Cortical and subcortical substrates of working memory in the right hemisphere: A connectome-based lesion-symptom mapping study.

Working Memory (WM) is a cognitive system whose crucial role is to temporarily hold and manipulate information. Early studies suggest that verbal WM is typically associated with left hemisphere (LH) brain regions, while the processing of visuospatial information in WM more specifically depends on the right hemisphere (RH). However, recent evidence suggests a more complex network involving both hemispheres' prefrontal and posterior parietal cortices in these processes. Unfortunately, previous lesion studies often examined only one modality (either verbal, or visuospatial) or one hemisphere, which limits the possible conclusions regarding non-lateralized hemispheric involvement. Using connectome-based lesion-symptom mapping on a large sample of patients with left (LBD) and right (RBD) focal brain damage, we examined whether gray matter damage and white matter disconnections predict deficits of WM updating in an N-back task. Patients were examined with two WM tasks that differed regarding modality (verbal, spatial) and cognitive load (1-back, 2-back). Behavioral outcomes indicated that RBD patients showed significant deficits in WM updating, regardless of task modality or load. This observation was supported by whole-brain voxel-based analysis, revealing associations between WM deficits and gray matter clusters in the RH. Specifically, damage to the right lateral frontal cortex including the brain region homologous to Broca's area was associated with verbal WM deficits, while damage to the right inferior parietal lobe and posterior temporal cortex predicted spatial WM deficits. Additionally, white matter analyses identified severely impacted tracts in the RH, predicting deficits in both verbal and spatial WM. Our findings suggest that the mental manipulation of both verbal and visuospatial information in WM updating relies on the integrity of the RH, irrespective of the specific type of information held in mind.

Improving Lesion Location Reproducibility in Handheld Breast Ultrasound.

Interoperator variability in the reproducibility of breast lesions found by handheld ultrasound (HHUS) can significantly interfere with clinical care. This study analyzed the features associated with breast mass position differences during HHUS. The ability of operators to reproduce the position of small masses and the time required to generate annotations with and without a computer-assisted scanning device (DEVICE) were also evaluated. This prospective study included 28 patients with 34 benign or probably benign small breast masses. Two operators generated manual and automated position annotations for each mass. The probe and body positions were systematically varied during scanning with the DEVICE, and the features describing mass movement were used in three logistic regression models trained to discriminate small from large breast mass displacements (cutoff: 10 mm). All models successfully discriminated small from large breast mass displacements (areas under the curve: 0.78 to 0.82). The interoperator localization precision was 6.6 ± 2.8 mm with DEVICE guidance and 19.9 ± 16.1 mm with manual annotations. Computer-assisted scanning reduced the time to annotate and reidentify a mass by 33 and 46 s on average, respectively. The results demonstrated that breast mass location reproducibility and exam efficiency improved by controlling operator actionable features with computer-assisted HHUS.

Hayling and stroop tests tap dissociable deficits and network-level neural correlates.

Although many executive function screens have been developed, it is not yet clear whether these assessments are equally effective in detecting post-stroke deficits of initiation and inhibition. This study presents a comparative analysis of the Stroop and Hayling tests aiming to evaluate whether these tests measure the same underlying cognitive functions and to identify the neural correlates of the deficits detected by both tasks. Sixty six stroke survivors and 70 healthy ageing controls completed the Hayling and Stroop tests. Stroke patients were found to exhibit qualitative performance differences across analogous Stroop and Hayling Test metrics intended to tap initiation and inhibition. The Stroop test was found to have high specificity to abnormal performance, but low sensitivity relative to the Hayling Test. Minimal overlap was present between the network-level correlates of analogous Stroop and Hayling Test metrics. Hayling Task strategy use metrics were significantly associated with distinct patterns of disconnection in stroke survivors, providing novel insight into the neural correlates of fine-grained behavioural patterns. Overall, these findings strongly suggest that the functions tapped by the Stroop and Hayling Test are both behaviourally and anatomically dissociable. The Hayling Test was found to offer improved sensitivity and detail relative to the Stroop test. This novel demonstration of the Hayling Test within the stroke population suggests that this task represents an effective measure for quantifying post-stroke initiation and inhibition deficits.

Emotional processing impairments in patients with insula lesions following stroke.

Functional imaging has helped to understand the role of the human insula as a major processing network for integrating input with the current state of the body. However, these studies remain at a correlative level. Studies that have examined insula damage show lesion-specific performance deficits. Case reports have provided anecdotal evidence for deficits following insula damage, but group lesion studies offer a number of advances in providing evidence for functional representation of the insula. We conducted a systematic literature search to review group studies of patients with insula damage after stroke and identified 23 studies that tested emotional processing performance in these patients. Eight of these studies assessed emotional processing of visual (most commonly IAPS), auditory (e.g., prosody), somatosensory (emotional touch) and autonomic function (heart rate variability). Fifteen other studies looked at social processing, including emotional face recognition, gaming tasks and tests of empathy. Overall, there was a bias towards testing only patients with right-hemispheric lesions, making it difficult to consider hemisphere specificity. Although many studies included an overlay of lesion maps to characterise their patients, most did not differentiate lesion statistics between insula subunits and/or applied voxel-based associations between lesion location and impairment. This is probably due to small group sizes, which limit statistical comparisons. We conclude that multicentre analyses of lesion studies with comparable patients and performance tests are needed to definitively test the specific function of parts of the insula in emotional processing and social interaction.

Cerebral small vessel disease and stroke: Linked by stroke aetiology, but not stroke lesion location or size.

BACKGROUND: Cerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. METHODS: In a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. RESULTS: With increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. CONCLUSIONS: In patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

Brain connectivity networks underlying resting heart rate variability in acute ischemic stroke.

Acute strokes can affect heart rate variability (HRV), the mechanisms how are not well understood. We included 42 acute stroke patients (2-7 days after ischemic stroke, mean age 66 years, 16 women). For analysis of HRV, 20 matched controls (mean age 60.7, 10 women) were recruited. HRV was assessed at rest, in a supine position and individual breathing rhythmus for 5 min. The coefficient of variation (VC), the root mean square of successive differences (RMSSD), the powers of low (LF, 0.04-0.14 Hz) and high (HF, 0.15-0.50 Hz) frequency bands were extracted. HRV parameters were z-transformed related to age- and sex-matched normal subjects. Z-values < -1 indicate reduced HRV. Acute stroke lesions were marked on diffusion-weighted images employing MRIcroN and co-registered to a T1-weighted structural volume-dataset. Using independent component analysis (ICA), stroke lesions were related to HRV. Subsequently, we used the ICA-derived lesion pattern as a seed and estimated the connectivity between these brain regions and seven common functional networks, which were obtained from 50 age-matched healthy subjects (mean age 68.9, 27 women). Especially, LF and VC were frequently reduced in patients. ICA revealed one covarying lesion pattern for LF and one similar for VC, predominantly affecting the right hemisphere. Activity in brain areas corresponding to these lesions mainly impact on limbic (r = 0.55 ± 0.08) and salience ventral attention networks (0.61 ± 0.10) in the group with reduced LF power (z-score < -1), but on control and default mode networks in the group with physiological LF power (z-score > -1). No different connectivity could be found for the respective VC groups. Our results suggest that HRV alteration after acute stroke might be due to affecting resting-state brain networks.

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.

White matter tract disconnection in Gerstmann's syndrome: Insights from a single case study.

It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.

Structural integrity of the insula and emotional facial recognition performance following stroke.

The role of the human insula in facial emotion recognition is controversially discussed, especially in relation to lesion-location-dependent impairment following stroke. In addition, structural connectivity quantification of important white-matter tracts that link the insula to impairments in facial emotion recognition has not been investigated. In a case-control study, we investigated a group of 29 stroke patients in the chronic stage and 14 healthy age- and gender-matched controls. Lesion location of stroke patients was analysed with voxel-based lesion-symptom mapping. In addition, structural white-matter integrity for tracts between insula regions and their primarily known interconnected brain structures was quantified by tractography-based fractional anisotropy. Our behavioural analyses showed that stroke patients were impaired in the recognition of fearful, angry and happy but not disgusted expressions. Voxel-based lesion mapping revealed that especially lesions centred around the left anterior insula were associated with impaired recognition of emotional facial expressions. The structural integrity of insular white-matter connectivity was decreased for the left hemisphere and impaired recognition accuracy for angry and fearful expressions was associated with specific left-sided insular tracts. Taken together, these findings suggest that a multimodal investigation of structural alterations has the potential to deepen our understanding of emotion recognition impairments after stroke.

Anatomical and functional predictors of disorientation after first-ever brain damage.

BACKGROUND AND OBJECTIVES: Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is associated with medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) - a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury. METHODS: Participants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation. RESULTS: Eighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = -0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus. CONCLUSION: Disorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.

The return of the lesion for localization and therapy.

Historically, pathological brain lesions provided the foundation for localization of symptoms and therapeutic lesions were used as a treatment for brain diseases. New medications, functional neuroimaging and deep brain stimulation have led to a decline in lesions in the past few decades. However, recent advances have improved our ability to localize lesion-induced symptoms, including localization to brain circuits rather than individual brain regions. Improved localization can lead to more precise treatment targets, which may mitigate traditional advantages of deep brain stimulation over lesions such as reversibility and tunability. New tools for creating therapeutic brain lesions such as high intensity focused ultrasound allow for lesions to be placed without a skin incision and are already in clinical use for tremor. Although there are limitations, and caution is warranted, improvements in lesion-based localization are refining our therapeutic targets and improved technology is providing new ways to create therapeutic lesions, which together may facilitate the return of the lesion.

Disconnection in a left-hemispheric temporo-parietal network impairs multiplication fact retrieval.

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

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.

The role of cognitive estimation in understanding the mental states of others.

Previous studies have emphasized the critical role of the prefrontal cortex in cognitive estimation and theory of mind, however, none of them has questioned the possible role of cognitive estimation processes in understanding the mental states of others. In this study, we compared 30 patients with focal prefrontal cortex damage and 30 control subjects matched by gender, age, and education level on their performances on a cognitive estimation task and two tasks assessing theory of mind: the "Faux-Pas" task and the Reading the Mind in the Eyes task. The results showed that patients were significantly impaired compared with control subjects on both abilities of cognitive estimation and theory of mind. Moreover, regression analyses showed that performance on theory of mind was predicted by the scores on cognitive estimation. Finally, using voxel-based lesion analysis, we identified a partially common bilaterally distributed prefrontal network involved in both these domains centred within the ventral and dorsomedial areas with extension to the dorsolateral prefrontal cortex.

Visualization of Resected Area in Endonasal Endoscopic Approach versus Transcranial Approach for Skull Base Meningiomas by Voxel-Based-Lesion Mapping.

BACKGROUND: We aimed to evaluate the resected area of endonasal endoscopic approach (EEA) and transcranial approach (TCA) for skull base meningiomas (SBMs) using voxel-based-lesion mapping and visualized the appropriate tumor location in each approach. METHODS: We retrospectively examined 182 patients with SBMs who underwent tumor resection in our hospital between 2014 and 2019. Pre- and post-operative SBMs were manually delineated on MRI to create the voxels-of-interest (VOIpre and VOIpost) and were registered onto the normalized brain (normalized VOIpre and normalized VOIpost). The resected map was created by subtracting normalized VOIpost from the normalized VOIpre divided by the number of cases. The resected maps of TCA and EEA were compared by subtracting them. RESULTS: Twenty patients underwent EEA and 135 patients underwent TCA. The tumor resected map demonstrated that the resected area of EEA frequently accumulated on the central skull base, while that of TCA accumulated near the central skull base. The border of both approaches matched the circle that connects neural foramens at the skull base. CONCLUSIONS: The resected area of SBMs by EEA and TCA was well visualized by voxel-based-lesion mapping. The circle connecting the neural foramens was the border of EEA and TCA.

The connectional anatomy of visual mental imagery: evidence from a patient with left occipito-temporal damage.

Most of us can use our "mind's eye" to mentally visualize things that are not in our direct line of sight, an ability known as visual mental imagery. Extensive left temporal damage can impair patients' visual mental imagery experience, but the critical locus of lesion is unknown. Our recent meta-analysis of 27 fMRI studies of visual mental imagery highlighted a well-delimited region in the left lateral midfusiform gyrus, which was consistently activated during visual mental imagery, and which we called the Fusiform Imagery Node (FIN). Here, we describe the connectional anatomy of FIN in neurotypical participants and in RDS, a right-handed patient with an extensive occipito-temporal stroke in the left hemisphere. The stroke provoked right homonymous hemianopia, alexia without agraphia, and color anomia. Despite these deficits, RDS had normal subjective experience of visual mental imagery and reasonably preserved behavioral performance on tests of visual mental imagery of object shape, object color, letters, faces, and spatial relationships. We found that the FIN was spared by the lesion. We then assessed the connectional anatomy of the FIN in the MNI space and in the patient's native space, by visualizing the fibers of the inferior longitudinal fasciculus (ILF) and of the arcuate fasciculus (AF) passing through the FIN. In both spaces, the ILF connected the FIN with the anterior temporal lobe, and the AF linked it with frontal regions. Our evidence is consistent with the hypothesis that the FIN is a node of a brain network dedicated to voluntary visual mental imagery. The FIN could act as a bridge between visual information and semantic knowledge processed in the anterior temporal lobe and in the language circuits.

Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics.

Apathy is a multi-dimensional syndrome associated with reduced initiation, executive function and emotion toward goal-directed behaviour. Affecting ∼30% of stroke patients, apathy can negatively impact rehabilitation outcomes and increase caregiver burden. However, relatively little is known about the multi-dimensional nature of post-stroke apathy and whether these dimensions map onto neuropsychological and neuroanatomical correlates. The present study aimed to address this question in a case series of stroke patients with apathy. 65 patients with acute stroke were assessed on a comprehensive battery of neuropsychological tasks and 12 patients were identified as having clinically significant apathy on one or more domains on the Dimensional Apathy Scale. Individual scores were compared to a group of healthy controls and normative data where available. Lesion mapping was completed from clinical CT and MRI scans to characterise the extent and locations of each patient's lesion. All participants performed significantly poorer than controls on one or more tasks. Difficulties with inhibition were observed across all dimensions. Prospective memory deficits were also common, while speed and social cognition were only reduced in initiation and emotional apathy, respectively. Verbal fluency was not impaired in any of the patients, despite previously established relationships with apathy. Lesions were predominantly located in right subcortical regions, with some additional frontal, temporal and cerebellar/brainstem involvement. There was substantial overlap in lesion locations within and between dimensions, such that similar apathy symptoms occurred in patients with very different lesion sites. Overall, our results suggest that neuropsychological and lesion profiles of apathy in stroke patients may be more complex and heterogenous than in neurodegenerative disease, possibly due to functional changes occurring beyond the lesion site.

Lesions in different prefrontal sectors are associated with different types of acquired personality disturbances.

"Frontal lobe syndrome" is a term often used to describe a diverse array of personality disturbances following frontal lobe damage. This study's guiding premise was that greater neuroanatomical specificity could be achieved by evaluating specific types of personality disturbances following acquired frontal lobe lesions. We hypothesized that three acquired personality disturbances would be associated with lesion involvement of distinct sectors of the prefrontal cortex (PFC): 1) emotional-social disturbance and ventromedial PFC, 2) hypoemotional disturbance and dorsomedial PFC, and 3) dysexecutive and dorsolateral PFC. In addition, we hypothesized that distressed personality disturbance would not be associated with focal PFC lesions in any sector. Each hypothesis was pre-registered and tested in 182 participants with adult-onset, chronic, focal brain lesions studied with an observational, cross-sectional design. Pre- and postmorbid personality was assessed by informant-rating with the Iowa Scales of Personality Change, completed by a spouse or family member. Two complementary analytic approaches were employed: 1) a hypothesis-driven region-of-interest (ROI) regression analysis examining the associations of lesions in specific PFC sectors with acquired personality disturbances; 2) a data-driven multivariate lesion-behavior mapping analysis, which was not limited to pre-specified regions. Each hypothesis received some support: (i) Emotional/social personality disturbance was most strongly associated with ventromedial PFC lesions in both statistical approaches. (ii) Hypoemotional disturbance was associated with dorsomedial PFC lesions in the ROI analyses, without any significant lesion-symptom mapping associations. (iii) Dysexecutive personality disturbance was associated with bilateral dorsolateral PFC lesions and ventromedial PFC lesions; lesion-symptom mapping showed maximal association of executive dysfunction with damage of the right middle frontal gyrus within the dorsolateral PFC. (iv) Distressed personality disturbance was not associated with lesions in any PFC sector. Altogether, the findings can be interpreted to indicate that damage to different prefrontal sectors may disrupt different anatomical-functional systems and result in distinct personality disturbances.

Alice in Wonderland syndrome: a lesion mapping study.

BACKGROUND AND PURPOSE: Alice in Wonderland syndrome (AIWS) is a rare neurological disorder, characterized by an erroneous perception of the body schema or surrounding space. It may be caused by a variety of neurological disorders, but to date, there is no agreement on which brain areas are affected. The aim of this study was to identify brain areas involved in AIWS. METHODS: We conducted a literature search for AIWS cases following brain lesions. Patients were classified according to their symptoms as type A (somesthetic), type B (visual), or type C (somesthetic and visual). Using a lesion mapping approach, lesions were mapped onto a standard brain template and sites of overlap were identified. RESULTS: Of 30 lesions, maximum spatial overlap was present in six cases. Local maxima were identified in the right occipital lobe, specifically in the extrastriate visual cortices and white matter tracts, including the ventral occipital fasciculus, optic tract, and inferior fronto-occipital fasciculus. Overlap was primarily due to type B patients (the most prevalent type, n = 22), who shared an occipital site of brain damage. Type A (n = 5) and C patients (n = 3) were rarer, with lesions disparately located in the right hemisphere (thalamus, insula, frontal lobe, hippocampal/parahippocampal cortex). CONCLUSIONS: Lesion-associated AIWS in type B patients could be related to brain damage in visual pathways located preferentially, but not exclusively, in the right hemisphere. Conversely, the lesion location disparity in cases with somesthetic symptoms suggests underlying structural/functional disconnections requiring further evaluation.