Cerebral Glucose Metabolism Is a Valuable Predictor of Survival in Patients with Lewy Body Diseases.

OBJECTIVE: Patients with Lewy body diseases have an increased risk of dementia, which is a significant predictor for survival. Posterior cortical hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (PET) precedes the development of dementia by years. We therefore examined the prognostic value of cerebral glucose metabolism for survival. METHODS: We enrolled patients diagnosed with Parkinson's disease (PD), Parkinson's disease with dementia, or dementia with Lewy bodies who underwent [18F]fluorodeoxyglucose PET. Regional cerebral metabolism of each patient was analyzed by determining the expression of the PD-related cognitive pattern (Z-score) and by visual PET rating. We analyzed the predictive value of PET for overall survival using Cox regression analyses (age- and sex-corrected) and calculated prognostic indices for the best model. RESULTS: Glucose metabolism was a significant predictor of survival in 259 included patients (n = 118 events; hazard ratio: 1.4 [1.2-1.6] per Z-score; hazard ratio: 1.8 [1.5-2.2] per visual PET rating score; both p < 0.0001). Risk stratification with visual PET rating scores yielded a median survival of 4.8, 6.8, and 12.9 years for patients with severe, moderate, and mild posterior cortical hypometabolism (median survival not reached for normal cortical metabolism). Stratification into 5 groups based on the prognostic index revealed 10-year survival rates of 94.1%, 78.3%, 34.7%, 0.0%, and 0.0%. INTERPRETATION: Regional cerebral glucose metabolism is a significant predictor of survival in Lewy body diseases and may allow an earlier survival prediction than the clinical milestone "dementia." Thus, [18F]fluorodeoxyglucose PET may improve the basis for therapy decisions, especially for invasive therapeutic procedures like deep brain stimulation in Parkinson's disease. ANN NEUROL 2024.

The Role of Ascending Ventral-Tegmental Fibers for Recovery after Stroke.

OBJECTIVES: The integrity of cortical motor networks and their descending effector pathway (the corticospinal tract [CST]) is a major determinant motor recovery after stroke. However, this view neglects the importance of ascending tracts and their modulatory effects on cortical physiology. Here, we explore the role of such a tract that connects dopaminergic ventral tegmental midbrain nuclei to the motor cortex (the VTMC tract) for post-stroke recovery. METHODS: Lesion data and diffusivity parameters (fractional anisotropy) of the ipsi- and contralesional VTMC tract and CST were obtained from 133 patients (63.9 ± 13.4 years, 45 women) during the acute and chronic stage after the first ever ischemic stroke in the middle cerebral artery territory. Degeneration of VTMC tract and CST was quantified and related to clinical outcome parameters (National Institute of Health Stroke Scale with motor and cortical symptom subscores; modified Fugl-Meyer upper extremity score; modified Ranking Scale [mRS]). RESULTS: A significant post-stroke degeneration occurred in both tracts, but only VTMC degeneration was associated with lesion size. Using multiple regression models, we dissected the impact of particular tracts on recovery: Changes in VTMC tract integrity were stronger associated with independence in daily activities (mRS), upper limb motor impairment (modified Fugl-Meyer upper extremity score) and cortical symptoms (aphasia, neglect) captured by National Institute of Health Stroke Scale compared to CST. Changes in CST integrity merely were associated with the degree of hemiparesis (National Institute of Health Stroke Scale motor subscale). INTERPRETATION: Post-stroke outcome is influenced by ascending (VTMC) and descending (CST) fiber tracts. Favorable outcome regarding independence (modified Ranking Scale), upper limb motor function (modified Fugl-Meyer upper extremity score), and cortical symptoms (aphasia, neglect) was more strongly related to the ascending than descending tract. ANN NEUROL 2023;93:922-933.

Cerebellar, Not Nigrostriatal Degeneration Impairs Dexterity in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA-P [multiple system atrophy-parkinsonian subtype]) and one with predominant cerebellar deficits (MSA-C [multiple system atrophy-cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA. OBJECTIVE: The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA. METHODS: We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA-P and 17 patients with MSA-C compared to 31 healthy controls (HC). Dexterity was assessed using the 9-Hole Peg Board (9HPB) performance. RESULTS: Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free-fluid compartment, was present in MSA-P and MSA-C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA-P showed more pronounced putaminal degeneration than MSA-C. In contrast, a cerebellopontine axonal degeneration was observed in MSA-P and MSA-C, with stronger effects in MSA-C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration. CONCLUSION: Cerebellar dysfunction contributes to impaired dexterity not only in MSA-C but also in MSA-P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Advanced therapies in Parkinson's disease: an individualized approach to their indication.

Device aided therapies (DAT) comprising the intrajejunal administration of levodopa/carbidopa intestinal gel (LCIG) and levodopa/carbidopa/entacapone intestinal gel (LECIG), the continuous subcutaneous application of foslevodopa/foscarbidopa or apomorphine infusion (CSAI) and deep brain stimulation (DBS) are used to treat Parkinson's disease with insufficient symptom alleviation under intensified pharmacotherapy. These DAT significantly differ in their efficacy profiles, indication, invasiveness, contraindications, and potential side effects. Usually, the evaluation of all these procedures is conducted simultaneously at the same point in time. However, as disease progression and symptom burden is extremely heterogeneous, clinical experience shows that patients reach the individual milestones for a certain therapy at different points in their disease course. Therefore, advocating for an individualized therapy evaluation for each DAT, requiring an ongoing evaluation. This necessitates that, during each consultation, the current symptomatology should be analyzed, and the potential suitability for a DAT be assessed. This work represents a critical interdisciplinary appraisal of these therapies in terms of their individual profiles and compares these DAT regarding contraindications, periprocedural considerations as well as their efficacy regarding motor- and non-motor deficits, supporting a personalized approach.

Understanding the concept of a novel tool requires interaction of the dorsal and ventral streams.

The left hemisphere tool-use network consists of the dorso-dorsal, ventro-dorsal, and ventral streams, each with distinct computational abilities. In the dual-loop model, the ventral pathway through the extreme capsule is associated with conceptual understanding. We performed a learning experiment with fMRI to investigate how these streams interact when confronted with novel tools. In session one, subjects observed pictures and video sequences in real world action of known and unknown tools and were asked whether they knew the tools and whether they understood their function. In session two, video sequences of unknown tools were presented again, followed again by the question of understanding their function. Different conditions were compared to each other and effective connectivity (EC) in the tool-use network was examined. During concept acquisition of an unknown tool, EC between dorsal and ventral streams was found posterior in fusiform gyrus and anterior in inferior frontal gyrus, with a functional interaction between BA44d and BA45. When previously unknown tools were presented for a second time, EC was prominent only between dorsal stream areas. Understanding the concept of a novel tool requires an interaction of the ventral stream with the dorsal streams. Once the concept is acquired, dorsal stream areas are sufficient.

[Synergies Instead of Rivalries - Expert Opinion on the Misunderstood Roles of Continuous Intrajejunal Levodopa Therapy and Deep Brain Stimulation in the Treatment of Parkinson̓s Disease]. / Synergien statt Rivalitäten ­ die missverstandenen Rollen von kontinuierlicher intrajejunaler Levodopatherapie und Tiefer Hirnstimulation in der Behandlung des Morbus Parkinson ­ eine Expertenmeinung.

In the therapy of Parkinson̓s disease, both the intrajejunal administration of Levodopa/Carbidopa Intestinal Gel (LCIG) and, more recently, Levodopa/Carbidopa/Entacapone Intestinal Gel (LECIG), as well as deep brain stimulation (DBS), are employed. These approaches differ significantly in their efficacy and side effect profiles, as well as the timing of their use. Yet, the initiation of therapy for both methods is often simultaneously considered when patients have reached an advanced stage of the disease. From the authors' perspective, however, patients may reach the milestones for the indication of one of these respective treatments at different points in the course of the disease. Individual disease progression plays a pivotal role in this regard. The concept that all patients become candidates for a specific treatment at a predefined time appears erroneous to the authors. In the context of this review, therefore, the therapeutic modalities are presented in terms of their efficacy for different symptoms, the notion of simultaneous timing of their initiation is questioned, and an individualized therapy evaluation is derived, with a focus on quality of life and participation.

Deep learning segmentation results in precise delineation of the putamen in multiple system atrophy.

OBJECTIVES: The precise segmentation of atrophic structures remains challenging in neurodegenerative diseases. We determined the performance of a Deep Neural Patchwork (DNP) in comparison to established segmentation algorithms regarding the ability to delineate the putamen in multiple system atrophy (MSA), Parkinson's disease (PD), and healthy controls. METHODS: We retrospectively included patients with MSA and PD as well as healthy controls. A DNP was trained on manual segmentations of the putamen as ground truth. For this, the cohort was randomly split into a training (N = 131) and test set (N = 120). The DNP's performance was compared with putaminal segmentations as derived by Automatic Anatomic Labelling, Freesurfer and Fastsurfer. For validation, we assessed the diagnostic accuracy of the resulting segmentations in the delineation of MSA vs. PD and healthy controls. RESULTS: A total of 251 subjects (61 patients with MSA, 158 patients with PD, and 32 healthy controls; mean age of 61.5 ± 8.8 years) were included. Compared to the dice-coefficient of the DNP (0.96), we noted significantly weaker performance for AAL3 (0.72; p < .001), Freesurfer (0.82; p < .001), and Fastsurfer (0.84, p < .001). This was corroborated by the superior diagnostic performance of MSA vs. PD and HC of the DNP (AUC 0.93) versus the AUC of 0.88 for AAL3 (p = 0.02), 0.86 for Freesurfer (p = 0.048), and 0.85 for Fastsurfer (p = 0.04). CONCLUSION: By utilization of a DNP, accurate segmentations of the putamen can be obtained even if substantial atrophy is present. This allows for more precise extraction of imaging parameters or shape features from the putamen in relevant patient cohorts. CLINICAL RELEVANCE STATEMENT: Deep learning-based segmentation of the putamen was superior to currently available algorithms and is beneficial for the diagnosis of multiple system atrophy. KEY POINTS: • A Deep Neural Patchwork precisely delineates the putamen and performs equal to human labeling in multiple system atrophy, even when pronounced putaminal volume loss is present. • The Deep Neural Patchwork-based segmentation was more capable to differentiate between multiple system atrophy and Parkinson's disease than the AAL3 atlas, Freesurfer, or Fastsurfer.

The dual-loop model for combining external and internal worlds in our brain.

Intelligible communication with others as well as covert conscious thought requires us to combine a representation of the external world with inner abstract concepts. Interaction with the external world through sensory perception and motor execution is arranged as sequences in time and space, whereas abstract thought and invariant categories are independent of the moment. Using advanced MRI-based fibre tracking on high resolution data from 183 participants in the Human Connectome Project, we identified two large supramodal systems comprising specific cortical regions and their connecting fibre tracts; a dorsal one for processing of sequences in time and space, and a ventral one for concepts and categories. We found that two hub regions exist in the executive front and the perceptive back of the brain where these two cognitive processes converge, constituting a dual-loop model. The hubs are located in the onto- and phylogenetically youngest regions of the cortex. We propose that this hub feature serves as the neural substrate for the more abstract sense of syntax in humans, i.e. for the system populating sequences with content in all cognitive domains. The hubs bring together two separate systems (dorsal and ventral) at the front and the back of the brain and create a closed-loop. The closed-loop facilitates recursivity and forethought, which we use twice; namely, for communication with others about things that are not there and for covert thought.

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

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

The ventral pathway of the human brain: A continuous association tract system.

The brain hemispheres can be divided into an upper dorsal and a lower ventral system. Each system consists of distinct cortical regions connected via long association tracts. The tracts cross the central sulcus or the limen insulae to connect the frontal lobe with the posterior brain. The dorsal stream is associated with sensorimotor mapping. The ventral stream serves structural analysis and semantics in different domains, as visual, acoustic or space processing. How does the prefrontal cortex, regarded as the platform for the highest level of integration, incorporate information from these different domains? In the current view, the ventral pathway consists of several separate tracts, related to different modalities. Originally the assumption was that the ventral path is a continuum, covering all modalities. The latter would imply a very different anatomical basis for cognitive and clinical models of processing. To further define the ventral connections, we used cutting-edge in vivo global tractography on high-resolution diffusion tensor imaging (DTI) data from 100 normal subjects from the human connectome project and ex vivo preparation of fiber bundles in the extreme capsule of 8 humans using the Klingler technique. Our data showed that ventral stream tracts, traversing through the extreme capsule, form a continuous band of fibers that fan out anteriorly to the prefrontal cortex, and posteriorly to temporal, occipital and parietal cortical regions. Introduction of additional volumes of interest in temporal and occipital lobes differentiated between the inferior fronto-occipital fascicle (IFOF) and uncinate fascicle (UF). Unequivocally, in both experiments, in all subjects a connection between the inferior frontal and middle-to-posterior temporal cortical region, otherwise known as the temporo-frontal extreme capsule fascicle (ECF) from nonhuman primate brain-tracing experiments was identified. In the human brain, this tract connects the language domains of "Broca's area" and "Wernicke's area". The differentiation in the three tracts, IFOF, UF and ECF seems arbitrary, all three pass through the extreme capsule. Our data show that the ventral pathway represents a continuum. The three tracts merge seamlessly and streamlines showed considerable overlap in their anterior and posterior course. Terminal maps identified prefrontal cortex in the frontal lobe and association cortex in temporal, occipital and parietal lobes as streamline endings. This anatomical substrate potentially facilitates the prefrontal cortex to integrate information across different domains and modalities.

Approximation to pain-signaling network in humans by means of migraine.

Nociceptive signals are processed within a pain-related network of the brain. Migraine is a rather specific model to gain insight into this system. Brain networks may be described by white matter tracts interconnecting functionally defined gray matter regions. Here, we present an overview of the migraine-related pain network revealed by this strategy. Based on diffusion tensor imaging data from subjects in the Human Connectome Project (HCP) database, we used a global tractography approach to reconstruct white matter tracts connecting brain regions that are known to be involved in migraine-related pain signaling. This network includes an ascending nociceptive pathway, a descending modulatory pathway, a cortical processing system, and a connection between pain-processing and modulatory areas. The insular cortex emerged as the central interface of this network. Direct connections to visual and auditory cortical association fields suggest a potential neural basis of phono- or photophobia and aura phenomena. The intra-axonal volume (Vintra ) as a measure of fiber integrity based on diffusion microstructure was extracted using an innovative supervised machine learning approach in form of a Bayesian estimator. Self-reported pain levels of HCP subjects were positively correlated with tract integrity in subcortical tracts. No correlation with pain was found for the cortical processing systems.

Anatomy of brain lesions after stroke predicts effectiveness of mirror therapy.

To improve clinical outcome, one longstanding goal in treating stroke patients has been an individual therapy based on functional and anatomical knowledge of the single patient. Therefore, in this study brain imaging of 36 chronic stroke patients was analyzed to identify parameters predicting clinical recovery. T1-weighted MRI was acquired to assess the lesion; functional MRI was used to visualize existing resources; DTI for the integrity of the corticospinal tract (CST) and long association tracts. These data were related to the clinical course. All patients were treated intensively with the mirror therapy (MT) only. After the training period, we analyzed which patient's feature would predict a beneficial course. Patients as a group improved after MT, but according to the fMRI activation of primary sensorimotor cortex (SMC), they could be divided in two groups with very diverging clinical outcome: those with ipsilesional SMC activation showed a noticeable increase of clinical scores, accompanied with ipsilesional activation in the frontal projection areas of the dorsal and ventral streams during action observation in fMRI. Those with contralesional SMC activation had lesions affecting both the dorsal and ventral stream and did not benefit from MT. The outcome for this therapy was not related to affection of CST. This study demonstrates that only in patients in which dorsal and ventral streams are not affected and therefore an interaction between these streams in post- and prerolandic regions is possible, MT can induce clinical improvement. Consequently, knowledge of the anatomical lesion can predict the beneficial course of MT.

Distinct Contributions of Dorsal and Ventral Streams to Imitation of Tool-Use and Communicative Gestures.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.

Large Vessel Occlusion in Acute Stroke.

Background and Purpose- To date, no clinical score has become widely accepted as an eligible prehospital marker for large vessel occlusion (LVO) and the need of mechanical thrombectomy (MT) in ischemic stroke. On the basis of pathophysiological considerations, we propose that cortical symptoms such as aphasia and neglect are more sensitive indicators for LVO and MT than motor deficits. Methods- We, thus, retrospectively evaluated a consecutive cohort of 543 acute stroke patients including patients with ischemia in the posterior circulation, hemorrhagic stroke, transient ischemic attack, and stroke mimics to best represent the prehospital setting. Results- Cortical symptoms alone showed to be a reliable indicator for LVO (sensitivity: 0.91; specificity: 0.70) and MT (sensitivity: 0.90; specificity: 0.60) in acute stroke patients, whereas motor deficits showed a sensitivity of 0.85 for LVO (specificity: 0.53) and 0.87 for MT (specificity: 0.48). Conclusions- We propose that in the prehospital setting, the presence of cortical symptoms is a reliable indicator for LVO and its presence justifies transportation to an MT-capable center.

Componential Network for the Recognition of Tool-Associated Actions: Evidence from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.

Visual neglect after left-hemispheric lesions: a voxel-based lesion-symptom mapping study in 121 acute stroke patients.

Visual neglect after left-hemispheric lesion is thought to be less frequent, less severe, and shorter lived than visuospatial attention deficits resulting from right-hemispheric lesions. However, reports exist opposing this assumption, and it is unclear how these findings fit into the current theories of visuospatial processing. Furthermore, only little is known about the exact structure-function relationship between visuospatial attention deficits and left-hemispheric stroke. We investigated neglect in 121 patients with acute left-hemispheric ischemic stroke by following clinical development from within the first 24 h of stroke onset until hospital discharge. Visuospatial attention deficits occurred in 17.4 % (n = 21). Voxel-based lesion-symptom mapping associated visual neglect to the right with lesion in the left superior and middle temporal gyrus, temporal pole, frontal operculum, and insula. Neglect severity, captured by the Center of Cancellation Score of the Bells test, was associated with lesion in the left anterior temporal lobe and the left frontal operculum. The left-hemispheric lesion pattern of neglect thus involves areas of the ventral attention system and partly mirrors the critical regions of the right hemisphere known to be associated with neglect. Based on our prospective analysis on a large cohort of patients with left-hemispheric stroke, this study shows that in a remarkable number of patients, the left hemisphere essentially contributes to an intact representation of space and clarifies the impact of the distinct left-hemispheric structures involved in visuospatial processing.

Brain activity underlying tool-related and imitative skills after major left hemisphere stroke.

Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion-symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative 'healthy' network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this 'healthy' network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired.

A formal analysis of alexia in persistent aura and a comparison to acquired pure alexia.

A patient is reported with reversible pure alexia in the context of migraine with aura. Following previous, anecdotal reports, the present study is the first to formally assess word reading, writing, and other linguistic and visual processing and to compare these to a patient with stroke-related pure alexia. The reading impairment, suggestive of letter-by-letter reading, was observed across 7 days but had remitted at a 3-month follow-up. The deficit also affected recognition of letters, suggesting a functional impairment at the level of letter recognition, not just word reading. It went along with reversible abnormalities in diffusion-weighted and fluid-attenuated inversion recovery imaging in areas known to be involved in word reading.