoding accuracies of regions belonging to the pMNS and the MS are correlated, suggesting that these two systems could interact for the generation of appropriate motor commands. Results are discussed in terms of motor simulation and inferential processes as part of a hierarchical generative model for action intention understanding and generation of appropriate motor commands.

Intentional binding as a marker of agency across the lifespan.

The feeling of control over actions and their external effects is known as Sense of Agency (SoAg). People usually have a distinctive SoAg for events caused by their own actions. However, if the agent is a child or an older person, this feeling of being responsible for the consequences of an action may differ from what an adult would feel. The idea would be that children and elderly may have a reduced SoAg since their frontal lobes are developing or have started to loose their efficiency. The aim of this study was to elucidate whether the SoAg changes across lifespan, using the Intentional Binding (i.e., the temporal attraction between a voluntary action and its sensory consequence) as implicit measure. Data show that children and elderly are characterized by a reduced SoAg as compared to adults. These findings provide a fundamental step in the characterization of SoAg dynamics throughout individuals' lifetime.

Asymmetry and Structure of the Fronto-Parietal Networks Underlie Visuomotor Processing in Humans.

Research in both humans and monkeys has shown that even simple hand movements require cortical control beyond primary sensorimotor areas. An extensive functional neuroimaging literature demonstrates the key role that cortical fronto-parietal regions play for movements such as reaching and reach-to-grasp. However, no study so far has examined the specific white matter connections linking the fronto-parietal regions, namely the 3 parallel pathways of the superior longitudinal fasciculus (SLF). The aim of the current study was to explore how selective fronto-parietal connections are for different kinds of hand movement in 30 right-handed subjects by correlating diffusion imaging tractography and kinematic data. We showed that a common network, consisting of bilateral SLF II and SLF III, was involved in both reaching and reach-to-grasp movements. Larger SLF II and SLF III in the right hemisphere were associated with faster speed of visuomotor processing, while the left SLF II and SLF III played a role in the initial movement trajectory control. Furthermore, the right SLF II was involved in the closing grip phase necessary for efficient grasping of the object. We demonstrated for the first time that individual differences in asymmetry and structure of the fronto-parietal networks were associated with visuomotor processing in humans.

Probing the reaching-grasping network in humans through multivoxel pattern decoding.

INTRODUCTION: The quest for a putative human homolog of the reaching-grasping network identified in monkeys has been the focus of many neuropsychological and neuroimaging studies in recent years. These studies have shown that the network underlying reaching-only and reach-to-grasp movements includes the superior parieto-occipital cortex (SPOC), the anterior part of the human intraparietal sulcus (hAIP), the ventral and the dorsal portion of the premotor cortex, and the primary motor cortex (M1). Recent evidence for a wider frontoparietal network coding for different aspects of reaching-only and reach-to-grasp actions calls for a more fine-grained assessment of the reaching-grasping network in humans by exploiting pattern decoding methods (multivoxel pattern analysis--MVPA). METHODS: Here, we used MPVA on functional magnetic resonance imaging (fMRI) data to assess whether regions of the frontoparietal network discriminate between reaching-only and reach-to-grasp actions, natural and constrained grasping, different grasp types, and object sizes. Participants were required to perform either reaching-only movements or two reach-to-grasp types (precision or whole hand grasp) upon spherical objects of different sizes. RESULTS: Multivoxel pattern analysis highlighted that, independently from the object size, all the selected regions of both hemispheres contribute in coding for grasp type, with the exception of SPOC and the right hAIP. Consistent with recent neurophysiological findings on monkeys, there was no evidence for a clear-cut distinction between a dorsomedial and a dorsolateral pathway that would be specialized for reaching-only and reach-to-grasp actions, respectively. Nevertheless, the comparison of decoding accuracy across brain areas highlighted their different contributions to reaching-only and grasping actions. CONCLUSIONS: Altogether, our findings enrich the current knowledge regarding the functional role of key brain areas involved in the cortical control of reaching-only and reach-to-grasp actions in humans, by revealing novel fine-grained distinctions among action types within a wide frontoparietal network.

Neural underpinnings of the 'agent brain': new evidence from transcranial direct current stimulation.

Intentional binding (IB) refers to the temporal compression between a voluntary action and its sensory effect, and it is considered an implicit measure of sense of agency (SoA), that is, the capacity to control one's own actions. IB has been thoroughly studied from a behavioural point of view but only few studies have investigated its neural underpinnings, always using the same two paradigms. Although providing evidence that the supplementary motor complex is involved, findings are still too scarce to draw definitive conclusions. The aim of the present study was to establish a causal relationship between the pre-supplementary motor area (pre-SMA), known for its key role in action planning and initiation, and IB by means of transcranial direct current stimulation (tDCS). Participants underwent anodal, cathodal and sham control stimulations during three separate sessions (Experiment I). Subsequently, they underwent the same stimulation protocol (Experiment II) using as control a region potentially involved in the processing of the sensory effects of voluntary action (i.e., the right primary auditory cortex for the auditory effects of action). A significant reduction in IB was found only after stimulation of the pre-SMA, which supports the causal contribution of this prefrontal area in the perceived linkage between action and its effects. As SoA could be disrupted in many psychiatric and neurological diseases, these results have direct clinical relevance as tDCS could be successfully used in this domain in virtue of the promising advantages it offers for rehabilitation.

Exploring manual asymmetries during grasping: a dynamic causal modeling approach.

Recording of neural activity during grasping actions in macaques showed that grasp-related sensorimotor transformations are accomplished in a circuit constituted by the anterior part of the intraparietal sulcus (AIP), the ventral (F5) and the dorsal (F2) region of the premotor area. In humans, neuroimaging studies have revealed the existence of a similar circuit, involving the putative homolog of macaque areas AIP, F5, and F2. These studies have mainly considered grasping movements performed with the right dominant hand and only a few studies have measured brain activity associated with a movement performed with the left non-dominant hand. As a consequence of this gap, how the brain controls for grasping movement performed with the dominant and the non-dominant hand still represents an open question. A functional magnetic resonance imaging (fMRI) experiment has been conducted, and effective connectivity (dynamic causal modeling, DCM) was used to assess how connectivity among grasping-related areas is modulated by hand (i.e., left and right) during the execution of grasping movements toward a small object requiring precision grasping. Results underlined boosted inter-hemispheric couplings between dorsal premotor cortices during the execution of movements performed with the left rather than the right dominant hand. More specifically, they suggest that the dorsal premotor cortices may play a fundamental role in monitoring the configuration of fingers when grasping movements are performed by either the right and the left hand. This role becomes particularly evident when the hand less-skilled (i.e., the left hand) to perform such action is utilized. The results are discussed in light of recent theories put forward to explain how parieto-frontal connectivity is modulated by the execution of prehensile movements.

The left side of motor resonance.

Motor resonance is defined as the internal activation of an observer's motor system, specifically attuned to the perceived movement. In social contexts, however, different patterns of observed and executed muscular activation are frequently required. This is the case, for instance, of seeing a key offered with a precision grip and received by opening the hand. Novel evidence suggests that compatibility effects in motor resonance can be altered by social response preparation. What is not known is how handedness modulates this effect. The present study aimed at determining how a left- and a right-handed actor grasping an object and then asking for a complementary response influences corticospinal activation in left- and right-handers instructed to observe the scene. Transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) were thus recorded from the dominant hands of left- and right-handers. Interestingly, requests posed by the right-handed actor induced a motor activation in the participants' respective dominant hands, suggesting that left-handers tend to mirror right-handers with their most efficient hand. Whereas requests posed by the left-handed actor activated the anatomically corresponding muscles (i.e., left hand) in all the participants, right-handers included. Motor resonance effects classically reported in the literature were confirmed when observing simple grasping actions performed by the right-handed actor. These findings indicate that handedness influences both congruent motor resonance and complementary motor preparation to observed actions.