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Clinical populations with basal ganglia pathologies may present with language production impairments, which are often described in combination with comprehension measures or attributed to motor, memory, or processing-speed problems. In this systematic review and meta-analysis, we studied word production in four (vascular and non-vascular) pathologies of the basal ganglia: stroke affecting the basal ganglia, small vessel disease, Parkinson's disease, and Huntington's disease. We compared scores of these clinical populations with those of matched cognitively unimpaired adults on four well-established production tasks, namely picture naming, category fluency, letter fluency, and past-tense verb inflection. We conducted a systematic search in PubMed and PsycINFO with terms for basal ganglia structures, basal ganglia disorders and language production tasks. A total of 114 studies were included, containing results for one or more of the tasks of interest. For each pathology and task combination, effect sizes (Hedges' g) were extracted comparing patient versus control groups. For all four populations, performance was consistently worse than that of cognitively unimpaired adults across the four language production tasks (p-values < 0.010). Given that performance in picture naming and verb inflection across all pathologies was quantified in terms of accuracy, our results suggest that production impairments cannot be fully explained by motor or processing-speed deficits. Our review shows that while language production difficulties in these clinical populations are not negligible, more evidence is necessary to determine the exact mechanism that leads to these deficits and whether this mechanism is the same across different pathologies. [ABSTRACT FROM AUTHOR]

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein-protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families. [ABSTRACT FROM AUTHOR]

According to the competition account of lexical selection in word production, conceptually driven word retrieval involves the activation of a set of candidate words in left temporal cortex and competitive selection of the intended word from this set, regulated by frontal cortical mechanisms. However, the relative contribution of these brain regions to competitive lexical selection is uncertain. In the present study, five patients with left prefrontal cortex lesions (overlapping in ventral and dorsal lateral cortex), eight patients with left lateral temporal cortex lesions (overlapping in middle temporal gyrus), and 13 matched controls performed a picture-word interference task. Distractor words were semantically related or unrelated to the picture, or the name of the picture (congruent condition). Semantic interference (related vs. unrelated), tapping into competitive lexical selection, was examined. An overall semantic interference effect was observed for the control and left-temporal groups separately. The left-frontal patients did not show a reliable semantic interference effect as a group. The left-temporal patients had increased semantic interference in the error rates relative to controls. Error distribution analyses indicated that these patients had more hesitant responses for the related than for the unrelated condition. We propose that left middle temporal lesions affect the lexical activation component, making lexical selection more susceptible to errors. [ABSTRACT FROM AUTHOR]

Whereas it has long been assumed that competition plays a role in lexical selection in word production (e.g., Levelt, Roelofs, & Meyer, ), recently Finkbeiner and Caramazza () argued against the competition assumption on the basis of their observation that visible distractors yield semantic interference in picture naming, whereas masked distractors yield semantic facilitation. We examined an alternative account of these findings that preserves the competition assumption. According to this account, the interference and facilitation effects of distractor words reflect whether or not distractors are strong enough to exceed a threshold for entering the competition process. We report two experiments in which distractor strength was manipulated by means of coactivation and visibility. Naming performance was assessed in terms of mean response time (RT) and RT distributions. In Experiment 1, with low coactivation, semantic facilitation was obtained from clearly visible distractors, whereas poorly visible distractors yielded no semantic effect. In Experiment 2, with high coactivation, semantic interference was obtained from both clearly and poorly visible distractors. These findings support the competition threshold account of the polarity of semantic effects in naming. [ABSTRACT FROM AUTHOR]

Studies investigating language commonly isolate one modality or process, focusing on comprehension or production. Here, we present a framework for a paradigm that combines both: the Concise Language Paradigm (CLaP), tapping into comprehension and production within one trial. The trial structure is identical across conditions, presenting a sentence followed by a picture to be named. We tested 21 healthy speakers with EEG to examine three time periods during a trial (sentence, pre-picture interval, picture onset), yielding contrasts of sentence comprehension, contextually and visually guided word retrieval, object recognition, and naming. In the CLaP, sentences are presented auditorily (constrained, unconstrained, reversed), and pictures appear as normal (constrained, unconstrained, bare) or scrambled objects. Imaging results revealed different evoked responses after sentence onset for normal and time-reversed speech. Further, we replicated the context effect of alpha-beta power decreases before picture onset for constrained relative to unconstrained sentences, and could clarify that this effect arises from power decreases following constrained sentences. Brain responses locked to picture-onset differed as a function of sentence context and picture type (normal vs. scrambled), and naming times were fastest for pictures in constrained sentences, followed by scrambled picture naming, and equally fast for bare and unconstrained picture naming. Finally, we also discuss the potential of the CLaP to be adapted to different focuses, using different versions of the linguistic content and tasks, in combination with electrophysiology or other imaging methods. These first results of the CLaP indicate that this paradigm offers a promising framework to investigate the language system. [ABSTRACT FROM AUTHOR]