A preliminary study of white matter disconnections underlying deficits in praxis in left hemisphere stroke patients.

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

What I think she thinks about my paralysed body: Social inferences about disability-related content in anosognosia for hemiplegia.

The neuropsychological disorder of anosognosia for hemiplegia (AHP) can offer unique insights into the neurocognitive processes of body consciousness and representation. Previous studies have found associations between selective social cognition deficits and anosognosia. In this study, we examined how such social cognition deficits may directly interact with representations of one's body as disabled in AHP. We used a modified set of previously validated Theory of Mind (ToM) stories to create disability-related content that was related to post-stroke paralysis and to investigate differences between right hemisphere damage patients with (n = 19) and without (n = 19) AHP. We expected AHP patients to perform worse than controls when trying to infer paralysis-related mental states in the paralysis-related ToM stories and explored whether such differences depended on the inference patients were asked to perform (e.g. self or other referent perspective-taking). Using an advanced structural neuroimaging technique, we expected selective social cognitive deficits to be associated with posterior parietal cortex lesions and deficits in self-referent perspective-taking in paralysis-related mentalising to be associated with frontoparietal disconnections. Group- and individual-level results revealed that AHP patients performed worse than HP controls when trying to infer paralysis-related mental states. Exploratory lesion analysis results revealed some of the hypothesised lesions, but also unexpected white matter disconnections in the posterior body and splenium of the corpus collosum associated with a self-referent perspective-taking in paralysis-related ToM stories. The study has implications for the multi-layered nature of body awareness, including abstract, social perspectives and beliefs about the body.

Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke.

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores-a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance. This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework's range of assessments and predictive power to increase even further through future crowdsourcing.

A fronto-insular-parietal network for the sense of body ownership.

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands.

Temporal judgments of actions following unilateral brain damage.

Sense of time is a complex construct, and its neural correlates remain to date in most part unknown. To complicate the frame, physical attributes of the stimulus, such as its intensity or movement, influence temporal perception. Although previous studies have shown that time perception can be compromised after a brain lesion, the evidence on the role of the left and right hemispheres are meager. In two experiments, the study explores the ability of temporal estimation of multi-second actions and non-biological movements in 33 patients suffering from unilateral brain lesion. Furthermore, the modulatory role of induced embodiment processes is investigated. The results reveal a joint contribution of the two hemispheres depending not only on different durations but also on the presence of actions. Indeed, the left hemisphere damaged patients find it difficult to estimate 4500 ms or longer durations, while the right hemisphere damaged patients fail in 3000 ms durations. Furthermore, the former fail when a biological action is shown, while the latter fail in non-biological movement. Embodiment processes have a modulatory effect only after right hemisphere lesions. Among neuropsychological variables, only spatial neglect influences estimation of non-biological movement.

Longitudinal prediction of motor dysfunction after stroke: a disconnectome study.

Motricity is the most commonly affected ability after a stroke. While many clinical studies attempt to predict motor symptoms at different chronic time points after a stroke, longitudinal acute-to-chronic studies remain scarce. Taking advantage of recent advances in mapping brain disconnections, we predict motor outcomes in 62 patients assessed longitudinally two weeks, three months, and one year after their stroke. Results indicate that brain disconnection patterns accurately predict motor impairments. However, disconnection patterns leading to impairment differ between the three-time points and between left and right motor impairments. These results were cross-validated using resampling techniques. In sum, we demonstrated that while some neuroplasticity mechanisms exist changing the structure-function relationship, disconnection patterns prevail when predicting motor impairment at different time points after stroke.

Motor awareness: a model based on neurological syndromes.

Motor awareness is a complex, multifaceted construct involving the awareness of both (i) one's motor state while executing a movement or remaining still and (ii) one's motor abilities. The analysis of neurological syndromes associated with motor disorders suggests the existence of various different components which are, however, integrated into a model of motor awareness. These components are: (i) motor intention, namely, a conscious desire to perform an action; (ii) motor monitoring and error recognition, that is, the capacity to check the execution of the action and identify motor errors; and (iii) a general awareness of one's own motor abilities and deficits, that is, the capacity to recognize the general state of one's motor abilities about the performance of specific actions and the potential consequences of motor impairment. Neuroanatomical correlates involving the parietal and insular cortices, the medial and lateral frontal regions, and subcortical structures (basal ganglia and limbic system) support this multi-component model. Specific damage (or disconnections) to these structures results in a number of different disorders in motor awareness, such as anosognosia for hemiplegia and apraxia, and a number of symptoms which are specific to motor intention disorders (e.g., the Anarchic Hand Syndrome and Tourette's Syndrome) or motor monitoring (e.g., Parkinson's and Huntington's diseases). All of these clinical conditions are discussed in the light of a motor awareness model.

The Role of White Matter Disconnection in the Symptoms Relating to the Anarchic Hand Syndrome: A Single Case Study.

The anarchic hand syndrome refers to an inability to control the movements of one's own hand, which acts as if it has a will of its own. The symptoms may differ depending on whether the brain lesion is anterior, posterior, callosal or subcortical, but the relative classifications are not conclusive. This study investigates the role of white matter disconnections in a patient whose symptoms are inconsistent with the mapping of the lesion site. A repeated neuropsychological investigation was associated with a review of the literature on the topic to identify the frequency of various different symptoms relating to this syndrome. Furthermore, an analysis of the neuroimaging regarding structural connectivity allowed us to investigate the grey matter lesions and white matter disconnections. The results indicated that some of the patient's symptoms were associated with structures that, although not directly damaged, were dysfunctional due to a disconnection in their networks. This suggests that the anarchic hand may be considered as a disconnection syndrome involving the integration of multiple antero-posterior, insular and interhemispheric networks. In order to comprehend this rare syndrome better, the clinical and neuroimaging data need to be integrated with the clinical reports available in the literature on this topic.

Anosognosia for theory of mind deficits: A single case study and a review of the literature.

Being aware of one's own ability to interact socially is crucial to everyday life. After a brain injury, patients may lose their capacity to understand others' intentions and beliefs, that is, the Theory of Mind (ToM). To date, the debate on the association between ToM and other cognitive deficits (in particular executive functions and behavioural disorders) remains open and data regarding awareness of ToM deficits are meagre. By means of an ad-hoc neuropsychological battery of tests, we report on a patient who suffers from ToM deficits and is not aware of these disorders, although aware of his other symptoms. The study is accompanied by a review of the literature (PRISMA guidelines) demonstrating that ToM deficits are independent of executive functions. Furthermore, an advanced lesion analysis including tractography was executed. The results indicate that: i) ToM deficits can be specific and independent of other cognitive symptoms; ii) unawareness may be specific for ToM impairment and not involve other disorders and iii) the medial structures of the limbic, monitoring and attentional systems may be involved in anosognosia for ToM impairment.

Neuro-cognitive architecture of executive functions: A latent variable analysis.

Executive functions refer to high-level cognitive processes that, by operating on lower-level mental processes, flexibly regulate and control our thoughts and goal-directed behavior. Despite their crucial role, the study of the nature and organization of executive functions still faces inherent difficulties. Moreover, most executive function models put under test until now are brain-free models: they are defined and discussed without assumptions regarding the neural bases of executive functions. By using a latent variable approach, here we tested a brain-centered model of executive function organization proposing that two distinct domain-general executive functions, namely, criterion setting and monitoring, may be dissociable both functionally and anatomically, with a left versus right hemispheric preference of prefrontal cortex and related neural networks, respectively. To this end, we tested a sample of healthy participants on a battery of computerized tasks assessing criterion setting and monitoring processes and involving diverse task domains, including the verbal and visuospatial ones, which are well-known to be lateralized. By doing this, we were able to specifically assess the influence of these task domains on the organization of executive functions and to directly contrast a process-based model of EF organization versus both a purely domain-based model and a process-based, but domain-dependent one. The results of confirmatory factor analyses showed that a purely process-based model reliably provided a better fit to the observed data as compared to alternative models, supporting the specific theoretical model that fractionates a subset of executive functions into criterion setting and monitoring with hemispheric specializations emerging regardless of the task domain.

Anosognosia for hemiplegia as a tripartite disconnection syndrome.

The syndrome of Anosognosia for Hemiplegia (AHP) can provide unique insights into the neurocognitive processes of motor awareness. Yet, prior studies have only explored predominately discreet lesions. Using advanced structural neuroimaging methods in 174 patients with a right-hemisphere stroke, we were able to identify three neural systems that contribute to AHP, when disconnected or directly damaged: the (i) premotor loop (ii) limbic system, and (iii) ventral attentional network. Our results suggest that human motor awareness is contingent on the joint contribution of these three systems.

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies.