Anna Sontheimer

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

BackgroundFor gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES).Methods and materialsThe authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR.ResultsTractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0u2009±u200910.4xa0% of the preoperative tumour volume, with a gross total resection in 60xa0% of patients.ConclusionThe intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Maps of the adult human hypothalamus.

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.

Electrical modulation of neuronal networks in brain-injured patients with disorders of consciousness: A systematic review

Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies.

Combined DTI Tractography and Functional MRI Study of the Language Connectome in Healthy Volunteers: Extensive Mapping of White Matter Fascicles and Cortical Activations

Despite a better understanding of brain language organization into large-scale cortical networks, the underlying white matter (WM) connectivity is still not mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and language functional magnetic resonance imaging (fMRI) in twenty healthy subjects to gain new insights into the macroscopic structural connectivity of language. Eight putative WM fascicles for language were probed using a deterministic DTI-FT technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF), uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional anisotropy) and precise cortical terminations were derived for each WM fascicle within both hemispheres. Connections between these WM fascicles and fMRI activations were studied to determine which WM fascicles are related to language. WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal segment of SLF and UF, and rightward for the frontoparietal segment of the SLF. The lateralization of the AF, IFOF and MdLF extended to differences in patterns of anatomical connections, which may relate to specific hemispheric abilities. The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI activations, suggesting that the lateralization of the AF is a structural substrate of hemispheric language dominance. We found consistent connections between fMRI activations and terminations of the eight WM fascicles, providing a detailed description of the language connectome. WM fascicle terminations were also observed beyond fMRI-confirmed language areas and reached numerous cortical areas involved in different functional brain networks. These findings suggest that the reported WM fascicles are not exclusively involved in language and might be related to other cognitive functions such as visual recognition, spatial attention, executive functions, memory, and processing of emotional and behavioral aspects.

Time-course of myelination and atrophy on cerebral imaging in 35 patients with PLP1-related disorders.

Brain magnetic resonance imaging (MRI) motor development score (MDS) correlations were used to analyze the natural time‐course of hypomyelinating PLP1‐related disorders (Pelizaeus‐Merzbacher disease [PMD] and spastic paraplegia type 2).

Inter-individual variations and hemispheric asymmetries in structural connectivity patterns of the inferior fronto-occipital fascicle: a diffusion tensor imaging tractography study

PurposePrecise knowledge of the structural connectivity of white matter fascicles could yield new insights into function and is important for neurosurgical planning. Therefore, we aimed to provide a detailed map of the cortical terminations of the inferior fronto-occipital fascicle (IFOF), with special emphasis on putative inter-individual variations and hemispheric asymmetries.MethodsDeterministic diffusion tensor imaging-based tractography was used to perform virtual dissection of the IFOF in 20 healthy subjects. The IFOF was probed from a single seed region of interest placed within the external/extreme capsule, i.e. the white matter region of “obligatory passage” along the known path of the IFOF. This enabled to reconstruct all the fibers belonging to the IFOF and to provide the complete map of their cortical terminations.ResultsWe observed widespread projections over a total of 11 cortical territories within the occipital, parietal, temporal and frontal lobes. Importantly, compared to previous studies we consistently found some inter-individual variability with several distinct patterns connecting subsets of the 11 cortical territories, and tangible differences between the two hemispheres. IFOF terminations within the superior parietal lobule were rightward lateralized, whereas terminations within the inferior frontal gyrus were leftward lateralized.ConclusionsOur results provide a clinically relevant map of IFOF’s cortical terminations, including intra- and inter-individual variations. Right–left differences in connectivity patterns might be related to known functional asymmetries in the human brain, and reinforce the general evidence that the IFOF likely supports distinct clinical features and functional roles according to the (affected) hemisphere, such as language and spatial attention.

Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human PLP1 -Related Disorders

Aims: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinating PLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition. Methods: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria: size, direction of main-stream fibers, and connectivity of bundles (extratelencephalic projections, commissural fibers, and intrahemispheric connections). Results: Age-adjusted multivariate analysis in 3 severity groups revealed increased isotropic diffusion in the superior cerebellar peduncle and grey matter in the most severe group, and larger tractogram volumes and increased numbers of fibers in the least severely affected group. Tractogram patterns showed preserved extratelencephalic projections and a main anterior-posterior aspect of intrahemispheric fibers in most patients, whereas interhemispheric connectivity was variable. The most severely affected and intermediate patients had less intrahemispheric connectivity, with a frequent predominant anterior-posterior direction of main-stream fibers. Interpretation: Diffusion tensor imaging and tractographic parameters can operate as biomarkers to distinguish clinical severity in PLP1-related disorders and could improve our understanding of hypomyelinating leukodystrophies.

fMRI study of graduated emotional charge for detection of covert activity using passive listening to narratives

Detection of awareness in patients with consciousness disorders is a challenge that can be facilitated by functional neuroimaging. We elaborated a functional magnetic resonance imaging (fMRI) protocol to detect covert activity in altered states of consciousness. We hypothesized that passive listening to narratives with graduated emotional charge triggers graduated cerebral activations. The fMRI protocol was designed in healthy subjects for further clinical applications. The emotional charge was graduated using voice familiarity and long-term declarative memory content: low emotional charge, unknown person telling general semantic memory; mean emotional charge, relative telling the same narratives; high emotional charge, same relative telling autobiographical memory. Autobiographical memory was subdivided into semantic autobiographical memory and episodic autobiographical memory. The protocol proved efficient at triggering graduated cerebral activations: low emotional charge, superior temporal gyri and sulci; mean emotional charge, same as low emotional charge plus bilateral premotor cortices and left inferior frontal gyrus; high emotional charge, cingulate, temporal, frontal, prefrontal and angular areas, thalamus and cerebellum. Semantic autobiographical memory revealed larger activations than episodic autobiographical memory. Independent ROI analysis confirmed the preponderant contribution of narratives with autobiographical memory content in triggering cerebral activation, not only in autobiographical memory-sensitive areas, but also in voice-sensitive, language-sensitive and semantic memory-sensitive areas.

Cerebral quantitative DTI and tractography in 25 patients with PLP1-related disorders

Objective: We used brain diffusion tensor imaging (DTI) and tractography to analyze the severity of patients with PLP1-related disorders (Pelizaeus- Merzbacher disease and spastic paraplegia type 2). Methods: Twenty-five male patients (ranged from 0.7 to 43.5 years) with PLP1- related disorder were included in this DTI study. Subjects were classified according to best motor function acquired before 5 years into five categories (from PMD0 without motor acquisition to PMD4 with autonomous walking). We performed a quantitative DTI study on different brain regions of white or grey matter, tracking of the cortico-spinal fascicles (CSF) and whole brain tractography. Results: No difference was observed between severity groups on quantitative DTI parameters (apparent diffusion coefficient, fractional anisotropy, radial and axial diffusivities) using two different DTI software. Tractography of the CSF did not reveal significant differences that could permit to distinguish severity groups. On the contrary, whole brain tractography seems to be a more relevant approach with high abnormalities in fibers from semi-oval centers and corpus callosum linked to clinical severity. Conclusion: To distinguish early the clinical severity of patients with PLP- pathies is a present challenge to consider early therapeutical approaches in these disorders. Tractography of whole brain could be an interesting way of classifying patients and following disease’s severity.

Cerebral atrophy is linked to clinical severity and worsens with aging in patients with Pelizaeus–Merzbacher disease and Spastic Paraplegia type 2

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