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Abstract

Objective: To determine whether neuroanatomically heterogeneous strokes causing hemichorea-hemiballismus localize to a common functional network. Methods: We identified 29 cases of lesion-induced hemichorea-hemiballismus from the literature and mapped each lesion volume onto a reference brain. Using a recently validated technique termed lesion network mapping, we tested whether these lesions belonged to the same functional network. To accomplish this, the network of brain regions functionally connected to each lesion was identified using a connectome dataset from healthy participants. Network maps were overlapped to identify any region functionally connected to our set of lesions. Specificity was evaluated using a case-control design; control cohorts included a group of similar lesions randomized to different brain locations and a second group of lesions causing a separate movement disorder, asterixis. Reproducibility was evaluated using an independent cohort of 10 additional hemichorea-hemiballismus cases. Results: Lesions showed heterogeneity in anatomical location, consistent with prior reports. However, at least 90% of these lesions showed network overlap in the posterolateral putamen. This result was specific to lesions causing hemichorea-hemiballismus and reproducible in an independent cohort. The putaminal overlap site was itself connected to a broader motor network that predicted the distribution of lesions causing hemichorea-hemiballismus. Conclusions: Strokes causing hemichorea-hemiballismus, while anatomically heterogeneous, localize to a common functional network. Specifically, lesions occur in regions functionally connected to the posterolateral putamen, a region previously implicated in hyperkinetic movement disorders. Lesion network mapping may be useful in identifying the neuroanatomical substrates of heterogeneous lesion-based disorders.

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... The search resulted in 618 articles, and the abstract or full text was read from 382 publications which were considered to be relevant according to their titles. These publications were subjected to additional inclusion/exclusion criteria in light of previous studies (Boes et al., 2015;Darby et al., 2017;Fasano, Laganiere, Lam, & Fox, 2017;Fisher, Towler, & Eimer, 2016;Joutsa, Horn, Hsu, & Fox, 2018;Laganiere, Boes, & Fox, 2016). The inclusion criteria were: (i) case description of motivational deficits in a patient; (ii) neurological examination documenting apathy or anhedonia symptoms presumed to be caused by an intraparenchymal brain lesion; and (iii) clearly delineated and circumscribed brain lesions displayed to be transcribed onto a standard brain template. ...
... Lesion locations from originally published figures were manually traced onto a standard template brain as described previously (Boes et al., 2015;Darby et al., 2017;Fasano et al., 2017;Fischer et al., 2016;Joutsa et al., 2018;Laganiere et al., 2016). Neuroanatomical landmarks were used to ensure accurate transfer onto the template. ...
... However, earlier works suggest that 2D slices can fill in equitable approximation of 3D lesions for lesion network mapping (Boes et al., 2015;Darby et al., 2017). In cases where multiple lesions were displayed, all lesions were mapped together and treated as a single lesion for ensuing analyses (Fasano et al., 2017;Laganiere et al., 2016). ...
Article
Motivational dysfunction constitutes one of the fundamental dimensions of psychopathology cutting across traditional diagnostic boundaries. However, it is unclear whether there is a common neural circuit responsible for motivational dysfunction across neuropsychiatric conditions. To address this issue, the current study combined a meta-analysis on psychiatric neuroimaging studies of reward/loss anticipation and consumption (4308 foci, 438 contrasts, 129 publications) with a lesion network mapping approach (105 lesion cases). Our meta-analysis identified transdiagnostic hypoactivation in the ventral striatum (VS) for clinical/at-risk conditions compared to controls during the anticipation of both reward and loss. Moreover, the VS subserves a key node in a distributed brain network which encompasses heterogeneous lesion locations causing motivation-related symptoms. These findings do not only provide the first meta-analytic evidence of shared neural alternations linked to anticipatory motivation-related deficits, but also shed novel light on the role of VS dysfunction in motivational impairments in terms of both network integration and psychological functions. Particularly, the current findings suggest that motivational dysfunction across neuropsychiatric conditions is rooted in disruptions of a common brain network anchored in the VS, which contributes to motivational salience processing rather than encoding positive incentive values.
... Based on the concept of diaschisis and the finding that symptoms are not attributed solely to the lesion itself but also to regions functionally connected to the lesion (Fasano et al., 2017), this technique utilizes normative connectome data to identify the networks associated with focal brain lesions without the need for special imaging sequences. This approach has been increasingly used to investigate the networks responsible for various neurological symptoms, including visual/auditory hallucinations, central post-stroke pain, subcortical aphasia (Boes et al., 2015), hemi-choreahemiballismus (Laganiere et al., 2016), Capgras syndrome (Darby et al., 2017), coma (Fischer et al., 2016), impaired decision making (Sutterer et al., 2016), freezing of gait (Fasano et al., 2017), and the rubber hand illusion (Wawrzyniak et al., 2018). Employing this unique methodology, we tested the hypothesis that lesions causing FAS would be connected to a common network of sites involved in motor speech function. ...
... (1) the volume of each lesion was transferred to a reference brain (i.e.; lesion mapping); (2) the network of brain regions functionally connected to each lesion was computed using resting-state functional connectivity MRI (rs-fc MRI) data from a large normative cohort; and (3) the resulting lesion (functional) network maps were thresholded and overlaid to identify common network sites across the lesions. The normative rs-fc MRI dataset was the same as that used in the previous lesion (functional) network mapping study (Boes et al., 2015;Laganiere et al., 2016;Darby et al., 2017), and consisted of 104 healthy participants (41 males, mean age 21.4 ± 2.8 years) from part of a publicly available dataset (The Brain Genomics Superstruct Project; http://neuroinformati cs.harvard.edu/gsp/) (Buckner). ...
... Each of the 25 lesion-seeded rs-fc MRI network maps was thresholded at a t value of positive or negative 4.05 (p < 0.00005, uncorrected), with reference to the previous lesion (functional) network mapping studies (Boes et al., 2015;Laganiere et al., 2016;Darby et al., 2017). After applying this threshold, the resulting network maps were binarized and overlapped to identify regions of shared positive or negative correlation. ...
Article
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Background Foreign accent syndrome (FAS) is a rare acquired speech disorder wherein an individual’s spoken accent is perceived as “foreign.” Most reported cases involve left frontal brain lesions, but it is known that various other lesions can also cause FAS. To determine whether heterogeneous FAS-causing lesions are localized to a common functional speech network rather than to a single anatomical site, we employed a recently validated image analysis technique known as “lesion network mapping.” Methods We identified 25 published cases of acquired neurogenic FAS without aphasia, and mapped each lesion volume onto a reference brain. We next identified the network of brain regions functionally connected to each FAS lesion using a connectome dataset from normative participants. Network maps were then overlapped to identify common network sites across the lesions. Results Classical lesion overlap analysis showed heterogeneity in lesion anatomical location, consistent with prior reports. However, at least 80% of lesions showed network overlap in the bilateral lower and middle portions of the precentral gyrus and in the medial frontal cortex. The left lower portion of the precentral gyrus is suggested to be the location of lesions causing apraxia of speech (AOS), and the middle portion is considered to be a larynx-specific motor area associated with the production of vowels and stop/nasal consonants and with the determination of pitch accent. Conclusions The lesions that cause FAS are anatomically heterogeneous, but they share a common functional network located in the bilateral posterior region of the frontal lobe. This network specifically includes not only the lower portion of the central gyrus, but also its middle region, which is referred to as the larynx motor cortex and is known to be associated with phonation. Our findings suggest that disrupted networks in FAS might be anatomically different from those in AOS.
... Estudios en los que se ha utilizado la tractografía determinística de imágenes ponderadas por difusión de alta resolución angular (HARDI, por sus siglas en inglés), basada en deconvolución esférica restringida y tractografía de filtro de partículas, se han descrito conexiones córtico-subcorticales de la ínsula con varias estructuras, como el tálamo, el putamen, el globo pálido y el caudado [8][9][10] . ...
... Además, la estimulación cortical conduce a la excitación de las neuronas subtalámicas, pero en ocasiones se combina con una inhibición 11,12,13 . La ínsula posterodorsal está especializada en la función auditiva, somestésica y motora, por lo que se puede indicar que la ínsula tiene un papel en la fisiopatología de los movimientos anormales 14 , como en el caso del hemibalismohemicorea 10,11,13 . Esto podría ser explicado por una reducción de la función inhibitoria de la ínsula por isquemia cerebral hacia las neuronas subtalámicas 10,15 . ...
... La ínsula posterodorsal está especializada en la función auditiva, somestésica y motora, por lo que se puede indicar que la ínsula tiene un papel en la fisiopatología de los movimientos anormales 14 , como en el caso del hemibalismohemicorea 10,11,13 . Esto podría ser explicado por una reducción de la función inhibitoria de la ínsula por isquemia cerebral hacia las neuronas subtalámicas 10,15 . ...
Article
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Resumen Introducción El síndrome hemicorea hemibalismo es una entidad clínica que se origina cuando hay una lesión en el núcleo subtalámico de Louis habitualmente. Las principales causas de este síndrome son por trastornos hiperglucémicos y la enfermedad cerebrovascular. En la casuística descrita se señala que existen otras regiones que pueden estar involucradas y ocasionar estos movimientos anormales, dadas por lesiones subcorticales, especialmente en los ganglios de la base. Sin embargo, al revisar la bibliografía, resulta muy infrecuente que estén involucradas estructuras corticales en la génesis de estos movimientos, lo que permite cuestionarse sobre el papel que tienen las redes o conexiones entre la corteza cerebral y los ganglios de la base en los movimientos involuntarios. Caso clínico El caso corresponde a una mujer de 93 años de edad quien inició con un síndrome hemicorea-hemibalismo por una enfermedad cerebrovascular isquémica aguda. Se documentó que la lesión isquémica estaba en la región insular derecha, tras ello, la paciente fue llevada a una trombólisis intravenosa con activador tisular del plasminógeno humano recombinante y tuvo una resolución de los síntomas. Posteriormente, durante su seguimiento, fue documentada una fibrilación auricular como agente etiológico. Conclusión Es el segundo caso reportado en la literatura de un síndrome hemicorea-hemibalismo causado por lesión insular. Resulta de mucho interés porque permite cuestionarse sobre las conexiones córtico-subcorticales relacionadas con la génesis de los trastornos de los movimientos, así como su fisiopatología. No existen conflictos de interés por parte de los autores.
... Following previous studies employing NLSM, we adopted seed-based connectivity analysis, with the lesion mask of each neurological patient as seed (Boes et al., 2015;Darby et al., 2017;Laganiere et al., 2016;Wawrzyniak et al., 2018). More specifically, for each neurological patient, and for each resting-state subject, a first level General Linear Model (GLM) was carried out, where functional images were modeled against the average time-course extracted from the patient's lesion site. ...
... To consider the whole spectrum of performance and potentially weaker patterns of deficit across all brain-damaged individuals, we used lesion-symptom mapping to identify neural structures associated with social inferential impairments on our ToM task from the whole population of 40 patients. In particular, in our study we employed a network-based lesionsymptom mapping (NLSM; Boes et al., 2015;Darby et al., 2017;Laganiere et al., 2016;Wawrzyniak et al., 2018), in which the lesion masks were "extended" to include those brain structures that are most frequently functionally connected with the damaged site based on normative connectome data (see methods). These network masks were modeled against the patients' accuracy in the three conditions of interest (B, E, Pa), with accuracy in the control Ph task, the overall lesion size, patients' gender, age, education level, MoCA score, and time poststroke specified as nuisance predictors (see methods). ...
... We run NLSM as an innovative way to account for lesion heterogeneity (Boes et al., 2015;Darby et al., 2017;Laganiere et al., 2016;Wawrzyniak et al., 2018). Yet, caution should be advised in assuming that results from an independent resting-state dataset is a good estimate of patients' impairment at the network level. ...
Article
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Neuroimaging studies suggest that understanding emotions in others engages brain regions partially common to those associated with more general cognitive Theory-of-Mind (ToM) functions allowing us to infer people's beliefs or intentions. However, neuropsychological studies on brain-damaged patients reveal dissociations between the ability to understand others' emotions and ToM. This discrepancy might underlie the fact that neuropsychological investigations often correlate behavioural impairments only to the lesion site, without considering the impact that the insult might have on other interconnected brain structures. Here we took a network-based approach, and investigated whether deficits in understanding people's emotional and cognitive states relate to damage to similar or differential structures. By combining information from 40 unilateral stroke damaged patients, with normative connectome data from 92 neurotypical individuals, we estimated lesion-induced dysfunctions across the whole brain, and modeled them in relation to patients' behavior. We found a striking dissociation between networks centered in the insular and prefrontal cortex, whose dysfunctions led to selective impairments in understanding emotions and beliefs respectively. Instead, no evidence was observed for neural structures shared between the two conditions. Overall, our data provide novel evidence of segregation between brain networks subserving social inferential abilities.
... HCP 3 T 937 shortened -0.74; HCP 7T -0.80; MBB -0.81), they were still significant (p<0.0001) and higher than 0.7. Finally, to test the specificity of the current LNM methods, we have applied the same case vs. controls LNM analysis strategy to other symptoms/syndromes (aphasia, N=12; asterixis, N=30, central poststroke pain, N=23; criminal behavior, N=17; delusions, N=15; freezing of gait, N=14) according to cases included in previous publications (Boes et al. 2015;Laganiere et al. 2016;Darby et al. 2018Darby et al. , 2017. In each case, the remaining syndromes and 2D A strong spatial correlation, Pearson's r varying from 0.85 to 0.99, between all lesional mania maps was obtained when comparing all network maps mania were used as controls. ...
... All these features are of critical importance for the use of LNM to study the pathophysiology of lesional neuropsychiatric syndromes (Boes et al. 2015;Laganiere et al. 2016), such as Capgras Syndrome (Darby et al. 2017), amnesia (Ferguson et al. 2019) or prosopagnosia (Cohen et al. 2019), as well as to clarify the neurobiological substrate for the therapeutic effects of different neuromodulation strategies (Siddiqi et al. 2021), among other objectives (Fox 2018). Moreover, it is also a fundamental property of LNM while it evolves as a potential clinical predictive tool, i.e., as a potential approach that can estimate the impact of brain lesions in impairing the functions of different regions and networks. ...
Article
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Lesion network mapping is a neuroimaging technique that explores the network of regions functionally connected to lesions causing a common syndrome. The technique uses resting state functional connectivity from large databases of healthy individuals, i.e., connectomes, and has allowed for important insight into the potential network mechanisms underlying several neuropsychiatric disorders. However, concerns regarding reproducibility have arisen, that may be due to the use of different connectomes, with variable MRI acquisition parameters and preprocessing methods. Here, we tested the impact of using different connectomes on the results of lesion network mapping for mania. We found results were reliable and consistent independent of the connectome used.
... Maps in E and F were obtained using a voxel-wise permutation-based 2-sample t test performed within FSL PALM (2000 permutations) and are displayed at an FWE-corrected level of P < 0.05. jci.org sected the combined mania lesion network (20,25,26,(29)(30)(31). We found that lesion locations associated with criminality and delusions intersected the mania network more than lesion locations associated with movement disorders or hallucinations (P < 0.0001; Figure 6, C and D). ...
... Analyses to test whether our results were being driven by choice of control lesions were performed in analyses maintaining the same mania lesions but changing control lesions. We replaced the original literature control cohort (n = 79) with an alternative literature control cohort consisting of different literature lesions included in previous publications by our group (n = 274), independent of whether the symptom profiles might overlap with those of mania and including numerous psychiatric symptoms (20,25,26,29,54). We also replaced our original clinical control cohort (n = 490) with an alternate clinical cohort of nonspecific lesions from a different source (n = 135) (116). ...
Article
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BACKGROUND Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS Lesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms. RESULTS Lesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms. CONCLUSIONS Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.
... Our earliest lesion network mapping studies used resting state functional connectivity data from 98 healthy young controls to identify connectivity with each lesion location (Boes et al., 2015;Fischer et al., 2016;Laganiere et al., 2016;Darby et al., 2017;Fasano et al., 2017). We chose this connectome dataset for convenience, as it was highquality, locally available, and part of a large ongoing data collection initiative (Holmes et al., 2015). ...
... We have used this approach in almost all recent papers, including Cohen et al. (2019), which is demonstrated visually in Fig. 1. Consistent with this principle, results that do not hold true across different thresholds should be made explicit and de-emphasized relative to results that are more robust, an approach we have also used in prior papers (Fischer et al., 2016;Laganiere et al., 2016;Fasano et al., 2017). ...
... Recently, a lesion network mapping method has been used to investigate the expanding localization of symptoms from heterogeneous lesions. 19,21 That method is based on lesionseeded, resting-state, functional connectivity. We based our extraction of a lesion's second link-step connectivity on that lesion network mapping method. ...
... [29][30][31][32][33] In addition, convergence between anatomical connectivity obtained from DTI analysis and functional connectivity obtained from rs-FC analysis has been detected, 34 and novel analyses such as lesion network mapping using fMRI signals obtained from white matter structures have been applied to study neurological disorders. 19,21,34 We validated the importance of indirectly damaged connectivity and confirmed the potential of our method for predicting recovery using rs-FC analysis. ...
Article
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Background Recovery prediction can assist in the planning for impairment-focused rehabilitation after a stroke. This study investigated a new prediction model based on a lesion network analysis. To predict the potential for recovery, we focused on the next link-step connectivity of the direct neighbors of a lesion. Methods We hypothesized that this connectivity would contribute to recovery after stroke onset. Each lesion in a patient who had suffered a stroke was transferred to a healthy subject. First link-step connectivity was identified by observing voxels functionally connected to each lesion. Next (second) link-step connectivity of the first link-step connectivity was extracted by calculating statistical dependencies between time courses of regions not directly connected to a lesion and regions identified as first link-step connectivity. Lesion impact on second link-step connectivity was quantified by comparing the lesion network and reference network. Results The lower the impact of a lesion was on second link-step connectivity in the brain network, the better the improvement in motor function during recovery. A prediction model containing a proposed predictor, initial motor function, age, and lesion volume was established. A multivariate analysis revealed that this model accurately predicted recovery at 3 months poststroke ( R ² = 0.788; cross-validation, R ² = 0.746, RMSE = 13.15). Conclusion This model can potentially be used in clinical practice to develop individually tailored rehabilitation programs for patients suffering from motor impairments after stroke.
... To identify the brain network underlying particular symptoms in brain-lesioned patients, a recently developed technique termed lesion network mapping (LNM) has been widely used [9][10][11][12][13][14][15][16][17][18][19][20] . LNM uses brain lesions as seeds to derive the brain network of specific symptoms based on a large cohort of resting-state normative connectomes. ...
... As such, no ethics board approval was obtained. No statistical methods were used to predetermine sample sizes, but our sample size is greater than that in most previous comparable studies 9,10,12,21 . The resolution of all analyses is 2 mm unless otherwise noted, and all statistical tests were performed using two-tailed t-tests. ...
Article
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Functional neuroimaging techniques have been widely used to probe the neural substrates of facial emotion processing in healthy people. However, findings are largely inconsistent across studies. Here, we introduce a new technique termed activation network mapping to examine whether heterogeneous functional magnetic resonance imaging findings localize to a common network for emotion processing. First, using the existing method of activation likelihood estimation meta-analysis, we showed that individual-brain-based reproducibility was low across studies. Second, using activation network mapping, we found that network-based reproducibility across these same studies was higher. Validation analysis indicated that the activation network mapping-localized network aligned with stimulation sites, structural abnormalities and brain lesions that disrupt facial emotion processing. Finally, we verified the generality of the activation network mapping technique by applying it to another cognitive process, that is, rumination. Activation network mapping may potentially be broadly applicable to localize brain networks of cognitive functions. Gong et al. introduce a new method, activation network mapping, for integration of neuroimaging findings.
... It is possible that cortical lesions causing LOC may not map to a single brain region, but to a connected brain network. Lesions causing a variety of different neuropsychiatric symptoms have recently been mapped to brain networks using a technique termed lesion network mapping (Boes et al., 2015;Darby, Laganiere, Pascual-Leone, Prasad, & Fox, 2017;Fasano, Laganiere, Lam, & Fox, 2017;Fischer et al., 2016;Fox, 2018;Laganiere, Boes, & Fox, 2016). With this technique, a large normative MRI database of resting-state functional connectivity (rs-fcMRI) is used to identify brain regions functionally connected to each lesion location. ...
... Lesions causing aphasia are connected to the left inferior frontal gyrus (Boes et al., 2015), lesions causing hemichorea are connected to the posterolateral putamen (Laganiere et al., 2016), and lesions causing freezing of gait are connected to the cerebellar locomotor region (Fasano et al., 2017). In this context, it is perhaps not surprising that lesions causing LOC are connected to the dorsal brainstem, the part of the brain known to be necessary for arousal and where lesions result in coma. ...
Article
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Brain lesions can provide unique insight into the neuroanatomical substrate of human consciousness. For example, brainstem lesions causing coma map to a specific region of the tegmentum. Whether specific lesion locations outside the brainstem are associated with loss of consciousness (LOC) remains unclear. Here, we investigate the topography of cortical lesions causing prolonged LOC (N = 16), transient LOC (N = 91), or no LOC (N = 64). Using standard voxel lesion symptom mapping, no focus of brain damage was associated with LOC. Next, we computed the network of brain regions functionally connected to each lesion location using a large normative connectome dataset (N = 1,000). This technique, termed lesion network mapping, can test whether lesions causing LOC map to a connected brain circuit rather than one brain region. Connectivity between cortical lesion locations and an a priori coma‐specific region of brainstem tegmentum was an independent predictor of LOC (B = 1.2, p = .004). Connectivity to the dorsal brainstem was the only predictor of LOC in a whole‐brain voxel‐wise analysis. This relationship was driven by anticorrelation (negative correlation) between lesion locations and the dorsal brainstem. The map of regions anticorrelated to the dorsal brainstem thus defines a distributed brain circuit that, when damaged, is most likely to cause LOC. This circuit showed a slight posterior predominance and had peaks in the bilateral claustrum. Our results suggest that cortical lesions causing LOC map to a connected brain circuit, linking cortical lesions that disrupt consciousness to brainstem sites that maintain arousal.
... By identifying a network of regions in a normative connectome that exhibit strong functional connectivity with a patient's structural lesion, the method can deduce where areas of projected connectivity disruption might relate to behavioral symptoms. The approach has identified regions that explain an impressive diversity of specific symptoms associated with variable structural lesions sites (Darby, Horn, Cushman, & Fox, 2018;Darby, Laganiere, Pascual-Leone, Prasad, & Fox, 2016;Fasano, Laganiere, Lam, & Fox, 2017;Ferguson, Yu, Poliakov, Friedman, & McClellan, 2017;Fischer et al., 2016;Laganiere, Boes, & Fox, 2016;Sutterer et al., 2016). Still, this approach does not measure brain function directly in patients and relies on structurally defined lesions. ...
Article
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The lesion method has been important for understanding brain-behavior relationships in humans, but has previously used maps based on structural damage. Lesion measurement based on structural damage may label partly damaged but functional tissue as abnormal, and moreover, ignores distant dysfunction in structurally intact tissue caused by deafferentation, diaschisis, and other processes. A reliable method to map functional integrity of tissue throughout the brain would provide a valuable new approach to measuring lesions. Here, we use machine learning on four dimensional resting state fMRI data obtained from left-hemisphere stroke survivors in the chronic period of recovery and control subjects to generate graded maps of functional anomaly throughout the brain in individual patients. These functional anomaly maps identify areas of obvious structural lesions and are stable across multiple measurements taken months and even years apart. Moreover, the maps identify functionally anomalous regions in structurally intact tissue, providing a direct measure of remote effects of lesions on the function of distant brain structures. Multivariate lesion-behavior mapping using functional anomaly maps replicates classic behavioral localization, identifying inferior frontal regions related to speech fluency, lateral temporal regions related to auditory comprehension, parietal regions related to phonology, and the hand area of motor cortex and descending corticospinal pathways for hand motor function. Further, this approach identifies relationships between tissue function and behavior distant from the structural lesions, including right premotor dysfunction related to ipsilateral hand movement, and right cerebellar regions known to contribute to speech fluency. Brain-wide maps of the functional effects of focal lesions could have wide implications for lesion-behavior association studies and studies of recovery after brain injury.
... First, we searched the literature for reports on AHP in which the picture of the lesions were shown (see section "Materials and Methods" for search criteria). Next, we traced each lesion in an atlas space (MNI-152) using the approach of Boes et al. (2015) validated for functional connectivity in several recent publications (Laganiere et al., 2016;Darby et al., 2017Darby et al., , 2018Cohen et al., 2019). Neuropsychological information on these cases was incomplete, and could not be used for analysis. ...
Article
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Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we use a similar indirect disconnection approach to study a group of patients with motor deficits without anosognosia (hemiparesis or hemiplegia, HP, n = 35), or motor deficits with AHP (n = 28). The HP lesions came from a database of stroke patients, while cases of AHP were selected from the published literature. Lesions were traced into an atlas from illustrations of the publications using a standard method. There was no region in the brain that was more damaged in AHP than HP. In terms of structural connectivity, AHP patients had a similar pattern of disconnection of motor pathways to HP patients. However, AHP patients also showed significant disconnection of the right temporo-parietal junction, right insula, right lateral and medial prefrontal cortex. These associative cortical regions were connected through several white matter tracts, including superior longitudinal fasciculus III, arcuate, fronto-insular, frontal inferior longitudinal, and frontal aslant. These tracts connected regions of different cognitive networks: default, ventral attention, and cingulo-opercular. These results were not controlled for clinical variables as concomitant symptoms and other disorders of body representation were not always available for co-variate analysis. In conclusion, we confirm recent studies of disconnection demonstrating that AHP is not limited to dysfunction of motor systems, but involves a much wider set of large-scale cortical networks.
... To identify the brain network underlying particular symptoms in brain-lesioned patients, a recently developed technique termed lesion network mapping (LNM) has been widely used (Boes et al., 2015;Darby, Joutsa, Burke, & Fox, 2018;Darby et al., 2019;Fasano, Laganiere, Lam, & Fox, 2017;Laganiere, Boes, & Fox, 2016). LNM uses brain lesions as seeds to derive the brain network of speci c symptoms based on a large cohort of resting-state normative connectomes. ...
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Facial emotion processing is a basic psychological function of the human brain. Functional neuroimaging techniques have been widely used to probe its neural substrates in healthy subjects. However, like many other psychological functions, functional activations during facial emotion processing have been reported throughout the brain, and the findings are largely inconsistent across studies. Here, we attempted to test whether heterogeneous functional neuroimaging findings of facial emotion processing localized to a connected network and whether network localization could partly explain the poor reproducibility observed. First, using the activation likelihood estimation (ALE) meta-analysis technique, we showed that individual-brain-based reproducibility was low across studies. Then, using a new technique termed ‘activation network mapping’, which was adapted from lesion network mapping, we found that network-based reproducibility across these same studies was rather high; also, these seemingly heterogeneous functional neuroimaging findings mainly localized to a common brain network. Finally, our localized network based on activation matched brain stimulation locations—and the network derived from it—that disrupted facial emotion processing. It also aligned well with structural abnormalities in alexithymia—a disorder characterized by a deficiency in the ability to identify emotions, and brain lesions that disrupt facial emotion processing. Our results suggest that heterogeneous functional neuroimaging findings of facial emotion processing in healthy people localize to a common connected network, which improves the seemingly poor reproducibility among functional neuroimaging studies. Activation network mapping may prove to be a novel network-based technique that is potentially broadly applicable to localize brain networks of cognitive functions based on brain activations in healthy individuals.
... We also evaluated the spatial organization of sites of network overlap. To visualize common sites of network overlap among the individual ROI-seeded networks we binarized the network results above a z-score of 8, corresponding to a threshold used previously for visualizing common sites of network overlap (Boes et al., 2015;Fischer et al., 2016;Fox, Buckner, et al., 2012;Laganiere, Boes, & Fox, 2016). An overlap image was generated to visualize areas with multiple overlapping networks as a color-coded overlap map using Connectome Workbench (https://www.humanconnectome.org/ ...
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Rapid eye movement (REM) sleep is a paradoxical state where the individual appears asleep while the electroencephalogram pattern resembles that of wakefulness. Regional differences in brain metabolism have been observed during REM sleep compared to wakefulness, but it is not known whether the spatial distribution of metabolic differences corresponds to known functional networks in the brain. Here, we use a combination of techniques to evaluate the networks associated with sites of REM sleep activation and deactivation from previously published positron emission tomography studies. We use seed‐based functional connectivity from healthy adults acquired during quiet rest to show that REM‐activation regions are functionally connected in a network that includes retrosplenial cingulate cortex, parahippocampal gyrus, and extrastriate visual cortices, corresponding to components of the default mode network and visual networks. Regions deactivated during REM sleep localize to right‐lateralized fronto‐parietal and salience networks. A negatively correlated relationship was observed between REM‐activation and deactivation networks. Together, these findings show that regional activation and deactivation patterns of REM sleep tend to occur in distinct functional connectivity networks that are present during wakefulness, providing insights regarding the differential contributions of brain regions to the distinct subjective experiences that occur during REM sleep (dreaming) relative to wakefulness.
... This functional map may thus correspond to the networklevel FC abnormalities caused by the lesion (functional disconnection, FDC). This method has been applied in many studies to investigate network dysfunction in a whole host of neurological and psychiatric conditions (Fischer et al., 2016;Laganiere et al., 2016;Darby et al., 2017Darby et al., , 2018aDarby et al., , b, 2019Fasano et al., 2017;Fox, 2018;Joutsa et al., 2018Joutsa et al., , 2019Cohen et al., 2019;Corp et al., 2019;Ferguson et al., 2019;Kim et al., 2019;Padmanabhan et al., 2019) that are either rare or when functional MRI data are lacking (Fox, 2018). ...
Article
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Behavioural deficits in stroke reflect both structural damage at the site of injury, and widespread network dysfunction caused by structural, functional, and metabolic disconnection. Two recent methods allow for the estimation of structural and functional disconnection from clinical structural imaging. This is achieved by embedding a patient's lesion into an atlas of functional and structural connections in healthy subjects, and deriving the ensemble of structural and functional connections that pass through the lesion, thus indirectly estimating its impact on the whole brain connectome. This indirect assessment of network dysfunction is more readily available than direct measures of functional and structural connectivity obtained with functional and diffusion MRI, respectively, and it is in theory applicable to a wide variety of disorders. To validate the clinical relevance of these methods, we quantified the prediction of behavioural deficits in a prospective cohort of 132 first-time stroke patients studied at 2 weeks post-injury (mean age 52.8 years, range 22-77; 63 females; 64 right hemispheres). Specifically, we used multivariate ridge regression to relate deficits in multiple functional domains (left and right visual, left and right motor, language, spatial attention, spatial and verbal memory) with the pattern of lesion and indirect structural or functional disconnection. In a subgroup of patients, we also measured direct alterations of functional connectivity with resting-state functional MRI. Both lesion and indirect structural disconnection maps were predictive of behavioural impairment in all domains (0.16 < R2 < 0.58) except for verbal memory (0.05 < R2 < 0.06). Prediction from indirect functional disconnection was scarce or negligible (0.01 < R2 < 0.18) except for the right visual field deficits (R2 = 0.38), even though multivariate maps were anatomically plausible in all domains. Prediction from direct measures of functional MRI functional connectivity in a subset of patients was clearly superior to indirect functional disconnection. In conclusion, the indirect estimation of structural connectivity damage successfully predicted behavioural deficits post-stroke to a level comparable to lesion information. However, indirect estimation of functional disconnection did not predict behavioural deficits, nor was a substitute for direct functional connectivity measurements, especially for cognitive disorders.
... Such inhibition would induce a loss of control of the internal globus pallidus (GPI) neurons which, in turn, can finally lead to loss of inhibition of the motor thalamus [3]. The classic knowledge, associating the dysfunction of STN with hemiballismus, emphasizes the interruption of excitatory input from the STN to the globus pallidus (GPi) (disrupting the indirect pathway) as the major mechanism of hemiballismus [4]. Laganiere, et al. found that motor pathways implicated in the hemiballismus were considerably complex and widely distributed throughout the brain [5]. ...
... However, stroke-related movement disorders, such as hemichorea-hemiballism (HCHB), occur only in a small percentage of cases. [1][2][3] Although its pathogenesis remains unclear, research previously conducted in the field suggests that the mechanisms involve the motor circuitry of the basal ganglia, despite the absence of a specific and reliably predictive anatomical location. We examined the clinical course of three HCHB cases contralateral to the vascular insult. ...
Article
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We examined pathogenesis and clinical features of three hemichorea-hemiballism (HCHB) cases. We studied their age, magnetic resonance imaging results, vascular risk factors, management, and outcomes. One man and two women (aged 74-86 years) demonstrated acute onset of HCHB, lasting for at least several months. Patients had one or more vascular risk factors, including hypertension and diabetes. All patients presented subacute or old infarction in the basal ganglia with contralateral symptoms. We administered clonazepam (0.5-1 mg/day), haloperidol (0.375-0.75 mg/day), or both as necessary and observed symptom-control. Vascular lesions in the basal ganglia were a contributing factor. Symptoms were controlled using pharmacotherapy with gamma-aminobutyric acid-agonist (clonazepam) or anti-dopaminergic (haloperidol) medication.
... Methods that localize symptoms to brain networks may provide a potential solution to this problem. In prior work, lesion network mapping has been used to localize abnormal motor symptoms (Laganiere et al., 2016;Fasano et al., 2017;Joutsa et al., 2018;Corp et al., 2019), cognitive symptoms (Boes et al., 2015;Sutterer et al., 2016;Ferguson et al., 2019), and neurobehavioural symptoms (Boes et al., 2015;Darby and Fox, 2017;Darby et al., 2017bDarby et al., , 2018a to symptom-specific brain networks. Symptoms-specific brain networks identified using these methods have also been found to be dysfunctional in psychiatric patients with similar symptoms (Darby et al., 2018b). ...
Article
There is both clinical and neuroanatomical variability at the single-subject level in Alzheimer's disease, complicating our understanding of brain-behaviour relationships and making it challenging to develop neuroimaging biomarkers to track disease severity, progression, and response to treatment. Prior work has shown that both group-level atrophy in clinical dementia syndromes and complex neurological symptoms in patients with focal brain lesions localize to brain networks. Here, we use a new technique termed 'atrophy network mapping' to test the hypothesis that single-subject atrophy maps in patients with a clinical diagnosis of Alzheimer's disease will also localize to syndrome-specific and symptom-specific brain networks. First, we defined single-subject atrophy maps by comparing cortical thickness in each Alzheimer's disease patient versus a group of age-matched, cognitively normal subjects across two independent datasets (total Alzheimer's disease patients = 330). No more than 42% of Alzheimer's disease patients had atrophy at any given location across these datasets. Next, we determined the network of brain regions functionally connected to each Alzheimer's disease patient's location of atrophy using seed-based functional connectivity in a large (n = 1000) normative connectome. Despite the heterogeneity of atrophied regions at the single-subject level, we found that 100% of patients with a clinical diagnosis of Alzheimer's disease had atrophy functionally connected to the same brain regions in the mesial temporal lobe, precuneus cortex, and angular gyrus. Results were specific versus control subjects and replicated across two independent datasets. Finally, we used atrophy network mapping to define symptom-specific networks for impaired memory and delusions, finding that our results matched symptom networks derived from patients with focal brain lesions. Our study supports atrophy network mapping as a method to localize clinical, cognitive, and neuropsychiatric symptoms to brain networks, providing insight into brain-behaviour relationships in patients with dementia.
... 4 Evidence shows the lesions typically involve a functional network connected to the posterolateral putamen. 8 Although not commonly recognized, hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is the second most common cause of hemichoreahemiballismus. 3 Over the past 90 years, numerous case reports have described patients with DM with acute and subacute onset of hemiballistic and hemichoreiform movements while in a hyperglycemic state or after its resolution. Reported cases have been limited to small numbers of patients with only a few larger-scale reviews of more than 20 patients. ...
Article
Swift identification of hemiballismus as a complication of poorly controlled type 2 diabetes mellitus may help facilitate optimal care through glycemic control and prevent debilitating loss of patients' function and autonomy, prolonged hospital stays, and overuse of resources.
... Lesion network mapping is a new technique that leverages the human connectome, a large dataset of resting state functional connectivity, to link symptoms to brain networks (Fox, 2018). This method has provided valuable insight towards better understanding the underlying substrates of a growing number of brain disorders, ranging from neurological syndromes such as parkinsonism and chorea (Laganiere et al., 2016), to more abstract neurobehavioural phenomena such as criminality (Darby et al., 2017) and coma (Fischer et al., 2016). Results generated from network mapping have also demonstrated utility for identifying therapeutic targets for neuromodulatory treatments such as TMS and deep brain stimulation (Fox et al., 2014;Joutsa et al., 2018b;Corp et al., 2019;Padmanabhan et al., 2019). ...
Article
Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically heterogeneous neuroimaging findings of migraine localize to a common brain network. We used meta-analytic coordinates of decreased grey matter volume in migraineurs as seed regions to generate resting state functional connectivity network maps from a normative connectome (n = 1000). Network maps were overlapped to identify common regions of connectivity across all coordinates. Specificity of our findings was evaluated using a whole-brain Bayesian spatial generalized linear mixed model and a region of interest analysis with comparison groups of chronic pain and a neurologic control (Alzheimer's disease). We found that all migraine coordinates (11/11, 100%) were negatively connected (t ≥ ±7, P < 10-6 family-wise error corrected for multiple comparisons) to a single location in left extrastriate visual cortex overlying dorsal V3 and V3A subregions. More than 90% of coordinates (10/11) were also positively connected with bilateral insula and negatively connected with the hypothalamus. Bayesian spatial generalized linear mixed model whole-brain analysis identified left V3/V3A as the area with the most specific connectivity to migraine coordinates compared to control coordinates (voxel-wise probability of ≥90%). Post hoc region of interest analyses further supported the specificity of this finding (ANOVA P = 0.02; pairwise t-tests P = 0.03 and P = 0.003, respectively). In conclusion, using coordinate-based network mapping, we show that regions of grey matter volume loss in migraineurs localize to a common brain network defined by connectivity to visual cortex V3/V3A, a region previously implicated in mechanisms of cortical spreading depression in migraine. Our findings help unify migraine neuroimaging literature and offer a migraine-specific target for neuromodulatory treatment.
... The result demonstrated that the causative lesions, while anatomically heterogeneous, localize to a single network with shared functional connectivity to the posterolateral putamen. [20] However, hemichorea-hemiballismus is still relatively rare even when the presumed network is markedly damaged. This observation might be explained by individual susceptibility and brain plasticity. ...
Article
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Introduction: Hemichorea-hemiballismus, which spans a spectrum of involuntary, continuous, nonpatterned movement involving one side of the body, can emerge as the initial manifestation of acute ischemic stroke. However, because of its rarity in the community, the diagnosis and treatment are often delayed. Patient concerns: We report a unique case of a 47-year-old female who presented with acute onset hemichorea-hemiballismus. No obvious focal sign apart from involuntary, continuous, nonpatterned movement of her left arm and leg was presented. Diagnosis: Initial diffusion-weighted magnetic resonance imaging (MRI) was negative but significant increase of blood flow velocity in the right middle cerebral artery (MCA) stem was revealed by transcranial doppler sonography. Repeated MRI showed acute infarction in the contralateral globus pallidus. Isolated dissection of the right MCA typified by intimal flap with double lumen was identified by digital subtraction angiography and high-resolution magnetic resonance imaging (HR-MRI). Interventions: The patient was initially treated with dual antiplatelet agents but the uncontrollable movement deteriorated during hospitalization. Antithrombotic therapy was then intensified with combination of tirofiban and low-molecular-weight heparin. Other symptomatic treatment included volume expansion with colloidal fluid to improve cerebral perfusion. Her involuntary movement gradually diminished and the patient was discharged with rivaroxaban 15 mg/daily. Outcomes: The patient had recovered with significant reduction in her hemichorea-hemiballismus. Three-month follow-up HR-MRI showed complete resolution of the MCA dissection lesions. Conclusion: Prompt recognition of acute onset hemichorea-hemiballismus as the manifestation of acute ischemic stroke in appropriate clinical setting may reduce diagnostic delay. Multiple imaging techniques including cerebral digital subtraction angiography and HR-MRI can be applied to diagnosis and further clarify the mechanism of stroke, which facilitate in selection of secondary prevention therapies.
... However, it has also been documented with lesions involving other brain regions (ie, cortex, caudate, putamen, thalamus, and brainstem), suggesting this may be part of a wider neural network most commonly involving the posterolateral putamen. 1 The differential diagnosis of acquired hemichorea-hemiballismus is broad, with stroke being the most common cause, however, arteriovenous malformations, cerebral trauma, hyperosmotic hyperglycemia, multiple sclerosis, and tumors have also been reported. 1,2 Infections remain a possible, although uncommon, etiology, including abscesses, meningeal tuberculosis, bacterial meningitis, encephalitis, and toxoplasmosis. 2 Here, we document the rare case of hemichorea-hemiballism as the presenting clinical sign of central nervous system tuberculosis (CNS-Tb). ...
... However, this can be difficult when the lesion is not in the traditional or expected location relative to the patient's symptoms. For example, patients with hemichorea can have lesions outside the subthalamic nucleus [18], patients with in hemiparkinsonism can have lesions outside the nigrostriatal tract [19], patients with amnesia can have lesion outside the hippocampus [20], and patients with poststroke depression can have lesions outside the left dorsolateral prefrontal cortex in [21]. In all these conditions, although the causal lesions were in heterogeneous locations, they fell within a common circuit specific to the symptom. ...
Article
Purpose of review: Focal lesions causing specific neurological or psychiatric symptoms can occur in multiple different brain locations, complicating symptom localization. Here, we review lesion network mapping, a technique used to aid localization by mapping lesion-induced symptoms to brain circuits rather than individual brain regions. We highlight recent examples of how this technique is being used to investigate clinical entities and identify therapeutic targets. Recent findings: To date, lesion network mapping has successfully been applied to more than 40 different symptoms or symptom complexes. In each case, lesion locations were combined with an atlas of human brain connections (the human connectome) to map heterogeneous lesion locations causing the same symptom to a common brain circuit. This approach has lent insight into symptoms that have been difficult to localize using other techniques, such as hallucinations, tics, blindsight, and pathological laughter and crying. Further, lesion network mapping has recently been applied to lesions that improve symptoms, such as tremor and addiction, which may translate into new therapeutic targets. Summary: Lesion network mapping can be used to map lesion-induced symptoms to brain circuits rather than single brain regions. Recent findings have provided insight into long-standing clinical mysteries and identified testable treatment targets for circuit-based and symptom-based neuromodulation.
... subthalamic nuclei). One possible network with a considerable role is the posterolateral putamen pathway, which was shown to be damaged in 90% of the patients in a hemichorea-hemiballismus case series with 29 patients 10 . The sites involved included the caudate nuclei, insular cortex and parietal lobe, regions that were also identified in our case series (Figure 1). ...
Article
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Background: Chorea is a movement disorder characterized by random, brief and migratory involuntary muscle contractions. It is defined as acute when present within hours to days. Three main causes for this scenario have emerged as most likely: vascular, toxic-metabolic and inflammatory. Objectives: To identify the prevalence of the main etiologies and major clinical findings of acute chorea in the emergency room of a tertiary-level referral center; and to suggest an approach for guiding the diagnostic workup and clinical management. Methods: We retrospectively reviewed the clinical aspects and neuroimaging data of 10 patients presenting with acute chorea at the neurological emergency room of our hospital from 2015 to 2019. Results: Stroke was the most common etiology (50% of the cases). All of them were ischemic. It was noteworthy that only one case demonstrated the classical ischemic topographic lesion at the contralateral subthalamic nuclei. Regarding nonvascular etiologies, nonketotic hyperglycemia was the major cause, followed by drug-related chorea. One patient showed inflammatory etiology, which was probably Sydenham chorea reactivation. Conclusion: Acute chorea is an uncommon and challenging problem at the emergency room, often associated with potentially treatable causes. We suggest that use of the acronym DANCE (Diagnosis of chorea, Acute stroke protocol, Normal glucose levels, Check neuroimaging, Exposure to drugs) could form a potential initial approach in the evaluation, in order to emphasize causes that require prompt proper management (e.g. thrombolysis).
... Strokes causing involuntary movement disorders, while anatomically heterogeneous, localize to a common functional network [10]. We have demonstrated in this case that hyperkinetic movement disorders can appear in patients with stroke lesions only in the subcortical white matter of frontal and parietal lobes. ...
... In addition to the current work in this area, I see a role for healthy brain connectivity, mapped onto an individual patient's brain, in identifying possible candidate regions for tumour spread Henderson et al., 2019;Mandelli et al., 2016;Yau et al., 2018;Zheng et al., 2019;Zhou et al., 2012). Analogous to the lesion network mapping approach pioneered by Michael Fox and colleagues, the network affected by a given tumour can be inferred from the healthy connectome, which therefore could suggest other regions belonging to the same network that are likely to also be affected (Boes et al., 2015;Burke et al., 2020;Corp et al., 2019;Fasano et al., 2017;Fox, 2018;Laganiere et al., 2016). In addition to healthy brain connectomics, there also exists a possible role for lesion covariance networks in predicting longitudinal tumour spread. ...
Thesis
Glioma tumours are among the most lethal brain disorders, claiming the lives of thousands of people in the United Kingdom each year. Despite the severity and prevalence of the condition, remarkably little is understood about the origins of gliomas, or the mechanisms that guide their spread within the brain. The aim of this thesis is to invoke a relatively new approach – brain network mapping – to provide insights into the origins of gliomas and their pathological spread along neural circuits. First, I provide a historical overview of both brain network mapping and glioma neurobiology, along with the recent advances and techniques popular in each field. In particular, I highlight preclinical research implying that gliomas originate from neural stem cells in the subventricular zone, as well as other work in mouse models demonstrating that gliomas infiltrate previously healthy brain networks. This thesis contributes three studies of clinical datasets which evaluate the hypothesis that glioma initiation and progression are guided by brain networks. In the first study, I describe convergent evidence from both intracranial electrocorticography recordings and resting-state functional imaging of four patients with low-grade gliomas that tumour-infiltrated cortex can participate in large-scale cognitive circuits responsive to executive function. These findings imply that gliomas integrate into neural circuits, suggesting that their development and maintenance could be sustained by functional brain networks. In support of this idea, I next demonstrate that the spatial distribution of gliomas in the brain follows the distribution of functional network hubs, as well as cellular and genomic factors related to gliomagenesis. These results suggest two possibilities regarding the origins of glioma: the predilection of gliomas to hub locations could be a result of the vulnerability of hubs to oncogenesis, or the result of tumours arriving at central network locations while spreading through brain networks. To help disambiguate between these possibilities, I developed a novel approach termed “lesion covariance network mapping” to identify networks of brain regions co-lesioned in glioma, which indicate areas along which tumours are inferred to spread. This method revealed that gliomas cluster around horns of the lateral ventricles, consistent with the hypothesis that these tumours originate from neurogenic niches within subventricular zone. The lesion covariance network method also demonstrated that glioma localisation patterns follow specific structural and functional connectivity networks disseminating from periventricular grey matter. Cumulatively, the findings of the thesis support a model wherein periventricular brain connectivity guides glioma development from the subventricular zone into distributed regions of the cortex. In the conclusion, I discuss potential clinical applications of the presented research, such as in supporting predictive modelling approaches to forecast glioma progression, for the purpose of planning pre-emptive radiation and surgical treatments of glioma.
... The The resting-state connectivity patterns are not strictly related to unwanted movements of the patients also when lesion network maps were used. According to the "lesion network overlap" concept (89), when lesions cause the same symptom in many patients and overlap in one brain region, the causal link between that region and the resulting symptom is strengthened. However, a distant lesion may induce morphological degenerations of other areas that are not involved in the area initially lesioned (the case of cerebellar olives and dentate nuclei in the most known clinical example), suggesting that functional connectivity alterations may induce degeneration due to disconnection (diaschisis) (90). ...
Article
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Consensus criteria on CorticoBasal Degeneration (CBD) include alien limb (AL) phenomena. However, the gist of the behavioral features of AL is still "a matter of debate". CBD-related AL has so far included the description of involuntary movements, frontal release phenomena (frontal AL), or asomatognosia (posterior or "real" AL). In this context, the most frequent symptoms are language and praxis deficits and cortical sensory misperception. However, asomatognosia requires, by definition, intact perception and cognition. Thus, to make a proper diagnosis of AL in the context of CBD, cognitive and language dysfunctions must be carefully verified and objectively assessed. We reviewed the current literature on AL in CBD and now propose that the generic use of the term AL should be avoided. This catch-all AL term should instead be deconstructed. We propose that the term AL is appropriate to describe clinical features associated with specific brain lesions. More discrete sets of regionally-bound clinical signs that depend on dysfunctions of specific brain areas need to be assessed and presented when posing the diagnosis. Thus, in our opinion, the AL term should be employed in association with precise descriptions of the accompanying involuntary movements, sensory misperceptions, agnosia-asomatognosia contents, as well as the presence of utilization behavior. The review also offers an overview of functional magnetic resonance imaging-based studies evaluating AL-related phenomena. In addition, we provide a complementary set of video clips depicting CBD-related involuntary movements that should not mistakenly be interpreted as signs of AL.
... 4 Although vascular infarcts resulting in HCHB may vary in anatomical location, they are localizable to a common functional network. 8 Both ischemic and haemorrhagic stroke account for the most common etiology of HCHB. In one study 11 of 21 patients had a stroke etiology, and in another series 18 of 25 patients had either ischemic or haemorrhagic stroke. ...
Article
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Introduction: Cerebrovascular disease often presents with "negative" symptoms such as weakness with reduced movement of body parts or sensory loss. Rarely do "positive" symptoms such as abnormal movements manifest in acute stroke, with hemichorea being a very rare manifestation. Case report: This is a case report of a 62-year-old chronic smoker with no known past medical history who presented with choreatic movements of his arm and leg. Magnetic resonance imaging of the brain showed changes consistent with an infarct in the right centrum semiovale. He was treated with dual antiplatelets and was noted to have subsequent improvement in symptoms. Conclusion: Recognition and awareness of stroke presenting as movement disorders in the emergency department can help prevent delays in diagnosis and treatment.
... However, in subsequent years, lesions in other brain structures were reported, such as the caudate, putamen, thalamus, and cortex [4][5][6][7]. More recently, lesion mapping techniques have shown that regions functionally connected to the posterolateral putamen were also involved [8]. Structural lesions in one of these regions can cause hemichorea-hemiballismus, with ischemic or hemorrhagic stroke being the most common etiology [1,9]. ...
Article
Full-text available
Background: Hemichorea-hemiballismus is a rare hyperkinetic movement disorder. Case report: A 90-year-old male developed left hemichorea-hemiballismus after his second dose of the Pfizer-BioNTech COVID-19 vaccine. A wide range of investigations including magnetic resonance imaging did not reveal an alternative cause. [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed increases in right putamen fixation compared to the left side. The patient showed significant improvement after five days of intravenous corticosteroids, with a normal FDG-PET. Discussion: This hemichorea-hemiballismus case shows dynamic restoration of putamen metabolism mirroring clinical evolution after administration of corticosteroids, suggesting an autoimmune COVID-19 vaccine-induced reaction.
... 14 Several such studies applying this method have been recently published, 63-65 along with reviews discussing the limitations of the process. 13,[66][67][68] The original purpose of the study by Darby et al., 63 Laganiere et al., 64 and Boes et al. 65 was to identify the neural substrates of peculiar neurological symptoms, which are difficult to identify by conventional lesion-symptom mapping methods, such as chorea and delusional misidentification. To this end, they focused on comparing patients with specific neurological symptoms and controls without those symptoms. ...
Article
The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.
... The technique, termed lesion network mapping 36 uses normative functional connectomes acquired in large samples of healthy participants to investigate into which network a specific lesion would fall in the average human brain. So far, the method has provided insights into different neuropsychiatric symptoms 35 , including movement disorders [37][38][39] and disorders of volition 40,41 . In a similar vein, a novel concept termed DBS network mapping has applied the same concept to stimulation sites 42 . ...
Article
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Brain lesions are a rare cause of tic disorders. However, they can provide unique insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain. We probed this using a normative functional connectome acquired in 1,000 healthy participants. We then examined the specificity of the identified network by contrasting tic-lesion connectivity maps to those seeding from 717 lesions associated with a wide array of neurological and/or psychiatric symptoms within the Harvard Lesion Repository. Finally, we determined the predictive utility of the tic-inducing lesion network as a therapeutic target for neuromodulation. Specifically, we collected retrospective data of 30 individuals with Tourette disorder, who underwent either thalamic (n = 15; centromedian/ventrooralis internus) or pallidal (n = 15; anterior segment of globus pallidus internus) deep brain stimulation and calculated whether connectivity between deep brain stimulation sites and the lesion network map could predict clinical improvements. Despite spatial heterogeneity, tic-inducing lesions mapped to a common network map, which comprised the insular cortices, cingulate gyrus, striatum, globus pallidus internus, thalami, and the cerebellum. Connectivity to a region within the anterior striatum (putamen) was specific to tic-inducing lesions when compared with control lesions. Connectivity between deep brain stimulation electrodes and the lesion network map was predictive of tic improvement, regardless of the deep brain stimulation target. Taken together, our results reveal a common brain network involved in tic generation which shows potential as a therapeutic target for neuromodulation.
... Regardless of the cause of the lesion, its size or precise location, evidence has accumulated over recent years in favor of the connectome hypothesis whereby the specific network(s) the lesion affects can predict many of the patient's responses across behavioral, cognitive or sensory-motor domains . A computational solution to map the lesion-driven disconnectivity to behavior was developed recently 1 , and it has been successfully applied to several conditions and pathologies 4,5,[7][8][9][10][11][12][13]15,16,18,19,[21][22][23] . Due to the simplicity of this method to correlate behavioral outcomes with the extent of lesion-driven disconnection, the strategy was referred to as Lesion Network Mapping (LNM). ...
Preprint
Full-text available
Lesion network mapping (LNM) has proved to be a successful technique to map symptoms to brain networks after acquired brain injury. Beyond the characteristics of a lesion, such as its etiology, size or location, LNM has shown that common symptoms in patients after injury may reflect the effects of their lesions on the same circuits, thereby linking symptoms to specific brain networks. Here, we extend LNM to its multimodal form, using a combination of functional and structural connectivity maps drawn from data from 1000 healthy participants in the Human Connectome Project. We applied the multimodal LNM to a cohort of 54 stroke patients with the aim of predicting sensorimotor behavior, as assessed through a combination of motor and sensory tests. Test scores were predicted using a Canonical Correlation Analysis with multimodal brain maps as independent variables, and cross-validation strategies were employed to overcome overfitting. The results obtained led us to draw three conclusions. First, the multimodal analysis reveals how functional connectivity maps contribute more than structural connectivity maps in the optimal prediction of sensorimotor behavior. Second, the maximal association solution between the behavioral outcome and multimodal lesion connectivity maps suggests an equal contribution of sensory and motor coefficients, in contrast to the unimodal analyses where the sensory contribution dominates in both structural and functional maps. Finally, when looking at each modality individually, the performance of the structural connectivity maps strongly depends on whether sensorimotor performance was corrected for lesion size, thereby eliminating the effect of larger lesions that produce more severe sensorimotor dysfunction. By contrast, the maps of functional connectivity performed similarly irrespective of any correction for lesion size. Overall, these results support the extension of LNM to its multimodal form, highlighting the synergistic and additive nature of different types of imaging modalities, and the influence of their corresponding brain networks on behavioral performance after acquired brain injury.
Article
A 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.
Chapter
Despite the prevalence of anhedonia across multiple psychiatric disorders, its relevance to treatment selection and prognostication can be unclear (Davey et al., Psychol Med 42(10):2071-81, 2012). Given the challenges in pharmacological and psychosocial treatment, there has been increasing attention devoted to neuroanatomically-targeted treatments. This chapter will present a brief introduction to circuit-targeted therapeutics in psychiatry (Sect. 1), an overview of brain mapping as it relates to anhedonia (Sect. 2), a review of existing studies on brain stimulation for anhedonia (Sect. 3), and a description of emerging approaches to circuit-based neuromodulation for anhedonia (Sect. 4).
Article
Mapping human brain function is a long-standing goal of neuroscience that promises to inform the development of new treatments for brain disorders. Early maps of human brain function were based on locations of brain damage or brain stimulation that caused a functional change. Over time, this approach was largely replaced by technologies such as functional neuroimaging, which identify brain regions in which activity is correlated with behaviours or symptoms. Despite their advantages, these technologies reveal correlations, not causation. This creates challenges for interpreting the data generated from these tools and using them to develop treatments for brain disorders. A return to causal mapping of human brain function based on brain lesions and brain stimulation is underway. New approaches can combine these causal sources of information with modern neuroimaging and electrophysiology techniques to gain new insights into the functions of specific brain areas. In this Review, we provide a definition of causality for translational research, propose a continuum along which to assess the relative strength of causal information from human brain mapping studies and discuss recent advances in causal brain mapping and their relevance for developing treatments. In this Review, Siddiqi et al. examine causal approaches to mapping human brain function. They provide a definition of causality for translational research, propose a framework for assessing causality strength in brain mapping studies and cover advances in techniques and their use in developing treatments for brain disorders.
Preprint
The substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy controls. Normative models identified that person-specific deviations from population expectations for regional grey matter volume were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience/ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia, and ADHD. Our findings indicate that while phenotypic differences between cases assigned the same diagnosis may arise from heterogeneity in the location of regional deviations, phenotypic similarities are attributable to dysfunction of common functional circuits and networks.
Article
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Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pathological processes and treatments as well as prognostic biomarkers. These tools have the real potential to inform patient-specific treatment strategies. Nevertheless, a realistic appraisal of clinical utility is needed that balances the growing excitement and interest in the field with important limitations associated with these techniques. Quality of the raw data, minutiae of the processing methodology, and the statistical models applied can all impact on the results and their interpretation. A lack of standardization in data acquisition and processing has also resulted in issues with reproducibility. This limitation has had a direct impact on the reliability of these tools and ultimately, confidence in their clinical use. Advances in MRI technology and computational power as well as automation and standardization of processing methods, including machine learning approaches, may help address some of these issues and make these tools more reliable in clinical use. In this review, we will highlight the current clinical uses of MRI connectomics in the diagnosis and treatment of neurological disorders; balancing emerging applications and technologies with limitations of connectivity analytic approaches to present an encompassing and appropriate perspective.
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The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied ‘lesion network-symptom-mapping’ to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the ‘positive PLC subnetwork’ is part of the emotional system and the ‘negative PLC subnetwork’ overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.
Chapter
Brain lesions, such as the ones caused by stroke or tumors, disrupt normal brain function and cause a wide spectrum of neurological and psychiatric symptoms. Studying brain lesions has formed the foundation for localization of symptoms throughout the history of neurology, providing unique causal evidence. In exceedingly rare cases, spontaneous brain lesions can improve pre-existing symptoms, which is referred to as paradoxical functional facilitation. Iatrogenic brain lesions can provide similar functional benefit. Both types of lesions have helped lead to identification of deep brain stimulation targets. However, paradoxical functional facilitation is rare and lesions improving similar symptoms can occur in multiple different neuroanatomical locations, leaving the optimal treatment target unclear. Emerging new techniques combining causal and beneficial brain lesions with the human connectome have opened the door for systematic search of new and improved therapeutic targets for functional neurosurgery.
Chapter
Hemiballism is an uncommon movement disorder that presents with unilateral, random flinging movements of the limbs. The movements vary considerably in intensity and severity from milder, lower amplitude choreic movements to larger amplitude ballistic movements involving the proximal joints of the limbs. The latter, in acute phases, can be of sufficient severity to present as a true emergency. Hemiballism is classically associated with ischemic lesions of the subthalamic nucleus (STN); however, the majority of cases actually involve basal ganglia structures outside the STN. An important common association is with diabetes, during episodes of severe nonketotic hyperosmolar hyperglycemia. Pathophysiology is related to abnormal firing patterns in the globus pallidus internus; intermittent firing bursts are followed by pauses, during which movements occur. The key treatment is antidopaminergic therapy, either with dopamine receptor blockers such as neuroleptics, or dopamine depletors such as tetrabenazine, valbenazine, or deutetrabenazine. Most patients respond well to medical treatment and spontaneous resolution is common. In extreme or persistent cases, functional neurosurgery can be very effective; either lesioning or deep brain stimulation of the globus pallidus.
Article
Background Our aim in this study was to evaluate the efficacy of magnetic resonance imaging (MRI) studies in the detection of brain regions effected by Sydenham chorea and to determine whether they provided data regarding the pathogenesis of Sydenham chorea. To this end, we assessed basal ganglia structures in Sydenham chorea patients and control group by quantitative MRI volumetric analysis. Methods Patients with a recent onset of chorea and control subjects matched for age and gender were included in the study. Medical history, laboratory tests, and physical and neurologic examinations were reviewed. All MRIs were considered within normal limits. High-resolution T1-weighted 3D magnetization-prepared rapid acquisition of gradient echo scans were used for quantitative volumetric assessment of the brain via the “volBrain” method. Results Twenty-four subjects with Sydenham chorea (16 girls and 8 boys, aged between 7 and 16 years) and 35 control subjects were evaluated. Mean age was 11.25 ± 2.89 years for Sydenham chorea patients and 10.58 ± 2.53 years for the controls. No significant difference was found relative to globus pallidus, caudate, and thalamic volumes between patients with Sydenham chorea and controls. The relative mean total, left, and right putamen volumes were significantly larger in patients with Sydenham chorea compared to controls ( P = .003, P = .018, P = .001, respectively). Conclusion Selective neuroanatomic differences in putamen among other basal ganglia structures and significant increases in size are consistent with a hypothesis of a cross-reactive antibody-mediated inflammation of the putamen as being the pathophysiologic mechanism for this disorder.
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Objective: The aim of this study was to determine common structural and functional networks associated with asymmetric step length after unilateral ischemic stroke. Methods: Thirty-nine chronic stroke patients were divided into two groups, based on the presence or absence of asymmetric step length. In each group, each lesion was mapped onto a brain magnetic resonance image. The structural and functional networks of brain regions connected to each lesion were identified using a public diffusion tensor and resting state function magnetic resonance image dataset. To identify brain regions associated with asymmetric step length, we conducted voxel-wise independent sample t-tests for structural and function lesion network maps. Results: At least 85% of lesions showed functional network overlap in the bilateral frontal lobe. Functional connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere was significantly decreased in group 1 compared to that in group 2. Conclusions: The dorsolateral prefrontal cortex may have an important role in compensating for an asymmetric step length after a unilateral stroke.
Article
A 78 year old lady, with a past medical history of hypertension, presented to the Accident & Emergency department after a sudden onset of right sided involuntary movements while she was having afternoon tea with her friends. Examination showed isolated unilateral chorea, affecting the right arm and leg (video). Her blood glucose and sodium levels were normal. The MRI head scan showed a left globus pallidus infarct (figure 1). Tetrabenazine was prescribed with very good response, and weaned off after 4 weeks. Hyperkinetic movement disorders are uncommon in acute stroke (1%)1. Lesions in regions functionally connected to the posterolateral putamen are implicated in hyperkinetic movement disorders2. The differential diagnosis includes hyperglycaemia, hyponatraemia and drug-induced chorea. In cases of sudden onset, it is important to recognise stroke as a possible cause to avoid missing reperfusion therapy opportunities
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A 59-year-old woman was admitted with acute left hemichorea-hemiballism. Blood glucose level was 87 mg/dL. Head CT scan showed old infarcts (figure). The patient underwent thrombolysis with IV alteplase (0.9 mg/kg) within 86 minutes of symptom onset, evolving with partial improvement after 2 hours (video) and complete resolution after 24 hours without other treatments. Brain MRI showed an acute stroke in the right insula (figure), known to be functionally connected to the posterolateral putamen.1 Hemichorea-hemiballism is an uncommon presentation of stroke and may be caused by insular, putaminal, and various other lesions connected to the same network.1,2
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A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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The goal of the Brain Genomics Superstruct Project (GSP) is to enable large-scale exploration of the links between brain function, behavior, and ultimately genetic variation. To provide the broader scientific community data to probe these associations, a repository of structural and functional magnetic resonance imaging (MRI) scans linked to genetic information was constructed from a sample of healthy individuals. The initial release, detailed in the present manuscript, encompasses quality screened cross-sectional data from 1,570 participants ages 18 to 35 years who were scanned with MRI and completed demographic and health questionnaires. Personality and cognitive measures were obtained on a subset of participants. Each dataset contains a T1-weighted structural MRI scan and either one (n=1,570) or two (n=1,139) resting state functional MRI scans. Test-retest reliability datasets are included from 69 participants scanned within six months of their initial visit. For the majority of participants self-report behavioral and cognitive measures are included (n=926 and n=892 respectively). Analyses of data quality, structure, function, personality, and cognition are presented to demonstrate the dataset's utility.
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Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer's disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation.
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Studies attempting to map post-stroke cognitive or motor symptoms to lesion location have been available in the literature for over 150 years. In the last two decades, two computational techniques have been developed to identify the lesion sites associated with behavioural impairments. Voxel Based Morphometry (VBM) has now been used extensively for this purpose in many different patient populations. More recently, Voxel-based Lesion Symptom Mapping (VLSM) was developed specifically for the purpose of identifying lesion-symptom relationships in stroke patients, and has been used extensively to study, among others functions, language, motor abilities and attention. However, no studies have compared the results of these two techniques so far. In this study we compared VLSM and VBM in a cohort of 20 patients with chronic post-stroke aphasia. Comparison of the two techniques showed overlap in regions previously found to be relevant for the tasks used, suggesting that using both techniques and looking for overlaps between them can increase the reliability of the results obtained. However, overall VBM and VLSM provided only partially concordant results and the differences between the two techniques are discussed.
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Many different types of hyperkinetic and hypokinetic movement disorders have been reported after ischaemic and haemorrhagic stroke. We searched the Medline database from 1966 to February 2008, retrieving 2942 articles from which 156 relevant case reports, case series and review articles were identified. The papers were then further reviewed and filtered and secondary references found. Here we review the different types of abnormal movements reported with anatomical correlation, epidemiology, treatment and prognosis. Post stroke movement disorders can present acutely or as a delayed sequel. They can be hyperkinetic (most commonly hemichorea-hemiballism) or hypokinetic (most commonly vascular parkinsonism). Most are caused by lesions in the basal ganglia or thalamus but can occur with strokes at many different locations in the motor circuit. Many are self limiting but treatment may be required for symptom control.
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Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders.
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The authors describe and illustrate an integrated trio of software programs for carrying out surface-based analyses of cerebral cortex. The first component of this trio, SureFit (Surface Reconstruction by Filtering and Intensity Transformations), is used primarily for cortical segmentation, volume visualization, surface generation, and the mapping of functional neuroimaging data onto surfaces. The second component, Caret (Computerized Anatomical Reconstruction and Editing Tool Kit), provides a wide range of surface visualization and analysis options as well as capabilities for surface flattening, surface-based deformation, and other surface manipulations. The third component, SuMS (Surface Management System), is a database and associated user interface for surface-related data. It provides for efficient insertion, searching, and extraction of surface and volume data from the database.
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Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke. We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs. Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case-control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6). Chorea is the commonest movement disorder following stroke and appears in older patients. Involuntary movements tend to persist despite the functional recovery of motor deficit. Deep vascular lesions are more frequent in patients with movement disorders.
Book
The first two editions of Stroke Syndromes were widely welcomed as authoritative reference works in the assessment and diagnosis of stroke. This revised and updated third edition remains the definitive guide to patterns and syndromes in stroke. A comprehensive survey of all types of neurological, neurophysiological and other clinical dysfunction due to stroke. The book contains descriptions of clinical problems encountered in stroke patients and their differential diagnosis, enhancing pattern recognition and enabling clinicians to differentiate between possible locations on the basis of symptoms and signs. The companion volume Uncommon Causes of Stroke completes this highly authoritative reference work which clinicians in neurology will find essential to the understanding and diagnosis of stroke.
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Objective: To determine which brain structures are involved in symptomatic unilateral dystonia caused by localized cerebral infarction. Design: Three-dimensional T1-weighted magnetic resonance imaging sequence and stereotactic analysis were used to analyze the topography of the lesions. Stereotactic localization of thalamic lesions was conducted according to the atlas of Hassler with a Voxtool software (Advantage Windows Workstation, General Electric, Milwaukee, Wis) workstation system. Patients: Eight patients with hemidystonia, segmental dystonia, or focal dystonia were selected from among 51 consecutive patients (between January 1988 and May 1993) with symptomatic unilateral dystonia. Results: Patients had dystonic spasms (n=4) or myoclonic dystonia (n=4). Lesions associated with dystonic spasms were located in the striatopallidal complex, and those with myoclonic dystonia were in the thalamus contralateral to the dystonia. Lesions of the striatopallidal complex involved the putamen posterior to the anterior commissure in all patients and extended variably into the dorsolateral part of the caudate nucleus, the posterior limb of the internal capsule, or the lateral segment of the globus pallidus. These lesions were centered in the "sensorimotor" part of the striatopallidal complex, with a trend toward a somatotopical distribution. Lesions of the thalamus were located in the ventral intermediate and ventral caudal nuclei, while the ventral oral anterior and posterior nuclei (which receive pallidal efferents) were largely spared. Conclusion: These results suggest that striatopallidal and thalamic dystonia may have different pathophysiologic bases.
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Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression. However, the antidepressant mechanism remains unknown and its therapeutic efficacy remains limited. Recent data suggest that some left DLPFC targets are more effective than others; however, the reasons for this heterogeneity and how to capitalize on this information remain unclear. Intrinsic (resting state) functional magnetic resonance imaging data from 98 normal subjects were used to compute functional connectivity with various left DLPFC TMS targets employed in the literature. Differences in functional connectivity related to differences in previously reported clinical efficacy were identified. This information was translated into a connectivity-based targeting strategy to identify optimized left DLPFC TMS coordinates. Results in normal subjects were tested for reproducibility in an independent cohort of 13 patients with depression. Differences in functional connectivity were related to previously reported differences in clinical efficacy across a distributed set of cortical and limbic regions. Dorsolateral prefrontal cortex TMS sites with better clinical efficacy were more negatively correlated (anticorrelated) with the subgenual cingulate. Optimum connectivity-based stimulation coordinates were identified in Brodmann area 46. Results were reproducible in patients with depression. Reported antidepressant efficacy of different left DLPFC TMS sites is related to the anticorrelation of each site with the subgenual cingulate, potentially lending insight into the antidepressant mechanism of TMS and suggesting a role for intrinsically anticorrelated networks in depression. These results can be translated into a connectivity-based targeting strategy for focal brain stimulation that might be used to optimize clinical response.
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Hemiballism is a rare movement disorder characterized by a high amplitude movement of an entire limb or limbs on one side of the body. The acute development of hemiballismus is often caused by focal lesions in the contralateral basal ganglia and STN. Many etiologies exist for this rare disorder with vascular causes and nonketotic hyperglycemia being the most common. Clearer understanding of the pathophysiology of hemiballism has led to important insights into the function and interaction of structures within the basal ganglia. Newer models of basal ganglia function have been proposed based on the study of the pathophysiology of hemiballism. Prognosis is favorable for most patients with complete resolution with or without treatment. Medical and surgical treatments are often successful in reducing or completely ameliorating the movements in those patients with more severe movements.
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Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset. The current study examined magnetic resonance imaging (MRI) measures of striatum and white matter volume in 85 individuals prospectively followed from pre-HD stage through diagnosable motor onset (incident cases) and 85 individuals individually matched with incident cases on CAG repeat length, sex, and age, who were not diagnosed with HD during the course of the study. Volumes of striatum and white matter were significantly smaller in individuals who would be diagnosed 1 to 4 years following the initial MRI scan, compared with those who would remain in the pre-HD stage. Putamen volume was the measure that best distinguished between the two groups. Results suggest that MRI volumetric measures may be helpful in selecting individuals for future clinical trials in pre-HD where HD motor onset is the primary outcome measure. In planning for multisite clinical trials in pre-HD, investigators may also want to consider using more objective measures, such as MRI volumes, in addition to onset of diagnosable movement disorder, as major outcome measures.
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We report a case of polycythemia vera with chorea in which the brain metabolism and dopamine system were investigated using 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and (99m)Tc-labeled tropane dopamine transporter ((99m)Tc-TRODAT-1) single photon emission computed tomography (SPECT). Along with normalization of the hematocrit and clinical symptoms after consecutive phlebotomies, the FDG PET scan and (99m)Tc-TRODAT-1 SPECT images returned towards normal. It is hypothesized that the development of polycythemia chorea is associated with a reversible alteration in the corticobasal ganglia metabolism and disturbed dopaminergic function.
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Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.
Article
Movement disorders associated with basal ganglia dysfunction comprise a spectrum of abnormalities that range from the hypokinetic disorders (of which Parkinson's disease is the best-known example) at one extreme to the hyperkinetic disorders (exemplified by Huntington's disease and hemiballismus) at the other. Both extremes of this movement disorder spectrum can be accounted for by postulating specific disturbances within the basal ganglia-thalamocortical 'motor' circuit. In this paper, Mahlon DeLong describes the changes in neuronal activity in the motor circuit in animal models of hypo- and hyperkinetic disorders.
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Using [18F]dopa, [11C]raclopride, C15O2, and positron emission tomography, we have assessed striatal dopamine storage capacity, dopamine D2-receptor integrity, and regional cerebral blood flow, respectively, of 6 patients with neuroacanthocytosis. The patients with neurocanthocytosis all had chorea and variable combinations of seizures, dementia, axonal neuropathy, and orolingual self-multiation. [18F]dopa positron emmission tomographic findings were compared with 30 normal controls and 16 patients with sporadic, L-dopa-responsive, Parkinson's disease. Caudate and anterior putamen [18F]dopa uptake were normal in patients with neuroacanthocytosis, but mean posterior putamen [18F]dopa uptake was reduced to 42% of normal, similar to that in patients with Parkinson's disease. In patients with neuroacanthocytosis, mean equilibrium caudate: cerebellum and putamen: cerebellum [11C]raclopride uptake ratios were reduced to 54% and 62% of normal, compatible with a 65% and 53% loss of caudate and putamen D2-receptor-binding sites, respectively. Striatal and frontal blood flow was also depressed. The severe loss of D2-receptor-bearing striatal neuron, with concomitant loss of dopaminergic projections from the nigra to the posterior putamen, is consistent with both chorea and extrapyramidal rigidity being features of patients with neuroacanthocytosis.
Article
Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in the authors' concepts of the structural and functional organization of these nuclei. Recent anatomical and physiological findings have further substantiated the concept of segregated basal ganglia-thalamocortical pathways, and reinforced the general principle that basal ganglia influences are transmitted only to restricted portions of the frontal lobe (even though the striatum receives projections from nearly the entire neocortex). Using the 'motor' circuit as a model, the authors have reexamined the available data on other portions of the basal ganglia-thalamocortical pathways and found that the evidence strongly suggests the existence of at least four additional circuits organized in parallel with the 'motor' circuit. In the discussion that follows, they review some of the anatomic and physiologic features of the 'motor circuit,' as well as the data that support the existence of the other proposed parallel circuits, which they have designated the 'oculomotor,' the 'dorsolateral prefrontal,' the 'lateral orbitofrontal,' and the 'anterior cingulate,' respectively. Each of these five basal ganglia-thalamocortical circuits appears to be centered upon a separate part of the frontal lobe. This list of basal ganglia-thalamocortical circuits is not intended to be exhaustive. In fact, if the conclusions suggested in this review are valid, future investigations might be expected to disclose not only further details (or the need for revisions) of these five circuits, but perhaps also the existence of additional parallel circuits whose identification is currently precluded by a paucity of data.
Article
We present a case of acute hemichorea-hemiballism associated with lacunar infarct documented by computerized tomography scan in the contralateral putamen and caudate nuclei. The pathoanatomic data of similar cases in the literature are reviewed with reference to the location of the responsible lesions. Acute hemichorea-hemiballism is most frequently caused by lacunar infarcts in the basal ganglia contralateral to the dyskinesia.
Article
While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease.
Article
To determine which brain structures are involved in symptomatic unilateral dystonia caused by localized cerebral infarction. Three-dimensional T1-weighted magnetic resonance imaging sequence and stereotactic analysis were used to analyze the topography of the lesions. Stereotactic localization of thalamic lesions was conducted according to the atlas of Hassler with a Voxtool software (Advantage Windows Workstation, General Electric, Milwaukee, Wis) workstation system. Eight patients with hemidystonia, segmental dystonia, or focal dystonia were selected from among 51 consecutive patients (between January 1988 and May 1993) with symptomatic unilateral dystonia. Patients had dystonic spasms (n=4) or myoclonic dystonia (n=4). Lesions associated with dystonic spasms were located in the striatopallidal complex, and those with myoclonic dystonia were in the thalamus contralateral to the dystonia. Lesions of the striatopallidal complex involved the putamen posterior to the anterior commissure in all patients and extended variably into the dorsolateral part of the caudate nucleus, the posterior limb of the internal capsule, or the lateral segment of the globus pallidus. These lesions were centered in the "sensorimotor" part of the striatopallidal complex, with a trend toward a somatotopical distribution. Lesions of the thalamus were located in the ventral intermediate and ventral caudal nuclei, while the ventral oral anterior and posterior nuclei (which receive pallidal efferents) were largely spared. These results suggest that striatopallidal and thalamic dystonia may have different pathophysiologic bases.
Article
The purpose of the study was to describe the range of abnormalities seen on cranial MR images of patients with Wilson's disease and correlate the findings with clinical severity, duration of disease, and duration of neurologic signs and symptoms before treatment. In those patients with serial studies, the changes on MR images were compared with the clinical response. Twenty-five patients with Wilson's disease underwent MR imaging of the brain using conventional spin-echo sequences (n = 25), phase maps (n = 8), and partially refocused interleaved multiple-echo sequences (n = 5). MR imaging findings were abnormal in 22 patients and normal in three patients. The basal ganglia were interpreted as abnormal in 19 (86%) of 22 patients, involving the putamen in 19 (86%), the thalami in 12 (54%), the caudate head in 10 (45%), and the globus pallidus in nine (41%). We found a predilection for involvement of the outer rim of the putamen and the ventral nuclear mass of the thalami. The claustrum was abnormal in three patients. The midbrain was abnormal in 17 (77%) of these 22 patients, affecting predominantly the tegmentum but also the substantia nigra, red nuclei, inferior tectum, and crura. The pons was abnormal in 18 (82%) of 22 patients, and the cerebellum was abnormal in 11 patients (50%), with involvement of the superior and middle cerebellar peduncles. Atrophy was present in 18 (82%) of 22 patients, and cortical white matter changes were apparent in 13 (59%) of 22 patients. The scan of one untreated patient revealed shortening of the T1 relaxation time in the thalami, which was consistent with the paramagnetic effects of copper. Phase maps and partially refocused interleaved multiple-echo sequences performed in eight and five patients, respectively, and used to reveal a susceptibility change induced by iron or copper showed normal findings. We found a significant inverse relationship between severity, but not extent, of change in signal intensity and the length of untreated disease (p = .030) and the total duration of disease (p = .015). The study group was too small to show a correlation with clinical findings. Changes seen on MR images matched the clinical response to treatment in only two of the seven patients who underwent follow-up studies. MR imaging revealed abnormalities in the basal ganglia, cerebral white matter, midbrain, pons, and cerebellum. The paramagnetic effects of copper were detected only in untreated patients. Patients with a longer duration of disease had less severe changes in signal intensity. MR imaging was of limited value in follow-up.
Article
To study consecutive patients with acute or delayed hyperkinetic movement disorders in the Lausanne Stroke Registry. We have identified 29 patients with acute or delayed movement disorders among 2500 patients who had their first-ever acute stroke in the Lausanne Stroke Registry. Department of Neurology, Lausanne University Hospital. Our patients presented with hemichorea-hemiballism (11 patients), hemidystonia (5 patients), stereotypias (2 patients), jerky dystonic unsteady hand (3 patients), asterixis (2 patients), initial limb-shaking (2 patients), bilateral tremor (1 patients), bilateral jaw myoclonus (1 patient), hemiakathisia (1 patient) and dysarthria-dyskinetic hand (1 patient). On neuroimaging a lesion was found in 25 of the 29 cases in the territory of the middle cerebral artery (7 deep, 2 superficial and 2 complete), the posterior cerebral artery (11 patients), both middle and posterior cerebral arteries (2 patients) or the anterior cerebral artery (1 patient). The jerky dystonic unsteady hand syndrome was associated with a specific lesion, an infarct in the territory of the posterior choroidal artery. Presumed small-vessel disease was the commonest cause of stroke (15 patients). Only 3 patients had persistent movements (> 6 months). Hyperkinetic movement disorders are uncommon in acute stroke (1%), the commonest types being hemichorea-hemiballism and hemidystonia. These movement disorders are associated with stroke involving the basal ganglia and adjacent white matter in the territory of the middle or the posterior cerebral artery. The jerky dystonic unsteady hand syndrome is specifically associated with a small infarct in the territory of the posterior choroidal artery. The abnormal movements usually regress spontaneously.
Article
The author describes 30 consecutive patients with unilateral stroke who had asterixis on presentation. The lesion location was as follows: thalamus in 19 (mostly, ventrolateral nucleus), frontal lobe in six, lenticulocapsular area in one, midbrain in two, and the cerebellum in two patients. Four patients had bilateral asterixis, and two patients with cerebellar lesions had ipsilateral asterixis. The asterixis may be caused by the abnormal control of arm posture maintenance due to functional dysregulation of the brainstem-spinal tracts from the cerebello-brainstem-thalamo-frontal lobe system.
Article
Chorea associated with non-ketotic hyperglycemia and high signal intensity lesions on T1-weighted brain magnetic resonance images (C-H-BG) is recognized as a unique syndrome that affects elderly women exclusively. However, its overall clinical features are unclear. The literature describing patients with C-H-BG from 1985 to 2001 was reviewed using MEDLINE. Their clinical features and those of four patients with C-H-BG at this hospital were analyzed. This study included 49 patients from the literature and four patients at this hospital. Their mean age at the onset was 71.1 years (range=22-92 years). Women were affected more frequently than men (men/women=17:30). The mean serum glucose level measured after the onset of chorea was 481.5 mg/dl (ranging from 169 to 1264), HbA1c level was 14.4% (ranging from 9.9 to 19.2), and the serum osmolarity was 305.9 mmol/kg (ranging from 291 to 335). Forty-seven patients developed hemichorea. Six patients developed bilateral chorea, and magnetic resonance imaging (MRI) showed bilateral basal ganglia lesions. MRI showed that putamen was involved in all cases (isolated putamen=31 patients, additional basal ganglia lesions=22 patients). None had lesions confined to the caudate nucleus or the globus pallidus. In all, except one, the anterior limb of the internal capsule was spared. Follow-up MRI studies were performed in 22 patients. In most, hemichorea improved along with the disappearance of the lesions. In 39 patients, chorea had ameliorated completely. The remaining 14 cases showed some improvement during the follow-up period. The chorea recurred in seven patients. C-H-BG is a benign disorder affecting the elderly. It affects men much more frequently than has been reported. The high signal intensity basal ganglia lesion on the T1-weighted brain MRI study was reversible, and correlated with the clinical improvement in chorea.
Article
Introduction The occurrence in adults of abnormal involuntary movements of the limbs on one side has been recorded for a long time. Some of the movements have been like those encountered in the choreas of children and have been called "hemichorea." Others have been ceaseless and violent, have involved the bigger limb joints, and have produced wider movements. These have been called "hemiballism." There has been a tendency to think of the adult hemichoreas and hemiballism as manifestions of the same process, the latter possibly being considered only a severer manifestation of the former.1 Other workers are chary of such a similarity and prefer to think of hemichorea and hemiballism as separate disorders, with probably different etiologies and dissimilar locales of the causative lesions.2 Most observers have concurred in the idea expressed by Whittier3: "Hemiballism is the apparently inevitable symptom in man of destruction localized in the
Article
Hemiballism is a rare movement disorder that presents with unilateral flinging movements of the limbs. In traditional teaching, it has been characterised as almost pathognomonic of a lesion in the subthalamic nucleus (STN). The prognosis was described as grave, with severe disability and death in many cases. However, review of more recent reports shows that the STN is directly involved in only a minority of cases. The prognosis is benign in most cases, with almost all patients responding well to treatment and many having spontaneous remission, although long-term prognosis of cerebrovascular disease may not be so good. There have also been recent insights into the pathophysiology of hemiballism, which have emphasised the importance of altered firing patterns in basal-ganglia structures. Recent studies have pointed to previously unrecognised causes, particularly non-ketotic hyperosmolar hyperglycaemia and complications of HIV infection, that may account for a substantial proportion of cases of hemiballism.
Article
A landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging-based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.
Article
Post-stroke hemichorea is an uncommon involuntary hyperkinetic disorder involving unilateral body parts. The incidence and precise lesion location of post-stroke hemichorea remain unclear. The authors describe 27 consecutive patients with hemichorea after stroke. The incidence of post-stroke hemichorea was 0.54 % (27 out of 5,009 patients). The lesions were located in the caudate and putamen (n = 6), cortex (n = 6), thalamus and subthalamic area (n = 4), subthalamus (n = 4), putamen (n = 3), caudate (n = 2), and the globus pallidus (n = 2). Over the mean follow-up period of 22 months, the hemichorea disappeared in 56% of the patients, while it persisted in others. The rate of disappearance of hemichorea was significantly higher in patients with cortical strokes than in those with subthalamic lesions (P < 0.05). We conclude that hemichorea is a rare manifestation of stroke and most often produced by lenticular lesions followed by subthalamic and cortical lesions. The functional prognosis is better in patients with cortical lesions than those with subthalamic strokes.
Article
Measures of brain activation (e.g., changes in scalp electrical potentials) have become the most popular method for inferring brain function. However, examining brain disruption (e.g., examining behavior after brain injury) can complement activation studies. Activation techniques identify regions involved with a task, whereas disruption techniques are able to discover which regions are crucial for a task. Voxel-based lesion mapping can be used to determine relationships between behavioral measures and the location of brain injury, revealing the function of brain regions. Lesion mapping can also correlate the effectiveness of neurosurgery with the location of brain resection, identifying optimal surgical targets. Traditionally, voxel-based lesion mapping has employed the chi-square test when the clinical measure is binomial and the Student's t test when measures are continuous. Here we suggest that the Liebermeister approach for binomial data is more sensitive than the chi-square test. We also suggest that a test described by Brunner and Munzel is more appropriate than the t test for nonbinomial data because clinical and neuropsychological data often violate the assumptions of the t test. We test our hypotheses comparing statistical tests using both simulated data and data obtained from a sample of stroke patients with disturbed spatial perception. We also developed software to implement these tests (MRIcron), made freely available to the scientific community.