Brain activation during processing of mouth actions in patients with disorders of consciousness.

In the past 2 decades, several attempts have been made to promote a correct diagnosis and possible restorative interventions in patients suffering from disorders of consciousness. Sensory stimulation has been proved to be useful in sustaining the level of arousal/awareness and to improve behavioural responsiveness with a significant effect on oro-motor functions. Recently, action observation has been proposed as a stimulation strategy in patients with disorders of consciousness, based on neurophysiological evidence that the motor cortex can be activated not only during action execution but also when actions are merely observed in the absence of motor output, or during listening to action sounds and speech. This mechanism is provided by the activity of mirror neurons. In the present study, a group of patients with disorders of consciousness (11 males, 4 females; median age: 55 years; age range: 19-74 years) underwent task-based functional MRI in which they had, in one condition, to observe and listen to the sound of mouth actions, and in another condition, to listen to verbs with motor or abstract content. In order to verify the presence of residual activation of the mirror neuron system, the brain activations of patients were compared with that of a group of healthy individuals (seven males, eight females; median age: 33.4 years; age range: 24-65 years) performing the same tasks. The results show that brain activations were lower in patients with disorders of consciousness compared with controls, except for primary auditory areas. During the audiovisual task, 5 out of 15 patients with disorders of consciousness showed only residual activation of low-level visual and auditory areas. Activation of high-level parieto-premotor areas was present in six patients. During the listening task, three patients showed only low-level activations, and six patients activated also high-level areas. Interestingly, in both tasks, one patient with a clinical diagnosis of vegetative state showed activations of high-level areas. Region of interest analysis on blood oxygen level dependent signal change in temporal, parietal and premotor cortex revealed a significant linear relation with the level of clinical functioning, assessed with coma recovery scale-revised. We propose a classification of the patient's response based on the presence of low-level and high-level activations, combined with the patient's functional level. These findings support the use of action observation and listening as possible stimulation strategies in patients with disorders of consciousness and highlight the relevance of combined methods based on functional assessment and brain imaging to provide more detailed neuroanatomical specificity about residual activated areas at both cortical and subcortical levels.

Lesion mapping and functional characterization of hemiplegic children with different patterns of hand manipulation.

Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.

Activation of Cerebellum, Basal Ganglia and Thalamus During Observation and Execution of Mouth, hand, and foot Actions.

Humans and monkey studies showed that specific sectors of cerebellum and basal ganglia activate not only during execution but also during observation of hand actions. However, it is unknown whether, and how, these structures are engaged during the observation of actions performed by effectors different from the hand. To address this issue, in the present fMRI study, healthy human participants were required to execute or to observe grasping acts performed with different effectors, namely mouth, hand, and foot. As control, participants executed and observed simple movements performed with the same effectors. The results show that: (1) execution of goal-directed actions elicited somatotopically organized activations not only in the cerebral cortex but also in the cerebellum, basal ganglia, and thalamus; (2) action observation evoked cortical, cerebellar and subcortical activations, lacking a clear somatotopic organization; (3) in the territories displaying shared activations between execution and observation, a rough somatotopy could be revealed in both cortical, cerebellar and subcortical structures. The present study confirms previous findings that action observation, beyond the cerebral cortex, also activates specific sectors of cerebellum and subcortical structures and it shows, for the first time, that these latter are engaged not only during hand actions observation but also during the observation of mouth and foot actions. We suggest that each of the activated structures processes specific aspects of the observed action, such as performing internal simulation (cerebellum) or recruiting/inhibiting the overt execution of the observed action (basal ganglia and sensory-motor thalamus).

Decoding point-light displays and fully visible hand grasping actions within the action observation network.

Action observation typically recruits visual areas and dorsal and ventral sectors of the parietal and premotor cortex. This network has been collectively termed as extended action observation network (eAON). Within this network, the elaboration of kinematic aspects of biological motion is crucial. Previous studies investigated these aspects by presenting subjects with point-light displays (PLDs) videos of whole-body movements, showing the recruitment of some of the eAON areas. However, studies focused on cortical activation during observation of PLDs grasping actions are lacking. In the present functional magnetic resonance imaging (fMRI) study, we assessed the activation of eAON in healthy participants during the observation of both PLDs and fully visible hand grasping actions, excluding confounding effects due to low-level visual features, motion, and context. Results showed that the observation of PLDs grasping stimuli elicited a bilateral activation of the eAON. Region of interest analyses performed on visual and sensorimotor areas showed no significant differences in signal intensity between PLDs and fully visible experimental conditions, indicating that both conditions evoked a similar motor resonance mechanism. Multivoxel pattern analysis (MVPA) revealed significant decoding of PLDs and fully visible grasping observation conditions in occipital, parietal, and premotor areas belonging to eAON. Data show that kinematic features conveyed by PLDs stimuli are sufficient to elicit a complete action representation, suggesting that these features can be disentangled within the eAON from the features usually characterizing fully visible actions. PLDs stimuli could be useful in assessing which areas are recruited, when only kinematic cues are available, for action recognition, imitation, and motor learning.

Effectiveness of action observation therapy based on virtual reality technology in the motor rehabilitation of paretic stroke patients: a randomized clinical trial.

BACKGROUND: The rehabilitation of paretic stroke patients uses a wide range of intervention programs to improve the function of impaired upper limb. A new rehabilitative approach, called action observation therapy (AOT) is based on the discovery of mirror neurons and has been used to improve the motor functions of adult stroke patients and children with cerebral palsy. Recently, virtual reality (VR) has provided the potential to increase the frequency and effectiveness of rehabilitation treatment by offering challenging and motivating tasks.  METHODS: The purpose of the present project is to design a randomized controlled six-month follow-up trial (RCT) to evaluate whether action observation (AO) added to standard VR (AO + VR) is effective in improving upper limb function in patients with stroke, compared with a control treatment consisting of observation of naturalistic scenes (CO) without any action content, followed by VR training (CO + VR). DISCUSSION: AO + VR treatment may provide an addition to the rehabilitative interventions currently available for recovery after stroke and could be utilized within standard sensorimotor training or in individualized tele-rehabilitation. TRIAL REGISTRATION: The trial has been prospectively registered on ClinicalTrials.gov. NCT05163210 . 17 December 2021.

Structural connectivity associated with the sense of body ownership: a diffusion tensor imaging and disconnection study in patients with bodily awareness disorder.

The brain mechanisms underlying the emergence of a normal sense of body ownership can be investigated starting from pathological conditions in which body awareness is selectively impaired. Here, we focused on pathological embodiment, a body ownership disturbance observed in brain-damaged patients who misidentify other people's limbs as their own. We investigated whether such body ownership disturbance can be classified as a disconnection syndrome, using three different approaches based on diffusion tensor imaging: (i) reconstruction of disconnectome maps in a large sample (N = 70) of stroke patients with and without pathological embodiment; (ii) probabilistic tractography, performed on the age-matched healthy controls (N = 16), to trace cortical connections potentially interrupted in patients with pathological embodiment and spared in patients without this pathological condition; (iii) probabilistic 'in vivo' tractography on two patients without and one patient with pathological embodiment. The converging results revealed the arcuate fasciculus and the third branch of the superior longitudinal fasciculus as mainly involved fibre tracts in patients showing pathological embodiment, suggesting that this condition could be related to the disconnection between frontal, parietal and temporal areas. This evidence raises the possibility of a ventral self-body recognition route including regions where visual (computed in occipito-temporal areas) and sensorimotor (stored in premotor and parietal areas) body representations are integrated, giving rise to a normal sense of body ownership.

Decoding grip type and action goal during the observation of reaching-grasping actions: A multivariate fMRI study.

During execution and observation of reaching-grasping actions, the brain must encode, at the same time, the final action goal and the type of grip necessary to achieve it. Recently, it has been proposed that the Mirror Neuron System (MNS) is involved not only in coding the final goal of the observed action, but also the type of grip used to grasp the object. However, the specific contribution of the different areas of the MNS, at both cortical and subcortical level, in disentangling action goal and grip type is still unclear. Here, twenty human volunteers participated in an fMRI study in which they performed two tasks: (a) observation of four different types of actions, consisting in reaching-to-grasp a box handle with two possible grips (precision, hook) and two possible goals (open, close); (b) action execution, in which participants performed grasping actions similar to those presented during the observation task. A conjunction analysis revealed the presence of shared activated voxels for both action observation and execution within several cortical areas including dorsal and ventral premotor cortex, inferior and superior parietal cortex, intraparietal sulcus, primary somatosensory cortex, and cerebellar lobules VI and VIII. ROI analyses showed a main effect for grip type in several premotor and parietal areas and cerebellar lobule VI, with higher BOLD activation during observation of precision vs hook actions. A grip x goal interaction was also present in the left inferior parietal cortex, with higher BOLD activity during precision-to-close actions. A multivariate pattern analysis (MVPA) revealed a significant accuracy for the grip model in all ROIs, while for the action goal model, significant accuracy was observed only for left inferior parietal cortex ROI. These findings indicate that a large network involving cortical and cerebellar areas is involved in the processing of type of grip, while final action goal appears to be mainly processed within the inferior parietal region, suggesting a differential contribution of the areas activated in this study.

Visceromotor roots of aesthetic evaluation of pain in art: an fMRI study.

Empathy for pain involves sensory and visceromotor brain regions relevant also in the first-person pain experience. Focusing on brain activations associated with vicarious experiences of pain triggered by artistic or non-artistic images, the present study aims to investigate common and distinct brain activation patterns associated with these two vicarious experiences of pain and to assess whether empathy for pain brain regions contributes to the formation of an aesthetic judgement (AJ) in non-art expert observers. Artistic and non-artistic facial expressions (painful and neutral) were shown to participants inside the scanner and then aesthetically rated in a subsequent behavioural session. Results showed that empathy for pain brain regions (i.e. bilateral insular cortex, posterior sector of the anterior cingulate cortex and the anterior portion of the middle cingulate cortex) and bilateral inferior frontal gyrus are commonly activated by artistic and non-artistic painful facial expressions. For the artistic representation of pain, the activity recorded in these regions directly correlated with participants' AJ. Results also showed the distinct activation of a large cluster located in the posterior cingulate cortex/precuneus for non-artistic stimuli. This study suggests that non-beauty-specific mechanisms such as empathy for pain are crucial components of the aesthetic experience of artworks.

Grasping and Manipulation: Neural Bases and Anatomical Circuitry in Humans.

Neurophysiological and neuroimaging evidence suggests a significant contribution of several brain areas, including subdivisions of the parietal and the premotor cortex, during the processing of different components of hand and arm movements. Many investigations improved our knowledge about the neural processes underlying the execution of reaching and grasping actions, while few studies have directly investigated object manipulation. Most studies on the latter topic concern the use of tools to achieve specific goals. Yet, there are very few studies on pure manipulation performed in order to explore and recognize objects, as well as on manipulation performed with a high level of manual dexterity. Another dimension that is quite neglected by the available studies on grasping and manipulation is, on the one hand, the contribution of the subcortical nodes, first of all the basal ganglia and cerebellum, to these functions, and, on the other hand, recurrent connections of these structures with cortical areas. In the first part, we have reviewed the parieto-premotor and subcortical circuits underlying reaching and grasping in humans, with a focus on functional neuroimaging data. Then, we have described the main structures recruited during object manipulation. We have also reported the contribution of recent structural connectivity techniques whereby the cortico-cortical and cortico-subcortical connections of grasping-related and manipulation-related areas in the human brain can be determined. Based on our review, we have concluded that studies on cortical and subcortical circuits involved in grasping and manipulation might be promising to provide new insights about motor learning and brain plasticity in patients with motor disorders.

Some evidence on Gerstmann's syndrome: A case study on a variant of the clinical disorder.

We describe the case of a bilingual patient with persistent symptoms largely, although not fully, consistent with those that are usually reported in Gerstmann's syndrome. Twenty months after a spontaneous primary intracranial hemorrhage, the patient was evaluated with a series of neuropsychological tasks and underwent an MRI investigation based on Diffusion Tensor Imaging probabilistic tractography. The patient suffered from dysgraphia (difficulty in the access to the graphemic representation of letter forms), autotopoagnosia (difficulties in locating body parts on verbal command), right-left confusion (difficulties in localizing right and left side of symmetrical body parts), and number processing/calculation impairments (predominant difficulties on transcoding tasks). Probabilistic tractography revealed a relatively spared superior longitudinal fasciculus and severe damage to the subcortical white matter connecting the angular gyrus with other parietal regions, such as the intraparietal sulcus and the supramarginal gyrus. Within the framework of the contemporary cognitive accounts of Gerstmann's syndrome, the case supports the assumption of an anatomical intraparietal disconnection more than a functional Grundstörung (core impairment).

Activation of cerebellum and basal ganglia during the observation and execution of manipulative actions.

Studies on action observation mostly described the activation of a network of cortical areas, while less investigation focused specifically on the activation and role of subcortical nodes. In the present fMRI study, we investigated the recruitment of cerebellum and basal ganglia during the execution and observation of object manipulation performed with the right hand. The observation conditions consisted in: (a) observation of manipulative actions; (b) observation of sequences of random finger movements. In the execution conditions, participants had to perform the same actions or movements as in (a) and (b), respectively. The results of conjunction analysis showed significant shared activations during both observation and execution of manipulation in several subcortical structures, including: (1) cerebellar lobules V, VI, crus I, VIIIa and VIIIb (bilaterally); (2) globus pallidus, bilaterally, and left subthalamic nucleus; (3) red nucleus (bilaterally) and left thalamus. These findings support the hypothesis that the action observation/execution network also involves subcortical structures, such as cerebellum and basal ganglia, forming an integrated network. This suggests possible mechanisms, involving these subcortical structures, underlying learning of new motor skills, through action observation and imitation.

Explicit Motor Imagery for Grasping Actions in Children With Spastic Unilateral Cerebral Palsy.

Background: Motor Imagery (MI) refers to mental simulation of a motor action without producing any overt movement. Previous studies showed that children with Unilateral Cerebral Palsy (UCP) are impaired in implicit MI, as demonstrated by the performance of Hand Laterality Judgment tasks. The aim of this study was to examine the specificity of explicit MI deficits in UCP children. Methods: A group of UCP children (n = 10; aged 9-14) performed a mental chronometry task consisting in grasping an object and placing it into a container, or in imagining to perform the same action. As control, a group of typically developing (TD) children, matched by age, performed the same task. Movement durations for executed and imagined trials were recorded. A subgroup of 7 UCP children and 10 TD children also underwent a session of functional MRI to examine the activation of parieto-frontal areas typically associated to MI processes, during the imagination of reaching-grasping actions performed with the paretic hand. Results: Behavioral results revealed the existence of a correlation between executed and imagined movement durations both in TD and UCP groups. Moreover, the regression analysis in TD children showed that higher scores in mental chronometry tasks were positively correlated to increased bilateral activation of the intraparietal sulcus (IPS), superior parietal lobule (SPL), and dorsal premotor (PMd) cortex. A similar analysis revealed in the UCP group a positive correlation between a higher score in the mental chronometry task and bilateral activations of IPS, and to activation of contralesional, right PMd, and putamen during imagination of grasping movements. Conclusions: These results provide new insights on the relationship between MI capacity and motor deficits in UCP children, suggesting the possibility of the use of explicit MI training to improve patient's upper limb motor functions.

Mirror Neuron System Activation in Children With Unilateral Cerebral Palsy During Observation of Actions Performed by a Pathological Model.

Background. Recent evidence suggested that Action Observation Therapy (AOT), based on observation of actions followed by immediate reproduction, could be a useful rehabilitative strategy for promoting functional recovery of children affected by unilateral cerebral palsy (UCP). AOT most likely exploits properties of the parieto-premotor mirror neuron system (MNS). This is more intensely activated when participants observe actions belonging to their own motor repertoire. Objective. The aim of the present study was to investigate the issue of whether MNS of UCP children is better activated by actions performed by a paretic hand rather than a healthy one. Methods. Using functional magnetic resonance imaging, we assessed brain activation in a homogeneous group of 10 right UCP children compared with that of 10 right-handed typically developing (TD) children, during observation of grasping actions performed by a healthy or a paretic hand. Results. The results revealed a significant activation within the MNS in both UCP and TD children, more lateralized to the left hemisphere in the TD group. Most important, region of interest (ROI) analysis on parietal and premotor regions showed that, in UCP, the MNS was more strongly activated by observation of actions performed by the paretic hand, a motor model more similar to the observer's motor repertoire. Conclusions. This study shows that children affected by spastic UCP exhibit enhanced activation of the MNS during observation of goal-directed actions performed by a pathological model with respect to a healthy one.

Application of an Intensive Rehabilitation Program After Very Late Recovery of Consciousness: A Single-Case Neurorehabilitation and Neuroimaging Study.

Late recovery of consciousness in vegetative state is considered as an exceptional outcome and has been reported prevalently in patients who suffered a traumatic brain injury. In these patients, the benefits of prolonging the rehabilitation, aimed at the recovery of autonomy in basic everyday activities, has been demonstrated. Here, we describe the application of an intensive multi-professional rehabilitation program carried out on a young female patient, with exceptionally late recovery of consciousness, specifically, after 7 years of vegetative state due to severe brain hemorrhage. Neuropsychological and functional assessment was conducted before and after the end of the rehabilitation program. In addition, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)-based probabilistic tractography were performed. Two follow-up neuropsychological and functional assessments were also conducted 6 and 29 months after the conclusion of the program. Functional results showed an improvement, maintained over time, in walking with assistance, cognitive efficiency, visual acuity and visual field, dysarthria, and execution of activities of daily living. Moreover, functional and structural magnetic resonance imaging (MRI) data documented the existence of preserved neural networks involved in sensory, motor, and linguistic tasks, which in all likelihood support the recovery process. This report suggests the possibility of undertaking an intensive rehabilitation program in patients who remain for long periods in altered states of consciousness, in spite of early negative prognosis.

Parieto-frontal mechanisms underlying observation of complex hand-object manipulation.

The observation of actions performed by others is believed to activate the Action Observation Network (AON). Previous evidence suggests that subjects with a specific motor skill show increased activation of the AON during observation of the same skill. The question arises regarding which modulation of the AON occurs during observation of novel complex manipulative actions that are beyond the personal motor repertoire. To address this issue, we carried out a functional MRI study in which healthy volunteers without specific hand motor skills observed videos displaying hand-object manipulation executed by an expert with high manual dexterity, by an actor with intermediate ability or by a naïve subject. The results showed that the observation of actions performed by a naïve model produced stronger activation in a dorso-medial parieto-premotor circuit including the superior parietal lobule and dorsal premotor cortex, compared to observation of an expert actor. Functional connectivity analysis comparing the observation of the naïve model with that of the expert model, revealed increased connectivity between dorsal areas of the AON. This suggests a possible distinction between ventral and dorsal brain circuits involved in the processing of different aspects of action perception, such as kinematics and final action goal.

Rehabilitation of unilateral spatial neglect: A combined behavioral and fMRI single-case study.

OBJECTIVE: Symptoms of visuospatial neglect occur frequently after unilateral brain damage. Neglect hampers general rehabilitation progress and is associated with reduced quality of life. Some of the rehabilitation programs developed to treat neglect have demonstrated behavioral improvements. However, only a few of them have addressed specifically the anatomo-functional correlates associated behavioral improvement. METHOD: Here we describe the case of a patient (GV) with a severe left neglect disorder as a consequence of a right hemisphere stroke. Eighteen weeks after the onset, he underwent a 10-week intensive neuropsychological rehabilitation program. Functional MRI (fMRI) during execution of a covert attention task, and a broad neuropsychological assessment were conducted before and after the training. RESULTS: The results show a significant improvement of the performance in neglect tasks after the rehabilitation program, although the remission of symptoms was not complete. fMRI data showed that the behavioral improvement was accompanied by an increase of activity in the dorsal premotor cortex and middle frontal gyrus bilaterally. Other activations were present only in the contralesional left hemisphere, including supplementary motor area and superior temporal gyrus. CONCLUSIONS: The implications of the results are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).