François Bonnetblanc

Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection

In the field of cognitive neuroscience, it is increasingly accepted that mentalizing is subserved by a complex frontotemporoparietal cortical network. Some researchers consider that this network can be divided into two distinct but interacting subsystems (the mirror system and the mentalizing system per se), which respectively process low-level, perceptive-based aspects and high-level, inference-based aspects of this sociocognitive function. However, evidence for this type of functional dissociation in a given neuropsychological population is currently lacking and the structural connectivities of the two mentalizing subnetworks have not been established. Here, we studied mentalizing in a large sample of patients (n = 93; 46 females; age range: 18-65 years) who had been resected for diffuse low-grade glioma-a rare tumour that migrates preferentially along associative white matter pathways. This neurological disorder constitutes an ideal pathophysiological model in which to study the functional anatomy of associative pathways. We mapped the location of each patients resection cavity and residual lesion infiltration onto the Montreal Neurological Institute template brain and then performed multilevel lesion analyses (including conventional voxel-based lesion-symptom mapping and subtraction lesion analyses). Importantly, we estimated each associative pathways degree of disconnection (i.e. the degree of lesion infiltration) and built specific hypotheses concerning the connective anatomy of the mentalizing subnetworks. As expected, we found that impairments in mentalizing were mainly related to the disruption of right frontoparietal connectivity. More specifically, low-level and high-level mentalizing accuracy were correlated with the degree of disconnection in the arcuate fasciculus and the cingulum, respectively. To the best of our knowledge, our findings constitute the first experimental data on the structural connectivity of the mentalizing network and suggest the existence of a dual-stream hodological system. Our results may lead to a better understanding of disorders that affect social cognition, especially in neuropathological conditions characterized by atypical/aberrant structural connectivity, such as autism spectrum disorders.

Modular control of pointing beyond arm's length.

Hand reaching and bipedal equilibrium are two important functions of the human motor behavior. However, how the brain plans goal-oriented actions combining target reaching with equilibrium regulation is not yet clearly understood. An important question is whether postural control and reaching are integrated in one single module or controlled separately. Here, we show that postural control and reaching motor commands are processed by means of a modular and flexible organization. Principal component and correlation analyses between pairs of angles were used to extract global and local coupling during a whole-body pointing beyond arms length. A low-dimensional organization of the redundant kinematic chain allowing simultaneous target reaching and regulation of the center of mass (CoM) displacement in extrinsic space emerged from the first analysis. In follow-up experiments, both the CoM and finger trajectories were constrained by asking participants to reach from a reduced base of support with or without knee flexion, or by moving the endpoint along a predefined trajectory (straight or semicircular trajectories). Whereas joint covaried during free conditions and under equilibrium restrictions, it was decomposed in two task-dependent and task-independent modules, corresponding to a dissociation of arm versus legs, trunk, and head coordination, respectively, under imposed finger path conditions. A numerical simulation supported the idea that both postural and focal subtasks are basically integrated into the same motor command and that the CNS is able to combine or to separate the movement into autonomous functional synergies according to the task requirements.

Disrupting posterior cingulate connectivity disconnects consciousness from the external environment.

Neurophysiological and neuroimaging studies including both patients with disorders of consciousness and healthy subjects with modified states of consciousness suggest a crucial role of the medial posteroparietal cortex in conscious information processing. However no direct neuropsychological evidence supports this hypothesis and studies including patients with restricted lesions of this brain region are almost non-existent. Using direct intraoperative electrostimulations, we showed in a rare patient that disrupting the subcortical connectivity of the left posterior cingulate cortex (PCC) reliably induced a breakdown in conscious experience. This acute phenomenon was mainly characterized by a transient behavioral unresponsiveness with loss of external connectedness. In all cases, when he regained consciousness, the patient described himself as in dream, outside the operating room. This finding suggests that functional integrity of the PPC connectivity is necessary for maintaining consciousness of external environment.

Pointing to double-step visual stimuli from a standing position: very short latency (express) corrections are observed in upper and lower limbs and may not require cortical involvement.

How fast can we correct a planned movement following an unexpected target jump? Subjects, starting in an upright standing position, were required to point to a target that randomly and unexpectedly jumps forward to a constant spatial location. Rapid motor corrections in the upper and lower limbs, with latency responses of less than 100 ms, were revealed by contrasting electromyographic activities in perturbed and unperturbed trials. The earliest responses were observed primarily in the anterior section of the deltoïdus anterior (shoulder) and the tibialis anterior (leg) muscles. Our findings indicate that visual on-going movement corrections may be accomplished via fast loops at the level of the upper and lower limbs and may not require cortical involvement.

Cognitive demands impair postural control in developmental dyslexia: A negative effect that can be compensated

Children with developmental dyslexia exhibit delayed reading abilities and various sensori-motor deficits. The way these various symptoms interact remain poorly understood. The objective of this study was twofold. First, we aimed to investigate whether postural control was impaired in dyslexic children when cognitive demands are increased. Second, we checked whether this effect could be reduced significantly by a treatment aiming to recalibrate ocular proprioception. Twelve dyslexic and fifteen treated dyslexic children (>3 months of treatment) were compared with twelve non-dyslexic children in two conditions (mean age: 11.6+/-2.1, 12.5+/-1.5 and 10.6+/-1.7 years respectively). In a first condition they maintained balance while fixating a point in front of them. In the second condition the postural task was combined with a silently reading one. Balance was assessed by means of a force plate. Results demonstrated that the mean velocity (i.e. the total length) of the center of pressure (CoP) displacement was increased in the reading task only for the dyslexic group. Interestingly, for the treated children, an inverse tendency was observed: the mean velocity (i.e. the total length) and the surface of the 90% confidence ellipse of the CoP displacement decreased for 13/15 patients and for 12/15 patients respectively, while performing the reading task. Values remained similar to those observed for the control children. Altogether, these results strongly suggest that cognitive demands can impair postural control in developmental dyslexia but this interaction could be normalized. These results sustain the hypothesis of a cerebellar origin for dyslexia.

A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients.

Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia.

Practice-Related Improvements in Postural Control During Rapid Arm Movement in Older Adults: A Preliminary Study

BACKGROUND Postural control associated with self-paced movement is critical for balance in older adults. The present study aimed to investigate the effects of a virtual reality-based program on the postural control associated with rapid arm movement in this population. METHODS From an upright standing position, participants performed rapid arm-raising movements toward a target. Practice-related changes were assessed by pre- and posttest comparisons of hand kinematics and center of pressure displacement parameters measured in a training group (mean age: 71.50 ± 2.67 years, n = 8) and a control group (mean age: 72.87 ± 3.09 years, n = 8). Training group participants took part in six sessions (35-40 minutes per session, three sessions per week). During the two test sessions, arm raising was analyzed under two conditions of stimuli: choice reaction time and simple reaction time. RESULTS We observed improvements in the arm movement after training under both conditions of stimuli. The initial phase of the center of pressure displacement, especially the anticipatory postural adjustments, was improved in the choice reaction time condition. CONCLUSIONS Our short training program resulted in motor optimization of the postural control associated with rapid arm movements, and this implies central changes in motor programming.

Delayed postural control during self-generated perturbations in the frail older adults

Purpose The aim of this study was to investigate the coordination between posture and movement in pathological aging (frailty) in comparison with normal aging, with the hypothesis that in pathological aging, postural control evolves towards a more reactive mode for which the perturbation induced by the movement is not anticipated and leads to delayed and late postural adjustments. Methods Elderly subjects performed rapid focal arm-raising movements towards a target, from an upright standing position in two stimuli conditions: simple reaction time and choice reaction time (CRT). Hand and center of pressure (CoP) kinematics were compared between a control group and a frail group of the same age. Results In frail individuals, the entire movement was impaired and slowed down. In addition, postural adjustments that classically precede and accompany the focal arm movement were delayed and reduced, especially in the CRT condition in which the motor prediction is more limited. Finally, a correlation between the time to CoP maximal velocity and the timed up- and-go score was observed. Conclusion In these patients, it was concluded that the control of the CoP displacement evolved from a proactive mode in which the perturbation associated with the arm movement is anticipated toward a more reactive mode in which the perturbation is compensated by late and delayed adjustments.

Ultra-fast recovery from right neglect after 'awake surgery' for slow-growing tumor invading the left parietal area.

It is now possible to perform resections of slow-growing tumors in awake patients. Using direct electrical stimulation, real-time functional mapping of the brain can be used to prevent the resection of essential areas near the tumor. Simple clinical observations of patients with a resection of slow-growing tumors have demonstrated substantial recovery within a few days of such ‘awake surgery’. The aim of this study was to investigate the kinetics of recovery following the resection of slow-growing tumors invading the left parietal area and to focus mainly on its rapidity. Two patients were assessed by standard line bisection tests and compared with eight healthy individuals. Independently of the pure nature of the symptoms, we report that the patients rapidly and substantially recovered from pronounced right neglect. They were tested 48 hours after the surgery and the recovery was significant for both patients after less than 4 hours. Strikingly, for one patient, recovery was ultra fast and substantial in the first practice session within less than 7 minutes: it occurred without verbal feedback and was substantially retained during the following testing session. Its rapidity suggests a process of unmasking redundant networks. With the slow growth of the lesion, the contralesional hemisphere is probably progressively prepared for rapid unmasking of homologue networks. These results have major clinical implications. For patients with an invading left-side tumor, it is now clear that line bisections are required before, during, and after awake surgery to: plan the surgery, control the quality of the resection, and also optimize the rehabilitation of the patient.

Equilibrium constraints do not affect the timing of muscular synergies during the initiation of a whole body reaching movement

The aim of this study was to determine whether the timing of the muscular synergies was influenced by the reduction of the base of support when we initiate a whole body reaching movement. To answer this question, we performed a principal component analysis on electromyographic activities of 24 muscles recorded on the leg, the trunk, and the arm. Our results demonstrated that during the initiation of the whole body pointing movement, only three principal components accounted for at least 95% of the variance for the overall muscular data, both when the equilibrium constraints were normal and when the base of support was reduced. These principal components were strongly correlated despite the fact that the center of mass forward displacement and the center of pressure backward displacements significantly decreased when the base of support was reduced. It suggests that the central nervous system did not change the overall timing of the muscular synergies when new equilibrium constraints were introduced in the task but was rather able to tune their amplitude as evidenced by the modification of the center of mass and center of pressure displacements.