Network Localization of Awareness in Visual and Motor Anosognosia.

OBJECTIVE: Unawareness of a deficit, anosognosia, can occur for visual or motor deficits and lends insight into awareness itself; however, lesions associated with anosognosia occur in many different brain locations. METHODS: We analyzed 267 lesion locations associated with either vision loss (with and without awareness) or weakness (with and without awareness). The network of brain regions connected to each lesion location was computed using resting-state functional connectivity from 1,000 healthy subjects. Both domain specific and cross-modal associations with awareness were identified. RESULTS: The domain-specific network for visual anosognosia demonstrated connectivity to visual association cortex and posterior cingulate while motor anosognosia was defined by insula, supplementary motor area, and anterior cingulate connectivity. A cross-modal anosognosia network was defined by connectivity to the hippocampus and precuneus (false discovery rate p < 0.05). INTERPRETATION: Our results identify distinct network connections associated with visual and motor anosognosia and a shared, cross-modal network for awareness of deficits centered on memory-related brain structures. ANN NEUROL 2023;94:434-441.

Generalized anosognosia, anosodiaphoria, and visual hallucinations with bilateral enucleation after severe bifrontal brain injury: a case report describing similarities with and differences from Anton syndrome.

Visual anosognosia, associated with confabulations and cortical blindness in the context of occipital lobe injury, is known as Anton syndrome. Patients with this syndrome strongly deny their vision loss and confabulate to compensate for both visual loss and memory impairments. In this article, we present a case of a patient with some similarities to Anton syndrome, however, with several differences in clinical presentation. Bifrontal brain injury, bilateral enucleation, affective indifference (anosodiaphoria), generalized anosognosia, and the conviction that vision will resume mark clear clinical differences with Anton syndrome. Differentiating these findings from Anton syndrome will help occupational therapists, neuropsychologists, speech-language pathologists, physical therapists, and physicians when assessing frontal lobe brain injury with total and partial visual loss. This case demonstrates that visual anosognosia and confabulations can occur without occipital lobe dysfunction or cortical blindness.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

The effect of offline anosognosia for hemispatial neglect on neglect rehabilitation in patients with subacute and chronic right hemispheric brain injury. A retrospective cohort study.

CLINICAL TRIALS REGISTRATION NUMBER: NCT05145855.

Effects of prism adaptation and visual scanning training on perceptual and response bias in unilateral spatial neglect.

In some patients with unilateral spatial neglect, symptoms reflect impaired lateralized spatial attention and representation (perceptual bias) whereas in others the inability to respond to stimuli located in contralesional space (response bias). Here, we investigated whether prismatic adaptation (PA) and visual scanning training (VST) differentially affect perceptual and response bias and whether rehabilitation outcome depends on the type of bias underlying symptoms. Two groups of neglect patients in the subacute phase were evaluated before, immediately after, and two weeks following 10 days of PA (n = 9) or VST (n = 9). Standard neuropsychological tests (i.e., Behavioural Inattentional Test, Diller cancellation test, and Line Bisection test) were administered to assess neglect symptoms, while the Landmark task was used to disentangle perceptual and response biases. Performance on the Landmark task revealed that PA was more effective in improving the perceptual bias, while VST mainly modulated the response bias. Neuropsychological tests performance suggested that VST is better suited to modulate neglect in patients with response bias, while PA may be effective in patients with both types of bias. These findings may offer novel insights into the efficacy of PA and VST in the rehabilitation of perceptual and response biases in patients with neglect.

Unilateral Spatial Neglect May Not Be Detected by Performance-Based Functional Neglect Assessment.

IMPORTANCE: Unilateral spatial neglect (neglect) poststroke is disabling. It is critical that people with neglect are identified so that treatment can be provided to maximize independence. However, there is some evidence to suggest that existing assessments may not adequately measure neglect. It is unclear whether assessments also fail to identify people with neglect entirely. OBJECTIVE: To determine whether there are stroke survivors who self-report neglect symptoms that are not detected by therapist-rated assessments and to compare self-report and therapist-ratings. DESIGN: Cross-sectional study. SETTING: U.S. university research center. PARTICIPANTS: Unilateral stroke survivors (N = 133). INTERVENTION: Not applicable. OUTCOMES AND MEASURES: The Catherine Bergego Scale (CBS) was administered to participants and scored by a trained occupational therapist. The parallel self-evaluation anosognosia form was also administered to participants to self-report and rate neglect symptoms. RESULTS: Forty-eight participants (36.1%) were classified as without neglect on the basis of therapist-rated total CBS scores, yet 30 (62.5%) of these 48 participants reported symptoms of neglect on the CBS self-evaluation anosognosia form. There was a significant difference (p < .001) between therapist-rated and self-rated total CBS scores. CONCLUSIONS AND RELEVANCE: Our results indicate that many stroke survivors report some level of disability associated with neglect yet do not meet the criteria to be classified as having neglect according to a commonly used therapist-rated performance-based measure. Plain-Language Summary: The findings of this study contribute to the evidence that existing assessments used by occupational therapists to measure performance-based neglect may not always detect neglect symptoms comprehensively in people poststroke. The finding also suggest that we may be missing neglect symptoms entirely. Occupational therapists should consider using various methods to assess for neglect, including patient self-report and comprehensive occupational profiles. Clinicians should also thoroughly screen all clients with stroke for neglect, regardless of lesion location.

Visual imagery deficits in posterior cortical atrophy.

Visual imagery has a close overlapping relationship with visual perception. Posterior cortical atrophy (PCA) is a neurodegenerative syndrome marked by early impairments in visuospatial processing and visual object recognition. We asked whether PCA would therefore also be marked by deficits in visual imagery, tested using objective forced-choice questionnaires, and whether imagery deficits would be selective for certain properties. We recruited four patients with PCA and a patient with integrative visual agnosia due to bilateral occipitotemporal strokes for comparison. We administered a test battery probing imagery for object shape, size, colour lightness, hue, upper-case letters, lower-case letters, word shape, letter construction, and faces. All subjects showed significant impairments in visual imagery, with imagery for lower-case letters most likely to be spared. We conclude that PCA subjects can show severe deficits in visual imagery. Further work is needed to establish how frequently this occurs and how early it can be found.

Discriminative value of different combinations of tests to detect unilateral neglect in patients with right hemisphere damage.

BACKGROUND AND PURPOSE: This study was undertaken to assess the most sensitive combination of tests to detect peripersonal unilateral neglect (UN) after stroke. METHODS: The present study is a secondary analysis of a previously reported multicentric study of 203 individuals with right hemisphere damage (RHD), mainly subacute stroke, 11 weeks postonset on average, and 307 healthy controls. A battery of seven tests, providing 19 age- and education-adjusted z-scores, were given: the bells test, line bisection, figure copying, clock drawing, overlapping figures test, and reading and writing. Statistical analyses used a logistic regression and a receiver operating characteristic (ROC) curve after adjustment on demographic variables. RESULTS: A combination of four z-scores based on the following three tests provided good discrimination of patients with RHD from matched healthy controls: the starting point and the difference between the number of omissions on left and right sides from the bells test, rightward deviation in bisection of long lines (20 cm), and left-sided omissions in a reading task. The area under the ROC curve was 0.865 (95% confidence interval = 0.83-0.901), with sensitivity = 0.68, specificity = 0.95, accuracy = 0.85, positive predictive value = 0.90, and negative predictive value = 0.82. CONCLUSIONS: The most sensitive and parsimonious combination of tests to detect UN after stroke relies on four scores from three simple tests (bells test, line bisection, and reading). Future study is warranted to assess its ability to account for the functional difficulties of UN in daily life in the patient's actual environment.

The Auditory Agnosias: a Short Review of Neurofunctional Evidence.

PURPOSE OF REVIEW: To investigate the neurofunctional correlates of pure auditory agnosia and its varieties (global, verbal, and nonverbal), based on 116 anatomoclinical reports published between 1893 and 2022, with emphasis on hemispheric lateralization, intrahemispheric lesion site, underlying cognitive impairments. RECENT FINDINGS: Pure auditory agnosia is rare, and observations accumulate slowly. Recent patient reports and neuroimaging studies on neurotypical subjects offer insights into the putative mechanisms underlying auditory agnosia, while challenging traditional accounts. Global auditory agnosia frequently results from bilateral temporal damage. Verbal auditory agnosia strictly correlates with language-dominant hemisphere lesions. Damage involves the auditory pathways, but the critical lesion site is unclear. Both the auditory cortex and associative areas are reasonable candidates, but cases resulting from brainstem damage are on record. The hemispheric correlates of nonverbal auditory input disorders are less clear. They correlate with unilateral damage to either hemisphere, but evidence is scarce. Based on published cases, pure auditory agnosias are neurologically and functionally heterogeneous. Phenotypes are influenced by co-occurring cognitive impairments. Future studies should start from these facts and integrate patient data and studies in neurotypical individuals.

We should be screening for benign paroxysmal positional vertigo (BPPV) in all older adults at risk of falling: a commentary on the World Falls Guidelines.

Benign paroxysmal positional vertigo (BPPV) is amongst the commonest causes of dizziness and falls in older adults. Diagnosing and treating BPPV can reduce falls, and thereby reduce fall-related morbidity and mortality. Recent World Falls Guidelines recommend formal assessment for BPPV in older adults at risk of falling, but only if they report vertigo. However, this recommendation ignores the data that (i) many older adults with BPPV experience dizziness as vague unsteadiness (rather than vertigo), and (ii) others may experience no symptoms of dizziness at all. BPPV without vertigo is due to an impaired vestibular perception of self-motion, termed 'vestibular agnosia'. Vestibular agnosia is found in ageing, neurodegeneration and traumatic brain injury, and results in dramatically increased missed BPPV diagnoses. Patients with BPPV without vertigo are typically the most vulnerable for negative outcomes associated with this disorder. We thus recommend simplifying the World Falls Guidelines: all older adults (>60 years) with objective or subjective balance problems, irrespective of symptomatic complaint, should have positional testing to examine for BPPV.

En kvinne i 60-årene som ikke lenger gjenkjente det hun så.

BACKGROUND: Neurological disorders can present with a vast array of visual disturbances. The constellation of symptoms and findings in this patient prompted workup for unusual causes of both stroke and neurodegenerative disorder. CASE PRESENTATION: A woman in her sixties presented with visual disturbances, followed by weakness in her right arm and aphasia three days later. Her close acquaintances had suspected progressive cognitive decline during the previous year. CT and MRI showed an occluded left posterior cerebral artery with a subacute occipito-temporal infarction. The finding of extensive white matter lesions and segmental arterial vasoconstriction necessitated further workup of vasculitis and hereditary small vessel disease, which were ruled out. The stroke aetiology was considered to be atherosclerotic intracranial large vessel disease. FDG-PET scan revealed decreased metabolism in the left hemisphere, and cerebrospinal biomarkers had slightly decreased beta-amyloid. The findings were suggestive of early Alzheimer's disease or primary progressive aphasia, but currently inconclusive. INTERPRETATION: Based on clinical-anatomical correlation, the patient's visual disturbances, in this case right hemianopsia and object agnosia, were solely related to the stroke and not to a neurodegenerative disorder. Knowledge and interpretation of visual agnosias can in many cases be clinically valuable.

Placebo Analgesia Reduces Costly Prosocial Helping to Lower Another Person's Pain.

Painkiller administration lowers pain empathy, but whether this also reduces prosocial behavior is unknown. In this preregistered study, we investigated whether inducing analgesia through a placebo painkiller reduced effortful helping. When given the opportunity to reduce the pain of another person, individuals experiencing placebo analgesia (n = 45 adults from Austria; 21 male, 24 female) made fewer prosocial choices at the lowest helping level and exerted less physical effort when helping, compared with controls whose pain sensitivity was unaltered (n = 45; 21 male, 24 female). Self-reported empathic unpleasantness positively correlated with prosocial choices across the whole sample. While not replicating group differences in empathy, a mediation analysis revealed that the level of unpleasantness to other people's pain fully mediated the effect of placebo analgesia on prosocial choices. Given the importance of prosociality for social cohesion, these findings have broad potential implications both for individuals under the influence of painkillers and for society at large.

Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations.

BACKGROUND AND PURPOSE: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. METHODS: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. RESULTS: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. CONCLUSIONS: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

Vestibular agnosia in traumatic brain injury and its link to imbalance.

Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment-from reflex to perception-is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a 'vestibular agnosia'. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants' report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls' average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls' mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses.

Reflected image processing abnormalities in dementia - a case series and review.

Dementia is a neurodegenerative condition with progressive decline in cognitive faculties and associated with different clinical phenomena. Mirror phenomenon in terms of both mirror agnosia and mirror image agnosia wherein there is difficulty in processing and perception of reflected images is not uncommonly seen, and understanding the same can contribute to early diagnosis and prognostication. We report two elderly women with Alzheimer's dementia and frontotemporal dementia, respectively, presenting with features of abnormalities in mirror image processing. The former had features of both mirror agnosia and mirror image agnosia and the latter had predominantly features of mirror image agnosia with preoccupation with her mirror image. Understanding neuroanatomical networks underlying these phenomena can help early identification and subtyping dementia. Clinically differentiating these phenomena from psychotic symptoms of dementia can help in initiating appropriate non-pharmacological measures rather than resorting to use of psychotropics, the use of which may be counterproductive.

Partial Balint's syndrome and left homonymous hemianopsia presenting after resection of a right occipito-parietal glioblastoma.

A 66-year-old left-handed male was admitted to our acute inpatient rehabilitation (AIR) unit following a resection of the right occipito-parietal glioblastoma. He presented with symptoms of horizontal oculomotor apraxia, contralateral optic ataxia and left homonymous hemianopsia. We diagnosed this patient with partial Bálint's syndrome (BS)- oculomotor apraxia, optic ataxia but not simultanagnosia. BS is typically caused by bilateral posterior parietal lesions, but we here describe a unique case due toresection of a right intracranial tumor. A short AIR stay allowed our patient to learn how to compensate for visuomotor and visuospatial deficits, and improved his quality of life significantly.

Walking through a narrow opening improves collision avoidance behavior in a patient with stroke and unilateral spatial neglect: an ABA single-case design.

We investigated the effect of a 3-week intervention-wherein a patient with unilateral spatial neglect walks through a narrow opening while entering from the contralesional side-to improve walking ability or ADL. A 66-year-old man was diagnosed with right parietal subcortical hemorrhage. We used an ABA single-case design; period B was set as the intervention. The intervention improved the continuous walking distance and balance ability and decreased the number of collisions when walking through the narrow opening; however, it exerted minimal effect on ADL. Thus, the intervention may effectively improve continuous physical or spatial attention behavior, regardless of ADL improvement.

Visuomotor misalignment induced through immersive virtual reality to improve spatial neglect: a case-series study.

One evidence-based treatment for spatial neglect is prism adaptation (PA) treatment. PA after-effects, i.e., the implicit shifts in the arm reaching position toward the neglected side of space after prism removal, are considered fundamental to PA treatment effects. In the present study, the arm reaching position was shifted through a visuomotor misalignment procedure using immersive virtual reality (VR). To examine whether this procedure might have a beneficial impact on spatial neglect, we conducted a multi-baseline experiment in three individuals with chronic left-sided neglect post stroke. Improved spatial neglect was observed in all participants immediately after 5 sessions with two rounds in each. Two participants demonstrated lasting or continuous improvement two weeks later. Participants' pattern of brain lesions did not appear to clearly explain performance differences. The findings suggest that VR-induced visuomotor misalignment may improve spatial neglect immediately after a multi-session treatment course. The optimal number of sessions will be determined by future studies with a larger sample size, which may also elucidate the number of sessions sufficient for sustained improvement in most patients. Further investigations will identify the neural mechanisms underlying VR-induced visuomotor misalignment, which may or may not be identical to PA after-effects.

Superior Parietal Lobule: A Role in Relative Localization of Multiple Different Elements.

Simultanagnosia is an impairment in processing multiple visual elements simultaneously consecutive to bilateral posterior parietal damage, and neuroimaging data have specifically implicated the superior parietal lobule (SPL) in multiple element processing. We previously reported that a patient with focal and bilateral lesions of the SPL performed slower than controls in visual search but only for stimuli consisting of separable lines. Here, we further explored this patient's visual processing of plain object (colored disk) versus object consisting of separable lines (letter), presented in isolation (single object) versus in triplets. Identification of objects was normal in isolation but dropped to chance level when surrounded by distracters, irrespective of eccentricity and spacing. We speculate that this poor performance reflects a deficit in processing objects' relative locations within the triplet (for colored disks), aggravated by a deficit in processing the relative location of each separable line (for letters). Confirming this, performance improved when the patient just had to detect the presence of a specific colored disk within the triplets (visual search instruction), while the inability to identify the middle letter was alleviated when the distracters were identical letters that could be grouped, thereby reducing the number of ways individual lines could be bound.

Pure word deafness: a case report of an atypical manifestation of Alzheimer's disease.

BACKGROUND: Auditory agnosia refers to the impairments in sound recognition despite intact hearing and written language abilities. When auditory agnosia is specific to spoken language, it can be indicated as pure word deafness (PWD), which is characterized by the isolated difficulty in understanding spoken language, despite preserved reading comprehension, recognition of nonverbal sounds, and production of written and spoken language. CASE: A middle-aged man with a high level of education developed a progressive speech disorder initially characterized by isolated phonemic errors during spontaneous speech and later enriched by difficulties in comprehending long sentences. The patient's past medical history was unremarkable except for hypertension. The neuropsychological picture was suggestive of PWD, while cerebrospinal fluid (CSF) analyses lead to a biomarker-based diagnosis of Alzheimer's disease (AD). PWD remained the prevalent cognitive deficit over the subsequent 4 years. CONCLUSIONS: This case report shows that the presence of isolated auditory agnosia or PWD should prompt consideration of a diagnosis of AD. It also suggests that the spectrum of atypical presentations of early-onset AD may be larger than what we currently think.