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.

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.

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.

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.

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.

Object size modulates fronto-parietal activity during reaching movements.

In both monkeys and humans, reaching-related sensorimotor transformations involve the activation of a wide fronto-parietal network. Recent neurophysiological evidence suggests that some components of this network host not only neurons encoding the direction of arm reaching movements, but also neurons whose involvement is modulated by the intrinsic features of an object (e.g. size and shape). To date, it has yet to be investigated whether a similar modulation is evident in the human reaching-related areas. To fill this gap, we asked participants to reach towards either a small or a large object while kinematic and electroencephalographic signals were recorded. Behavioral results showed that the precision requirements were taken into account and the kinematics of reaching was modulated depending on the object size. Similarly, reaching-related neural activity at the level of the posterior parietal and premotor cortices was modulated by the level of accuracy determined by object size. We therefore conclude that object size is engaged in the neural computations for reach planning and execution, consistent with the results from physiological studies in non-human primates.

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.

Social grasping: from mirroring to mentalizing.

Because the way we grasp an object varies depending on the intention with which the object is grasped, monitoring the properties of prehensile movements may provide access to a person's intention. Here we investigate the role of visual kinematics in the implicit coding of intention, by using functional brain imaging while participants observed grasping movements performed with social versus individual intents. The results show that activation within the mirror system is stronger during the observation of socially intended movements relative to individual movements. Moreover, areas that form the mentalizing system are more active during social grasping movements. These findings demonstrate that, in the absence of context information, social information conveyed by action kinematics modulates intention processing, leading to a transition from mirroring to mentalizing.

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.

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.

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.

Coding observed motor acts: different organizational principles in the parietal and premotor cortex of humans.

Understanding actions of conspecifics is a fundamental social ability depending largely on the activation of a parieto-frontal network. Using functional MRI (fMRI), we studied how goal-directed movements (i.e., motor acts) performed by others are coded within this network. In the first experiment, we presented volunteers with video clips showing four different motor acts (dragging, dropping, grasping, and pushing) performed with different effectors (foot, hand, and mouth). We found that the coding of observed motor acts differed between premotor and parietal cortex. In the premotor cortex, they clustered according to the effector used, and in the inferior parietal lobule (IPL), they clustered according to the type of the observed motor act, regardless of the effector. Two subsequent experiments in which we directly contrasted these four motor acts indicated that, in IPL, the observed motor acts are coded according to the relationship between agent and object: Movements bringing the object toward the agent (grasping and dragging) activate a site corresponding approximately to the ventral part of the putative human AIP (phAIP), whereas movements moving the object away from the agent (pushing and dropping) are clustered dorsally within this area. These data provide indications that the phAIP region plays a role in categorizing motor acts according to their behavioral significance. In addition, our results suggest that in the case of motor acts typically done with the hand, the representations of such acts in phAIP are used as templates for coding motor acts executed with other effectors.

Testing the effects of end-goal during reach-to-grasp movements in Parkinson's disease.

Previous evidence suggests that hand shaping during reaching is modulated by the presence and the nature of the end-goal following object's grasp. Here we test whether such modulation is maintained in Parkinson's disease (PD). Six participants with PD and six healthy participants took part in the study. Participants were requested to reach towards a bottle filled with water, and then: (1) grasp it without performing any subsequent action; (2) grasp it and place it accurately on a target area; (3) grasp it and pour its contents within a container. The results showed that participants shaped their hand differently depending on the presence or absence of an action following object's grasp. However, the request to perform an action after grasp determined a modulation of hand kinematics which was delayed for PD than for control participants. Further, whereas for control participants the nature of the end-goal determined a modulation of hand shaping, for PD patients such modulation was not evident. Data are discussed in terms of the role played by basal ganglia in implementing anticipatory mechanisms for the control of manipulative activities. We contend that in PD patients these mechanisms are not totally compromised, but their implementation depends on the action information that has to be anticipated.

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.

The cortical control of visually guided grasping.

People have always been fascinated by the exquisite precision and flexibility of the human hand. When hand meets object, we confront the overlapping worlds of sensorimotor and cognitive functions. The complex apparatus of the human hand is used to reach for objects, grasp and lift them, manipulate them, and use them to act on other objects. This review examines what is known about the control of the hand by the cerebral cortex. It compares and summarizes results from behavioral neuroscience, electrophysiology, and neuroimaging to provide a detailed description of the neural circuits that facilitate the formation of grip patterns in human and nonhuman primates.

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.

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.