Nicolas Menjot de Champfleur

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.

Assessment of White Matter Injury and Outcome in Severe Brain Trauma: A Prospective Multicenter Cohort

Background:Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). Methods:In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. Results:Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75–0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54–0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. Conclusions:White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

INTRODUCTION The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. MATERIALS AND METHODS Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. RESULTS The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. DISCUSSION Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. CONCLUSION The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF).

Long-term Outcomes of CLIPPERS (Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids) in a Consecutive Series of 12 Patients

BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE To describe the disease course of CLIPPERS. DESIGN A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING Academic research. PATIENTS Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES The therapeutic management of CLIPPERS was evaluated. RESULTS Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

Magnetic resonance imaging evaluation of cerebral cavernous malformations with susceptibility-weighted imaging.

BACKGROUND:Cerebral cavernous malformations (CCMs) can be sporadic or inherited, the latter characterized by multiple lesions. Novel imaging sequences have increased the sensitivity of detecting multiple CCMs. OBJECTIVE:To compare T2-weighted gradient echo (T2*GRE) and susceptibility-weighted imaging (SWI) sequences in familial and sporadic CCM to assess their respective sensitivity. METHODS:This prospective study included 23 consecutive cases grouped as multifocal/familial CCMs (n = 14), solitary/clustered sporadic CCMs with developmental venous anomaly (n = 8), and postirradiation CCMs (n = 1). Brain magnetic resonance imaging included T2*GRE and SWI sequences. Two radiologists independently counted the number of lesions on each sequence. The difference in the number of lesions on both sequences was compared, and interobserver agreement was evaluated. RESULTS:In multifocal/familial cases, a mean of 34.7 lesions were detected on T2*GRE and 66.9 on SWI (P = .001). The difference of lesion prevalence with the 2 techniques was significant (P = .006), with strong interobserver correlation for the T2*GRE sequence (P < .001) and SWI sequence (P < .001). Patients with solitary/clustered sporadic CCMs, including those associated with venous anomaly, had no difference in lesion prevalence in the 2 sequences. CONCLUSION:SWI is more sensitive than T2*GRE in detecting CCM in multifocal/familial CCMs. Among cases classified as solitary/clustered with conventional imaging, including those associated with venous anomaly, the SWI did not impart additional sensitivity or reveal occult lesions not evident on T2*GRE sequence. No case was changed from the solitary/clustered to the multifocal clinical category because of SWI.

Diffusion Tractography: Methods, Validation and Applications in Patients with Neurosurgical Lesions

Diffusion tensor imaging (DTI) tractography is increasingly used in presurgical mapping in tumors located in eloquent areas since it is the only non invasive technique that permits in vivo dissection of white matter tracts. Concordance between the DTI tracts and subcortical electrical intraoperative mapping is high, and DTI tractography has proven useful to guide surgery. However, it presents limitations due to the technique and the tumor, which must be known before using the images in the operative room. This review focuses on the possibilities and limits of DTI imaging in intraoperative tumoral mapping and presents an overview of current knowledge.

Suicidal Behavior Is Associated with Reduced Corpus Callosum Area

BACKGROUND Corpus callosum (CC) size has been associated with cognitive and emotional deficits in a range of neuropsychiatric and mood disorders. As such deficits are also found in suicidal behavior, we investigated specifically the association between CC atrophy and suicidal behavior. METHODS We studied 435 right-handed individuals without dementia from a cohort of community-dwelling persons aged 65 years and over (the ESPRIT study). They were divided in three groups: suicide attempters (n = 21), affective control subjects (AC) (n = 180) without history of suicide attempt but with a history of depression, and healthy control subjects (HC) (n = 234). T1-weighted magnetic resonance images were traced to measure the midsagittal areas of the anterior, mid, and posterior CC. Multivariate analysis of covariance was used to compare CC areas in the three groups. RESULTS Multivariate analyses adjusted for age, gender, childhood trauma, head trauma, and total brain volume showed that the area of the posterior third of CC was significantly smaller in suicide attempters than in AC (p = .020) and HC (p = .010) individuals. No significant differences were found between AC and HC. No differences were found for the anterior and mid thirds of the CC. CONCLUSIONS Our findings emphasize a reduced size of the posterior third of the CC in subjects with a history of suicide, suggesting a diminished interhemispheric connectivity and a possible role of CC in the pathophysiology of suicidal behavior. Further studies are needed to strengthen these results and clarify the underlying cellular changes leading to these morphometric differences.

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.

Evidence of a middle longitudinal fasciculus in the human brain from fiber dissection

A rostrocaudal pathway connecting the temporal and parietal lobes was described in monkeys using autoradiography and was named the middle longitudinal fasciculus (MdLF). Recently, the use of diffusion tensor tractography has allowed it to be depicted in human volunteers. In the present study, a technique of fiber dissection was used in 18 cadaveric human brains to investigate the presence of this fasciculus and to detail its anatomical relationships. On the basis of our findings, fiber dissection provides evidence for a long horizontal bundle medial to the arcuate fasciculus and extending to the superior temporal gyrus. Its fibers occupy the lateral‐most layer of the upper portion of the stratum sagittale and partially cover the inferior fronto‐occipital fasciculus, which is situated deeper and slightly inferiorly. Whereas MdLF fibers continue on a relatively superficial level to reach the superior temporal gyrus, the inferior fronto‐occipital fasciculus penetrates the deep temporal white matter and crosses the insular lobe. Although diffusion tensor imaging suggests that the MdLF terminates in the angular gyrus, this was not confirmed by the present study. These long association fibers continue onward posteriorly into upper portions of the occipital lobe. Further studies are needed to understand the role of the MdLF in brain function.

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.