The neuroanatomy of visual extinction following right hemisphere brain damage: Insights from multivariate and Bayesian lesion analyses in acute stroke.

Multi-target attention, that is, the ability to attend and respond to multiple visual targets presented simultaneously on the horizontal meridian across both visual fields, is essential for everyday real-world behaviour. Given the close link between the neuropsychological deficit of extinction and attentional limits in healthy subjects, investigating the anatomy that underlies extinction is uniquely capable of providing important insights concerning the anatomy critical for normal multi-target attention. Previous studies into the brain areas critical for multi-target attention and its failure in extinction patients have, however, produced heterogeneous results. In the current study, we used multivariate and Bayesian lesion analysis approaches to investigate the anatomical substrate of visual extinction in a large sample of 108 acute right hemisphere stroke patients. The use of acute stroke patient data and multivariate/Bayesian lesion analysis approaches allowed us to address limitations associated with previous studies and so obtain a more complete picture of the functional network associated with visual extinction. Our results demonstrate that the right temporo-parietal junction (TPJ) is critically associated with visual extinction. The Bayesian lesion analysis additionally implicated the right intraparietal sulcus (IPS), in line with the results of studies in neurologically healthy participants that highlighted the IPS as the area critical for multi-target attention. Our findings resolve the seemingly conflicting previous findings, and emphasise the urgent need for further research to clarify the precise cognitive role of the right TPJ in multi-target attention and its failure in extinction patients.

Reducing alertness does not affect line bisection bias in neurotypical participants.

Alertness, or one's general readiness to respond to stimulation, has previously been shown to affect spatial attention. However, most of this previous research focused on speeded, laboratory-based reaction tasks, as opposed to the classical line bisection task typically used to diagnose deficits of spatial attention in clinical settings. McIntosh et al. (Cogn Brain Res 25:833-850, 2005) provide a form of line bisection task which they argue can more sensitively assess spatial attention. Ninety-eight participants were presented with this line bisection task, once with and once without spatial cues, and both before and after a 50-min vigilance task that aimed to decrease alertness. A single participant was excluded due to potentially inconsistent behaviour in the task, leaving 97 participants for the full analyses. While participants were, on a group level, less alert after the 50-min vigilance task, they showed none of the hypothesised effects of reduced alertness on spatial attention in the line bisection task, regardless of with or without spatial cues. Yet, they did show the proposed effect of decreased alertness leading to a lower level of general attention. This suggests that alertness has no effect on spatial attention, as measured by a line bisection task, in neurotypical participants. We thus conclude that, in neurotypical participants, the effect of alertness on spatial attention can be examined more sensitively with tasks requiring a speeded response compared to unspeeded tasks.

Evolution of Neuropsychological Deficits in First-Ever Isolated Ischemic Thalamic Stroke and Their Association With Stroke Topography: A Case-Control Study.

BACKGROUND: The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation. METHODS: Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography. RESULTS: Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1-Q3]: 39.1 [36.1-44.1]), language (31.8 [31.0-43.8]), and executive functions (43.8 [35.5-48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6-61.0], language: 55.7 [42.3-61.1], executive functions: 51.3 [50.1-56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8-55.9]) and executive (49.5 [44.3-55.1]) deficits and no verbal memory deficits (48.1 [42.5-54.7]) at 1 month compared with controls (59.0 [47.0-64.5]; 59.6 [51.1-61.3]; 52.5 [44.2-55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5-51.9]), language (47.5 [41.8-54.1]), and executive functions (48.2 [46.2-59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7-59.9]; 57.0 [51.2-62.9]; 57.4 [51.2-60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border. CONCLUSIONS: All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.

Multi-target attention and visual short-term memory capacity are closely linked in the intraparietal sulcus.

The existing literature suggests a critical role for both the right intraparietal sulcus (IPS) and the right temporo-parietal junction (TPJ) in our ability to attend to multiple simultaneously-presented lateralized targets (multi-target attention), and the failure of this ability in extinction patients. Currently, however, the precise role of each of these areas in multi-target attention is unclear. In this study, we combined the theory of visual attention (TVA) with functional magnetic resonance imaging (fMRI) guided continuous theta burst stimulation (cTBS) in neurologically healthy subjects to directly investigate the role of the right IPS and TPJ in multi-target attention. Our results show that cTBS at an area of the right IPS associated with multi-target attention elicits a reduction of visual short-term memory capacity. This suggests that the right IPS is associated with a general capacity-limited encoding mechanism that is engaged regardless of whether targets have to be attended or remembered. Curiously, however, cTBS to the right IPS failed to elicit extinction-like behavior in our study, supporting previous suggestions that different areas of the right IPS may provide different contributions to multi-target attention. CTBS to the right TPJ failed to induce a change in either TVA parameters or extinction-like behavior.

'Whose atlas I use, his song I sing?' - The impact of anatomical atlases on fiber tract contributions to cognitive deficits after stroke.

Nowadays, different anatomical atlases exist for the anatomical interpretation of the results from neuroimaging and lesion analysis studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. A major problem with the use of different atlases in different studies, however, is that the anatomical interpretation of neuroimaging and lesion analysis results might vary as a function of the atlas used. This issue might be particularly prominent in studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. We used a single large-sample dataset of right brain damaged stroke patients with and without cognitive deficit (here: spatial neglect) to systematically compare the influence of three different, widely-used white matter fiber tract atlases (1 histology-based atlas and 2 DTI tractography-based atlases) on conclusions concerning the involvement of white matter fiber tracts in the pathogenesis of cognitive dysfunction. We both calculated the overlap between the statistical lesion analysis results and each long association fiber tract (topological analyses) and performed logistic regressions on the extent of fiber tract damage in each individual for each long association white matter fiber tract (hodological analyses). For the topological analyses, our results suggest that studies that use tractography-based atlases are more likely to conclude that white matter integrity is critical for a cognitive (dys)function than studies that use a histology-based atlas. The DTI tractography-based atlases classified approximately 10 times as many voxels of the statistical map as being located in a long association white matter fiber tract than the histology-based atlas. For hodological analyses on the other hand, we observed that the conclusions concerning the overall importance of long association fiber tract integrity to cognitive function do not necessarily depend on the white matter atlas used, but conclusions may vary as a function of atlas used at the level of individual fiber tracts. Moreover, these analyses revealed that hodological studies that express the individual extent of injury to each fiber tract as a binomial variable are more likely to conclude that white matter integrity is critical for a cognitive function than studies that express the individual extent of injury to each fiber tract as a continuous variable.

Neural Correlates of Spatial Attention and Target Detection in a Multi-Target Environment.

Our ability to attend and respond in a multi-target environment is an essential and distinct human skill, as is dramatically demonstrated in stroke patients suffering from extinction. We performed a functional magnetic resonance imaging study to determine the neural anatomy associated with attending and responding to simultaneously presented targets. In healthy subjects, we tested the hypothesis that the right intraparietal sulcus (IPS) is associated both with the top-down direction of attention to multiple target locations and the bottom-up detection of multiple targets, whereas the temporo-parietal junction (TPJ) is predominantly associated with the bottom-up detection of multiple targets. We used a cued target detection task with a high proportion of catch trials to separately estimate top-down cue-related and bottom-up target-related neural activity. Both cues and targets could be presented unilaterally or bilaterally. We found no evidence of target-related neural activation specific to bilateral situations in the TPJ, but observed both cue-related and target-related neural activation specific to bilateral situations in the right IPS and target-related neural activity specific to bilateral situations in the right inferior frontal gyrus (IFG). We conclude that the IPS and the IFG of the right hemisphere underlie our ability to attend and respond in a multi-target environment.

Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients.

BACKGROUND: The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. METHODS: We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. RESULTS: Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). CONCLUSIONS: These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG.

Depression and anxiety in acute ischemic stroke involving the anterior but not paramedian or inferolateral thalamus.

Background and objectives: Emotional and cognitive deficits are prevalent in strokes involving the thalamus. In contrast to cognitive deficits, emotional deficits have not been studied prospectively in isolated thalamic stroke. Methods: In 37 ischemic thalamic stroke patients (57.0 [50.0; 69.5] years [median (Q1; Q3)], 21 males, 5 anterior, 12 paramedian, 20 inferolateral vascular territory), and 37 non-stroke control patients matched for age and sex, we prospectively examined depression, anxiety, activities of daily living, and quality of life at 1, 6, 12, and 24 months post-stroke using the Hospital-Anxiety-and-Depression Scale (HADS), Nürnberger-Alters-Alltagsaktivitäten scale (NAA), and Short Form-36 (SF36) questionnaire. Voxel-based lesion-symptom mapping (VLSM) and lesion-subtraction analyzes were performed to determine associations between questionnaire scores and thalamic stroke topography. Results: At 1 month post-stroke, anterior thalamic stroke patients had higher depression scores [8.0 (7.5; 10.5)] than paramedian [4.5 (1.0; 5.8)] and inferolateral [4.0 (1.0; 7.0)] thalamic stroke patients. Furthermore, anterior thalamic stroke patients had higher anxiety scores [11.0 (8.0; 14.5)] than their matched controls [2.5 (2.0; 2.5)], paramedian [4.5 (1.0; 5.8)] and inferior [4.0 (1.0; 7.0)] thalamic stroke patients. Depression and anxiety scores in anterior thalamic stroke patients remained high across the follow-up [depression: 9.0 (3.5; 13,8); anxiety:10.05 (2.8, 14.5)].Physical health assessed by SF36 was intact in anterior [1 month post-stroke: T-score = 55.9 (37.0; 57.6)] but reduced in inferolateral [44.5(32.4; 53.1)] thalamic stroke, whereas mental health was reduced in anterior thalamic stroke [32.0 (29.8; 47.3)].VLSM confirmed that voxels in the anterior thalamus around Montreal Neurological Institute (MNI) coordinates X = -8, Y = -12, Z = 2 were more often affected by the stroke in depressed (HADS-score ≥ 8) than non-depressed (HADS-score < 8) patients and voxels around coordinates X = -10, Y = -12, Z = 2 were more often affected in anxious (HADS-score ≥ 8) than non-anxious (HADS-score < 8) patients. Conclusion: Anterior, but not paramedian or inferolateral thalamic stroke was associated with depression and anxiety. Even though our results are mostly significant in the left thalamus, this observation on stroke laterality might be confounded by the fact that the right hemisphere was underrepresented in our study.

Early determination of somatosensory cortex in the human brain.

The developing brain possesses a high potential for neuroplasticity. Yet, this remarkable potential of (re-)organization is not a general principle. It seems to vary among different functional systems. Here, we show that distinct brain structures involved in somatosensory processing are already prenatally determined so that a pre- or perinatally acquired (congenital) brain damage of such structures results in a persistent somatosensory deficit. Eleven patients with hemiparesis due to congenital cortico-subcortical unilateral stroke who showed versus not showed a somatosensory deficit were contrasted with magnetic resonance imaging lesion-behavior mapping. The brain areas which were typically damaged in patients with a somatosensory deficit but typically spared in patients without a somatosensory deficit were located in the primary and secondary somatosensory cortex (S1, S2) as well as the inferior parietal cortex directly neighboring S1 and S2. The results argue for an early functional determination of primary and secondary somatosensory cortex, without substantial capacities for (re-)organization. They demonstrate that cortical damage of these areas cannot be compensated by shifting the functional representation to undamaged parts of the cortex.

Lesion-symptom mapping corroborates lateralization of verbal and nonverbal memory processes and identifies distributed brain networks responsible for memory dysfunction.

Memory disorders are a common consequence of cerebrovascular accident (CVA). However, uncertainties remain about the exact anatomical correlates of memory impairment and the material-specific lateralization of memory function in the brain. We used lesion-symptom mapping (LSM) in patients with first-time CVA to identify which brain structures are pivotal for verbal and nonverbal memory and to re-examine whether verbal and nonverbal memory functions are lateralized processes in the brain. The cognitive performance of a relatively large cohort of 114 patients in five classic episodic memory tests was analysed with factor analysis. Two factors were extracted that distinguished the verbal and nonverbal components of these memory tests, and their scores were subsequently tested for anatomical correlates by combining univariate and multivariate LSM. LSM analysis revealed for the verbal factor exclusively left-hemispheric insular, subcortical and adjacent white matter regions and for the nonverbal factor exclusively right-hemispheric temporal, occipital, insular, subcortical and adjacent white matter structures. These results corroborate the long-standing hypothesis of a material-specific lateralization of memory function in the brain and confirm a robust association between right temporal lobe lesions and nonverbal memory dysfunction. The right-hemispheric correlates for the nonverbal aspects of episodic memory include not only classic memory structures in the medial temporal lobe but also a more distributed network that includes cortical and subcortical structures also known for implicit memory processes.

Manual, semi-automated, and automated delineation of chronic brain lesions: a comparison of methods.

The exact delineation of chronic brain lesions is a crucial step when investigating the relationship between brain structure and (dys-)function. For this, manual tracing, although very time-consuming, is still the gold standard. In order to assess the possible contributions from other methods, we compared manual tracing of lesion boundaries with a newly developed semi-automated and a fully automated approach for lesion definition in a sample of chronic stroke patients (n=11, 5m, median age 12, range 10-30years). Manual tracing requires substantially more human input (4.8-9.6h/subject) than semi-automated (24.9min/subject) and automated processing (1min/subject). When compared with manual tracing as the gold standard, both the semi-automated (tested with 4 different smoothing filters) and the automated approach towards lesion definition performed on an acceptable level, with an average Dice's similarity index of .53-.60 (semi-automated) and .49 (automated processing). In all semi-automated and automated approaches, larger lesions were identified with a significantly higher performance than smaller lesions, as were central versus peripheral voxels, indicating that the surface-to-volume ratio explains this trend. The automated approach failed to identify two lesions. In several cases, indirect lesion effects (such as enlarged ventricles) were detected using the semi-automated or the automated approach. We conclude that manual tracing remains the gold standard for exact lesion delineation, but that semi-automated and automated approaches may be alternatives for larger lesions and/or larger studies. The detection of indirect lesion effects may be another application of such approaches in the future.

The role of temporo-parietal cortex in subcortical visual extinction.

Visual extinction is an intriguing defect of awareness in stroke patients, referring to the unsuccessful perception of contralesional events under conditions of competition. Previous studies have investigated the cortical and subcortical brain structures that, when damaged or inactivated, provoke visual extinction. The present experiment asked how lesions of subcortical structures may contribute to the appearance of visual extinction. We investigated whether lesions centering on right basal ganglia may induce dysfunction in distant, structurally intact cortical structures. Normalized perfusion-weighted MRI was used to identify structurally intact but abnormally perfused brain tissue, that is, zones that are receiving enough blood supply to remain structurally intact but not enough to function normally. We compared patients with right basal ganglia lesions showing versus not showing visual extinction. In the extinction patients, the contrast revealed cortical malperfusion that clustered around the right TPJ. It seems as if malfunction of this area is a critical aspect in visual extinction not only after cortical lesion but also in the case of subcortical basal ganglia damage. Our results support the idea that a normally functioning TPJ area plays a decisive role for the attentional network involved in detecting of visual stimuli under conditions of competition.

About the role of visual field defects in pure alexia.

Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments-particularly the pronounced increases in fixation frequency and viewing time as a function of word length-may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendations.

Covert orienting of attention and overt eye movements activate identical brain regions.

This study investigated the anatomical relationship between covert and overt shifts of attention. Previous studies have found that the areas of the brain activated by covert and overt shifts of attention are very similar. However, despite a general agreement between studies there are a few issues that merit closer inspection. Primarily, the tasks aiming to produce covert or overt shifts of attention were not always comparable. Secondly, the previous studies disagreed on whether greater neural activity is elicited by covert shifts or overt shifts of attention. Thirdly, the previous studies differed on whether the shifts of attention were exogenously or endogenously driven. Finally, the statistical analyses used by all previous studies failed to account for between subject variability. The present study was designed to address all these issues. Twelve healthy subjects performed either covert or overt shifts of attention while the functional magnetic resonance imaging (fMRI) signal was continuously measured. In line with the previous studies, the present study showed a virtually complete overlap between areas of the brain recruited during covert shifts of attention and areas of the brain recruited during overt shifts of attention. Furthermore, using endogenously driven shifts of attention this study found that overt shifts of attention resulted in higher levels of activation in the brain than covert shifts of attention. The results of this study provide support for the premotor theory of attention that posits that the attentional and motor systems are the result of neural activation in the same areas of the brain.

A hitchhiker's guide to lesion-behaviour mapping.

Lesion-behaviour mapping is an influential and popular approach to anatomically localise cognitive brain functions in the human brain. Multiple considerations, ranging from patient selection, assessment of lesion location and patient behaviour, spatial normalisation, statistical testing, to the anatomical interpretation of obtained results, are necessary to optimize a lesion-behaviour mapping study and arrive at meaningful conclusions. Here, we provide a hitchhiker's guide, giving practical guidelines and references for each step of the typical lesion-behaviour mapping study pipeline.

Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage.

Pre- or perinatally acquired ("congenital") left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7-32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development.

Early sensory processing in right hemispheric stroke patients with and without extinction.

While extinction is most commonly viewed as an attentional disorder and not as a consequence of a failure to process contralesional sensory information, it has been speculated that early sensory processing of contralesional targets in extinction patients might not be fully normal. We used a masked visuo-motor response priming paradigm to study the influence of both contralesional and ipsilesional peripheral subliminal prime stimuli on central target performance, allowing us to compare the strength of the early sensory processing associated with these prime stimuli between right brain damaged patients with and without extinction as well as healthy elderly subjects. We found that the effect of an informative subliminal prime in the left contralesional visual field on central target performance was significantly reduced in both right brain damaged patients with and without extinction. The results suggest that a low-level early sensory deterioration of the neural representation for contralesional prime stimuli is a general consequence of right hemispheric brain damage unrelated to the presence or absence of extinction. This suggests that the presence of a spatial bias against contralesional information is not sufficient to elicit extinction. For extinction to occur, this spatial bias might need to be accompanied by a pathological (non-directional) reduction of attentional capacity.

Fast semi-automated lesion demarcation in stroke.

Lesion-behaviour mapping analyses require the demarcation of the brain lesion on each (usually transverse) slice of the individual stroke patient's brain image. To date, this is generally thought to be most precise when done manually, which is, however, both time-consuming and potentially observer-dependent. Fully automated lesion demarcation methods have been developed to address these issues, but these are often not practicable in acute stroke research where for each patient only a single image modality is available and the available image modality differs over patients. In the current study, we evaluated a semi-automated lesion demarcation approach, the so-called Clusterize algorithm, in acute stroke patients scanned in a range of common image modalities. Our results suggest that, compared to the standard of manual lesion demarcation, the semi-automated Clusterize algorithm is capable of significantly speeding up lesion demarcation in the most commonly used image modalities, without loss of either lesion demarcation precision or lesion demarcation reproducibility. For the three investigated acute datasets (CT, DWI, T2FLAIR), containing a total of 44 patient images obtained in a regular clinical setting at patient admission, the reduction in processing time was on average 17.8 min per patient and this advantage increased with increasing lesion volume (up to 60 min per patient for the largest lesion volumes in our datasets). Additionally, our results suggest that performance of the Clusterize algorithm in a chronic dataset with 11 T1 images was comparable to its performance in the acute datasets. We thus advocate the use of the Clusterize algorithm, integrated into a simple, freely available SPM toolbox, for the precise, reliable and fast preparation of imaging data for lesion-behaviour mapping analyses.

Errors on the Trail Making Test Are Associated with Right Hemispheric Frontal Lobe Damage in Stroke Patients.

Measures of performance on the Trail Making Test (TMT) are among the most popular neuropsychological assessment techniques. Completion time on TMT-A is considered to provide a measure of processing speed, whereas completion time on TMT-B is considered to constitute a behavioral measure of the ability to shift between cognitive sets (cognitive flexibility), commonly attributed to the frontal lobes. However, empirical evidence linking performance on the TMT-B to localized frontal lesions is mostly lacking. Here, we examined the association of frontal lesions following stroke with TMT-B performance measures (i.e., completion time and completion accuracy measures) using voxel-based lesion-behavior mapping, with a focus on right hemispheric frontal lobe lesions. Our results suggest that the number of errors, but not completion time on the TMT-B, is associated with right hemispheric frontal lesions. This finding contradicts common clinical practice-the use of completion time on the TMT-B to measure cognitive flexibility, and it underscores the need for additional research on the association between cognitive flexibility and the frontal lobes. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether our observation is specific for right frontal lesions.

Disorganized behavior on Link's cube test is sensitive to right hemispheric frontal lobe damage in stroke patients.

One of Luria's favorite neuropsychological tasks for challenging frontal lobe functions was Link's cube test (LCT). The LCT is a cube construction task in which the subject must assemble 27 small cubes into one large cube in such a manner that only the painted surfaces of the small cubes are visible. We computed two new LCT composite scores, the constructive plan composite score, reflecting the capability to envisage a cubical-shaped volume, and the behavioral (dis-) organization composite score, reflecting the goal-directedness of cube construction. Voxel-based lesion-behavior mapping (VLBM) was used to test the relationship between performance on the LCT and brain injury in a sample of stroke patients with right hemisphere damage (N = 32), concentrated in the frontal lobe. We observed a relationship between the measure of behavioral (dis-) organization on the LCT and right frontal lesions. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether this observation is specific for right frontal lesions.