[Neurology]. / Neurologie.

In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis.

Electrostimulation mapping of comprehension of auditory and visual words.

In order to spare functional areas during the removal of brain tumours, electrical stimulation mapping was used in 90 patients (77 in the left hemisphere and 13 in the right; 2754 cortical sites tested). Language functions were studied with a special focus on comprehension of auditory and visual words and the semantic system. In addition to naming, patients were asked to perform pointing tasks from auditory and visual stimuli (using sets of 4 different images controlled for familiarity), and also auditory object (sound recognition) and Token test tasks. Ninety-two auditory comprehension interference sites were observed. We found that the process of auditory comprehension involved a few, fine-grained, sub-centimetre cortical territories. Early stages of speech comprehension seem to relate to two posterior regions in the left superior temporal gyrus. Downstream lexical-semantic speech processing and sound analysis involved 2 pathways, along the anterior part of the left superior temporal gyrus, and posteriorly around the supramarginal and middle temporal gyri. Electrostimulation experimentally dissociated perceptual consciousness attached to speech comprehension. The initial word discrimination process can be considered as an "automatic" stage, the attention feedback not being impaired by stimulation as would be the case at the lexical-semantic stage. Multimodal organization of the superior temporal gyrus was also detected since some neurones could be involved in comprehension of visual material and naming. These findings demonstrate a fine graded, sub-centimetre, cortical representation of speech comprehension processing mainly in the left superior temporal gyrus and are in line with those described in dual stream models of language comprehension processing.

Anatomical correlates for category-specific naming of objects and actions: a brain stimulation mapping study.

The production of object and action words can be dissociated in aphasics, yet their anatomical correlates have been difficult to distinguish in functional imaging studies. To investigate the extent to which the cortical neural networks underlying object- and action-naming processing overlap, we performed electrostimulation mapping (ESM), which is a neurosurgical mapping technique routinely used to examine language function during brain-tumor resections. Forty-one right-handed patients who had surgery for a brain tumor were asked to perform overt naming of object and action pictures under stimulation. Overall, 73 out of the 633 stimulated cortical sites (11.5%) were associated with stimulation-induced language interferences. These interference sites were very much localized (<1 cm(2) ), and showed substantial variability across individuals in their exact localization. Stimulation interfered with both object and action naming over 44 sites, whereas it specifically interfered with object naming over 19 sites and with action naming over 10 sites. Specific object-naming sites were mainly identified in Broca's area (Brodmann area 44/45) and the temporal cortex, whereas action-naming specific sites were mainly identified in the posterior midfrontal gyrus (Brodmann area 6/9) and Broca's area (P = 0.003 by the Fisher's exact test). The anatomical loci we emphasized are in line with a cortical distinction between objects and actions based on conceptual/semantic features, so the prefrontal/premotor cortex would preferentially support sensorimotor contingencies associated with actions, whereas the temporal cortex would preferentially underpin (functional) properties of objects.

The neural basis for writing from dictation in the temporoparietal cortex.

Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to-motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region.

Segregation of lexical and sub-lexical reading processes in the left perisylvian cortex.

A fundamental issue in cognitive neuroscience is the existence of two major, sub-lexical and lexical, reading processes and their possible segregation in the left posterior perisylvian cortex. Using cortical electrostimulation mapping, we identified the cortical areas involved on reading either orthographically irregular words (lexical, "direct" process) or pronounceable pseudowords (sublexical, "indirect" process) in 14 right-handed neurosurgical patients while video-recording behavioral effects. Intraoperative neuronavigation system and Montreal Neurological Institute (MNI) stereotactic coordinates were used to identify the localization of stimulation sites. Fifty-one reading interference areas were found that affected either words (14 areas), or pseudo-words (11 areas), or both (26 areas). Forty-one (80%) corresponded to the impairment of the phonological level of reading processes. Reading processes involved discrete, highly localized perisylvian cortical areas with individual variability. MNI coordinates throughout the group exhibited a clear segregation according to the tested reading route; specific pseudo-word reading interferences were concentrated in a restricted inferior and anterior subpart of the left supramarginal gyrus (barycentre x = -68.1; y = -25.9; z = 30.2; Brodmann's area 40) while specific word reading areas were located almost exclusively alongside the left superior temporal gyrus. Although half of the reading interferences found were nonspecific, the finding of specific lexical or sublexical interferences is new evidence that lexical and sublexical processes of reading could be partially supported by distinct cortical sub-regions despite their anatomical proximity. These data are in line with many brain activation studies that showed that left superior temporal and inferior parietal regions had a crucial role respectively in word and pseudoword reading and were core regions for dyslexia.

Electrostimulation mapping of spatial neglect.

BACKGROUND: Cortical and subcortical electrostimulation mapping during awake brain surgery for tumor removal is usually used to minimize deficits. OBJECTIVE: To use electrostimulation to study neuronal substrates involved in spatial awareness in humans. METHODS: Spatial neglect was studied using a line bisection task in combination with electrostimulation mapping of the right hemisphere in 50 cases. Stimulation sites were identified with Talairach coordinates. The behavioral effects induced by stimulation, especially eye movements and deviations from the median, were quantified and compared with preoperative data and a control group. RESULTS: Composite and highly individualized spatial neglect maps were generated. Both rightward and leftward deviations were induced, sometimes in the same patient but for different stimulation sites. Group analysis showed that specific and reproducible line deviations were induced by stimulation of discrete cortical areas located in the posterior part of the right superior and middle temporal gyri, inferior parietal lobe, and inferior postcentral and inferior frontal gyri (P < .05). Fiber tracking identified stimulated subcortical areas important to spare as sections of fronto-occipital and superior longitudinal II fascicles. According to preoperative and postoperative neglect battery tests, the specificity and sensitivity of intraoperative line bisection tests were 94% and 83%, respectively. CONCLUSION: In humans, discrete cortical areas that are variable in location between individuals but mainly located within the right posterior Sylvian fissure sustain visuospatial attention specifically toward the contralateral or ipsilateral space direction. Line bisection mapping was found to be a reliable method for minimizing spatial neglect caused by brain tumor surgery.

Binaural stimulation through cochlear implants in postlingual deafness: a positron emission tomographic study of word recognition.

HYPOTHESIS: Bilateral stimulation through cochlear implants induces a brain activity pattern closer to the normal one than unilateral stimulation. BACKGROUND: Although it has been shown that speech comprehension through bilateral cochlear implants leads to better performances than after unilateral implantation, the existence of neural underpinnings of this improvement remains to be studied. METHODS: We performed an H2O positron emission tomographic study of word recognition in 5 patients with bilateral cochlear implants and 5 normal-hearing controls. Subjects had to distinguish words from nonwords in binaural and monaural conditions. RESULTS: There was no overactivation in patients for binaural stimulation, with a hypoactivation in the right temporal cortex. For monaural stimulation, patients demonstrated more activation contralaterally to the stimulation side in the posterior temporal cortex and in the cerebellum. CONCLUSION: Binaural stimulation through cochlear implants is advantageous compared with the monaural at the neurofunctional level because the pattern of brain activity is closer to the normal one.

Anatomical correlates for category-specific naming of living and non-living things.

INTRODUCTION: Selective naming categories impairments for living and non-living things are widely reported in brain damaged patients. Electrostimulation mapping was used to study the possible anatomical segregation of living/non-living categories in a prospective series of patients operated on for tumor removal. MATERIALS AND METHODS: Fifty brain mappings (patients with no language impairment; range: 14-80 years; mean: 48 years; 26 males; 5 left handed) were performed in 46 left and 4 right hemispheres using two linguistically controlled tasks (naming for living and non-living things) during an awake surgery procedure. Fifteen regions and four macro cortical areas were designed to analyze the distribution of the interference sites. RESULTS: Over 761 sites stimulated in the lateral hemispheres, 130 naming interferences sites were detected in small cortical areas (<1cm(2)). High individual variability was observed for living/non-living word retrieval localization and organization with a majority (62%) of shared living/non-living interferences. Specific living (12%) or non-living (26%) interferences were found too. In group analysis, no statistical significant anatomical localization was observed for living items in left lateral hemispheric cortex. A statistical significant representation of interference sites for non-living objects was found (Generalized Estimating Equation methodology, z-test=2.28, p=0.027) in the left posterolateral temporoparietal cortex. No influence of histopathology, gender and age on anatomical localization of naming categories was detected. CONCLUSION: The existence of dedicated neural structures for naming non-living things in the left posterolateral temporoparietal cortex is supported by this study although high individual differences exist in the organization of word categories retrieval.

Children with dyslexia reveal abnormal native language representations: evidence from a study of mismatch negativity.

Although a deficit perceiving phonemes, as indexed by the mismatch negativity (MMN), is apparent in developmental dyslexia (DD), studies have not yet addressed whether this deficit might be a result of deficient native language speech representations. The present study examines how a native-vowel prototype and an atypical vowel are discriminated by 9-year-old children with (n = 14) and without (n = 12) DD. MMN was elicited in all conditions in both groups. The control group revealed enhanced MMN to the native-vowel prototype in comparison to the atypical vowel. Children with DD did not show enhanced MMN amplitude to the native-vowel prototype, suggesting impaired tuning to native language speech representations. Furthermore, higher MMN amplitudes to the native-vowel prototype correlated with more advanced reading (r = - .47) and spelling skills (r = - .52).

An investigation of prototypical and atypical within-category vowels and non-speech analogues on cortical auditory evoked related potentials (AERPs) in 9 year old children.

The present study examined cortical auditory evoked related potentials (AERPs) for the P1-N250 and MMN components in children 9 years of age. The first goal was to investigate whether AERPs respond differentially to vowels and complex tones, and the second goal was to explore how prototypical language formant structures might be reflected in these early auditory processing stages. Stimuli were two synthetic within-category vowels (/y/), one of which was preferred by adult German listeners ("prototypical-vowel"), and analogous complex tones. P1 strongly distinguished vowels from tones, revealing larger amplitudes for the more difficult to discriminate but phonetically richer vowel stimuli. Prototypical language phoneme status did not reliably affect AERPs; however P1 amplitudes elicited by the prototypical-vowel correlated robustly with the ability to correctly identify two prototypical-vowels presented in succession as "same" (r=-0.70) and word reading fluency (r=-0.63). These negative correlations suggest that smaller P1 amplitudes elicited by the prototypical-vowel predict enhanced accuracy when judging prototypical-vowel "sameness" and increased word reading speed. N250 and MMN did not differentiate between vowels and tones and showed no correlations to behavioural measures.

Impaired visual hand recognition in preoperative patients during brachial plexus anesthesia: importance of peripheral neural input for mental representation of the hand.

BACKGROUND: Perceptual illusions described in healthy subjects undergoing regional anesthesia (RA) are probably related to short-term plastic brain changes. We addressed whether performance on an implicit mental rotation task reflects these RA-induced changes in body schema brain representations. Studying these changes in healthy volunteers may shed light on normal function and the central mechanisms of pain. METHODS: Performance pattern was studied in upper limb-anesthetized subjects on a left/right hand judgment task, which is known to involve motor imagery processes relating to hand posture. Three conditions were used: control (i.e., absence of deafferentation), RA (i.e., deafferentation), and vision (i.e., deafferentated limb exposed to view). To limit potential bias such as order effect, the control state was recorded in a randomized manner. RESULTS: All subjects described perceptual illusions of their anesthetized limb. They were slower and less accurate on the task during RA compared with control. Response patterns were similar in all conditions, suggesting sensitivity of performance to arm/hand biomechanical constraints. Vision was associated with an increase in the proportion of correct responses and a reduction of the response times in hand judgment and was accompanied by disappearance of the lateralization of the underlying mental representations, which was identified during RA. CONCLUSIONS: These results suggest the following: (1) the right/left judgment task involves mental simulation of hand movements, (2) underlying mental representations and their neural substrates are subject to acute alterations after RA, and (3) the proprioceptive deficit induced by RA is influenced by the subject's ability to see the anesthetized limb.

Superior voice recognition in a patient with acquired prosopagnosia and object agnosia.

Anecdotally, it has been reported that individuals with acquired prosopagnosia compensate for their inability to recognize faces by using other person identity cues such as hair, gait or the voice. Are they therefore superior at the use of non-face cues, specifically voices, to person identity? Here, we empirically measure person and object identity recognition in a patient with acquired prosopagnosia and object agnosia. We quantify person identity (face and voice) and object identity (car and horn) recognition for visual, auditory, and bimodal (visual and auditory) stimuli. The patient is unable to recognize faces or cars, consistent with his prosopagnosia and object agnosia, respectively. He is perfectly able to recognize people's voices and car horns and bimodal stimuli. These data show a reverse shift in the typical weighting of visual over auditory information for audiovisual stimuli in a compromised visual recognition system. Moreover, the patient shows selectively superior voice recognition compared to the controls revealing that two different stimulus domains, persons and objects, may not be equally affected by sensory adaptation effects. This also implies that person and object identity recognition are processed in separate pathways. These data demonstrate that an individual with acquired prosopagnosia and object agnosia can compensate for the visual impairment and become quite skilled at using spared aspects of sensory processing. In the case of acquired prosopagnosia it is advantageous to develop a superior use of voices for person identity recognition in everyday life.

Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature.

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson's disease and 22 control subjects underwent 3-T magnetic resonance imaging with T2*-weighted, whole-brain T1-weighted and diffusion tensor imaging scans. The mean R2* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson's disease and control subjects. Comparisons were also performed using voxel-based analysis of R2*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson's disease displayed significantly higher R2* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson's disease from controls. The markers comprising discriminating combinations were R2* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson's physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R2*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson's disease and, possibly, of other subcortical pathologies.

Mental representations of action: the neural correlates of the verbal and motor components.

Recent theories have hypothesized that semantic representations of action verbs and mental representations of action may be supported by partially overlapping, distributed brain networks. An fMRI experiment in healthy participants was designed to identify the common and specific regions in three different tasks from a common set of object drawings (manipulable man-made objects (MMO) and biological objects (MBO)): the generation of action words (GenA), the mental simulation of action (MSoA) and the mime of an action with the right hand (MimA). A fourth task, object naming (ON), was used as control for input/output effects. A null conjunction identified a common neural network consisting of nine regions distributed over premotor, parietal and occipital cortices. Within this common network, GenA elicited significantly more activation than either ON or MSoA in the left inferior frontal region, while MSoA elicited significantly more activation than either ON or GenA in the left superior parietal lobule. Both MSoA and GenA activated the left inferior parietal lobule more than ON. Furthermore, the left superior parietal cortex was activated to a greater extent by MMO than by MBO regardless of the tasks. These results suggest that action-denoting verbs and motor representations of the same actions activate a common frontal-parietal network. The left inferior parietal cortex and the left superior parietal cortex are likely to be involved in the retrieval of spatial-temporal features of object manipulation; the former might relate to the grasping and manipulation of any object while the latter might be linked to specific object-related gestures.

Volume and iron content in basal ganglia and thalamus.

Magnetic resonance imaging (MRI) studies have highlighted the possibility to investigate brain iron content in vivo. In this study, we combined T2* relaxometry and automatic segmentation of basal ganglia based on T1-weighted images in healthy subjects, with the aim of characterizing age related changes in volume and iron-related relaxivity values (R2*) of these structures. Thirty healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes were calculated for the selected subcortical structures (pallidum, putamen, thalamus and caudate nucleus). Our results showed a correlation between R2* values and iron concentration as calculated from published post-mortem data. Furthermore, we observed a shrinkage/iron increase with a different pattern in the anatomical regions selected in this work, suggesting that the age-related changes on these MR parameters are specific to the subcortical structure considered. In particular, the putamen demonstrated a decrease of volume and an increase of iron level, with the posterior region of this structure appearing more disposed to iron deposition. Our work suggests that combining volumetry and iron estimation in MRI permits to investigate in vivo neurophysiological and neuropathological changes of basal ganglia.

Cortical calculation localization using electrostimulation.

OBJECT: A naming task has been used to spare cortical areas involved in language. In the present study, a calculation task was combined with electrostimulation mapping (awake surgery) to spare cortical areas involved in calculation in patients undergoing surgery for brain lesions. The organization of language and calculation areas was analyzed in relation to these surgical data. METHODS: Twenty patients with brain lesions close to areas possibly involved in calculation (dominant parietal lobe and F2) were prospectively studied over a 4-year period. Four patients had preoperative symptoms of acalculia and therefore were not included in the brain mapping procedure. RESULTS: In 16 patients, direct electrostimulation caused calculation interferences in localized small cortical areas (< 2 cm(2)). Of the 53 calculation interferences found, 23 were independent of language areas, especially those in the inferior left parietal lobule. Various patterns of interference were observed (11 complete acalculia, 5 acalculia with wrong answers, 2 hesitations, and 5 mixed responses), although error patterns were fairly similar across angular, parietal, and frontal stimulation sites. Calculation areas in 4 patients could not be spared for oncological reasons; postoperatively, 3 of these patients showed significant acalculia symptoms. In contrast, none of the patients whose calculation areas were spared had arithmetic difficulties 1 month after surgery. Improvements in acalculia symptoms after surgery were also found in 3 of the 4 patients with preoperative calculation difficulties. CONCLUSIONS: To limit the risk of personal and professional disturbances caused by acquired anarithmetia in patients undergoing surgery for brain tumors or epilepsy, the authors think it is necessary to use a calculation task during brain mapping, especially when operating in the dominant parietal lobe.

Functional MRI follow-up study of language processes in healthy subjects and during recovery in a case of aphasia.

BACKGROUND AND PURPOSE: The goal of this study was to develop a functional MRI (fMRI) paradigm robust and reproducible enough in healthy subjects to be adapted for a follow-up study aiming at evaluating the anatomical substratum of recovery in poststroke aphasia. METHODS: Ten right-handed subjects were studied longitudinally using fMRI (7 of them being scanned twice) and compared with a patient with conduction aphasia during the first year of stroke recovery. RESULTS: Controls exhibited reproducible activation patterns between subjects and between sessions during language tasks. In contrast, the patient exhibited dynamic changes in brain activation pattern, particularly in the phonological task, during the 2 fMRI sessions. At 1 month after stroke, language homotopic right areas were recruited, whereas large perilesional left involvement occurred later (12 months). CONCLUSIONS: We first demonstrate intersubject robustness and intrasubject reproducibility of our paradigm in 10 healthy subjects and thus its validity in a patient follow-up study over a stroke recovery time course. Indeed, results suggest a spatiotemporal poststroke brain reorganization involving both hemispheres during the recovery course, with an early implication of a new contralateral functional neural network and a later implication of an ipsilateral one.

Demand on verbal working memory delays haemodynamic response in the inferior prefrontal cortex.

Event-related functional magnetic resonance imaging was used to test the involvement of the inferior prefrontal cortex in verbal working memory. Pairs of French nouns were presented to ten native French speakers who had to make semantic or grammatical gender decisions. Verbal working memory involvement was manipulated by making the categorization of the second noun optional. Decisions could be made after processing the first noun only (RELEASE condition) or after processing the two nouns (HOLD condition). Reaction times suggested faster processing for gender than for semantic category in RELEASE. Despite the absence of anatomical difference across tasks and conditions in the wide activated network, the haemodynamic response peak latencies of the inferior prefrontal cortex were significantly delayed in HOLD versus RELEASE while no such peak delay was observed in the superior temporal gyrus. Interestingly, this pattern did not interact with language tasks. This study shows that cognitive manipulation can influence haemodynamic time-course and suggests that the main cognitive process determining inferior prefrontal activation is verbal working memory rather than specific linguistic processes such as grammatical or semantic analysis.