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1.
Neuroimage Clin ; 40: 103516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37769366

RESUMO

The neuroanatomical correlates of basic semantic composition have been investigated in previous neuroimaging and lesion studies, but research on the electrophysiology of the involved processes is scarce. A large literature on sentence-level event-related potentials (ERPs) during semantic processing has identified at least two relevant components - the N400 and the P600. Other studies demonstrated that these components are reduced and/or delayed in people with aphasia (PWA). However, it remains to be shown if these findings generalize beyond the sentence level. Specifically, it is an open question if an alteration in ERP responses in PWA can also be observed during basic semantic composition, providing a potential future diagnostic tool. The present study aimed to elucidate the electrophysiological dynamics of basic semantic composition in a group of post-stroke PWA. We included 20 PWA and 20 age-matched controls (mean age 58 years) and measured ERP responses while they performed a plausibility judgment task on two-word phrases that were either meaningful ("anxious horse"), anomalous ("anxious wood") or had the noun replaced by a pseudoword ("anxious gufel"). The N400 effect for anomalous versus meaningful phrases was similar in both groups. In contrast, unlike the control group, PWA did not show an N400 effect between pseudoword and meaningful phrases. Moreover, both groups exhibited a parietal P600 effect towards pseudoword phrases, while PWA showed an additional P600 over frontal electrodes. Finally, PWA showed an inverse correlation between the magnitude of the N400 and P600 effects: PWA exhibiting no or even reversed N400 effects towards anomalous and pseudoword phrases showed a stronger P600 effect. These results may reflect a compensatory mechanism which allows PWA to arrive at the correct interpretation of the phrase. When compositional processing capacities are impaired in the early N400 time-window, PWA may make use of a more elaborate re-analysis process reflected in the P600.


Assuntos
Afasia , Semântica , Humanos , Masculino , Feminino , Animais , Cavalos , Pessoa de Meia-Idade , Potenciais Evocados/fisiologia , Eletroencefalografia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Afasia/diagnóstico por imagem , Afasia/etiologia , Compreensão/fisiologia
2.
Neurophotonics ; 10(2): 023517, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36873247

RESUMO

Over its 30 years of existence, functional near-infrared spectroscopy (fNIRS) has matured into a highly versatile tool to study brain function in infants and young children. Its advantages, amongst others, include its ease of application and portability, the option to combine it with electrophysiology, and its relatively good tolerance to movement. As shown by the impressive body of fNIRS literature in the field of cognitive developmental neuroscience, the method's strengths become even more relevant for (very) young individuals who suffer from neurological, behavioral, and/or cognitive impairment. Although a number of studies have been conducted with a clinical perspective, fNIRS cannot yet be considered as a truly clinical tool. The first step has been taken in this direction by studies exploring options in populations with well-defined clinical profiles. To foster further progress, here, we review several of these clinical approaches to identify the challenges and perspectives of fNIRS in the field of developmental disorders. We first outline the contributions of fNIRS in selected areas of pediatric clinical research: epilepsy, communicative and language disorders, and attention-deficit/hyperactivity disorder. We provide a scoping review as a framework to allow the highlighting of specific and general challenges of using fNIRS in pediatric research. We also discuss potential solutions and perspectives on the broader use of fNIRS in the clinical setting. This may be of use to future research, targeting clinical applications of fNIRS in children and adolescents.

3.
Child Dev ; 94(3): e166-e180, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36716199

RESUMO

Consonants and vowels differentially contribute to lexical acquisition. From 8 months on, infants' preferential reliance on consonants has been shown to predict their lexical outcome. Here, the predictive value of German-learning infants' (n = 58, 29 girls, 29 boys) trajectories of consonant and vowel perception, indicated by the electrophysiological mismatch response, across 2, 6, and 10 months for later lexical acquisition was studied. The consonant-perception trajectory from 2 to 6 months (ß = -2.95) and 6 to 10 months (ß = -.91), but not the vowel-perception trajectory, significantly predicted receptive vocabulary at 12 months. These results reveal an earlier predictive value of consonant perception for word learning than previously found, and a particular role of the longitudinal maturation of this skill in lexical acquisition.


Assuntos
Fonética , Percepção da Fala , Masculino , Feminino , Lactente , Humanos , Aprendizagem , Vocabulário , Aprendizagem Verbal
4.
Neuropsychologia ; 180: 108465, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36586718

RESUMO

BACKGROUND AND OBJECTIVES: Syntactic competence relies on a left-lateralized network converging on hubs in inferior-frontal and posterior-temporal cortices. We address the question whether anodal transcranial direct current stimulation (a-tDCS) over these hubs can modulate comprehension of sentences, whose syntactic complexity systematically varied along the factors embedding depths and canonicity. Semantic content and length of the sentences were kept identical and forced choice picture matching was required after the full sentence had been presented. METHODS: We used a single-blind, within-subject, sham-controlled design, applying a-tDCS targeting left posterior tempo-parietal (TP) and left inferior frontal cortex (FC). Stimulation sites were determined by individual neuro-navigation. 20 participants were included of whom 19 entered the analysis. Results were analysed using (generalized) mixed models. In a pilot-experiment in another group of 20 participants we validated the manipulation of syntactic complexity by the two factors embedding depth and argument-order. RESULTS: Reaction times increased and accuracy decreased with higher embedding depth and non-canonical argument order in both experiments. Notably a-tDCS over TP enhanced sentence-to-picture matching, while FC-stimulation showed no consistent effect. Moreover, the analysis disclosed a session effect, indicating improvements of task performance especially regarding speed. CONCLUSIONS: We conclude that the posterior 'hub' of the neuronal network affording syntactic analysis represents a 'bottleneck', likely due to working-memory capacity and the challenges of mapping semantic to syntactic information allowing for role assignment. While this does not challenge the role of left inferior-frontal cortex for syntax processing and novel-grammar learning, the application of highly established syntactic rules during sentence comprehension may be considered optimized, thus not augmentable by a-tDCS in the uncompromised network. SIGNIFICANCE STATEMENT: Anodal transcranial direct current stimulation (a-tDCS) over left temporo-parietal cortex enhances comprehension of complex sentences in uncompromised young speakers. Since a-tDCS over left frontal cortex did not elicit any change, the 'bottleneck' for the understanding of complex sentences seems to be the posterior, temporo-parietal rather than the anterior inferior-frontal 'hub' of language processing. Regarding the attested role of inferior-frontal cortex in syntax processing, we suggest that its function is optimized in competent young speakers, preventing further enhancement by (facilitatory) tDCS. Results shed light on the functional anatomy of syntax processing during sentence comprehension; moreover, they open perspectives for research in the lesioned language network of people with syntactic deficits due to aphasia.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Método Simples-Cego , Compreensão/fisiologia , Imageamento por Ressonância Magnética , Idioma , Lobo Frontal/fisiologia , Mapeamento Encefálico
5.
Behav Res Methods ; 55(1): 236-262, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35378676

RESUMO

For experimental research on language production, temporal precision and high quality of the recorded audio files are imperative. These requirements are a considerable challenge if language production is to be investigated online. However, online research has huge potential in terms of efficiency, ecological validity and diversity of study populations in psycholinguistic and related research, also beyond the current situation. Here, we supply confirmatory evidence that language production can be investigated online and that reaction time (RT) distributions and error rates are similar in written naming responses (using the keyboard) and typical overt spoken responses. To assess semantic interference effects in both modalities, we performed two pre-registered experiments (n = 30 each) in online settings using the participants' web browsers. A cumulative semantic interference (CSI) paradigm was employed that required naming several exemplars of semantic categories within a seemingly unrelated sequence of objects. RT is expected to increase linearly for each additional exemplar of a category. In Experiment 1, CSI effects in naming times described in lab-based studies were replicated. In Experiment 2, the responses were typed on participants' computer keyboards, and the first correct key press was used for RT analysis. This novel response assessment yielded a qualitatively similar, very robust CSI effect. Besides technical ease of application, collecting typewritten responses and automatic data preprocessing substantially reduce the work load for language production research. Results of both experiments open new perspectives for research on RT effects in language experiments across a wide range of contexts. JavaScript- and R-based implementations for data collection and processing are available for download.


Assuntos
Idioma , Semântica , Humanos , Tempo de Reação/fisiologia , Psicolinguística , Internet , Reconhecimento Visual de Modelos/fisiologia
6.
J Speech Lang Hear Res ; 65(12): 4774-4796, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36455138

RESUMO

PURPOSE: Persons with unilateral brain damage in the right hemisphere (RH) or left hemisphere (LH) show limitations in processing linguistic prosody, with yet inconclusive results on their ability to process prosodically marked structural boundaries for syntactic ambiguity resolution. We aimed at systematically investigating production and comprehension of three prosodic cues (f 0 range, final lengthening, and pause) at structural boundaries in coordinate sequences in participants with right hemisphere brain damage (RHDP) and participants with left hemisphere brain damage (LHDP). METHOD: Twenty RHDP and 15 LHDP participated in our study. Comprehension experiment: Participants and a control group listened to coordinate name sequences with internal grouping by a prosodically marked structural boundary (grouped condition, e.g., "(Gabi und Leni) # und Nina") or without internal grouping (ungrouped condition, e.g., "Gabi und Leni und Nina") and had to identify the target condition. The strength and combinations of prosodic cues in the stimuli were manipulated. Production experiment: Participants were asked to produce coordinate sequences in the two conditions (grouped, ungrouped) in two different tasks: a Reading Aloud and a Repetition experiment. Accuracy of participants' productions was subsequently assessed in a rating study and productions were analyzed with respect to use of prosodic cues. RESULTS: In the Comprehension experiment, RHDP and LHDP had overall lower identification accuracies than unimpaired control participants and LHDP were found to have particular problems with boundary identification when the pause cue was reduced. In production, LHDP and RHDP employed all three prosodic cues for boundary marking, but struggled to clearly mark prosodic boundaries in 28% of all productions. Both groups showed better performance in reading aloud than in repetition. LHDP relied more on using f 0 range and pause duration to prosodically mark structural boundaries, whereas RHDP employed final lengthening more vigorously than LHDP in reading aloud. CONCLUSIONS: We conclude that processing of linguistic prosody is affected in RHDP and LHDP, but not completely impaired. Therefore, prosody can serve as a relevant communicative resource. However, it should also be considered as a target area for assessment and treatment in both groups. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21637505.


Assuntos
Compreensão , Percepção da Fala , Humanos , Leitura , Sinais (Psicologia) , Linguística , Encéfalo
7.
Front Neurol ; 13: 988359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237627

RESUMO

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

8.
JAMA Netw Open ; 5(9): e2232672, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129707

RESUMO

Importance: Language development builds on speech perception, with early disruptions increasing the risk for later language difficulties. Although a major postpartum depressive episode is associated with language development, this association has not been investigated among infants of mothers experiencing a depressed mood at subclinical levels after birth, even though such a mood is frequently present in the first weeks after birth. Understanding whether subclinical depressed maternal mood after birth is associated with early language development is important given opportunities of coping strategies for subclinical depressed mood. Objective: To examine whether depressed maternal mood at subclinical levels 2 months after birth is associated with infant speech perception trajectories from ages 2 to 6.5 months. Design, Setting, and Participants: In this longitudinal cohort study conducted between January 1, 2018, and October 31, 2019, 46 healthy, monolingual German mother-infant dyads were tested. The sample was recruited from the infants database of the Max Planck Institute for Human Cognitive and Brain Sciences. Initial statistical analysis was performed between January 1 and March 31, 2021; the moderation analysis (results reported herein) was conducted between July 1 and July 31, 2022. Exposures: Mothers reported postpartum mood via the German version of the Edinburgh Postnatal Depression Scale (higher scores indicated higher levels of depressed mood, with a cutoff of 13 points indicating a high probability of clinical depression) when their infants were 2 months old. Main Outcomes and Measures: Electrophysiological correlates of infant speech perception (mismatch response to speech stimuli) were tested when the infants were aged 2 months (initial assessment) and 6.5 months (follow-up). Results: A total of 46 mothers (mean [SD] age, 32.1 [3.8] years) and their 2-month-old children (mean [SD] age, 9.6 [1.2] weeks; 23 girls and 23 boys) participated at the initial assessment, and 36 mothers (mean [SD] age, 32.2 [4.1] years) and their then 6.5-month-old children (mean [SD] age, 28.4 [1.5 weeks; 18 girls and 18 boys) participated at follow-up. Moderation analyses revealed that more depressed maternal subclinical postpartum mood (mean [SD] Edinburgh Postnatal Depression Scale score, 4.8 [3.6]) was associated with weaker longitudinal changes of infants' electrophysiological brain responses to syllable pitch speech information from ages 2 to 6.5 months (coefficient: 0.68; 95% CI, 0.03-1.33; P = .04). Conclusions and Relevance: The results of this cohort study suggest that infant speech perception trajectories are correlated with subclinical depressed mood in postpartum mothers. This finding lays the groundwork for future research on early support for caregivers experiencing depressed mood to have a positive association with children's language development.


Assuntos
Depressão Pós-Parto , Percepção da Fala , Adulto , Criança , Estudos de Coortes , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Relações Mãe-Filho , Período Pós-Parto
9.
Dev Cogn Neurosci ; 56: 101127, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35763917

RESUMO

Infants rapidly advance in their speech perception, electrophysiologically reflected in the transition from an immature, positive-going to an adult-like, negative-going mismatch response (MMR) to auditory deviancy. Although the MMR is a common tool to study speech perception development, it is not yet completely understood how different speech contrasts affect the MMR's characteristics across development. Thus, a systematic longitudinal investigation of the MMR's maturation depending on speech contrast is necessary. We here longitudinally explored the maturation of the infant MMR to four critical speech contrasts: consonant, vowel, vowel-length, and pitch. MMRs were obtained when infants (n = 58) were 2, 6 and 10 months old. To evaluate the maturational trajectory of MMRs, we applied second-order latent growth curve models. Results showed positive-going MMR amplitudes to all speech contrasts across all assessment points that decreased over time towards an adult-like negativity. Notably, the developmental trajectories of speech contrasts differed, implying that infant speech perception matures with different rates and trajectories throughout the first year, depending on the studied auditory feature. Our results suggest that stimulus-dependent maturational trajectories need to be considered when drawing conclusions about infant speech perception development reflected by the infant MMR.


Assuntos
Percepção da Fala , Estimulação Acústica , Adulto , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Humanos , Lactente , Fala/fisiologia , Percepção da Fala/fisiologia
10.
Alzheimer Dis Assoc Disord ; 36(1): 44-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35001030

RESUMO

BACKGROUND: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA). OBJECTIVE: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA. METHOD: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed. RESULTS: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%). CONCLUSION: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA.


Assuntos
Afasia Primária Progressiva , Afasia Primária Progressiva não Fluente , Afasia Primária Progressiva/diagnóstico , Humanos , Idioma
11.
Neuroimage ; 246: 118767, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856377

RESUMO

The breakdown of rapid and accurate retrieval of words is a hallmark of aphasic speech and a prime target of therapeutic intervention. Complementary, psycho- and neurolinguistic research have developed a spectrum of models, how and by which neuronal network uncompromised speakers can rely on remarkable lexical retrieval capacities. Motivated by both lines of research we invited 32 participants with a chronic left hemispheric brain lesion to name pictures in the presence of distractor words. This picture-word-interference (PWI) paradigm is widely used in psycho- and neurolinguistic research. We find that also after brain lesion categorically related words (CAT â†’ [dog]picture) impede naming, while associatively related words (BONE â†’ [dog]picture) ease access, when compared to unrelated distractor words. The effects largely affecting latencies in neurotypical populations, are reproduced for error rate in our participants with lesions in the language network. Unsurprisingly, overall naming abilities varied greatly across patients. Notably, however, the two effects (categorical interference / associative facilitation) differ between participants. Correlating performance with lesion patterns we find support for the notion of a divergence of brain areas affording different aspects of the task: (i) lesions in the left middle temporal gyurs (MTG) deteriorate overall naming, confirming previous work; more notably, (ii) lesions comprising the inferior frontal hub (inferior frontal gyrus, IFG) of the language-network increase the interference effect for the categorical condition; on the contrary, (iii) lesions to the mid-to-posterior temporal hub (posterior middle and superior temporal gyri, pMTG/ pSTG) increase the facilitatory effect for the associative condition on error rates. The findings can be accommodated in a neuro-linguistic framework, which localizes lexical activation but also lexical interference in posterior parts of the language network (pMTG/pITG); conversely, selection between co-activated categorically related entries is afforded by frontal language areas (IFG). While purely experimental in nature our study highlights that lesion site differentially influences specific aspects of word retrieval. Since confrontational naming is a cornerstone of aphasia rehabilitation, this may be of note when designing and evaluating novel therapeutic regimes.


Assuntos
Afasia , Córtex Cerebral , Disfunção Cognitiva , Rede Nervosa , Reconhecimento Visual de Modelos/fisiologia , Psicolinguística , Adulto , Idoso , Afasia/diagnóstico por imagem , Afasia/patologia , Afasia/fisiopatologia , Associação , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Semântica
12.
Cortex ; 146: 116-140, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856428

RESUMO

Our study examines the lexical representation and processing of compounds in participants with aphasia (PWA) and language-unimpaired control speakers. Participants were engaged in primed picture-naming in German, a language that marks for grammatical gender. Gender-marked determiners served as primes (dermasc, diefem, dasneut [the]) and noun-noun compounds as targets (e.g., Goldneutfischmasc [goldfish]). Experiment 1 tested whether the compound's constituents are activated at a lexical-syntactic level during production. Primes were gender-congruent either with the morphological head of the target compound (e.g., dermasc for the target Goldneutfischmasc), or its modifier (dasneut for Goldneutfischmasc), or incongruent with both (diefem). Head congruency of prime and target produced strong facilitatory effects across groups. Modifier congruent primes produced contrasting effects. Modifier congruency speeded up picture naming in the controls and PWA with isolated deficits of lexical access (PWA-lex) but they delayed picture naming in PWA with additional deficits of phonological encoding (PWA-pho). Both patterns suggest that the lemmas of both constituents of compound targets and their grammatical gender are activated during compound retrieval, in line with a multiple-lemma representation of compounds. Experiment 2 explored the nature of the observed effects compared to a gender-neutral control condition. While facilitatory effects were shown by PWA-lex and the controls, PWA-pho did not profit from congruent primes but showed inhibitory effects by incongruent primes, exclusively. Inhibitory effects were also attested for the controls but not for PWA-lex. The functional origin of determiner priming effects and their theoretical and clinical implications are discussed in the framework of current accounts.


Assuntos
Afasia , Idioma , Humanos , Linguística
13.
J Cogn Neurosci ; 33(8): 1612-1633, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34496369

RESUMO

When we refer to an object or concept by its name, activation of semantic and categorical information is necessary to retrieve the correct lexical representation. Whereas in neurotypical individuals it is well established that semantic context can interfere with or facilitate lexical retrieval, these effects are much less studied in people with lesions to the language network and impairment at different steps of lexical-semantic processing. Here, we applied a novel picture naming paradigm, where multiple categorically related and unrelated words were presented as distractors before a to-be-named target picture. Using eye tracking, we investigated preferential fixation on the cohort members versus nonmembers. Thereby, we can judge the impact of explicit acknowledgment of the category and its effect on semantic interference. We found that, in contrast to neurotypical participants [van Scherpenberg, C., Abdel Rahman, R., & Obrig, H. A novel multiword paradigm for investigating semantic context effects in language production. PLoS One, 15, e0230439, 2020], participants suffering from mild to moderate aphasia did not show a fixation preference on category members but still showed a large interference effect of ∼35 msec, confirming the implicit mechanism of categorical interference. However, preferential fixation on the categorically related cohort words correlated with clinical tests regarding nonverbal semantic abilities and integrity of the anterior temporal lobe. This highlights the role of supramodal semantics for explicit recognition of a semantic category, while semantic interference is triggered if the threshold of lexical cohort activation is reached. Confirming psycholinguistic evidence, the demonstration of a large and persistent interference effect through implicit lexico-semantic activation is important to understand deficits in people with a lesion in thelanguage network, potentially relevant for individualized intervention aiming at improving naming skills.


Assuntos
Afasia , Semântica , Afasia/etiologia , Humanos , Idioma , Reconhecimento Visual de Modelos , Lobo Temporal
14.
Mol Psychiatry ; 26(10): 5824-5832, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34561610

RESUMO

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.


Assuntos
Demência Frontotemporal , Proteína C9orf72/genética , Demência Frontotemporal/genética , Genótipo , Humanos , Masculino , Mutação , Estudos Retrospectivos , Sequenciamento do Exoma , Proteínas tau/genética
15.
Brain Commun ; 3(2): fcab090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34159319

RESUMO

Semantic composition is the ability to combine single words to form complex meanings and is an essential component for successful communication. Evidence from neuroimaging studies suggests that semantic composition engages a widely distributed left-hemispheric network, including the anterior temporal lobe, the inferior frontal gyrus and the angular gyrus. To date, the functional relevance of these regions remains unclear. Here, we investigate the impact of lesions to key regions in the semantic network on basic semantic composition. We conducted a multivariate lesion-behaviour mapping study in 36 native German speaking participants with chronic lesions to the language network after left-hemispheric stroke. During the experiment, participants performed a plausibility judgement task on auditorily presented adjective-noun phrases that were either meaningful ('anxious horse'), anomalous ('anxious salad') or had the noun replaced by a pseudoword ('anxious gufel'), as well as a single-word control condition ('horse'). We observed that reduced accuracy for anomalous phrases is associated with lesions in left anterior inferior frontal gyrus, whereas increased reaction times for anomalous phrases correlates with lesions in anterior-to-mid temporal lobe. These results indicate that anterior inferior frontal gyrus is relevant for accurate semantic decisions, while anterior-to-mid temporal lobe lesions lead to slowing of the decision for anomalous two-word phrases. These differential effects of lesion location support the notion that anterior inferior frontal gyrus affords executive control for decisions on semantic composition while anterior-to-mid temporal lobe lesions slow the semantic processing of the individual constituents of the phrase.

17.
Neurophotonics ; 8(1): 012101, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33442557

RESUMO

The application of functional near-infrared spectroscopy (fNIRS) in the neurosciences has been expanding over the last 40 years. Today, it is addressing a wide range of applications within different populations and utilizes a great variety of experimental paradigms. With the rapid growth and the diversification of research methods, some inconsistencies are appearing in the way in which methods are presented, which can make the interpretation and replication of studies unnecessarily challenging. The Society for Functional Near-Infrared Spectroscopy has thus been motivated to organize a representative (but not exhaustive) group of leaders in the field to build a consensus on the best practices for describing the methods utilized in fNIRS studies. Our paper has been designed to provide guidelines to help enhance the reliability, repeatability, and traceability of reported fNIRS studies and encourage best practices throughout the community. A checklist is provided to guide authors in the preparation of their manuscripts and to assist reviewers when evaluating fNIRS papers.

18.
Alzheimers Dement (Amst) ; 13(1): e12262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35005196

RESUMO

INTRODUCTION: The behavioral variant of frontotemporal dementia (bvFTD) is a rare neurodegenerative disease. Reliable predictors of disease progression have not been sufficiently identified. We investigated multivariate magnetic resonance imaging (MRI) biomarker profiles for their predictive value of individual decline. METHODS: One hundred five bvFTD patients were recruited from the German frontotemporal lobar degeneration (FTLD) consortium study. After defining two groups ("fast progressors" vs. "slow progressors"), we investigated the predictive value of MR brain volumes for disease progression rates performing exhaustive screenings with multivariate classification models. RESULTS: We identified areas that predict disease progression rate within 1 year. Prediction measures revealed an overall accuracy of 80% across our 50 top classification models. Especially the pallidum, middle temporal gyrus, inferior frontal gyrus, cingulate gyrus, middle orbitofrontal gyrus, and insula occurred in these models. DISCUSSION: Based on the revealed marker combinations an individual prognosis seems to be feasible. This might be used in clinical studies on an individualized progression model.

19.
Brain Inj ; 34(8): 1051-1060, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32511937

RESUMO

AIM: To evaluate the combined effect of compensation therapy and functional training on working memory (WM) in patients with acquired injury and chronic cognitive deficits by investigating the dose-response relationship and specificity of transfer effects. RESEARCH DESIGN: Double-blind randomized controlled trial. METHODS: All patients underwent 4 weeks of compensation therapy in a day-care setting. In addition, they received either 20 sessions of computer-based WM training (n = 11) or attention training (n = 9). Transfer effects on cognition and their functional relevance in daily life were assessed before treatment, after 2 weeks (10 additional training sessions), and after 4 weeks (20 additional training sessions) of therapy. RESULTS: The combined treatment led to significant improvements in WM performance, verbal memory, and self-reported changes in daily life. The amount of training was identified to modulate efficacy: Significant improvements showed only in the later training phase. We observed no differences between the two training schemes (WM vs. attentional training). CONCLUSIONS: Even in the chronic phase after brain lesion WM performance can be enhanced by the combination of compensation therapy and computerized cognitive training when applied intensely; both a more general attention and a specific WM training regimen are effective.


Assuntos
Lesões Encefálicas , Memória de Curto Prazo , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Cognição , Humanos , Testes Neuropsicológicos , Resultado do Tratamento
20.
PLoS One ; 15(4): e0230439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275715

RESUMO

Semantic context modulates precision and speed of language production. Using different experimental designs including the Picture-Word-Interference (PWI) paradigm, it has consistently been shown that categorically related distractor words (e.g., cat) inhibit retrieval of the target picture name (dog). Here we introduce a novel variant of the PWI paradigm in which we present 8 words prior to a to be named target picture. Within this set, the number of words categorically related was varied between 3 and 5, and the picture to be named was either related or unrelated to the respective category. To disentangle interacting effects of semantic context we combined different naming paradigms manipulating the number of competitors and assessing the effect of repeated naming instances. Evaluating processing of the cohort by eye-tracking provided us with a metric of the (implicit) recognition of the semantic cohort. Results replicate the interference effect in that overall naming of pictures categorically related to the distractor set was slower compared to unrelated pictures. However, interference did not increase with increasing number of distractors. Tracking this effect across naming repetitions, we found that interference is prominent at the first naming instance of every picture only, whereby it is stable across distractor conditions, but dissipates across the experiment. Regarding eye-tracking our data show that participants fixated longer on semantically related items, indicating the identification of the lexico-semantic cohort. Our findings confirm the validity of the novel paradigm and indicate that besides interference during first exposure, repeated exposure to the semantic context may facilitate picture naming and counteract lexical interference.


Assuntos
Idioma , Reconhecimento Visual de Modelos , Semântica , Atenção , Humanos , Reconhecimento Psicológico
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