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More than a century ago, Broca (1861), Wernicke (1874) and Lichteim (1885) laid the foundations for the first anatomo-functional model of language, secondarily enriched by Geschwind (1967), leading to the Broca-Wernicke-Lichteim-Geschwind model. This model included the frontal, parietal, and temporal cortices as well as a subcortical structure, which could be the striatum, whose nature and role have remained unclear. Although the emergence of language deficits in patients with striatal injury has challenged the cortical language models developed over the past 30 years, the integration of the striatum into language processing models remains rare. The main argument for not including the striatum in language processing is that the disorders observed in patients with striatal dysfunction may result from the striatal role in cognitive functions beyond language, and not from the impairment of language itself. Indeed, unraveling the role of the striatum and the frontal cortex, linked by the fronto-striatal pathway, is a challenge. Here, we first reviewed the studies that explored the link between striatal functions and the different levels of language (phonetics, phonology, morphology, syntax, and lexico-semantics). We then looked at the language models, which included the striatum, and found that none of them captured the diversity of experimental data in this area. Finally, we propose an integrative anatomo-functional model of language processing combining traditional language processing levels and some "executive" functions, known to improve the efficiency and fluidity of language: control, working memory, and attention. We argue that within this integrative model, the striatum is a central node of a verbal executive network that regulates, monitors, and controls the allocations of limited cognitive resources (verbal working memory and verbal attention), whatever the language level. This model combines data from neurology, psycholinguistics, and cognitive science., (Copyright © 2021. Published by Elsevier B.V.)

Mild encephalopathy/encephalitis with reversible splenial lesion (MERS) is a transient clinico-radiological syndrome characterized by non-specific encephalopathy and specific magnetic resonance imaging (MRI) pattern. MRI shows an ovoid lesion in the mid-splenium of the corpus callosum (SCC), with signal-intensity anomaly similar to stroke but vanishing within few weeks. Although there are a lot of child MERS cases descriptions, there are just a few adult-onset reported. Our goal is to provide a better clinical and radiological description of this entity. We reported nine adult-onset cases of MERS managed in our stroke unit between 2017 and 2019. The study of our adult series suggests that epilepsy and the context of an infection are very common in MERS. Adult cases show frequent focal neurological deficits and few encephalopathies compared to children. The measurement of very low ADC values in SCC lesion is a new radiological feature of MERS that should be systematically assessed in suspected cases to differentiate this complex syndrome from SCC strokes., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Time processing over intervals of hundreds of milliseconds to minutes, also known as interval timing, is associated with the striatum. Huntington's disease patients (HD) with striatal degeneration have impaired interval timing, but the extent and specificity of these deficits remain unclear. Are they specific to the temporal domain, or do they extend to the spatial domain too? Do they extend to both the perception and production of interval timing? Do they appear before motor symptoms in Huntington's disease (Pre-HD)? We addressed these issues by assessing both temporal abilities (in the seconds range) and spatial abilities (in the cm range) in 20 Pre-HD, 25 HD patients, and 25 healthy Controls, in discrimination, bisection and production paradigms. In addition, all participants completed a questionnaire assessing temporal and spatial disorientation in daily life, and the gene carriers (i.e., HD and Pre-HD participants) underwent structural brain MRI. Overall, HD patients were more impaired in the temporal than in the spatial domain in the behavioral tasks, and expressed a greater disorientation in the temporal domain in the daily life questionnaire. In contrast, Pre-HD participants showed no sign of a specific temporal deficit. Furthermore, MRI analyses indicated that performances in the temporal discrimination task were associated with a larger striatal grey matter volume in the striatum in gene carriers. Altogether, behavioral, brain imaging and questionnaire data support the hypothesis that the striatum is a specific component of interval timing processes. Evaluations of temporal disorientation and interval timing processing could be used as clinical tools for HD patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD. Here, we investigated cortical sulcal depth, related to degenerative process, as well as cortical sulcal length, related to developmental process, in early-stage HD and age-matched healthy controls. This morphometric analysis revealed significant differences in the HD participants compared with the healthy controls bilaterally in the central and intra-parietal sulcus, but also in the left intermediate frontal sulcus and calcarine fissure. As the primary visual cortex is not connected to the striatum, the latter result adds to the increasing in vivo evidence for primary cortical degeneration in HD. Those sulcal measures that differed between HD and healthy populations were mainly atrophy-related, showing shallower sulci in HD. Conversely, the sulcal morphometry also revealed a crucial difference in the imprint of the Sylvian fissure that could not be related to loss of grey matter volume: an absence of asymmetry in the length of this fissure in HD. Strong asymmetry in that cortical region is typically observed in healthy development. As the formation of the Sylvian fissure appears early in utero, and marked asymmetry is specifically found in this area of the neocortex in newborns, this novel finding likely indicates the foetal timing of a disease-specific, genetic interplay with neurodevelopment., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Fifty-one patients from open-label pilot trials have been transplanted in Huntington's disease (HD) using human fetal cells; clinical data and follow-up are available in 30 of them. These open-label studies were mostly designed for safety and feasibility. However, signs of long-term efficacy have been reported in 4 out of 30 patients, differences in tissue preparation, surgical procedure, patients characteristics, immunosuppression regimens, clinical, and imaging assessments, makes it difficult to define the optimal procedure for future trials. Forty-five patients have now been grafted in the multicentric intracerebral grafting trial in Huntington's in France (MIG-HD) and Belgium, and 22 in Germany in a randomized delayed start design. Whereas the 10 patients published from the German cohort showed no improvement, the results from the MIG-HD trial are still under analysis. However, the MIG-HD trial has already changed cell transplantation for HD by showing alloimmunization with graft rejection in one patient and HLA antibodies against the transplant in others. Moreover, MIG-HD has established a new surgical procedure to avoid subdural hematoma, the most frequent adverse effect in transplant in HD, and a surgical strategy to eradicate eventual choroid cysts. By reviewing all the published results, new avenues are provided for optimization for cell preparation, delivery methods, standardization of clinical assessment, and surgical procedure with blind video scoring, imaging, and electrophysiology. Future trials should capitalize on a new CAPIT-HD2 battery to determine efficacy with sufficiently long pre and postgraft follow-up, using patient stratification and randomization, control of alloimmunization, HLA monitoring, and standardization of the consent procedure., (© 2017 Elsevier B.V. All rights reserved.)

During speech perception, listeners compensate for phonological rules of their language. For instance, English place assimilation causes green boat to be typically pronounced as greem boat; English listeners, however, perceptually compensate for this rule and retrieve the intended sound (n). Previous research using EEG has focused on rules with clear phonetic underpinnings, showing that perceptual compensation occurs at an early stage of speech perception. We tested whether this early mechanism also accounts for the compensation for more complex rules. We examined compensation for French voicing assimilation, a rule with abstract phonological restrictions on the contexts in which it applies. Our results reveal that perceptual compensation for this rule by French listeners modulates an early ERP component. This is evidence that early stages of speech sound categorization are sensitive to complex phonological rules of the native language., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Clinical neural transplantation in Huntington's disease has moved forward as a series of small studies, which have provided some preliminary proof of principle that neural transplantation can provide benefit. However, to date, such benefits have not been robust, and there are a number of important issues that need to be addressed. These include defining the optimum donor tissue conditions and host characteristics in order to produce reliable benefit in transplant recipients, and whether, and for how long, immunosuppression is needed. Further clinical studies will be required to address these, and other issues, in order to better understand the processes leading to a properly functioning neural graft. Such studies will pave the way for future clinical trials of renewable donor sources, in particular, stem cell-derived neuronal progenitor grafts., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease., Methods: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity., Findings: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two., Interpretation: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.