Neural signatures of Trail Making Test performance: evidence from lesion-mapping and neuroimaging studies

The Trail Making Test (TMT) is an extensively used neuropsychological instrument for the assessment of set-switching ability across a wide range of neurological conditions. However, the exact nature of the cognitive processes and associated brain regions contributing to the performance on the TMT remains unclear. In this review, we first introduce the TMT by discussing its administration and scoring approaches. We then examine converging evidence and divergent findings concerning the brain regions related to TMT performance, as identified by lesion-symptom mapping studies conducted in brain-injured patients and functional magnetic resonance imaging studies conducted in healthy participants. After addressing factors that may account for the heterogeneity in the brain regions reported by these studies, we identify future research endeavours that may permit disentangling the different processes contributing to the TMT performance and relating them to specific brain circuits

A comparison of lesion mapping analyses based on CT versus MR imaging in stroke

It is commonly asserted that MRI-derived lesion masks outperform CT-derived lesion masks in lesion-mapping analysis. However, no quantitative analysis has been conducted to support or refute this claim. This study reports an objective comparison of lesion-mapping analyses based on CT- and MRI-derived lesion masks to clarify how input imaging type may ultimately impact analysis results. Routine CT and MRI data were collected from 85 acute stroke survivors. These data were employed to create binarized lesion masks and conduct lesion-mapping analyses on simulated behavioral data. Following standard lesion-mapping analysis methodology, each voxel or region of interest (ROI) were considered as the underlying “target” within CT and MRI data independently. The resulting thresholded z-maps were compared between matched CT- and MRI-based analyses. Paired MRI- and CT-derived lesion masks were found to exhibit significant variance in location, overlap, and size. In ROI-level simulations, both CT and MRI-derived analyses yielded low Dice similarity coefficients, but CT analyses yielded a significantly higher proportion of results which overlapped with target ROIs. In single-voxel simulations, MRI-based lesion mapping was able to include more voxels than CT-based analyses, but CT-based analysis results were closer to the underlying target voxel. Simulated lesion-symptom mapping results yielded by paired CT and MRI lesion-symptom mapping analyses demonstrated moderate agreement in terms of Dice coefficient when systematic differences in cluster size and lesion overlay are considered. Overall, these results suggest that CT and MR-derived lesion-symptom mapping results do not reliably differ in accuracy. This finding is critically important as it suggests that future studies can employ CT-derived lesion masks if these scans are available within the appropriate time-window

Dissociating ego- and allocentric neglect after stroke: prevalence, laterality and outcome predictors

AbstractVisuospatial neglect is a neuropsychological condition commonly experienced after stroke, whereby a patient is unable to attend to stimuli on their contralesional side. We aimed to investigate whether egocentric and allocentric neglect are functionally dissociable and differ in prevalence, laterality and outcome predictors. A consecutive sample of 366 acute stroke patients completed the Broken Hearts test from the Oxford Cognitive Screen. A subsample of 160 patients was followed up 6 months later. We evaluated the association between egocentric and allocentric neglect, contrasted the prevalence and severity of left-sided versus right-sided neglect, and determined the predictors of persistence versus recovery at follow up. Clinically, we found a double dissociation between ego- and allocentric neglect, with 50% of the neglect patients showing ‘only’ egocentric neglect and 25% ‘only’ allocentric neglect. Importantly, patients with only allocentric neglect did not demonstrate any egocentric spatial bias in the locations of the allocentric errors. Left-sided egocentric neglect was more prevalent and more severe than right-sided egocentric neglect, though right-sided neglect was still highly prevalent in the acute stroke sample (35%). Leftsided allocentric neglect was more severe but not more prevalent than right-sided allocentric neglect. Overall recovery of neglect was high: 81% of egocentric and 75% of allocentric neglect patients recovered. Severity of neglect was the only significant behavioural measure for predicting recovery at 6 months.</jats:p

Deficit in feature-based attention following a left thalamic lesion

Selective attention enables us to prioritise the processing of relevant over irrelevant information. The model of priority maps with stored attention weights provides a conceptual framework that accounts for the visual prioritisation mechanism of selective attention. According to this model, high attention weights can be assigned to spatial locations, features, or objects. Converging evidence from neuroimaging and neuropsychological studies propose the involvement of thalamic and frontoparietal areas in selective attention. However, it is unclear whether the thalamus is critically involved in generating different types of modulatory signals for attentional selection. The aim of the current study was to investigate feature- and spatial-based selection in stroke survivors with subcortical thalamic and non-thalamic lesions. A single case with a left-hemispheric lesion extending into the thalamus, five cases with right-hemispheric lesions sparing the thalamus and 34 healthy, age-matched controls participated in the study. Participants performed a go/no-go task on task-relevant stimuli, while ignoring simultaneously presented task-irrelevant stimuli. Stimulus relevance was determined by colour or spatial location. The thalamic lesion case was specifically impaired in feature-based selection but not in spatial-based selection, whereas performance of non-thalamic lesion patients was similar to controls’ performance in both types of selective attention. In summary, our thalamic lesion case showed difficulties in computing differential attention weights based on features, but not based on spatial locations. The results suggest that different modulatory signals are generated mediating attentional selection for features versus space in the thalamus

Right- and Left-Lateralised Neglect are not Anatomically Homologous: A Voxel-Lesion Symptom Mapping Study

Visuospatial neglect is a heterogenous syndrome which can occur following damage to either right or left hemisphere areas. This study employs voxel-lesion symptom mapping to identify the neural correlates of left and right egocentric and allocentric neglect in a large acute stroke cohort.A cohort of 446 acute stroke survivors (age = 26-95, 44% female) completed neuropsychological neglect assessment and routine clinical imaging. Similar to previous investigations, left egocentric and left allocentric neglect were associated with damage to distinct clusters of voxels within the posterior parietal and temporo-parietal junction areas. Unlike previous investigations, right egocentric neglect was found to most strongly associated with damage to more posterior voxels within left occipital cortical areas. Right allocentric neglect was found to be most strongly associated with damage to the anterior limb of the left internal capsule. Interestingly, the right hemisphere homologues of the areas implicated in right-lateralised neglect were not overlapping with those associated with left neglect impairment. This dissociation was present across both egocentric and allocentric neglect impairment. The results of this investigation suggest that right egocentric/allocentric neglect should not be characterised as a consequence of damage to left-hemisphere homologues of the right hemisphere attentional systems. These findings support the characterisation of visuospatial neglect as a heterogenous cluster of impairments rather than a unitary syndrome and provide novel insight into the neural correlates of spatial attention.</p

Deficit in feature-based attention following a left thalamic lesion

Selective attention enables us to prioritise the processing of relevant over irrelevant information. The model of priority maps with stored attention weights provides a conceptual framework that accounts for the visual prioritisation mechanism of selective attention. According to this model, high attention weights can be assigned to spatial locations, features, or objects. Converging evidence from neuroimaging and neuropsychological studies propose the involvement of thalamic and frontoparietal areas in selective attention. However, it is unclear whether the thalamus is critically involved in generating different types of modulatory signals for attentional selection. The aim of the current study was to investigate feature- and spatial-based selection in stroke survivors with subcortical thalamic and non-thalamic lesions. A single case with a left-hemispheric lesion extending into the thalamus, five cases with right-hemispheric lesions sparing the thalamus and 34 healthy, age-matched controls participated in the study. Participants performed a go/no-go task on task-relevant stimuli, while ignoring simultaneously presented task-irrelevant stimuli. Stimulus relevance was determined by colour or spatial location. The thalamic lesion case was specifically impaired in feature-based selection but not in spatial-based selection, whereas performance of non-thalamic lesion patients was similar to controls' performance in both types of selective attention. In summary, our thalamic lesion case showed difficulties in computing differential attention weights based on features, but not based on spatial locations. The results suggest that different modulatory signals are generated mediating attentional selection for features versus space in the thalamus.status: publishe

Right- and Left-Lateralised Neglect are not Anatomically Homologous: A Voxel-Lesion Symptom Mapping Study

Visuospatial neglect is a heterogenous syndrome which can occur following damage to either right or left hemisphere areas. This study employs voxel-lesion symptom mapping to identify the neural correlates of left and right egocentric and allocentric neglect in a large acute stroke cohort. A cohort of 446 acute stroke survivors (age = 26-95, 44% female) completed neuropsychological neglect assessment and routine clinical imaging. Similar to previous investigations, left egocentric and left allocentric neglect were associated with damage to distinct clusters of voxels within the posterior parietal and temporo-parietal junction areas. Unlike previous investigations, right egocentric neglect was found to most strongly associated with damage to more posterior voxels within left occipital cortical areas. Right allocentric neglect was found to be most strongly associated with damage to the anterior limb of the left internal capsule. Interestingly, the right hemisphere homologues of the areas implicated in right-lateralised neglect were not overlapping with those associated with left neglect impairment. This dissociation was present across both egocentric and allocentric neglect impairment. The results of this investigation suggest that right egocentric/allocentric neglect should not be characterised as a consequence of damage to left-hemisphere homologues of the right hemisphere attentional systems. These findings support the characterisation of visuospatial neglect as a heterogenous cluster of impairments rather than a unitary syndrome and provide novel insight into the neural correlates of spatial attention