Marc Teichmann

The Role of the Striatum in Processing Language Rules: Evidence from Word Perception in Huntington's Disease

On the assumption that linguistic faculties reflect both lexical storage in the temporal cortex and combinatorial rules in the striatal circuits, several authors have shown that striatal-damaged patients are impaired with conjugation rules while retaining lexical knowledge of irregular verbs [Teichmann, M., Dupoux, E., Kouider, S., Brugires, P., Boiss, M. F., Baudic, S., Cesaro, P., Peschanski, M., & Bachoud-Lvi, A. C. (2005). The role of the striatum in rule application. The model of Huntingtons disease at early stage. Brain, 128, 11551167; Ullman, M. T., Corkin, S., Coppola, M., Hickok, G., Growdon, J. H., Koroshetz, W. J., & Pinker, S. (1997). A neural dissociation within language: Evidence that the mental dictionary is part of declarative memory, and that grammatical rules are processed by the procedural system. Journal of Cognitive Neuroscience, 9, 266276]. Yet, such impairment was documented only with explicit conjugation tasks in the production domain. Little is known about whether it generalizes to other language modalities such as perception and whether it refers to implicit language processing or rather to intentional rule operations through executive functions. We investigated these issues by assessing perceptive processing of conjugated verb forms in a model of striatal dysfunction, namely, in Huntingtons Disease (HD) at early stages. Rule application and lexical processes were evaluated in an explicit task (acceptability judgments on verb and nonword forms) and in an implicit task (lexical decision on frequency-manipulated verb forms). HD patients were also assessed in executive functions, and striatal atrophy was evaluated with magnetic resonance imaging (bicaudate ratio). Results from both tasks showed that HD patients were selectively impaired for rule application but lexical abilities were spared. Bicaudate ratios correlated with rule scores on both tasks, whereas executive parameters only correlated with scores on the explicit task. We argue that the striatum has a core function in linguistic rule application generalizing to perceptive aspects of morphological operations and pertaining to implicit language processes. In addition, we suggest that the striatum may enclose computational circuits that underpin explicit manipulation of regularities.

Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept

Preclinical Alzheimers disease (AD) is a relatively recent concept describing an entity characterized by the presence of a pathophysiological biomarker signature characteristic for AD in the absence of specific clinical symptoms. There is rising interest in the scientific community to define such an early target population mainly because of failures of all recent clinical trials despite evidence of biological effects on brain amyloidosis for some compounds. A conceptual framework has recently been proposed for this preclinical phase of AD. However, few data exist on this silent stage of AD. We performed a systematic review to investigate how the concept is defined across studies. The review highlights the substantial heterogeneity concerning the three main determinants of preclinical AD: “normal cognition,” “cognitive decline,” and “AD pathophysiological signature.” We emphasize the need for a harmonized nomenclature of the preclinical AD concept and standardized population‐based and case‐control studies using unified operationalized criteria.

Distinct brain perfusion pattern associated with CSF biomarkers profile in primary progressive aphasia

Objective A new classification of primary progressive aphasia (PPA) was recently proposed to differentiate between non-fluent aphasia (NF-PPA), semantic variant of PPA (S-PPA) and logopenic aphasia (LPA) by their phenotypic presentations. CSF biomarkers (BM) may differentiate PPA with atypical Alzheimers disease (AD) that presents with LPA from PPA with frontotemporal lobe degeneration that presents with either NF-PPA or S-PPA. Single photon emission computed tomography (SPECT) was used to investigate brain hypoperfusion differences among PPA subtypes according to their CSF AD profiles. Methods 34 PPA patients underwent lumbar puncture and brain perfusion SPECT. PPA patients were classified into two subgroups according to theAβ42:tau ratio: PPA BM positive (with an AD CSF profile) and PPA BM negative (not having an AD CSF profile). The biological classification was made while blind to the phenotypical presentation. The brain perfusion profiles of the PPA subgroups were compared with those of 24 healthy subjects. Results PPA BM positive patients had left-side predominant hypoperfusion in the temporoparietal cortex that extended to the dorsolateral prefrontal cortex and perisylvian region while PPA BM negative patients had hypoperfusion that was predominant in the temporal poles (p<10−4 corrected). Conclusion Distinct hypoperfusion patterns in PPA BM positive and PPA BM negative patients were observed, similar to those that have been described for S-PPA and LPA. These results support using CSF biomarkers to classify PPA.

The role of the striatum in phonological processing: evidence from early stages of Huntington's disease.

The linguistic role of subcortical structures such as the striatum is still controversial. According to the claim that language processing is subdivided into a lexical memory store and a computational rule system (Pinker, 1999) several studies on word morphology (e.g., Ullman et al., 1997) and on syntax (e.g., Teichmann et al., 2005) have suggested that the striatum is specifically dedicated to the latter component. However, little is known about whether the striatum is involved in phonological operations and whether its role in linguistic rule application generalizes to phonological processing. We investigated this issue by assessing perceptual compensation for assimilation rules in a model of striatal disorders, namely in the early stages of Huntingtons disease (HD). In Experiment 1 we used a same-different task with isolated words to evaluate whether phoneme perception is intact in HD. In Experiment 2 a word detection task in phrasal contexts allowed for assessing both phoneme perception and perceptual compensation for the French regressive assimilation rule. Results showed that HD patients have normal performance with both phoneme perception in isolated words and regressive assimilation rules. However, in phrasal contexts they display reduced abilities of phoneme discrimination. These findings challenge the striatum-rule claim and suggest a more fine-grained function of striatal structures in linguistic rule processing. Alternative explanatory frameworks of the striatum-language link are discussed.

A Cortical-Subcortical Syntax Pathway Linking Broca's Area and the Striatum

Combinatorial syntax has been shown to be underpinned by cortical key regions such as Brocas area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico‐to‐cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex‐centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca‐striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel‐based lesion‐symptom mapping (VLSM) to provide an anatomo‐functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico‐cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca‐striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract‐lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca‐striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax‐network models, by adding a deep “Broca‐caudate pathway,” and are consistent with functional accounts of frontostriatal circuits. Hum Brain Mapp 36:2270–2283, 2015.

Logopenic progressive aphasia beyond Alzheimer's—an evolution towards dementia with Lewy bodies

Primary progressive aphasia (PPA) is an umbrella term which identifies a group of neurodegenerative diseases manifested by relatively isolated language disorders. The logopenic variant (LPA), is characterised by a ‘word-on-the-tip-of-the-tongue phenomenon’ and anomia as well as by comprehension and repetition difficulties for sentences due to verbal working memory deficits.1 Cortical atrophy typically affects the left temporal-parietal junction.1 According to most studies LPA is primarily due to underlying Alzheimers Disease (AD) pathology as suggested by biomarker findings from positron emission tomography with Pittsburgh compound B binding to amyloid deposits (PET-PIB) imaging and CSF (cerebrospinal fluid) β-amyloid and τ measures as well as by neuropathological data.2 However, PET-PIB and CSF data are drawn from relatively small PPA populations, which makes it difficult to conclude that LPA is invariably underpinned by AD pathology. Furthermore, neuropathological results from the most important sample of LPA patients have demonstrated that only seven out of 11 patients had AD while the remaining four patients had pathology characteristic of frontotemporal lobar degeneration.2 Finally, follow-up studies showing that LPA …

Free and Cued Selective Reminding Test – accuracy for the differential diagnosis of Alzheimer's and neurodegenerative diseases: a large-scale biomarker-characterized monocenter cohort study (ClinAD)

The International Working Group recommended the Free and Cued Selective Reminding Test (FCSRT) as a sensitive detector of the amnesic syndrome of the hippocampal type in typical Alzheimers disease (AD). But does it differentiate AD from other neurodegenerative diseases?

The Brain Network of Naming: A Lesson from Primary Progressive Aphasia.

Objective Word finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to-lexical information which also subserves lexical-to-semantic mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking. Methods We addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture-naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical-semantic hub. Results and Conclusions Our results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid-temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies.

Defining the spectrum of frontotemporal dementias associated with TARDBP mutations

Objectives: We describe the largest series of patients with TARDBP mutations presenting with frontotemporal dementia (FTD) and review the cases in the literature to precisely characterize FTD diseases associated with this genotype. Methods: The phenotypic characteristics of 29 TARDBP patients, including 10 new French and Dutch cases and 19 reviewed from the literature, were evaluated. Results: The most frequent phenotype was a behavioral variant frontotemporal dementia (bvFTD), but a significant proportion (40%) of our patients had semantic (svFTD) or nonfluent variants (nfvFTD) at onset; and svFTD was significantly more frequent in TARDBP carriers than in other FTD genotypes (p < 0.001). Remarkably, only a minority (40%) of our patients secondarily developed amyotrophic lateral sclerosis (ALS). Two patients carried a homozygous mutation but strikingly different phenotypes (bvFTD and ALS) indicating that homozygosity does not result in a specific phenotype. Earlier age at onset in children than parents generations, mimicking an apparent “anticipation” (21.8 ± 9.3 years, p = 0.001), and possible reduced penetrance were present in most families. Conclusions: This study enlarges the phenotypic spectrum of TARDBP and will have important clinical implications: (1) FTD can be the only clinical manifestation of TARDBP mutations; (2) Initial language or semantic disorders might be indicative of a specific genotype; (3) Mutations should be searched in all FTD phenotypes after exclusion of major genes, even in the absence of ALS in the proband or in family history; (4) reduced penetrance and clinical variability should be considered to deliver appropriate genetic counseling.

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia

Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small‐cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv‐PPA), applying a rigorous study design to a large, homogeneous sv‐PPA cohort.