Clinical Screening for Posterior Cortical Atrophy.

BACKGROUND: Posterior cortical atrophy (PCA) is a progressive neurologic syndrome that presents with complex visual deficits. Although PCA is most commonly a form of Alzheimer disease (AD), its early diagnosis is usually delayed due to a lack of understanding for how best to clinically screen for the syndrome. OBJECTIVE: To identify neurobehavioral screening tasks for PCA-beyond simple visual constructions-that can be administered in clinic or at bedside. METHOD: We compared the performance of 12 individuals who met neuroimaging-supported consensus criteria for PCA with that of 12 matched individuals with typical AD (tAD) and 24 healthy controls (HC) on clinic/bedside tasks measuring (a) complex figure copying, (b) Balint syndrome, (c) visual object agnosia, (d) color identification, (e) figure-ground discrimination, (f) global-local processing, (g) dressing apraxia, (h) ideomotor apraxia, and (i) Gerstmann syndrome. RESULTS: All of the individuals with PCA were impaired on the figure-ground discrimination task compared with half of the tAD group and no HC. Approximately half of the PCA group had Balint syndrome, dressing apraxia, and ideomotor apraxia compared with none in the tAD group. Difficulty copying a complex figure, global-local processing impairment, and Gerstmann syndrome did not distinguish between the two dementia groups. CONCLUSION: The figure-ground discrimination task can be used successfully as an overall screening measure for PCA, followed by specific tasks for Balint syndrome and dressing and limb apraxia. Findings reinforce PCA as a predominant occipitoparietal disorder with dorsal visual stream involvement and parietal signs with spatiomotor impairments.

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.

Case study: a patient with agenesis of the corpus callosum with minimal associated neuropsychological impairment.

This is a case study of an 88-year-old man who presented with agenesis of the corpus callosum and colpocephaly. Symptomatically, he reported a sudden onset of mild, intermittent left hand apraxia, but denied any previous manifestations consistent with this type of brain malformation. The patient underwent neuroimaging, evaluation by neurology, and comprehensive neuropsychological testing to determine the nature of any other associated impairments. Test results indicated that he was, with a few exceptions, neuropsychologically normal. He performed well on tests that are highly sensitive to acquired brain dysfunction. His most notable deficit was failed performance in the simultaneous and coordinated use of both hands in using tactile and proprioceptive feedback on the Tactual Performance Test. This case is discussed in terms of plasticity of the developing brain, including compensatory mechanisms, highlighting the variability in clinical outcome in the context of congenital brain malformation. This case study illustrates the strong influence of cerebral plasticity as well as a possible circumscribed manifestation of interhemispheric disconnection.

Callosal disconnection and limb-kinetic apraxia.

According to Liepmann, patients with limb-kinetic apraxia (LKA) have a loss of upper limb deftness-dexterity. Prior studies have revealed in right-handed patients that, whereas injury of the left hemisphere induces an ipsilesional LKA, injury to the right hemisphere does not induce an ipsilesional LKA. There are at least two possible means by which the left hemisphere may influence the deftness of the left hand, either by callosal connections or by ipsilesional corticospinal projections. The purpose of this study was to learn whether a patient with a focal lesion of the corpus callosum had a callosal disconnection LKA. This 57-year-old right-handed man had a memory impairment, and upon brain imaging, was found to have a septum pellucidum cyst, which was causing mild ventricular obstruction to the occipital and temporal horns. He underwent an endoscopic-assisted fenestration of the septum pellucidum. Postoperative imaging revealed a lesion of the mesial portion of his corpus callosum and an assessment of praxis revealed that he had both a limb-kinetic and ideomotor apraxia of his left but not his right hand. The observation that this man had a callosal disconnection LKA of his left hand suggests that in some people it is the left hemisphere's premotor or motor cortex that enables the right hemisphere's motor system to program deft movements of the left hand.

Ideomotor apraxia in agrammatic and logopenic variants of primary progressive aphasia.

There are few studies examining praxis in subjects with primary progressive aphasia. The aim of this study was to examine the pattern and severity of ideomotor apraxia in subjects with logopenic and agrammatic variants of primary progressive aphasia and to determine if the presence of ideomotor apraxia correlated with specific neuroanatomical structural abnormalities. Subjects with primary progressive aphasia were prospectively recruited and classified according to published criteria. Using the apraxia subtest of the Western Aphasia Battery, pattern and severity of ideomotor apraxia was examined in all subjects diagnosed with agrammatic and logopenic variants of primary progressive aphasia. The study included 47 subjects, 21 diagnosed with agrammatic variant of primary progressive aphasia and 26 with logopenic variant primary progressive aphasia. Subjects with agrammatic aphasia were older at onset than the logopenic variant (67.2 vs. 61.7 years, p = 0.02), but there was no difference in illness duration prior to evaluation. Those with logopenic aphasia showed more cognitive impairment on the Mini-Mental Status Examination (agrammatic = 26.7/30, logopenic = 22/30, p = 0.002), and a trend for more severe language impairment as measured by the Western Aphasia Battery-Aphasia Quotient (agrammatic = 82.3, logopenic = 75.2, p = 0.11). Strong correlations were found between Western Aphasia Battery-Aphasia Quotient and total apraxia, instrumental apraxia, and complex apraxia, while average to modest correlations were seen with upper limb apraxia and facial apraxia. After adjusting for age, mental status performance, and Western Aphasia Battery-Aphasia Quotient score, those with agrammatic aphasia had a higher degree of total apraxia (p = 0.004), facial apraxia (p = 0.03), instrumental apraxia (p = 0.0006), and complex apraxia (p = 0.0006) than those with logopenic aphasia. The agrammatic variant of primary progressive aphasia was associated with greater praxis deficits but less cognitive impairment than the logopenic variant. The presence of ideomotor apraxia was associated with grey matter loss in the left lateral premotor cortex with extension into the motor cortex. These findings suggest that although some affected areas in the agrammatic and logopenic variants of primary progressive aphasia overlap, there exists an area that is more affected in the agrammatic variant than the logopenic variant that accounts for the greater association of agrammatic aphasia with ideomotor apraxia.

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.

Association of ideomotor apraxia with frontal gray matter volume loss in corticobasal syndrome.

OBJECTIVE: To determine the brain areas associated with specific components of ideomotor apraxia (IMA) in corticobasal syndrome (CBS). DESIGN: Case-control and cross-sectional study. PARTICIPANTS: Forty-eight patients with CBS and 14 control subjects. Intervention Administration of the Test of Oral and Limb Apraxia. MAIN OUTCOME MEASURES: Differences between patients with CBS and healthy controls and associations between areas of gray matter volume and IMA determined by voxel-based morphometry in patients with CBS. RESULTS: Overall, IMA was associated with decreased gray matter volume in the left supplemental motor area, premotor cortex, and caudate nucleus of patients with CBS. The overall degree of apraxia was independent of the side of motor impairment. Praxis to imitation (vs command) was particularly impaired in the patients with CBS. Patients demonstrated equal impairment in transitive and intransitive praxis. CONCLUSIONS: In patients with CBS, IMA is associated with left posterior frontal cortical and subcortical volume loss. Despite showing left frontal volume loss associated with IMA, patients with CBS have particularly impaired imitation of gestures. These findings suggest either that the IMA of CBS affects a route of praxis that bypasses motor engrams or that motor engrams are affected but that they exist in areas other than the inferior parietal cortex.

A model-based approach to understanding apraxia in Corticobasal Syndrome.

Limb apraxia is a neurological disorder of higher cognitive function characterized by an inability to perform purposeful skilled movements and not attributable to an elementary sensorimotor dysfunction or comprehension difficulty. Corticobasal Syndrome (CBS) is an akinetic rigid syndrome with asymmetric onset and progression with at least one basal ganglia feature (rigidity, limb dystonia or myoclonus) and one cortical feature (limb apraxia, alien hand syndrome or cortical sensory loss). Even though limb apraxia is highly prevalent in CBS (70-80%), very few studies have examined the performance of CBS patients on praxis measures in detail. This review aims to (1) briefly summarize the clinical, neuroanatomical and pathological findings in CBS, (2) briefly outline what limb apraxia is and how it is assessed, (3) to comprehensively review the literature on limb apraxia in CBS to date and (4) to briefly summarize the literature on other forms of apraxia, such as limb-kinetic apraxia and buccofacial apraxia. Overall, the goal of the review is to bring a model-based perspective to the findings available in the literature to date on limb apraxia in CBS.

Update on apraxia.

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.

Cortico-cortical networks in patients with ideomotor apraxia as revealed by EEG coherence analysis.

We sought to determine whether coherent networks which circumvent lesioned cortex are seen in patients with ideomotor apraxia (IMA) while performing tool-use pantomimes. Five normal subjects and five patients with IMA (three patients with corticobasal degeneration and two with left hemisphere stroke) underwent 64-channel EEG recording while performing three tool-use pantomimes with their left hand in a self-paced manner. Beta band (20-22 Hz) coherence indicates that normal subjects have a dominant left hemisphere network responsible for praxis preparation, which was absent in patients. Corticobasal degeneration patients showed significant coherence increase between left parietal-right premotor areas. Left hemisphere stroke patients showed significant coherence increases in a right parietofrontal network. The right hemisphere appears to store useable praxis representations in IMA patients with left hemisphere damage.

Abnormal reliance on object structure in apraxics' learning of novel object-related actions.

We assessed the prediction that object structural cues could benefit the learning of object-action relationships in ideomotor apraxia (IMA). A total of 15 patients with left-hemisphere stroke, 11 of whom exhibited IMA, and 10 healthy subjects were trained to match novel gestures to novel tool pictures that were either High- or Low-Afforded by their associated tools. Learning was assessed with recognition and production tests. Only IMA patients demonstrated better recognition of High- than Low-Afforded gestures, and their recognition of High-Afforded gestures was statistically comparable to the other groups. This finding suggests that apraxics may rely abnormally on object structure when learning to associate novel gestures and tools. Finally, the "affordance benefit" was associated with relative sparing of structures in the dorsal visual processing stream. These data are consistent with the proposal that two routes may mediate skilled action, one specialized for stored information, and the other responsive to object structure, and that deficient gesture learning may be compensated by "bootstrapping" intact dorsal stream coding of action.

Left inferior parietal representations for skilled hand-object interactions: evidence from stroke and corticobasal degeneration.

Patients with ideomotor apraxia (IM) are frequently more impaired in the production and imitation of object-related (transitive) than non-object-related, symbolic (intransitive) gestures, but reasons for this dissociation, and its anatomical underpinnings, remain unclear. Our theoretical model of praxis (Buxbaum, 2001) postulates that left inferior parietal lobe (IPL) gesture representations store information about postures and movements of the body and hand for skillful manipulation of familiar objects; in contrast, bilateral fronto-parietal dynamic calculations provide constantly-updated information about the current position and movement of the body and hand for both familiar and novel, transitive and intransitive movements. This account predicts distinct patterns of IM in patients with left IPL damage versus bilateral fronto-parietal involvement. Consistent with predictions, 16 stroke patients with left IPL damage were more impaired with transitive than intransitive gestures, whereas 4 patients with bilateral fronto-parietal damage due to corticobasal degeneration (CBD) were not [F (1, 18) = 8.5 p < .01]. Additionally, the hand posture component of transitive gestures was the most impaired aspect of gesture in CVA, but tended to be the least impaired aspect of gesture in CBD [F (3, 54) = 5.1, p < .005]. Finally, CVA patients were more impaired with transitive hand postures than meaningless or intransitive hand postures, whereas CBD patients showed the opposite pattern. These data indicate that the left IPL mediates representations of skilled hand-object interactions, as distinct from dynamic coding of the body in space, and suggest that the IPL maps between representations of object identity in the ventral stream and spatial body representations mediated by the dorsal system.

Impaired imitation of meaningless gestures in ideomotor apraxia: a conceptual problem not a disorder of action control? A single case investigation.

A defining characteristic of ideomotor apraxia is an inability to imitate meaningless gestures. This is widely interpreted as being due to difficulties in the formulation or execution of motor programs for complex action, but an alternative view is that there is a higher level cognitive problem in conceptualisation of the target posture. In a single case with inferior left parietal and temporal damage, severely impaired imitation was accompanied by preserved motor skill and spatial awareness but inability to make a conceptual match between the fingers of his own hand and an observed hand. Also, he was able to match pictures of visually similar gestures but not cartoon drawings of gestures which were conceptually the same but visually dissimilar. Knowledge of body structure seemed largely intact as he was only slightly inaccurate in showing correspondences between locations on drawings of a human figure and his own body, or a visually dissimilar figure. This indicated that difficulty on matching gestures was specific to representation of body posture rather than body structure, or that gesture imitation tasks place higher demand on a structural representation of the body. These data imply that for at least some cases of ideomotor apraxia, impaired gesture imitation is due to a deficit in representing the observed posture and is not a deficit in memory for action or of motor control.

Neuropsychological evidence for a strategic control of multiple routes in imitation.

Previous studies have suggested that imitators can reproduce known gestures shown by a model using a semantic, indirect route, and novel gestures using a sublexical, direct route. In the present study we aimed at testing the validity of such a dual-route model of action imitation. Patients with either left-brain damage (LBD) or right-brain damage (RBD) were tested on an action imitation task. Actions were either meaningful (n = 20) or meaningless (n = 20), and were presented in an intermingled list and, on a different day, in separate lists. We predicted that, in the mixed condition, patients would use a direct route to imitate meaningful and meaningless actions, as it allows the imitation of both action types. In the blocked condition, patients were expected to select the semantic route for meaningful actions and the direct route for meaningless actions. As hypothesized, none of the 32 patients showed dissociations between imitation of meaningful and meaningless actions in the mixed presentation. In contrast, eight patients showed a dissociation between imitation of meaningful actions and imitation of meaningless actions in the blocked presentation. Moreover, two of these patients showed a classical double dissociation between the imitation of the two action types. Results were interpreted in support of the validity of a dual-route model for explaining action imitation. We argue that the decrease in imitation of meaningful actions, relative to meaningless actions, is caused by a damage of the semantic route, and that the decline in imitation of meaningless actions, relative to meaningful actions, is produced by a breakdown of the direct route. The brain areas that were lesioned in all six LBD patients who showed a dissociation were in the superior temporal gyrus and the angular gyrus, whereas the two RBD subjects had common lesions of the pallidum and of the putamen. The brain structures affected in our patients with selective apraxia are consistent with those reported before in other neuropsychological reports. They are also in agreement with areas found activated in imaging studies in which the neural mechanisms underlying imitation were examined.

Deficits in movement planning and intrinsic coordinate control in ideomotor apraxia.

Two central issues in the field of motor control are the coordinate frame in which movements are controlled and the distinction between movement planning and online correction. In this study we used these issues to frame several hypotheses about the deficits underlying ideomotor apraxia (IMA). In particular, we examined whether ideomotor apraxics exhibited (1) deficits in movement control in intrinsic (body relative) coordinates with better control in extrinsic (workspace relative) coordinates, (2) deficits in movement planning that are compensated for by an overreliance on online correction, or (3) both deficits. Patients with IMA and two comparison groups performed movement tasks that relied preferentially on either intrinsic or extrinsic coordinate control when online correction was either possible or impossible. Participants performed posture imitation and grasp imitation movements to body- and object-relative end positions in the presence or absence of visual feedback. Consistent with the intrinsic coordinate control hypothesis, patients with IMA showed a significantly greater disparity than the other two groups between movements made to body-relative and object-relative targets as well as between imitation of meaningless postures and grasping. Consistent with the correction overreliance hypothesis, the IMA group was more disrupted than the other groups by the removal of vision. Thus, IMA patients exhibit behavioral patterns consistent with both deficient intrinsic coordinate control and overreliance upon visual feedback. Finally, lesion analysis suggests that damage to the left inferior parietal lobe (Brodmann's areas 39 and 40) may play a key role in both behavioral deficits.

On beyond mirror neurons: internal representations subserving imitation and recognition of skilled object-related actions in humans.

A considerable recent literature argues that the same representations, encoded by inferior prefrontal and parietal cells known as "mirror neurons", may be activated in both production and recognition of object-related actions. Here, we test several predictions derived from the contemporary literature on the parity between production and recognition and the putative emergence of the mirror neuron system from a system coding hand-object interactions. Forty-four patients with left-hemisphere stroke, 21 of whom exhibited ideomotor apraxia, performed a number of pantomime imitation and recognition tasks, and performance was scored with respect to hand posture, arm posture, amplitude, and timing. Consistent with predictions, there were strong relationships between object-related pantomime imitation and object-related pantomime recognition, and between imitation and recognition of the hand posture component of object-related actions. Skilled object-related gesture representations are likely to be closely tied to evolutionarily more primitive systems controlling object grasping, to emerge from a mapping between object and action information coded by ventral and dorsal streams, and to be lateralized to the left hemisphere in humans.