Left Cerebellar Lesions may be Associated with an Increase in Spatial Neglect-like Symptoms.

Each cerebellar hemisphere projects to the contralateral cerebral hemisphere. Previous research suggests a lateralization of cognitive functions in the cerebellum that mirrors the cerebral cortex, with attention/visuospatial functions represented in the left cerebellar hemisphere, and language functions in the right cerebellar hemisphere. Although there is good evidence supporting the role of the right cerebellum with language functions, the evidence supporting the notion that attention and visuospatial functions are left lateralized is less clear. Given that spatial neglect is one of the most common disorders arising from right cortical damage, we reasoned that damage to the left cerebellum would result in increased spatial neglect-like symptoms, without necessarily leading to an official diagnosis of spatial neglect. To examine this disconnection hypothesis, we analyzed neglect screening data (line bisection, cancellation, figure copying) from 20 patients with isolated unilateral cerebellar stroke. Results indicated that left cerebellar patients (n = 9) missed significantly more targets on the left side of cancellation tasks compared to a normative sample. No significant effects were observed for right cerebellar patients (n = 11). A lesion overlap analysis indicated that Crus II (78% overlap), and lobules VII and IX (66% overlap) were the regions most commonly damaged in left cerebellar patients. Our results are consistent with the notion that the left cerebellum may be important for attention and visuospatial functions. Given the poor prognosis typically associated with neglect, we suggest that screening for neglect symptoms, and visuospatial deficits more generally, may be important for tailoring rehabilitative efforts to help maximize recovery in cerebellar patients.

Comprehensive voxel-wise, tract-based, and network lesion mapping reveals unique architectures of right and left visuospatial neglect.

Visuospatial neglect is a common, post-stroke cognitive impairment which is widely considered to be a disconnection syndrome. However, the patterns of disconnectivity associated with visuospatial neglect remain unclear. Here, we had 480 acute stroke survivors [age = 72.8 (SD = 13.3), 44.3% female, 7.5 days post-stroke (SD = 11.3)] undertake routine clinical imaging and standardised visuospatial neglect testing. The data were used to conduct voxel-wise, tract-level, and network-level lesion-mapping analyses aimed at localising the neural correlates of left and right egocentric (body-centred) and allocentric (object-centred) visuospatial neglect. Only minimal anatomical homogeneity was present between the correlates of right and left egocentric neglect across all analysis types. This finding challenges previous work suggesting that right and left visuospatial neglect are anatomically homologous, and instead suggests that egocentric neglect may involve damage to a shared, but hemispherically asymmetric attention network. By contrast, egocentric and allocentric neglect was associated with disconnectivity in a distinct but overlapping set of network edges, with both deficits related to damage across the dorsal and ventral attention networks. Critically, this finding suggests that the distinction between egocentric and allocentric neglect is unlikely to reflect a simple dichotomy between dorsal versus ventral networks dysfunction, as is commonly asserted. Taken together, the current findings provide a fresh perspective on the neural circuitry involved in regulating visuospatial attention, and provide important clues to understanding the cognitive and perceptual processes involved in this common and debilitating neuropsychological syndrome.

"Look straight ahead"-A new test to diagnose spatial neglect by computed tomography.

Spatial neglect is the dominant behavioral disorder after right hemisphere brain lesions. Reliabel diagnosis by formal neuropsychological testing is often achieved only later during hospitalization, leading to delays in targeted therapies. We propose a way to diagnose spatial neglect right at admission. We measured the conjugated eye deviation (CED) on the initial computed tomography (CT) scans, in combination with the verbal instruction "Please look straight ahead" during the scan. The command was implemented in the scanner program and automatically played before a cranial CT started. This prospective study included a total 46 consecutive subjects (16 patients with first ever right brain damage and no spatial neglect, 12 patients with first ever right brain damage and spatial neglect, and 18 healthy controls). The right brain damaged groups were submitted to paper pencil tests to access the diagnosis of a spatial neglect after radiological confirmation of the brain damage during the initial phase of their hospitalisation. This procedure allowed us to define a cut-off value of 14.1 degrees of CED to the ipsilesional side to differentiate right hemispheric stroke patients with versus without spatial neglect with a confidence interval of 99%. This simple addition to a radiological routine procedure provides a new tool to help diagnose spatial neglect at the earliest stage possible and thus offers the possibility of providing patients with optimized rehabilitative therapy from a very early stage on.

The flubbed body: Pathological body size representation in personal neglect.

Personal Neglect (PN) is a disorder in which patients fail to attend or explore the contralateral side of their body. An increasing number of studies have considered PN as a form of body representation disorder frequently observed following damage to parietal areas. The extent and the direction of the body misrepresentation is still unclear with recent studies suggesting a general reduction of contralesional hand size. However, little is known about the specificity of this representation and whether the misrepresentation also generalises to other body parts. We explored the features of the representation of the hands and face in a group of 9 right brain damaged patients with (PN+) and without PN (PN-), when compared to a healthy control group. For this, we used a body size estimation task with pictures, in which patients were required to choose the one that most closely matched the perceived size of their body part. We found that PN + patients showed a labile body representation for both hands and face, having a larger distorted representational range. Interestingly, in comparison with PN + patients and healthy controls, PN- patients also showed misrepresentation of the left contralesional hand which could be related to impaired motor performance of their upper limb. Our findings are discussed within a theoretical framework suggesting a reliance on multisensory integration (body representation, ownership, and motor influences) for an ordered representation of the size of the body.

The neuroanatomy of visuospatial neglect: A systematic review and analysis of lesion-mapping methodology.

While visuospatial neglect is commonly associated with damage to the right posterior parietal cortex, neglect is an anatomically heterogenous syndrome. This project presents a systematic review of 34 lesion-mapping studies reporting on the anatomical correlates of neglect. Specifically, the reported correlates of egocentric versus allocentric, acute versus chronic, personal versus extra-personal, and left versus right hemisphere neglect are summarised. The quality of each included lesion-mapping analysis was then evaluated to identify methodological factors which may help account for the reported variance in correlates of neglect. Overall, the existing literature strongly suggests that egocentric and allocentric neglect represent anatomically dissociable conditions and that the anatomy of these conditions may not be entirely homologous across hemispheres. Studies which have compared the anatomy of acute versus chronic neglect have found that these conditions are associated with distinct lesion loci, while studies comparing the correlates of peripersonal/extrapersonal neglect are split as to whether these neglect subtypes are anatomically dissociable. The included studies employed a wide range of lesion-mapping analysis techniques, each producing results of varying quality and generalisability. This review concludes that the reported underlying anatomical correlates of heterogeneous visuospatial neglect vary considerably. Future, high quality studies are needed to investigate patterns of disconnection associated with clearly defined forms of visuospatial neglect in large and representative samples.

Right hemispheric white matter hyperintensities improve the prediction of spatial neglect severity in acute stroke.

White matter hyperintensities (WMH) are frequently observed in brain scans of elderly people. They are associated with an increased risk of stroke, cognitive decline, and dementia. However, it is unknown yet if measures of WMH provide information that improve the understanding of poststroke outcome compared to only state-of-the-art stereotaxic structural lesion data. We implemented high-dimensional machine learning models, based on support vector regression, to predict the severity of spatial neglect in 103 acute right hemispheric stroke patients. We found that (1) the additional information of right hemispheric or bilateral voxel-based topographic WMH extent indeed yielded a significant improvement in predicting acute neglect severity (compared to the voxel-based stroke lesion map alone). (2) Periventricular WMH appeared more relevant for prediction than deep subcortical WMH. (3) Among different measures of WMH, voxel-based maps as measures of topographic extent allowed more accurate predictions compared to the use of traditional ordinally assessed visual rating scales (Fazekas-scale, Cardiovascular Health Study-scale). In summary, topographic WMH appear to be a valuable clinical imaging biomarker for predicting the severity of cognitive deficits and bears great potential for rehabilitation guidance of acute stroke patients.

Disconnections in personal neglect.

Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory).

Reaction time analysis in patients with mild left unilateral spatial neglect employing the modified Posner task: vertical and horizontal dimensions.

Unilateral spatial neglect (USN) is a common neurological syndrome that develops after a right hemisphere lesion. By examining the performance of the modified Posner task added to the vertical dimensions of the left and right visual fields, we studied whether the lower left area had different neglect symptoms than the other locations. 41 patients with right hemisphere damage were classified into those with mild USN (USN+ ; n = 20) and without USN (USN- ; n = 21). Twenty older participants made up the healthy control (HC; n = 20) group. All participants recorded deficits in the paper-and-pencil tests established for neglect and reaction times in the modified Posner task. In the paper-and-pencil tests, there was no difference in deficit between the upper and lower left visual fields in any of the groups. According to the modified Posner task, the USN+ group exhibited delays in reaction time in the lower left visual field rather than the upper left visual field. Importantly, reaction times were delayed, and USN symptoms persisted, particularly for the lower left quadrant. Our findings imply that the modified Posner task can accurately uncover neglect symptoms in the case of mild USN.

Spatial attention in children with perinatal stroke.

Spatial neglect is a common feature of right hemisphere damage in adults, but less is known about spatial inattention following early brain damage. We used a Posner-based cueing task to examine hemispatial neglect and aspects of attention in children with perinatal stroke in either left (LH) or right hemisphere (RH) and controls. A visual perception task assessed the speed of visual perception. A spatial attention cueing task (the E-task) measured the ability to discriminate the direction of a target stimulus ("E"), when presented on the left or right side of the screen. This task provided indices of performance for attention orienting, disengagement and reorienting. Children with LH lesions had slowed visual perception compared to controls. Children with RH lesions did not demonstrate similar deficits. On the E-task, groups with both LH and RH lesions demonstrated lower accuracy on both left and right sides compared to controls. Children with LH lesions also showed impaired attention orienting and disengagement on left and right sides compared to controls, while children with RH lesions were most impaired in orienting and disengagement on their contralesional side. Children with LH lesions demonstrated more extensive attentional deficits than children with RH lesions. These results suggest that development of spatial attention may require different neural networks than maintenance of attention.

Rehabilitation of somatoparaphrenia with misoplegia: insights from a single case-pilot study.

Somatoparaphrenia lacka ownership of a paralyzed limb, i.e., the illusion that one's limbs belong to someone else. Somatoparaphrenia is one of the many forms of body misperceptions. We report a case of somatoparaphrenia with misoplegia, characterized by the absence of anosognosia for hemiplegia and personal neglect, following a surgical operation for left parietal meningioma. The patient received a novel multidisciplinary treatment, including motor rehabilitation training, traditional physiotherapy and robotic rehabilitation using the Hunova Movendo Technology and psychological counseling. At the end of the training, the patient improved in global cognitive functioning, mood, motor abilities, and the perception of herself and her body, reducing the sense of estrangement and repulsion in the lower right limb. Our result showed the importance of a specific neuropsychological assessment in patients with parietal brain lesions and the usefulness of an integrated psychological and motor approach in rehabilitating patients with somatoparaphrenia, primarily when associated with misoplegia.

Neural mechanisms of psychosis vulnerability and perceptual abnormalities in the ALS-FTD spectrum.

OBJECTIVE: The aims of this study were to (i) explore psychotic experiences across the entire amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum from a clinical and genetic perspective, (ii) determine the rate of abnormal perceptual experiences across the five sensory modalities and (iii) explore the neurobiological factors that lead to psychosis vulnerability in ALS-FTD. METHODS: In a prospective case-controlled study design, 100 participants were enrolled including ALS (n = 37, 24% satisfied criteria for ALS-Plus), ALS-FTD (n = 11), bvFTD (n = 27) and healthy controls (n = 25). Psychotic experiences, perceptual abnormalities and psychosocial factors were determined by means of the clinical interview and carer and patient reports. Voxel-based morphometry analyses determined atrophy patterns in patients experiencing psychosis-like experiences and other perceptual abnormalities. RESULTS: The rates of psychotic experiences and abnormalities of perception in each sensory modality were high across the entire ALS-FTD continuum. The rate was highest in those with C9orf72 expansions. Rates were also high in patients with pure ALS including psychosis measured by carer-based reports (18%) and self-report measures of psychotic-like experiences (21%). In an ENTER regression model, social anxiety and ACE-III scores were the best predictors of psychosis proneness, accounting for 44% of the score variance. Psychosis-like experiences and perceptual abnormalities were associated with a predominantly frontal and temporal pattern of atrophy that extended to the cerebellum and centred on the anterior thalamus. INTERPRETATION: The model for psychosis proneness in ALS-FTD likely includes complex interactions between cognitive, social and neurobiological factors that determine vulnerability to psychosis and that may have relevance for individualised patient management.

Dissociation between visuospatial neglect assessment tasks and its neuroanatomical substrates: a case report.

Visuospatial neglect possesses significant heterogeneity in clinical features and neuroanatomical substrates. Behavioral dissociations on different neglect tasks have been reported in the past, and the investigation of their respective anatomical correlates at cortical and, to a lesser degree, subcortical levels has been attempted in stroke studies. We report a patient with a neoplasm occupying the right ventral post-central gyrus and anterior supramarginal gyrus. The patient was admitted preoperatively with dissociation on the performance of neglect tasks, showing clinical deficits in the line bisection task and clock drawing, but not on the cancelation task. The patient underwent an awake craniotomy for tumor excision. Intraoperative visuospatial mapping was employed by applying direct electrical stimulation (DES) to the supramarginal gyrus and the ventral branch of the superior longitudinal fasciculus (SLF III) during the line bisection task. According to our findings, DES was ineffective at the cortical level, but it induced strong rightward bias when applied subcortically at the SLF III. By combining our preoperative and intraoperative anatomical and clinical data, we suggest that the posterior part of the SLF III might have a distinct role in the perceptual component of neglect. Our findings are discussed within the context of previous literature supporting the notion that particular behavioral features of spatial neglect are mediated by different white-matter connections.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Degenerative dementia with proximal radial and lower vertical spatial neglect.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.

Game theoretical mapping of white matter contributions to visuospatial attention in stroke patients with hemineglect.

White matter bundles linking gray matter nodes are key anatomical players to fully characterize associations between brain systems and cognitive functions. Here we used a multivariate lesion inference approach grounded in coalitional game theory (multiperturbation Shapley value analysis, MSA) to infer causal contributions of white matter bundles to visuospatial orienting of attention. Our work is based on the characterization of the lesion patterns of 25 right hemisphere stroke patients and the causal analysis of their impact on three neuropsychological tasks: line bisection, letter cancellation, and bells cancellation. We report that, out of the 11 white matter bundles included in our MSA coalitions, the optic radiations, the inferior fronto-occipital fasciculus and the anterior cingulum were the only tracts to display task-invariant contributions (positive, positive, and negative, respectively) to the tasks. We also report task-dependent influences for the branches of the superior longitudinal fasciculus and the posterior cingulum. By extending prior findings to white matter tracts linking key gray matter nodes, we further characterize from a network perspective the anatomical basis of visual and attentional orienting processes. The knowledge about interactions patterns mediated by white matter tracts linking cortical nodes of attention orienting networks, consolidated by further studies, may help develop and customize brain stimulation approaches for the rehabilitation of visuospatial neglect.

Anton's Syndrome associated with autotopagnosia.

We describe an unusual case of a 68-year-old male affected by cerebral amyloid angiopathy and cortical blindness associated with Anton's syndrome. In addition, our patient presented with autotopagnosia, a form of agnosia characterized by loss of body spatial representation. Neuropsychological assessment evidenced cognitive impairment. Magnetic Resonance Imaging showed hemorrhagic foci in the left occipital and right occipito-parietal lobe, paratrigonal white matter, and post-ischemic parenchymal gliosis. The pattern-reversal of visual evoked potentials were indicative bilateral visual pathway of integrity of the. After a neurological damage, patients could show a denial of their own deficit; however, the association between anosognosia and autotopagnosia represents a rare neurological condition. The simultaneous onset of unusual neuropsychological syndromes could be related to involvement of a complex brain network.

Higher Cortical Visual Disorders.

PURPOSE OF REVIEW: This article reviews the disorders that result from disruption of extrastriate regions of the cerebral cortex responsible for higher visual processing. For each disorder, a historical perspective is offered and relevant neuroscientific studies are reviewed. RECENT FINDINGS: Careful analysis of the consequences of lesions that disrupt visual functions such as facial recognition and written language processing has improved understanding of the role of key regions in these networks. In addition, modern imaging techniques have built upon prior lesion studies to further elucidate the functions of these cortical areas. For example, functional MRI (fMRI) has identified and characterized the response properties of ventral regions that contribute to object recognition and dorsal regions that subserve motion perception and visuospatial attention. Newer network-based functional imaging studies have shed light on the mechanisms behind various causes of spontaneous visual hallucinations. SUMMARY: Understanding the regions and neural networks responsible for higher-order visual function helps the practicing neurologist to diagnose and manage associated disorders of visual processing and to identify and treat responsible underlying disease.

Longitudinal progression of posterior cortical atrophy over 11 years: Relationship between lesion topology and clinical deficits.

Posterior cortical atrophy (PCA) is a rare form of dementia primarily characterized by slowly progressing deterioration of visual processing corresponding to atrophy in the posterior parietal and occipital cortices with less prominent memory loss than are usually seen in other forms of dementia such as Alzheimer's Disease (AD). In the present case report, we describe longitudinal data over a period of 11 years regarding clinical and neuropsychological impairments and their relation to the location and extent of cortical changes related to higher order visual processing in a patient with posterior cortical atrophy. In our patient, visual processing deficits concerning space, motion and object perception emerged at the age of 50 and continued to worsen. By the age of 58, while the perception of contrast, color and figure-ground separation appeared undisturbed the patient exhibited pronounced dorsal- and ventral-related visual deficits, which continued to worsen with age. The patient's MRI scans over the course of the disease revealed increasing circumscribed and bilateral atrophy of the parietal and occipital cortices, with a right-sided predominance. The specific localization of cortical atrophy, the slow progression characterized by visual processing deficits and relatively preserved memory were the main criteria for the diagnosis of posterior cortical atrophy. The case report also highlights the importance of an early extensive neurological and neuropsychological evaluation of visual deficits that occur without the presence of ophthalmological disease.

Brain Activations During Optokinetic Stimulation in Acute Right-Hemisphere Stroke Patients and Hemispatial Neglect: An fMRI Study.

Objective. Leftward optokinetic stimulation (OKS) is a promising therapeutic approach for right-hemisphere stroke patients with left hemispatial neglect. We questioned whether the putative neural basis is an activation of frontoparietal brain regions involved in the control of eye movements and spatial attention. Methods. We used functional magnetic resonance imaging to investigate brain activations during OKS in acute right-hemisphere stroke patients (RHS, n = 19) compared with healthy control subjects (HC, n = 9). Based on neuropsychological testing we determined the ipsilesional attention bias in all RHS patients, 11 showed manifest hemispatial neglect. Results. In HC subjects, OKS in either direction led to bilateral activation of the visual cortex (V1-V4), frontal (FEF) and supplementary (SEF) eye fields, intraparietal sulcus (IPS), basal ganglia, and thalamus. RHS patients' activations were generally reduced compared with HC. Nevertheless, leftward OKS bilaterally activated the visual cortex (V1-V4), FEF, SEF, IPS, and thalamus. The neural response to OKS was negatively correlated with patients' behavioral impairment: The greater the individual attention bias/neglect the weaker the brain activations. Conclusion. In RHS patients, leftward OKS activates frontoparietal regions (FEF, IPS) that are spared from structural brain damage and functionally involved in both oculomotor control and spatial attention. This may provide a neural basis for the known therapeutic effects of OKS on hemispatial neglect. In acute stroke stages, reduced activation levels correlating with neglect severity indicate functional downregulation of the underlying dorsal attention network. Therefore, chronic RHS patients with less severe neglect after recovery of network disturbances may be more suitable candidates for OKS rehabilitation.