A connectivity model of the anatomic substrates underlying ideomotor apraxia: A meta-analysis of functional neuroimaging studies.

BACKGROUND: Patients with ideomotor apraxia (IMA) present with selective impairments in higher-order motor cognition and execution without damage to any motor or sensory pathways. Although extensive research has been conducted to determine the regions of interest (ROIs) underlying these unique impairments, previous models are heterogeneous and may be further clarified based on their structural connectivity, which has been far less described. OBJECTIVE: The goal of this research is to propose an anatomically concise network model for the neurophysiologic basis of IMA, specific to the voluntary pantomime, imitation and tool execution, based on intrinsic white matter connectivity. METHODS: We utilized meta-analytic software to identify relevant ROIs in ideomotor apraxia as reported in the literature based on functional neuroimaging data with healthy participants. After generating an activation likelihood estimation (ALE) of relevant ROIs, cortical parcellations overlapping the ALE were used to construct an anatomically precise model of anatomic substrates using the parcellation scheme outlined by the Human Connectome Project (HCP). Deterministic tractography was then performed on 25 randomly selected, healthy HCP subjects to determine the structural connectivity underlying the identified ROIs. RESULTS: 10 task-based fMRI studies met our inclusion criteria and the ALE analysis demonstrated 6 ROIs to constitute the IMA network: SCEF, FOP4, MIP, AIP, 7AL, and 7PC. These parcellations represent a fronto-parietal network consisting mainly of intra-parietal, U-shaped association fibers (40%) and long-range inferior fronto-occipital fascicle (IFOF) fibers (50%). These findings support previous functional models based on dual-stream motor processing. CONCLUSION: We constructed a preliminary model demonstrating the underlying structural interconnectedness of anatomic substrates involved in higher-order motor functioning which is seen impaired in IMA. Our model provides support for previous dual-stream processing frameworks discussed in the literature, but further clarification is necessary with voxel-based lesion studies of IMA to further refine these findings.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Parietal Involvement in Constructional Apraxia as Measured Using the Pentagon Copying Task.

Deficits in copying ("constructional apraxia") is generally defined as a multifaceted deficit. The exact neural correlates of the different types of copying errors are unknown. To assess whether the different categories of errors on the pentagon drawing relate to different neural correlates, we examined the pentagon drawings of the MMSE in persons with subjective cognitive complaints, mild cognitive impairment, or early dementia due to Alzheimer's disease. We adopted a qualitative scoring method for the pentagon copy test (QSPT) which categorizes different possible errors in copying rather than the dichotomous categories "correct" or "incorrect." We correlated (regional) gray matter volumes with performance on the different categories of the QSPT. Results showed that the total score of the QSPT was specifically associated with parietal gray matter volume and not with frontal, temporal, and occipital gray matter volume. A more fine-grained analysis of the errors reveals that the intersection score and the number of angles share their underlying neural correlates and are associated with specific subregions of the parietal cortex. These results are in line with the idea that constructional apraxia can be attributed to the failure to integrate visual information correctly from one fixation to the next, a process called spatial remapping.

A progressive breakdown of the body in space.

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. The final diagnosis was that of a corticobasal degeneration, where the rare occurrence of a progressively emerging syndrome of self-management loss within peripersonal space is observed.

Deficient supplementary motor area at rest: Neural basis of limb kinetic deficits in Parkinson's disease.

Parkinson's disease (PD) patients frequently suffer from limb kinetic apraxia (LKA) affecting quality of life. LKA denotes an impairment of precise and independent finger movements beyond bradykinesia, which is reliably assessed by coin rotation (CR) task. BOLD fMRI detected activation of a left inferior parietal-premotor praxis network in PD during CR. Here, we explored which network site is most critical for LKA using arterial spin labeling (ASL). Based on a hierarchical model, we hypothesized that LKA would predominantly affect the functional integrity of premotor areas including supplementary motor areas (SMA). Furthermore, we suspected that for praxis function with higher demand on temporal-spatial processing such as gesturing, inferior parietal lobule (IPL) upstream to premotor areas would be essential. A total of 21 PD patients and 20 healthy controls underwent ASL acquisition during rest. Behavioral assessment outside the scanner involved the CR, finger tapping task, and the test of upper limb apraxia (TULIA). Whole-brain analysis of activity at rest showed a significant reduction of CR-related perfusion in the left SMA of PD. Furthermore, the positive correlation between SMA perfusion and CR, seen in controls, was lost in patients. By contrast, TULIA was significantly associated with the perfusion of left IPL in both patients and controls. In conclusion, the findings suggest that LKA in PD are linked to an intrinsic disruption of the left SMA function, which may only be overcome by compensatory network activation. In addition, gestural performance relies on IPL which remains available for functional recruitment in early PD.

Callosal ideomotor apraxia in Alzheimer's disease.

BACKGROUND/OBJECTIVE: Impaired ability to perform skilled movements with the left upper limb in patients with corpus callosum injury has been well described (callosal apraxia) with some displaying spatial-temporal errors primarily in response to verbal commands (verbal callosal disconnection apraxia), with imitation, and when using actual tools (callosal ideomotor apraxia). Additionally some patients with callosal injury also make content errors when selecting and using the incorrect tool with their left upper limb (callosal conceptual apraxia). Interestingly, patients with Alzheimer's disease (AD) reveal anatomic evidence of callosal degeneration but callosal apraxia in AD has not been described. The purpose of this study was to learn whether patients with AD display forms of callosal apraxia. METHOD: Participants were 22 right-handed patients with AD and 24 matched controls. Both upper limbs were tested by having subjects pantomime transitive movements to command and imitation. Participants also viewed pictures of an incomplete task and attempted to pantomime the action needed to complete the task. RESULTS AND CONCLUSIONS: When compared to controls, the participants with AD demonstrated ideomotor and conceptual apraxias of both upper limbs; however, ideomotor apraxia of their left hand was more robust than that of their right hand, suggesting a hemispheric disconnection.

A critical review of closing-in.

When performing complex actions, like graphic copying or imitation of gestures, some patients may perform these actions very close to, or directly on the top of the model. This peculiar behavior, known as closing-in, is the focus of the present literature review, which will provide a critical picture of the research in this field, highlighting the difficulties in defining and assessing closing-in and the contrasting results about the nature and the characteristics of this phenomenon. Most importantly, we will discuss the 2 hypotheses proposed to explain closing-in, namely the compensation and the attraction account, in light of the most recent work. This critical review will provide substantial evidence that closing-in represent a primitive default tendency in which movements are attracted toward the focus of attention. On the other hand, the possibility that this interpretation might not be fully exhaustive and that different components of closing-in might exist will also be discussed. (PsycINFO Database Record

Crossover learning of gestures in two ideomotor apraxia patients: A single case experimental design study.

Crossover learning may aid rehabilitation in patients with neurological disorders. Ideomotor apraxia (IMA) is a common sequela of left-brain damage that comprises a deficit in the ability to perform gestures to verbal commands or by imitation. This study elucidated whether crossover learning occurred in two post-stroke IMA patients without motor paralysis after gesture training approximately 2 months after stroke onset. We quantitatively analysed the therapeutic intervention history and investigated whether revised action occurred during gesture production. Treatment intervention was to examine how to influence improvement and generalisation of the ability to produce the gesture. This study used an alternating treatments single-subject design, and the intervention method was errorless learning. Results indicated crossover learning in both patients. Qualitative analysis indicated that revised action occurred during the gesture-production process in one patient and that there were two types of post-revised action gestures: correct and incorrect gestures. We also discovered that even when a comparably short time had elapsed since stroke onset, generalisation was difficult. Information transfer between the left and right hemispheres of the brain via commissural fibres is important in crossover learning. In conclusion, improvements in gesture-production skill should be made with reference to the left cerebral hemisphere disconnection hypothesis.

Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study.

BACKGROUND AND PURPOSE: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant. METHODS: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale. RESULTS: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors. CONCLUSIONS: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills.

Callosal apraxia: a 34-year follow-up study.

Loss of ability of the left upper limb (LUL) to correctly produce spatial and temporal components of skilled purposeful movements was reported 34 years ago in a woman with a callosal infarction. To learn about recovery, we recently reexamined this woman. This woman was tested for ideomotor apraxia by asking her to pantomime to command and to seeing pictures of tools. Whereas she performed normally with her right upper limb, her LUL remained severely apraxic, making many spatial (postural and movement) errors. Initially, she did not reveal loss of finger-hand deftness (limb-kinetic apraxia), and when tested again with the coin rotation task, her left hand performance was normal. Without vision, she could name objects placed in her left hand but not name numbers written in this hand. Since this woman had a callosal lesion, failure to recover cannot be accounted for by left hemisphere inhibition of her right hemisphere. Although failure for her LUL to improve may have been related to not using her LUL for skilled actions, her right hemisphere was able to observe transitive actions, and this failure of her LUL to produce skilled purposeful movements suggests her right hemisphere may have not had the capacity to learn these movement representations. Without vision, her ability to recognize objects with her left hand, but not numbers written on her left palm, suggests graphesthesia may require that her left hand did not have access to movement representations important for programming these numbers when writing.

Dysfunction of the Human Mirror Neuron System in Ideomotor Apraxia: Evidence from Mu Suppression.

Stroke patients with ideomotor apraxia (IMA) have difficulties controlling voluntary motor actions, as clearly seen when asked to imitate simple gestures performed by the examiner. Despite extensive research, the neurophysiological mechanisms underlying failure to imitate gestures in IMA remain controversial. The aim of the current study was to explore the relationship between imitation failure in IMA and mirror neuron system (MNS) functioning. Mirror neurons were found to play a crucial role in movement imitation and in imitation-based motor learning. Their recruitment during movement observation and execution is signaled in EEG recordings by suppression of the lower (8-10 Hz) mu range. We examined the modulation of EEG in this range in stroke patients with left (n = 21) and right (n = 15) hemisphere damage during observation of video clips showing different manual movements. IMA severity was assessed by the DeRenzi standardized diagnostic test. Results showed that failure to imitate observed manual movements correlated with diminished mu suppression in patients with damage to the right inferior parietal lobule and in patients with damage to the right inferior frontal gyrus pars opercularis-areas where major components of the human MNS are assumed to reside. Voxel-based lesion symptom mapping revealed a significant impact on imitation capacity for the left inferior and superior parietal lobules and the left post central gyrus. Both left and right hemisphere damages were associated with imitation failure typical of IMA, yet a clear demonstration of relationship to the MNS was obtained only in the right hemisphere damage group. Suppression of the 8-10 Hz range was stronger in central compared with occipital sites, pointing to a dominant implication of mu rather than alpha rhythms. However, the suppression correlated with De Renzi's apraxia test scores not only in central but also in occipital sites, suggesting a multifactorial mechanism for IMA, with a possible impact for deranged visual attention (alpha suppression) beyond the effect of MNS damage (mu suppression).

Isolated buccofacial apraxia subsequent to a left ventral premotor cortex infarction.

Buccofacial apraxia (BFA, or oral apraxia) is a nonspeech skilled movement disorder that involves orofacial structures in the absence of paresis. BFA usually co-occurs with aphasia or apraxia of speech (AOS) and isolated BFA is an extremely rare phenomenon. The brain regions correlated with BFA have been studied in patients with concomitant aphasia or limb apraxia. Therefore, the exact brain regions responsible for BFA remain unclear. We report a patient with pure BFA and discuss the localization of the brain lesion.

Teaching video neuroimages: callosal apraxia: a straightforward model of ideomotor apraxia.

A 57-year-old right-handed man complained of difficulty using his hands post-coronary artery bypass graft (figure). Neurologic examination revealed signs of callosal disconnection without hemiparesis. When asked to perform limb gestures like "brush your teeth" or "wave goodbye," the right hand performed flawlessly whereas the left hand was severely apraxic (video on the Neurology Web site at www.neurology.org).

Inter- and intrahemispheric dissociations in ideomotor apraxia: a large-scale lesion-symptom mapping study in subacute brain-damaged patients.

Pantomimes of object use require accurate representations of movements and a selection of the most task-relevant gestures. Prominent models of praxis, corroborated by functional neuroimaging studies, predict a critical role for left parietal cortices in pantomime and advance that these areas store representations of tool use. In contrast, lesion data points to the involvement of left inferior frontal areas, suggesting that defective selection of movement features is the cause of pantomime errors. We conducted a large-scale voxel-based lesion-symptom mapping analyses with configural/spatial (CS) and body-part-as-object (BPO) pantomime errors of 150 left and right brain-damaged patients. Our results confirm the left hemisphere dominance in pantomime. Both types of error were associated with damage to left inferior frontal regions in tumor and stroke patients. While CS pantomime errors were associated with left temporoparietal lesions in both stroke and tumor patients, these errors appeared less associated with parietal areas in stroke than in tumor patients and less associated with temporal in tumor than stroke patients. BPO errors were associated with left inferior frontal lesions in both tumor and stroke patients. Collectively, our results reveal a left intrahemispheric dissociation for various aspects of pantomime, but with an unspecific role for inferior frontal regions.

Tool-use and the left hemisphere: what is lost in ideomotor apraxia?

Impaired tool related action in ideomotor apraxia is normally ascribed to loss of sensorimotor memories for habitual actions (engrams), but this account has not been tested against a hypothesis of a general deficit in representation of hand-object spatial relationships. Rapid reaching for familiar tools was compared with reaching for abstract objects in apraxic patients (N=9) and in a control group with right hemisphere posterior stroke. The apraxic patients alone showed an impairment in rotating the wrist to correctly grasp an inverted tool but not when inverting the hand to avoid a barrier and grasp an abstract object, and the severity of the impairment in tool reaching correlated with pantomime of tool-use. A second experiment with two apraxic patients tested whether barrier avoidance was simply less spatially demanding than reaching for a tool. However, the patient with damage limited to the inferior parietal lobe still showed a selective problem for tools. These results demonstrate that some apraxic patients are selectively impaired in their interaction with familiar tools, and this cannot be explained by the demands of the task on postural or spatial representation. However, traditional engram theory cannot account for associated problems with imitation of novel actions nor the absence of any correlated deficit in recognition of the methods of grasp of common tools. A revised theory is presented which follows the dorsal and ventral streams model (Milner & Goodale, 2008) and proposes preservation of motor control by the dorsal stream but impaired modulating input to it from the conceptual systems of the left temporal lobe.

Gesture comprehension, knowledge and production in Alzheimer's disease.

BACKGROUND AND PURPOSE: Although apraxia is a typical consequence of Alzheimer's disease (AD), the profile of apraxic impairments is still subject to debate. Here, we analysed apraxia components in patients with AD with mild-to-moderate or moderately severe dementia. METHODS: Thirty-one patients were included. We first evaluated simple gestures, that is, the imitation of finger and hand configurations, symbolic gestures (recognition, production on verbal command and imitation), pantomimes (recognition, production on verbal command, imitation and production with the object), general knowledge and complex gestures (tool-object association, function-tool association, production of complex actions and knowledge about action sequences). Tests for dementia (Mini Mental State Examination and the Dementia Rating Scale), language disorders, visual agnosia and executive function were also administered. RESULTS: Compared with controls, patients showed significant difficulties (P ≤ 0.01) in subtests relating to simple gestures (except for the recognition and imitation of symbolic gestures). General knowledge about tools, objects and action sequences was less severely impaired. Performance was frequently correlated with the severity of dementia. Multiple-case analyses revealed that (i) the frequency of apraxia depended on the definition used, (ii) ideomotor apraxia was more frequent than ideational apraxia, (iii) conceptual difficulties were slightly more frequent than production difficulties in the early stage of AD and (iv) difficulties in gesture recognition were frequent (especially for pantomimes). CONCLUSION: Patients with AD can clearly show gesture apraxia from the mild-moderate stage of dementia onwards. Recognition and imitation disorders are relatively frequent (especially for pantomimes). We did not find conceptual difficulties to be the main problem in early-stage AD.

Impaired finger dexterity in Parkinson's disease is associated with praxis function.

A controversial concept suggests that impaired finger dexterity in Parkinson's disease may be related to limb kinetic apraxia that is not explained by elemental motor deficits such as bradykinesia. To explore the nature of dexterous difficulties, the aim of the present study was to assess the relationship of finger dexterity with ideomotor praxis function and parkinsonian symptoms. Twenty-five patients with Parkinson's disease participated in the study. Their left and right arms were tested independently. Testing was done in an OFF and ON state as defined by a modified version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Finger dexterity was assessed by a coin rotation (CR) task and ideomotor praxis using a novel test of upper limb apraxia (TULIA), in which the patients were requested to imitate and pantomime 48 meaningless, as well as communicative and tool-related gestures. Coin rotation significantly correlated with TULIA irrespective of the motor state and arm involved, but not with the MDS-UPDRS. This association was significantly influenced by Hoehn and Yahr stage. The strong association of finger dexterity with praxis function but not the parkinsonian symptoms indicates that impaired finger dexterity in Parkinson's disease may be indeed apraxic in nature, yet, predominantly in advanced stages of the disease when cortical pathology is expected to develop. The findings are discussed within a cognitive-motor model of praxis function.

Coordination deficits in ideomotor apraxia during visually targeted reaching reflect impaired visuomotor transformations.

Ideomotor limb apraxia, commonly defined as a disorder of skilled, purposeful movement, is characterized by spatiotemporal deficits during a variety of actions. These deficits have been attributed to damage to, or impaired retrieval of, stored representations of learned actions, especially object-related movements. However, such deficits might also arise from impaired visuomotor transformation mechanisms that operate in parallel to or downstream from mechanisms for storage of action representations. These transformation processes convert extrinsic visual information into intrinsic neural commands appropriate for the desired motion. These processes are a key part of the movement planning process and performance errors due to inadequate transformations have been shown to increase with the dynamic complexity of the movement. This hypothesis predicts that apraxic patients should show planning deficits when reaching to visual targets, especially when the coordination and/or dynamic requirements of the task increase. Three groups (18 healthy controls, 9 non-apraxic and 9 apraxic left hemisphere damaged patients) performed reaching movements to visual targets that varied in the degree of interjoint coordination required. Relative to the other two groups, apraxic patients made larger initial direction errors and showed higher variability during their movements, especially when reaching to the target with the highest intersegmental coordination requirement. These problems were associated with poor coordination of shoulder and elbow torques early in the movement, consistent with poor movement planning. These findings suggest that the requirement to transform extrinsic visual information into intrinsic motor commands impedes the ability to accurately plan a visually targeted movement in ideomotor limb apraxia.

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels > or =7 microg/l is 46%. Therefore, selection of patients with an AFP level above 7 microg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.