Localizing apraxia in corticobasal syndrome: a morphometric MRI study.

Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied. 3D-T1-weighted images were analyzed via the automated recon-all Freesurfer version 6.0 pipeline. Vertex-based multivariate General Linear Model analysis was applied to correlate GAT scores with cortical thickness. Deficits in imitation of meaningless gestures correlated with bilateral superior parietal atrophy, extending to the angular and supramarginal gyri, particularly on the left. Finger imitation relied predominantly on superior parietal lobes, whereas the left angular and supramarginal gyri, in addition to superior parietal lobes, were critical for hand imitation. The widespread bilateral clusters of atrophy in CBS related to apraxia indicate different pathophysiological mechanisms mediating praxis in neurodegenerative disorders compared to vascular lesions, with implications both for our understanding of praxis and for the rehabilitation approaches of patients with apraxia.

Longitudinal flortaucipir, metabolism and volume differ between phonetic and prosodic speech apraxia.

Progressive apraxia of speech (PAOS) is a neurodegenerative motor-speech disorder that most commonly arises from a four-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic subtype by slow and segmented speech and the mixed subtype by a combination of both but lack of predominance of either. There is some evidence that cross-sectional patterns of neurodegeneration differ across subtypes, although it is unknown whether longitudinal patterns of neurodegeneration differ. We examined longitudinal patterns of atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose-PET and tau uptake on flortaucipir-PET in a large cohort of subjects with PAOS that had been followed for many years. Ninety-one subjects with PAOS (51 phonetic, 40 prosodic) were recruited by the Neurodegenerative Research Group. Of these, 54 (27 phonetic, 27 prosodic) returned for annual follow-up, with up to seven longitudinal visits (total visits analysed = 217). Volumes, metabolism and flortaucipir uptake were measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with PAOS subtypes being compared at baseline, 4 years from baseline, and in terms of rates of change. The phonetic group showed smaller volumes and worse metabolism in Broca's area and the striatum at baseline and after 4 years, and faster rates of change in these regions, compared with the prosodic group. There was also evidence of faster spread of hypometabolism and flortaucipir uptake into the temporal and parietal lobes in the phonetic group. In contrast, the prosodic group showed smaller cerebellar dentate, midbrain, substantia nigra and thalamus volumes at baseline and after 4 years, as well as faster rates of atrophy, than the phonetic group. Greater hypometabolism and flortaucipir uptake were also observed in the cerebellar dentate and substantia nigra in the prosodic group. Mixed findings were observed in the supplementary motor area and precentral cortex, with no clear differences observed across phonetic and prosodic groups. These findings support different patterns of disease spread in PAOS subtypes, with corticostriatal patterns in the phonetic subtype and brainstem and thalamic patterns in the prosodic subtype, providing insight into the pathophysiology and heterogeneity of PAOS.

Diffusion tensor imaging-based multi-fiber tracking reconstructions can regionally differentiate phonetic versus prosodic subtypes of progressive apraxia of speech.

Two subtypes of progressive apraxia of speech (PAOS) have been recognized: phonetic PAOS (PAOS_ph) where speech output is dominated by distorted sound substitutions and prosodic PAOS (PAOS_pr) which is dominated by segmented speech. We investigate whether these PAOS subtypes have different white matter microstructural abnormalities measured by diffusion tensor tractography. Thirty-three patients with PAOS (21 PAOS_ph and 12 PAOS_pr) and 19 healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent diffusion MRI. Using a whole-brain tractography approach, fractional anisotropy (FA) and mean diffusivity (MD) were extracted for cortico-cortical, cortico-subcortical, cortical-projection, and cerebello-cortical white matter tracts. A hierarchical linear model was applied to assess tract-level FA and MD across groups. Both PAOS_ph and PAOS_pr showed degeneration of cortico-cortical, cortico-subcortical, cortical-projection, and cerebello-cortical white matter tracts compared to controls. However, degeneration of the body of corpus callosum, superior thalamic radiation, and superior cerebellar peduncle was greater in PAOS_pr compared to PAOS_ph, and degeneration of the inferior segment of the superior longitudinal fasciculus (SLF) was greater in PAOS_ph compared to PAOS_pr. Worse parkinsonism correlated with greater degeneration of cortico-cortical and cortico-subcortical tracts in PAOS_ph. Apraxia of speech articulatory error score correlated with degeneration of the superior cerebellar peduncle tracts in PAOS_pr. Phonetic and prosodic PAOS involve the compromise of a similar network of tracts, although there are connectivity differences between types. Whereas clinical parameters are the current gold standard to distinguish PAOS subtypes, our results allege the use of DTI-based tractography as a supplementary method to investigate such variants.

Mechanisms and neuroanatomy of response selection in tool and non-tool action tasks: Evidence from left-hemisphere stroke.

The ability to select between potential actions is central to the complex process of tool use. After left hemisphere stroke, individuals with limb apraxia make more hand action errors when gesturing the use of tools with conflicting hand actions for grasping-to-move and use (e.g., screwdriver) relative to tools that are grasped-to-move and used with the same hand action (e.g., hammer). Prior research indicates that this grasp-use interference effect is driven by abnormalities in the competitive action selection process. The goal of this project was to determine whether common mechanisms and neural substrates support the competitive selection of task-appropriate responses in both tool and non-tool domains. If so, the grasp-use interference effect in a tool use gesturing task should be correlated with response interference effects in the classic Eriksen flanker and Simon tasks, and at least partly overlapping neural regions should subserve the 3 tasks. Sixty-four left hemisphere stroke survivors (33 with apraxia) participated in the tool- and non-tool interference tasks and underwent T1 anatomical MRI. There were robust grasp-use interference effects (grasp-use conflict test) and response interference effects (Eriksen flanker and Simon tasks), but these effects were not correlated. Lesion-symptom mapping analyses showed that lesions to the left inferior parietal lobule, ventral premotor cortex, and insula were associated with grasp-use interference. Lesions to the left inferior parietal lobule, postcentral gyrus, insula, caudate, and putamen were associated with response interference in the Eriksen flanker task. Lesions to the left caudate and putamen were also associated with response interference in the Simon task. Our results suggest that the selection of hand posture for tool use is mediated by distinct cognitive mechanisms and partly distinct neuroanatomic substrates from those mapping a stimulus to an appropriate motor response in non-tool domains.

Acoustic Analysis and Neuroimaging Correlates of Diadochokinetic Rates in Mild-Moderate Primary Progressive Apraxia of Speech.

Speech rate can be judged clinically using diadochokinetic (DDK) tasks, such as alternating motion rates (AMR) and sequential motion rates (SMR). We evaluated whether acoustic AMR/SMR speech rates would differentiate primary progressive apraxia of speech (PPAOS) from healthy controls, and determined how DDK rates relate to phonetic and prosodic speech characteristics and brain metabolism on FDG-PET. Rate was calculated for each of three AMRs (repetitions of 'puh', 'tuh', and 'kuh') and for SMRs (repetitions of 'puhtuhkuh') for 27 PPAOS patients and 52 controls who underwent FDG-PET. PPAOS patients were slower than controls on all DDK tasks. All DDK rates correlated with apraxia of speech severity, with strongest associations with prosodic speech features. Slower DDK rates were associated with hypometabolism in the right cerebellar dentate and left supplementary motor area. Performance on AMR rate, not just SMR rate, may be impaired in mild PPAOS, but sensitivity and specificity require further study.

Spatial patterns of elevated magnetic susceptibility in progressive apraxia of speech.

PURPOSE: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. METHODS: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. RESULTS: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS. CONCLUSION: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ready for clinical differential diagnosis, the present study contributes to our understanding of magnetic susceptibility changes and the pathophysiology of PAOS.

Clinicopathological associations of hemispheric dominance in primary progressive apraxia of speech.

OBJECTIVE: Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is not known whether greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features. METHODS: In 51 prospectively recruited PPAOS patients who completed [18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), we classified patients as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET. SPM and statistical analyses of regional metabolic values were performed. Diagnosis of PPAOS was made if apraxia of speech was present and aphasia absent. Thirteen patients completed ioflupane-123I (dopamine transporter [DAT]) scans. We compared cross-sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver-operating curve (AUROC) determined as a measure of effect size. RESULTS: In all, 49% of the PPAOS patients were classified as left-dominant, 31% as right-dominant, and 20% as symmetric, which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right-dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC 0.79), behavioral disturbances (AUROC 0.84), including disinhibition symptoms (AUROC 0.82) and negative behaviors (AUROC 0.82), and parkinsonism (AUROC 0.75) compared to left-dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left-dominant (AUROC 0.89) and right-dominant PPAOS (AUROC 0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p = 0.01). CONCLUSIONS: Patients with PPAOS and a right-dominant pattern of hypometabolism on FDG-PET have the fastest rates of decline of behavioral and motor features.

A Selective Hand Posture Apraxia in an Individual With Posterior Cortical Atrophy and Probable Corticobasal Syndrome.

A selective impairment for making hand postures that are required to use specific tools has rarely been reported in individuals with acquired brain injury, and such an impairment has not been documented at all in individuals with degenerative disorders. We describe an individual with posterior cortical atrophy and probable corticobasal syndrome who was unable to use tools because of an inability to make the proper hand posture required for each tool. This individual was, however, able to use the tools properly once her hand postures were corrected, and her ability to manipulate the tools (ie, timing, arm posture, and amplitude) was intact. Also, she had no difficulty with a test of her manipulation knowledge. Areas of hypoperfusion observed by single-photon emission computerized tomography included the anterior intraparietal sulcus in the left parietal lobe, which is an area that has been proposed to control hand postures. This selective impairment might be explained by the reasoning-based hypothesis for apraxia, which attributes hand posture errors in the absence of manipulation errors to dysfunction in one of the three independent pathways that subserve tool use, rather than the manipulation-based hypothesis for apraxia, which attributes hand posture errors to impaired manipulation knowledge. This is the first case with a degenerative disorder that revealed a selective impairment for making hand postures for tool use, which might be explained mainly by apraxia of hand postures along with visuospatial dysfunction (simultanagnosia) and/or sensory disturbance.

Functional connectivity to the premotor cortex maps onto longitudinal brain neurodegeneration in progressive apraxia of speech.

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative motor speech disorder affecting the ability to produce speech. If agrammatic aphasia is present, it can be referred to as the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). We investigated whether resting-state functional MRI (rs-fMRI) connectivity from disease "epicenters" correlated with longitudinal gray matter atrophy and hypometabolism in nfvPPA and PPAOS. Eighteen nfvPPA and 23 PPAOS patients underwent clinical assessment, structural MRI, rs-fMRI, and [18F] fluorodeoxyglucose (FDG)-PET at baseline and ∼2 years follow-up. Rates of neurodegeneration in nfvPPA and PPAOS correlated with functional connectivity to the premotor, motor, and frontal cortex. Connectivity to the caudate and thalamus was more strongly associated with rates of hypometabolism than atrophy. Connectivity to the left Broca's area was more strongly associated with rates of atrophy and hypometabolism in nfvPPA. Finally, functional connectivity to a network of regions, and not to a single epicenter, correlated with rates of neurodegeneration in PPAOS and nfvPPA, suggesting similar biological mechanisms driving disease progression, with regional differences related to language.

Role of Diffusion Tensor Tractography in Diagnosis of Limb-Kinetic Apraxia in Stroke Patients: A Mini-Narrative Review.

Limb-kinetic apraxia (LKA) is an execution disorder of movements caused by an injury to the secondary motor area (the supplementary motor area and premotor cortex) with preservation of an intact corticospinal tract (CST). A precise diagnosis of LKA is often limited because it is made based on the clinical observation of movement characteristics with confirmation of the CST state, and no specific clinical assessment tools for LKA have been developed. Diffusion tensor tractography (DTT) enables a three-dimensional estimation of the neural tracts related to LKA, such as the CST and corticofugal tract from the secondary motor area. This article reviewed 5 DTT-based studies on LKA-related neural tracts in stroke patients. These studies suggest that DTT could be a useful diagnostic tool for LKA along with previous diagnostic tools, such as brain magnetic resonance imaging and transcranial magnetic stimulation. In particular, DTT for the affected corticofugal tract can provide useful evidence for diagnosing LKA when clinicians cannot observe the movement characteristics because of severe weakness after a severe injury to the affected CST. Furthermore, a reviewed study suggested that LKA might be related to the unaffected neural tracts for motor function when the affected neural tracts were severely injured. This review summarizes the role of DTT in the diagnosis of LKA in stroke patients.

Tractography of supplementary motor area projections in progressive speech apraxia and aphasia.

Progressive apraxia of speech (AOS) is a motor speech disorder affecting the ability to produce phonetically or prosodically normal speech. Progressive AOS can present in isolation or co-occur with agrammatic aphasia and is associated with degeneration of the supplementary motor area. We aimed to assess breakdowns in structural connectivity from the supplementary motor area in patients with any combination of progressive AOS and/or agrammatic aphasia to determine which supplementary motor area tracts are specifically related to these clinical symptoms. Eighty-four patients with progressive AOS or progressive agrammatic aphasia were recruited by the Neurodegenerative Research Group and underwent neurological, speech/language, and neuropsychological testing, as well as 3 T diffusion magnetic resonance imaging. Of the 84 patients, 36 had apraxia of speech in isolation (primary progressive apraxia of speech, PPAOS), 40 had apraxia of speech and agrammatic aphasia (AOS-PAA), and eight had agrammatic aphasia in isolation (progressive agrammatic aphasia, PAA). Tractography was performed to identify 5 distinct tracts connecting to the supplementary motor area. Fractional anisotropy and mean diffusivity were assessed at 10 positions along the length of the tracts to construct tract profiles, and median profiles were calculated for each tract. In a case-control comparison, decreased fractional anisotropy and increased mean diffusivity were observed along the supplementary motor area commissural fibers in all three groups compared to controls. PPAOS also had abnormal diffusion in tracts from the supplementary motor area to the putamen, prefrontal cortex, Broca's area (frontal aslant tract) and motor cortex, with greatest abnormalities observed closest to the supplementary motor area. The AOS-PAA group showed abnormalities in the same set of tracts, but with greater involvement of the supplementary motor area to prefrontal tract compared to PPAOS. PAA showed abnormalities in the left prefrontal and frontal aslant tracts compared to both other groups, with PAA showing greatest abnormalities furthest from the supplementary motor area. Severity of AOS correlated with tract metrics in the supplementary motor area commissural and motor cortex tracts. Severity of aphasia correlated with the frontal aslant and prefrontal tracts. These findings provide insight into how AOS and agrammatism are differentially related to disrupted diffusivity, with progressive AOS associated with abnormalities close to the supplementary motor area, and the frontal aslant and prefrontal tracts being particularly associated with agrammatic aphasia.

Single-case disconnectome lesion-symptom mapping: Identifying two subtypes of limb apraxia.

Influential theories of skilled action posit that distinct cognitive mechanisms and neuroanatomic substrates support meaningless gesture imitation and tool use pantomiming, and poor performance on these tasks are hallmarks of limb apraxia. Yet prior research has primarily investigated brain-behavior relations at the group level; thus, it is unclear whether we can identify individuals with isolated impairments in meaningless gesture imitation or tool use pantomiming whose performance is associated with a distinct neuroanatomic lesion profile. The goal of this study was to test the hypothesis that individuals with disproportionately worse performance in meaningless gesture imitation would exhibit cortical damage and white matter disconnection in left fronto-parietal brain regions, whereas individuals with disproportionately worse performance in tool use pantomiming would exhibit cortical damage and white matter disconnection in left temporo-parietal brain regions. Fifty-eight participants who experienced a left cerebrovascular accident took part in a meaningless gesture imitation task, a tool use pantomiming task, and a T1 structural MRI. Two participants were identified who had relatively small lesions and disproportionate impairments on one task relative to the other, as well as below-control-level performance on one task and not the other. Using these criteria, one participant was disproportionately impaired at meaningless gesture imitation, and the other participant was disproportionately impaired at pantomiming tool use. Graph theoretic analysis of each participant's structural disconnectome demonstrated that disproportionately worse meaningless gesture imitation performance was associated with disconnection among the left inferior parietal lobule, the left superior parietal lobule, and the left middle and superior frontal gyri, whereas disproportionately worse tool use pantomiming performance was associated with disconnection between left temporal and parietal regions. Our results demonstrate that relatively focal lesions to specific portions of the Tool Use Network can be associated with distinct limb apraxia subtypes.

Speech apraxia and oral apraxia: association or dissociation? A multivariate lesion-symptom mapping study in acute stroke patients.

The anatomical relationship between speech apraxia (SA) and oral apraxia (OA) is still unclear. To shed light on this matter we studied 137 patients with acute ischaemic left-hemisphere stroke and performed support vector regression-based, multivariate lesion-symptom mapping. Thirty-three patients presented with either SA or OA. These two symptoms mostly co-occurred (n = 28), except for few patients with isolated SA (n = 2) or OA (n = 3). All patient with either SA or OA presented with aphasia (p < 0.001) and these symptoms were highly associated with apraxia (p < 0.001). Co-occurring SA and OA were predominantly associated with insular lesions, while the insula was completely spared in the five patients with isolated SA or OA. Isolated SA occurred in case of frontal lesions (prefrontal gyrus and superior longitudinal fasciculus), while isolated OA occurred in case of either temporoparietal or striatocapsular lesions. Our study supports the notion of a predominant, but not exclusive, role of the insula in verbal and non-verbal oral praxis, and indicates that frontal regions may contribute exclusively to verbal oral praxis, while temporoparietal and striatocapsular regions contribute to non-verbal oral praxis. However, since tests for SA and OA so far intrinsically also investigate aphasia and apraxia, refined tests are warranted.

Distinct cognitive components and their neural substrates underlying praxis and language deficits following left hemisphere stroke.

Apraxia is characterised by multiple deficits of higher motor functions, primarily caused by left hemisphere (LH) lesions to parietal-frontal praxis networks. While previous neuropsychological and lesion studies tried to relate the various apraxic deficits to specific lesion sites, a comprehensive analysis of the different apraxia profiles and the related (impaired) motor-cognitive processes as well as their differential neural substrates in LH stroke is lacking. To reveal the cognitive mechanisms that underlie the different patterns of praxis and (related) language deficits, we applied principal component analysis (PCA) to the scores of sub-acute LH stroke patients (n = 91) in several tests of apraxia and aphasia. Voxel-based lesion-symptom mapping (VLSM) analyses were then used to investigate the neural substrates of the identified components. The PCA yielded a first component related to language functions and three components related to praxis functions, with each component associated with specific lesion patterns. Regarding praxis functions, performance in imitating arm/hand gestures was accounted for by a second component related to the left precentral gyrus and the inferior parietal lobule. Imitating finger configurations, pantomiming the use of objects related to the face, and actually using objects loaded on component 3, related to the left anterior intraparietal sulcus and angular gyrus. The last component represented the imitation of bucco-facial gestures and was linked to the basal ganglia and LH white matter tracts. The results further revealed that pantomime of (limb-related) object use depended on both the component 2 and 3, which were shared with gesture imitation and actual object use. Data support and extend the notion that apraxia represents a multi-componential syndrome comprising different (impaired) motor-cognitive processes, which dissociate - at least partially - from language processes. The distinct components might be disturbed to a varying degree following LH stroke since they are associated with specific lesion patterns within the LH.

Gesture errors in left and right hemisphere damaged patients: A behavioural and anatomical study.

OBJECTIVE: Erroneous gesture execution is at the core of motor cognition difficulties in apraxia. While a taxonomy of errors may provide important information about the nature of the disorder, classifications are currently often inconsistent. This study aims to identify the error categories which distinguish apraxic from non-apraxic patients. METHOD: Two groups of mixed (bucco-facial and limb) and bucco-facial apraxic patients suffering from stroke were compared to non-apraxic, left and right hemisphere damaged patients in tasks tapping the ability to perform limb and bucco-facial actions. The errors were analysed and classified into 6 categories relating to content, configuration or movement, spatial or temporal parameters and unrecognisable actions. Furthermore, an anatomical investigation (VLMS) was conducted in the whole group of left hemisphere damaged patients to investigate potential correlates of the various error categories. RESULTS: Although all the above error typologies may be observed, the most indicative of mixed apraxia is the content-related one in all the typologies of actions (transitive and intransitive), and configuration errors in transitive ones. Configuration and content errors in mouth actions seem to be typical of bucco-facial apraxia. Spatial errors are similar in both apraxic and right brain damaged, non-apraxic patients. A lesion mapping analysis of left-brain damaged patients demonstrates that all but the spatial error category are associated with the fronto-parietal network. Moreover, content errors are also associated with fronto-insular lesions and movement errors with damage to the paracentral territory (precentral and postcentral gyri). Spatial errors are often associated to ventral frontal lesions. CONCLUSIONS: Bucco-facial and mixed apraxic patients make different types of errors in different types of actions. Not all errors are equally indicative of apraxia. In addition, the various error categories are associated with at least partially different neural correlates.

Anatomical correlates of recovery in apraxia: A longitudinal lesion-mapping study in stroke patients.

OBJECTIVE: This study investigates the clinical course of recovery of apraxia after left-hemisphere stroke and the underlying neuroanatomical correlates for persisting or recovering deficits in relation to the major processing streams in the network for motor cognition. METHODS: 90 patients were examined during the acute (4.74 ± 2.73 days) and chronic (14.3 ± 15.39 months) stage after left-hemisphere stroke for deficits in meaningless imitation, as well as production and conceptual errors in tool use pantomime. Lesion correlates for persisting or recovering deficits were analyzed with an extension of the non-parametric Brunner-Munzel rank-order test for multi-factorial designs (two-way repeated-measures ANOVA) using acute images. RESULTS: Meaningless imitation and tool use production deficits persisted into the chronic stage. Conceptual errors in tool use pantomime showed an almost complete recovery. Imitation errors persisted after occipitotemporal and superior temporal lesions in the dorso-dorsal stream. Chronic pantomime production errors were related to the supramarginal gyrus, the key structure of the ventro-dorsal stream. More anterior lesions in the ventro-dorsal stream (ventral premotor cortex) were additionally associated with poor recovery of production errors in pantomime. Conceptual errors in pantomime after temporal and supramarginal gyrus lesions persisted into the chronic stage. However, they resolved completely when related to angular gyrus or insular lesions. CONCLUSION: The diverging courses of recovery in different apraxia tasks can be related to different mechanisms. Critical lesions to key structures of the network or entrance areas of the processing streams lead to persisting deficits in the corresponding tasks. Contrary, lesions located outside the core network but inducing a temporary network dysfunction allow good recovery e.g., of conceptual errors in pantomime. The identification of lesion correlates for different long-term recovery patterns in apraxia might also allow early clinical prediction of the course of recovery.

Characterising factors underlying praxis deficits in chronic left hemisphere stroke patients.

Limb apraxia, a disorder of skilled action not consequent on primary motor or sensory deficits, has traditionally been defined according to errors patients make on neuropsychological tasks. Previous models of the disorder have failed to provide a unified account of patients' deficits, due to heterogeneity in the patients and tasks used. In this study we hypothesised that we may be able to map apraxic deficits onto principal components, some of which may be specific, whilst others may align with other cognitive disorders. We implemented principal component analysis (PCA) to elucidate core factors of the disorder in a preliminary cohort of 41 unselected left hemisphere chronic stroke patients who were tested on a comprehensive and validated apraxia screen. Three principal components were identified: posture selection, semantic control and multi-demand sequencing. These were submitted to a lesion symptom mapping (VBCM) analysis in a subset of 24 patients, controlled for lesion volume, age and time post-stroke. The first component revealed no significant structural correlates. The second component was related to regions in inferior frontal gyrus, primary motor area, and adjacent parietal opercular (including inferior parietal and supramarginal gyrus) areas. The third component was associated with lesions within the white matter underlying the left sensorimotor cortex, likely involving the 2nd branch of the left superior longitudinal fasciculus as well as the posterior orbitofrontal cortex (pOFC). These results highlight a significant role of common cognitive functions in apraxia, which include action selection, and sequencing, whilst more specific deficits may relate to semantic control. Moreover, they suggest that previously described 'ideomotor' and 'ideational' deficits may have a common neural basis within semantic control. Further research using this technique would help elucidate the cognitive processes underlying limb apraxia, its neural correlates and their relationship with other cognitive disorders.