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Apraxia is classically defined as difficulty performing learned, skilled gestures. In this review, we describe the range of motor impairments classified as apraxia, focusing on ideomotor limb apraxia. We present several prominent models of praxis to explain the variety of difficulties seen in patients with apraxia. We also discuss the large-scale frontal-parietal-basal ganglia network thought to underlie praxis. In this context, we highlight the common occurrence of limb apraxia in corticobasal degeneration, a neurodegenerative condition characterized by frontal, parietal, and basal ganglia disease.

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, ‘indirect’, and perceptual ‘direct’ routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients’ structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to ‘direct’ and ‘indirect’ action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

Background The motor‐cognitive syndrome apraxia is a common stroke sequela and severely affects the outcome after stroke by impairing activities of daily living. Notably, like in many health conditions, there is a massive backlog regarding studies on sex differences in patients with apraxia despite common knowledge that sex influences praxis performance in healthy participants. We investigated putative sex differences in apraxic stroke patients at the behavioral and neural levels. Methods We retrospectively analysed the data of a cohort of 102 left‐hemisphere stroke patients in the (sub)acute phase who were apraxic according to the Cologne Apraxia Screening (KAS). We conducted voxel‐based lesion–symptom mapping (VLSM) to elucidate the lesion patterns. Further, in an age‐matched subsample (tolerance of 5 years) with equal numbers of men and women, behavioral comparisons and a VLSM analysis were conducted to explore differential sex‐related lesion patterns. Results Overall, apraxic deficits were associated with lesions in the parietal, temporal, and frontal regions in the cohort of 102 left‐hemisphere stroke patients. The age‐matched cohort consisted of 30 women and 30 men and showed no significant differences in demographic and clinical characteristics. There were no performance differences between men and women at the behavioral level regarding praxis functions. In contrast, VLSM revealed differential lesion patterns by sex. Male compared to female apraxic stroke patients significantly more often showed lesions that affected the left inferior frontal gyrus. Conclusion The data suggest a differential organization of the praxis system in men and women, warranting further exploration.

Progressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech‐language‐related WM tracts identified using DTI tractography in PAOS. Twenty‐two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir‐PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non‐fluent variant/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole‐brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI‐studio) and specific tracts were identified using an automatic fiber tracking atlas‐based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal‐occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (p < .0001) and elevated flortaucipir SUVR (p = .0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC] = 0.83), followed by the left arcuate fasciculus (AUROC = 0.75) and left frontal aslant tract (AUROC = 0.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech/language difficulties in PAOS. Structural connectomics assessment of the supplementary motor area (SMA) in progressive apraxia of speech (PAOS) subjects. White matter connectivity representation from cortical regions involved in the language network (LN) shows lower fractional anisotropy (FA) and larger mean diffusivity (MD) and standardized uptake value ratio (SUVR) values than control. The addition of SMA to the speech and LN demonstrates further FA decrease in MD and SUVR increase likely due to the involvement of SMA in the disease.

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca’s region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24 % ( n  = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare ( n  = 2, 4 %). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

Patients with progressive apraxia of speech (PAOS) often develop atypical parkinsonian features suggestive of corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP), and typically have an underlying 4-repeat tauopathy at autopsy. We describe three cases of PAOS with underlying Pick’s disease, a 3-repeat tauopathy, who lacked CBS or PSP features during life. We reviewed patients enrolled in the Neurodegenerative Research Group’s ongoing studies on speech and language disorders and identified those with PAOS who had autopsy-confirmed Pick’s disease. All patients had comprehensive neurologic, speech-language, and neuropsychological assessments, as well as multimodal neuroimaging, during life. Three female patients presented with phonetic PAOS without parkinsonism. Patient 1 had speech onset at age 54, later developed behavioral variant frontotemporal dementia (bvFTD), and died at 64. Patient 2 had speech onset at 47, early bvFTD features, prominent frontal and temporal involvement, and died at 53. Patient 3 had speech onset at 58, minimal behavioral changes, primarily frontal involvement on imaging, and died at 63. Our findings highlight that Pick's disease can present with PAOS and may be distinguished from 4R-tau PAOS by an absence of motoric CBS/PSP features and, in some cases, by prominent temporal hypometabolism with bvFTD development. These atypical features may prove useful in the antemortem identification of Pick's disease as a cause of PAOS. •Progressive apraxia of speech typically shares features with 4R tauopathies.•We report three autopsy-confirmed cases of PAOS with underlying 3R tau.•Early behavioral changes and lack of parkinsonism may be clinical clues to 3R tau.•Prominent temporal involvement on imaging may be a marker of 3R tau.

Background Primary progressive apraxia of speech is a neurodegenerative disorder characterized by early, isolated speech impairment due to impairment of motor speech planning and programming. Patients with PPAOS have varying disease durations from the estimated onset of the first symptom to death. Clinicopathological and neuroimaging features related to disease duration are unknown for PPAOS. We determine whether clinical, neuroimaging, or pathological features are associated with disease duration in primary progressive apraxia of speech (PPAOS). Methods We analyzed data from 41 PPAOS participants who were enrolled and longitudinally followed to death in NIH‐funded studies over 15 years. Demographic, clinical, and genetic features were ed. Brain volumes of cortical, subcortical, and brainstem regions were calculated. Regional tau lesion count (burden) was assessed histologically. Spearman rank correlations were performed between disease duration and variables of interest, followed by multiple regression analyses. Results Disease duration did not correlate with any baseline demographic, clinical, or pathologic features. Shorter disease duration correlated with a faster rate of behavioral change and of apraxia of speech severity over time, smaller baseline volumes of the superior frontal lobe and supplementary motor cortex, and higher tau burden in the locus ceruleus (ρ = −0.5, p = 0.03). Multiple regression analysis identified rate of behavioral change and volume loss in the superior frontal lobe as key clinical and neuroimaging variables, respectively. Conclusion In patients with PPAOS, we found shorter disease duration to be related to behavioral dyscontrol and involvement of the frontal lobe, as well as a higher burden of 4‐repeat tau lesions in the locus ceruleus.

Individuals with heterozygous 16p11.2 deletions reportedly suffer from a variety of difficulties with speech and language. Indeed, recent copy-number variant screens of children with childhood apraxia of speech (CAS), a specific and rare motor speech disorder, have identified three unrelated individuals with 16p11.2 deletions. However, the nature and prevalence of speech and language disorders in general, and CAS in particular, is unknown for individuals with 16p11.2 deletions. Here we took a genotype-first approach, conducting detailed and systematic characterization of speech abilities in a group of 11 unrelated children ascertained on the basis of 16p11.2 deletions. To obtain the most precise and replicable phenotyping, we included tasks that are highly diagnostic for CAS, and we tested children under the age of 18 years, an age group where CAS has been best characterized. Two individuals were largely nonverbal, preventing detailed speech analysis, whereas the remaining nine met the standard accepted diagnostic criteria for CAS. These results link 16p11.2 deletions to a highly penetrant form of CAS. Our findings underline the need for further precise characterization of speech and language profiles in larger groups of affected individuals, which will also enhance our understanding of how genetic pathways contribute to human communication disorders.

Abstract Four right-handed patients who presented with an isolated impairment of speech or language had transactive response DNA-binding protein of 43 kDa (TDP-43) type B pathology. Comportment and pyramidal motor function were preserved at presentation. Three of the cases developed axial rigidity and oculomotor findings late in their course with no additional pyramidal or lower motor neuron impairments. However, in all 4 cases, postmortem examination disclosed some degree of upper and lower motor neuron disease (MND) pathology in motor cortex, brainstem, and spinal cord. Although TDP-43 type B pathology is commonly associated with MND and behavioral variant frontotemporal dementia, it is less recognized as a pathologic correlate of primary progressive aphasia and/or apraxia of speech as the presenting syndrome. These cases, taken together, contribute to the growing heterogeneity in clinical presentations associated with TDP pathology. Additionally, 2 cases demonstrated left anterior temporal lobe atrophy but without word comprehension impairments, shedding light on the relevance of the left temporal tip for single-word comprehension.

Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its specific symptomatology has not been examined, limiting prognostic counselling and application of targeted therapies. Here we examine the communication phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1 variants, 25 with 17q21.31 microdeletion), aged 1.0–27.0 years were assessed for oral-motor, speech, language, literacy, and social functioning. Early history included hypotonia and feeding difficulties. Speech and language development was delayed and atypical from onset of first words (2; 5–3; 5 years of age on average). Speech was characterised by apraxia (100%) and dysarthria (93%), with stuttering in some (17%). Speech therapy and multi-modal communication (e.g., sign-language) was critical in preschool. Receptive and expressive language abilities were typically commensurate (79%), both being severely affected relative to peers. Children were sociable with a desire to communicate, although some (36%) had pragmatic impairments in domains, where higher-level language was required. A common phenotype was identified, including an overriding ‘double hit’ of oral hypotonia and apraxia in infancy and preschool, associated with severely delayed speech development. Remarkably however, speech prognosis was positive; apraxia resolved, and although dysarthria persisted, children were intelligible by mid-to-late childhood. In contrast, language and literacy deficits persisted, and pragmatic deficits were apparent. Children with KdVS require early, intensive, speech motor and language therapy, with targeted literacy and social language interventions as developmentally appropriate. Greater understanding of the linguistic phenotype may help unravel the relevance of KANSL1 to child speech and language development.