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.

Benefit of visual speech information for word comprehension in post-stroke aphasia.

Aphasia is a language disorder that often involves speech comprehension impairments affecting communication. In face-to-face settings, speech is accompanied by mouth and facial movements, but little is known about the extent to which they benefit aphasic comprehension. This study investigated the benefit of visual information accompanying speech for word comprehension in people with aphasia (PWA) and the neuroanatomic substrates of any benefit. Thirty-six PWA and 13 neurotypical matched control participants performed a picture-word verification task in which they indicated whether a picture of an animate/inanimate object matched a subsequent word produced by an actress in a video. Stimuli were either audiovisual (with visible mouth and facial movements) or auditory-only (still picture of a silhouette) with audio being clear (unedited) or degraded (6-band noise-vocoding). We found that visual speech information was more beneficial for neurotypical participants than PWA, and more beneficial for both groups when speech was degraded. A multivariate lesion-symptom mapping analysis for the degraded speech condition showed that lesions to superior temporal gyrus, underlying insula, primary and secondary somatosensory cortices, and inferior frontal gyrus were associated with reduced benefit of audiovisual compared to auditory-only speech, suggesting that the integrity of these fronto-temporo-parietal regions may facilitate cross-modal mapping. These findings provide initial insights into our understanding of the impact of audiovisual information on comprehension in aphasia and the brain regions mediating any benefit.

Shared and distinct routes in speech and gesture imitation: Evidence from stroke.

Dual-route models of high-level (praxis) actions distinguish between an "indirect" semantic route mediating meaningful gesture imitation, and a "direct" sensory-motor route mediates meaningless gesture imitation. Similarly, dual-route language models distinguish between an indirect route mediating production and repetition of words, and a direct route mediating non-word repetition. Although aphasia and limb apraxia frequently co-occur following left-hemisphere cerebrovascular accident (LCVA), it is unclear which aspects of these functional-neuroanatomic dual-route architectures are shared across praxis and language domains. This study focused on gesture imitation to test the hypothesis that semantic information (and portions of the indirect route) are shared across domains, whereas two distinct dorsal routes mediate sensory-motor mapping. Forty chronic LCVA and 17 neurotypical controls completed semantic memory and language tasks and imitated 3 types of gesture stimuli: (1) labeled/"named" meaningful, (2) unnamed meaningful, and (3) meaningless gestures. The comparison of accuracy between meaningless versus unnamed meaningful gestures examined the benefits of semantic information, while the comparison of unnamed meaningful versus named meaningful imitation examined additional benefits of linguistic cueing. Mixed-effects models examined group by task interaction effects on gesture ability. We found that for patients with LCVA, unnamed meaningful gestures were imitated more accurately than meaningless gestures, suggesting that semantic information was beneficial, but there was no benefit of labeling. Reduced benefit of semantic information on gesture accuracy was associated with lesions to inferior frontal and posterior temporal regions as well as semantic memory performance on a pictorial (non-gesture) task. In contrast, there was no relationship between meaningless gesture imitation and nonword repetition, indicating that measures of direct route performance are not associated across language and action. These results provide preliminary evidence that portions of the indirect semantic route are shared across the language and action domains, while two direct sensory-motor mapping routes mediate word repetition and gesture imitation.

Gesture profiles distinguish primary progressive aphasia variants.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. There are three main variants of PPA - semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) - that can be challenging to distinguish. Limb praxis may also be affected in PPA, but it is unclear whether different variants of PPA are associated with differences in gesture production. Prior research with neurotypical individuals indicates that the left temporal lobe is a critical locus of manipulable object and hand posture representations. Moreover, when imitating gestures, individuals whose strokes include the left temporal lobe show reduced benefit of gesture meaning and disproportionate impairment in hand posture as compared to arm kinematics. We tested the hypothesis that svPPA - who typically exhibit primarily temporal lobe atrophy - would differentially show these expected patterns of gesture imitation performance. Nineteen participants with PPA completed meaningful and meaningless gesture imitation tasks, and performance was scored for hand posture and arm kinematics accuracy. Generalized logistic mixed-effect regression models controlling for dementia severity showed overall benefits from gesture meaning, and greater impairments in hand posture than arm kinematics. We also found that svPPA participants were the most impaired in gesture imitation overall. Critically, there was also a significant three-way interaction of group, meaning, and gesture component: only svPPA participants showed relative impairments of hand posture for meaningful gestures as well as meaningless gestures. Thus, unlike lvPPA and nfvPPA, the hand postures of svPPA failed to benefit from gesture meaning. This research extends prior findings on the role of the temporal lobe in hand posture representations associated with manipulable objects, and is the first to indicate that there may be distinct gesture imitation patterns as a function of PPA variant. Characterizing componential gesture deficits in PPA may help to inform differential diagnosis, compensatory communication strategies, and cognitive praxis models of PPA.

Action imitation via trajectory-based or posture-based planning.

Imitation is a significant daily activity involved in social interaction and motor learning. Imitation has been theorized to be performed in at least two ways. In posture-based imitation, individuals reproduce how the body should look and feel, and are sensitive to the relative positioning of body parts. In trajectory imitation, individuals mimic the spatiotemporal motion path of the end effector. There are clear anecdotal situations in which one might benefit from imitating postures (when learning ballet) or trajectories (when learning to reach around objects). However, whether these are in fact distinct methods of imitation, and if so, whether they may be applied interchangeably to perform the same task, remain unknown. If these are indeed separate mechanisms that rely on different computational and neural resources, a cost should be incurred when switching from using one mechanism to the other within the context of a single task. Therefore, observing a processing cost would both provide evidence that these are indeed two distinct mechanisms, and that they may be used interchangeably when trying to imitate the same stimulus. To test this, twenty-five healthy young adults performed a sequential multitasking imitation task. Participants were first instructed to pay attention to the limb postures or the hand path of a video-recorded model, then performed a neutral, congruent, or incongruent intervening motor task. Finally, participants imitated the modeled movement. We examined both spatial and temporal imitation accuracy as well as individual spatial consistency. When the primary task involved imitating trajectories, analysis of individual consistency suggested a processing cost: movements following the posture-matching intervening task were less consistent with baseline (neutral) performance, suggesting performance may be disrupted by the incongruence. This effect was not observed when imitating limb postures. In summary, we present initial evidence for a difference between posture matching and trajectory imitation as a result of instructions and intervening tasks that is consistent with the existence of two computationally distinct imitation mechanisms.

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.

Proprioception-based movement goals support imitation and are disrupted in apraxia.

The ability to imitate observed actions serves as an efficient method for learning novel movements and is specifically impaired (without concomitant gross motor impairments) in the neurological disorder of limb apraxia, a disorder common after left hemisphere stroke. Research with apraxic patients has advanced our understanding of how people imitate. However, the role of proprioception in imitation has been rarely assessed directly. Prior work has proposed that proprioceptively sensed body position is transformed into a visual format, supporting the attainment of a desired imitation goal represented visually (i.e., how the movement should look when performed). In contrast, we hypothesized a more direct role for proprioception: we suggest that movement goals are also represented proprioceptively (i.e., how a desired movement should feel when performed), and the ability to represent or access such proprioceptive goals is deficient in apraxia. Using a novel imitation task in which a robot cued meaningless trajectories proprioceptively or visually, we probed the role of each sensory modality. We found that patients with left hemisphere stroke were disproportionately worse than controls at imitating when cued proprioceptively versus visually. This proprioceptive versus visual disparity was associated with apraxia severity as assessed by a traditional imitation task, but could not be explained by general proprioceptive impairment or speed-accuracy trade-offs. These data suggest that successful imitation depends in part on the ability to represent movement goals in terms of how those movements should feel, and that deficits in this ability contribute to imitation impairments in patients with apraxia.

Does spatial perspective in virtual reality affect imitation accuracy in stroke patients?

Imitation is an important daily activity involved in social interactions, motor learning, and is commonly used for rehabilitation after stroke. Moreover, deficits in imitation of novel movements commonly occur after left hemisphere stroke (LCVA) in the syndrome of limb apraxia. In the current study, we used a novel virtual reality (VR) imitation paradigm to assess two factors that have remained underexplored in novel movement imitation: the imitation of complex, dynamic full-arm movements, and the effect of spatial perspective. VR holds promise as a tool for a number of clinical assessments and treatments, but has very rarely been studied in the context of imitation or diagnosis of apraxia. Thirty participants (18 with LCVA and 12 age- and education-matched controls) wore a VR headset and observed and imitated an instructor avatar demonstrating arm movements. Three spatial perspectives were examined within-subjects: first-person, third-person mirror, and third-person anatomical. Movements of the ipsilesional (left) arm were recorded and qualitatively coded for accuracy compared to the instructor avatar. Participants also completed embodiment questionnaires, a measure of limb apraxia (imitation of video-recorded meaningless movements), and three computerized background tasks that were hypothesized to evoke some of the same processing requirements of each of the three perspective conditions: a block-matching task, a block-mirroring task, and a mental rotation task. Imitation accuracy was highest in the first-person perspective, consistent with predictions, but did not differ between third-person mirror and anatomical. Surprisingly, patients and controls performed similarly on the imitation task for all spatial perspectives, with overall modest accuracy in both groups, and both patients and controls felt a moderate level of embodiment of their own avatar. Higher imitation accuracy related to quicker block-matching reaction times and higher mental rotation accuracy, regardless of perspective, but was unrelated to imitation of video-recorded meaningless movements. In sum, virtual reality provides advantages in terms of experimental manipulation and control but may present challenges in detecting clinical imitation deficits (limb apraxia).

Virtual Reality Treatment Displaying the Missing Leg Improves Phantom Limb Pain: A Small Clinical Trial.

BACKGROUND: Phantom limb pain (PLP) is a common and in some cases debilitating consequence of upper- or lower-limb amputation for which current treatments are inadequate. OBJECTIVE: This small clinical trial tested whether game-like interactions with immersive VR activities can reduce PLP in subjects with transtibial lower-limb amputation. METHODS: Seven participants attended 5-7 sessions in which they engaged in a visually immersive virtual reality experience that did not require leg movements (Cool! TM), followed by 10-12 sessions of targeted lower-limb VR treatment consisting of custom games requiring leg movement. In the latter condition, they controlled an avatar with 2 intact legs viewed in a head-mounted display (HTC Vive TM). A motion-tracking system mounted on the intact and residual limbs controlled the movements of both virtual extremities independently. RESULTS: All participants except one experienced a reduction of pain immediately after VR sessions, and their pre session pain levels also decreased over the course of the study. At a group level, PLP decreased by 28% after the treatment that did not include leg movements and 39.6% after the games requiring leg motions. Both treatments were successful in reducing PLP. CONCLUSIONS: This VR intervention appears to be an efficacious treatment for PLP in subjects with lower-limb amputation.

Aberrant activity in an intact residual muscle is associated with phantom limb pain in above-knee amputees.

Many individuals who undergo limb amputation experience persistent phantom limb pain (PLP), but the underlying mechanisms of PLP are unknown. The traditional hypothesis was that PLP resulted from maladaptive plasticity in sensorimotor cortex that degrades the neural representation of the missing limb. However, a recent study of individuals with upper limb amputations has shown that PLP is correlated with aberrant electromyographic (EMG) activity in residual muscles, posited to reflect a retargeting of efferent projections from a preserved representation of a missing limb. Here, we assessed EMG activity in a residual thigh muscle (vastus lateralis, VL) in patients with transfemoral amputations during cyclical movements of a phantom foot. VL activity on the amputated side was compared to that recorded on patients' intact side while they moved both the phantom and intact feet synchronously. VL activity in the patient group was also compared to a sample of control participants with no amputation. We show that phantom foot movement is associated with greater VL activity in the amputated leg than that seen in the intact leg as well as that exhibited by controls. The magnitude of residual VL activity was also positively related to ratings of PLP. These results show that phantom limb movement is associated with aberrant activity in a residual muscle after lower-limb amputation and provide evidence of a positive relationship between this activity and phantom limb pain.NEW & NOTEWORTHY This study is the first to assess residual muscle activity during movement of a phantom limb in individuals with lower limb amputations. We find that phantom foot movement is associated with aberrant recruitment of a residual thigh muscle and that this aberrant activity is related to phantom limb pain.

Scene context shapes category representational geometry during processing of tools.

Tools are ubiquitous in human environments and to think about them we use concepts. Increasingly, conceptual representation is thought to be dynamic and sensitive to the goals of the observer. Indeed, observer goals can reshape representational geometry within cortical networks supporting concepts. In the present study, we investigated the novel hypothesis that task-irrelevant scene context may implicitly alter the representational geometry of regions within the tool network. Participants performed conceptual judgments on images of tools embedded in scenes that either suggested their use (i.e., a kitchen timer sitting on a kitchen counter with vegetables in a frying pan) or that they would simply be moved (i.e., a kitchen timer sitting in an open drawer with other miscellaneous kitchen items around). We investigated whether representations in the tool network reflect category, grip, and shape information using a representational similarity analysis (RSA). We show that a) a number of regions of the tool network reflect category information about tools and b) category information predicts patterns in supramarginal gyrus more strongly in use contexts than in move contexts. Together, these results show that information about tool category is distributed across different regions of the tool network and that scene context helps shape the representational geometry of the tool network.

Treating limb apraxia via action semantics: a preliminary study.

Limb apraxia is evident in approximately 50% of patients after left hemisphere cerebral vascular accident (LCVA) and increases disability and caregiver dependence. Individuals with apraxia exhibit abnormalities in spatio-temporal aspects of gesture production and/or in knowledge of tool-related actions (action semantics). This preliminary study of three LCVA participants aimed to (i) explore the efficacy of a novel Action Network Treatment (ANT) that focused on improving the semantic association between tool actions and other types of tool knowledge, an intervention inspired by successful semantic network treatments in aphasia (e.g., Edmonds et al., 2009), and (ii) explore whether there are individuals with apraxia who benefit from ANT relative to a version of a comparatively well-studied existing apraxia treatment (Smania et al., 2006; Smania et al., 2000) that shapes gesture via focus on practicing the spatio-temporal aspects of gesture production (Tool Use Treatment or TUT). One participant demonstrated treatment benefits from both ANT and TUT, while another only benefited from TUT. These findings indicate that our novel semantic network strengthening approach to gesture training may be efficacious in at least some individuals with apraxia, and provide a foundation for future study of the characteristics of people with apraxia who benefit from each approach.

Multimodal comprehension in left hemisphere stroke patients.

Hand gestures, imagistically related to the content of speech, are ubiquitous in face-to-face communication. Here we investigated people with aphasia's (PWA) processing of speech accompanied by gestures using lesion-symptom mapping. Twenty-nine PWA and 15 matched controls were shown a picture of an object/action and then a video-clip of a speaker producing speech and/or gestures in one of the following combinations: speech-only, gesture-only, congruent speech-gesture, and incongruent speech-gesture. Participants' task was to indicate, in different blocks, whether the picture and the word matched (speech task), or whether the picture and the gesture matched (gesture task). Multivariate lesion analysis with Support Vector Regression Lesion-Symptom Mapping (SVR-LSM) showed that benefit for congruent speech-gesture was associated with 1) lesioned voxels in anterior fronto-temporal regions including inferior frontal gyrus (IFG), and sparing of posterior temporal cortex and lateral temporal-occipital regions (pTC/LTO) for the speech task, and 2) conversely, lesions to pTC/LTO and sparing of anterior regions for the gesture task. The two tasks did not share overlapping voxels. Costs from incongruent speech-gesture pairings were associated with lesioned voxels in these same anterior (for the speech task) and posterior (for the gesture task) regions, but crucially, also shared voxels in superior temporal gyrus (STG) and middle temporal gyrus (MTG), including the anterior temporal lobe. These results suggest that IFG and pTC/LTO contribute to extracting semantic information from speech and gesture, respectively; however, they are not causally involved in integrating information from the two modalities. In contrast, regions in anterior STG/MTG are associated with performance in both tasks and may thus be critical to speech-gesture integration. These conclusions are further supported by associations between performance in the experimental tasks and performance in tests assessing lexical-semantic processing and gesture recognition.

Structural Disconnection of the Tool Use Network after Left Hemisphere Stroke Predicts Limb Apraxia Severity.

Producing a tool use gesture is a complex process drawing upon the integration of stored knowledge of tools and their associated actions with sensory-motor mechanisms supporting the planning and control of hand and arm actions. Understanding how sensory-motor systems in parietal cortex interface with semantic representations of actions and objects in the temporal lobe remains a critical issue and is hypothesized to be a key determinant of the severity of limb apraxia, a deficit in producing skilled action after left hemisphere stroke. We used voxel-based and connectome-based lesion-symptom mapping with data from 57 left hemisphere stroke participants to assess the lesion sites and structural disconnection patterns associated with poor tool use gesturing. We found that structural disconnection among the left inferior parietal lobule, lateral and ventral temporal cortices, and middle and superior frontal gyri predicted the severity of tool use gesturing performance. Control analyses demonstrated that reductions in right-hand grip strength were associated with motor system disconnection, largely bypassing regions supporting tool use gesturing. Our findings provide evidence that limb apraxia may arise, in part, from a disconnection between conceptual representations in the temporal lobe and mechanisms enabling skilled action production in the inferior parietal lobule.

Predictors of Arm Nonuse in Chronic Stroke: A Preliminary Investigation.

Background. Nonuse (NU) after stroke is characterized by failure to use the contralesional arm despite adequate capacity. It has been suggested that NU is a consequence of the greater effort and/or attention required to use the affected limb, but such accounts have not been directly tested, and we have poor understanding of the predictors of NU. Objective. We aimed to provide preliminary evidence regarding demographic, neuropsychological (ie, apraxia, attention/arousal, neglect), and psychological (ie, self-efficacy) factors that may influence NU in chronic stroke. Methods. Twenty chronic stroke survivors with mild to moderate sensory-motor impairment characterized by the Upper-Extremity Fugl-Meyer (UEFM) were assessed for NU with a modified version of the Actual Amount of Use Test (AAUT), which measures the disparity between amount of use in spontaneous versus forced conditions. Participants were also assessed with measures of limb apraxia, spatial neglect, attention/arousal, and self-efficacy. Using stepwise multiple regression, we determined which variables predicted AAUT NU scores. Results. Scores on the UEFM as well as attention/arousal predicted the degree of NU (P < .05). Attention/arousal predicted NU above and beyond UEFM (P < .05). Conclusions. The results are consistent with the importance of attention and engagement necessary to fully incorporate the paretic limb into daily activities. Larger-scale studies that include additional behavioral (eg, sensation, proprioception, spasticity, pain, mental health, motivation) and neuroanatomical measures (eg, lesion volume and white matter connectivity) will be important for future investigations.

Reduced competition between tool action neighbors in left hemisphere stroke.

When pantomiming the use of tools, patients with limb apraxia after left hemisphere stroke (LCVA) produce more spatiotemporal hand action errors with tools associated with conflicting actions for use versus grasp-to-pick-up (e.g., corkscrew) than tools having a single action for both use and grasp (e.g., hammer). There are two possible accounts for this pattern of results. Reduced performance with 'conflict' tools may simply reflect weakened automaticity of use action activation, which is evident only when the use and grasp actions are not redundant. Alternatively, poor use performance may reflect a reduced ability of appropriate tool use actions to compete with task-inappropriate action representations. To address this issue, we developed a Stroop-like experiment in which 21 LCVA and 8 neurotypical participants performed pantomime actions in blocks containing two tools that were similar ("neighbors") in terms of hand action or function, or were unrelated on either dimension. In a congruent condition, they pantomimed the use action associated with the visually presented tool, whereas in an incongruent condition, they pantomimed the use action for the other tool in the block. Relative to controls and other task conditions, LCVA participants showed reductions in hand action errors in incongruent relative to congruent action trials; furthermore, the degree of reduction in this incongruence effect was related to the participants' susceptibility to grasp-on-use conflict in a separate test of pantomime to the sight of tools. Support vector regression lesion-symptom mapping analyses identified the left inferior frontal gyrus, supramarginal gyrus, and superior longitudinal fasciculus as core neuroanatomical sites associated with abnormal performance. Collectively, the results indicate that weakened activation of tool use actions in limb apraxia gives rise to reduced ability of these actions to compete for task-appropriate selection when competition arises within single tools (grasp-on-use conflict) as well as between two tools (reduced neighborhood effects).

Gesturing tool use and tool transport actions modulates inferior parietal functional connectivity with the dorsal and ventral object processing pathways.

Interacting with manipulable objects (tools) requires the integration of diverse computations supported by anatomically remote regions. Previous functional neuroimaging research has demonstrated the left supramarginal (SMG) exhibits functional connectivity to both ventral and dorsal pathways, supporting the integration of ventrally-mediated tool properties and conceptual knowledge with dorsally-computed volumetric and structural representations of tools. This architecture affords us the opportunity to test whether interactions between the left SMG, ventral visual pathway, and dorsal visual pathway are differentially modulated when participants plan and generate tool-directed gestures emphasizing functional manipulation (tool use gesturing) or structure-based grasping (tool transport gesturing). We found that functional connectivity between the left SMG, ventral temporal cortex (bilateral fusiform gyri), and dorsal visual pathway (left superior parietal lobule/posterior intraparietal sulcus) was maximal for tool transport planning and gesturing, whereas functional connectivity between the left SMG, left ventral anterior temporal lobe, and left frontal operculum was maximal for tool use planning and gesturing. These results demonstrate that functional connectivity to the left SMG is differentially modulated by tool use and tool transport gesturing, suggesting that distinct tool features computed by the two object processing pathways are integrated in the parietal lobe in the service of tool-directed action.

The role of conflict, feedback, and action comprehension in monitoring of action errors: Evidence for internal and external routes.

The mechanisms and brain regions underlying error monitoring in complex action are poorly understood, yet errors and impaired error correction in these tasks are hallmarks of apraxia, a common disorder associated with left hemisphere stroke. Accounts of monitoring of language posit an internal route by which production planning or competition between candidate representations provide predictive signals that monitoring is required to prevent error, and an external route in which output is monitored using the comprehension system. Abnormal reliance on the external route has been associated with damage to brain regions critical for sensory-motor transformation and a pattern of gradual error 'clean-up' called conduite d'approche (CD). Action pantomime data from 67 participants with left hemisphere stroke were consistent with versions of internal route theories positing that competition signals monitoring requirements. Support Vector Regression Lesion Symptom Mapping (SVR-LSM) showed that lesions in the inferior parietal, posterior temporal, and arcuate fasciculus/superior longitudinal fasciculus predicted action conduite d'approche, overlapping the regions previously observed in the language domain. A second experiment with 12 patients who produced substantial action CD assessed whether factors impacting the internal route (action production ability, competition) versus external route (vision of produced actions, action comprehension) influenced correction attempts. In these 'high CD' patients, vision of produced actions and integrity of gesture comprehension interacted to determine successful error correction, supporting external route theories. Viewed together, these and other data suggest that skilled actions are monitored both by an internal route in which conflict aids in detection and correction of errors during production planning, and an external route that detects mismatches between produced actions and stored knowledge of action appearance. The parallels between language and action monitoring mechanisms and neuroanatomical networks pave the way for further exploration of common and distinct processes across these domains.

Movement Imitation via an Abstract Trajectory Representation in Dorsal Premotor Cortex.

Humans are particularly good at copying novel and meaningless gestures. The mechanistic and anatomical basis for this specialized imitation ability remains largely unknown. One idea is that imitation occurs by matching body configurations. Here we propose an alternative route to imitation that depends on a body-independent representation of the trajectory path of the end-effector. We studied a group of patients with strokes in the left frontoparietal cortices. We found that they were equally impaired at imitating movement trajectories using the ipsilesional limb (i.e., the nonparetic side) that were cued either by an actor using their whole arm or just by a cursor, suggesting that body configuration information is not always critical for imitation and that a representation of abstract trajectory shape may suffice. In addition, imitation ability was uncorrelated to the ability to identify the trajectory shape, suggesting that imitation deficits were unlikely to arise from perceptual impairments. Finally, a lesion-symptom mapping analysis found that imitation deficits were associated with lesions in left dorsal premotor but not parietal cortex. Together, these findings suggest a novel body-independent route to imitation that relies on the ability to plan abstract movement trajectories within dorsal premotor cortex.SIGNIFICANCE STATEMENT The ability to imitate is critical for rapidly learning to produce new gestures and actions, but how the brain translates observed movements into motor commands is poorly understood. Examining the ability of patients with strokes affecting the left hemisphere revealed that meaningless gestures can be imitated by succinctly representing only the motion of the hand in space, rather than the posture of the entire arm. Moreover, performance deficits correlated with lesions in dorsal premotor cortex, an area not previously associated with impaired imitation of arm postures. These findings thus describe a novel route to imitation that may also be impaired in some patients with apraxia.

Bilateral functional connectivity at rest predicts apraxic symptoms after left hemisphere stroke.

Increasing evidence indicates that focal lesions following stroke cause alterations in connectivity among functional brain networks. Functional connectivity between hemispheres has been shown to be particularly critical for predicting stroke-related behavioral deficits and recovery of motor function and attention. Much less is known, however, about the relevance of interhemispheric functional connectivity for cognitive abilities like praxis that rely on strongly lateralized brain networks. In the current study, we examine correlations between symptoms of apraxia-a disorder of skilled action that cannot be attributed to lower-level sensory or motor impairments-and spontaneous, resting brain activity in functional MRI in chronic left hemisphere stroke patients and neurologically-intact control participants. Using a data-driven approach, we identified 32 regions-of-interest in which pairwise functional connectivity correlated with two distinct measures of apraxia, even when controlling for age, head motion, lesion volume, and other artifacts: overall ability to pantomime the typical use of a tool, and disproportionate difficulty pantomiming the use of tools associated with different, competing use and grasp-to-move actions (e.g., setting a kitchen timer versus picking it up). Better performance on both measures correlated with stronger interhemispheric functional connectivity. Relevant regions in the right hemisphere were often homologous to left hemisphere areas associated with tool use and action. Additionally, relative to overall pantomime accuracy, disproportionate difficulty pantomiming the use of tools associated with competing use and grasp actions was associated with weakened functional connectivity among a more strongly left-lateralized and peri-Sylvian set of brain regions. Finally, patient performance on both measures of apraxia was best predicted by a model that incorporated information about lesion location and functional connectivity, and functional connectivity continued to explain unique variance in behavior even after accounting for lesion loci. These results indicate that interhemispheric functional connectivity is relevant even for a strongly lateralized cognitive ability like praxis and emphasize the importance of the right hemisphere in skilled action.