Multivariate Lesion-symptom Mapping Research Articles

Strategic infarct location for post-stroke cognitive impairment: A multivariate lesion-symptom mapping study

Lesion location is an important determinant for post-stroke cognitive impairment. Although several ‘strategic’ brain regions have previously been identified, a comprehensive map of strategic brain regions for post-stroke cognitive impairment is lacking due to limitations in sample size and methodology. We aimed to determine strategic brain regions for post-stroke cognitive impairment by applying multivariate lesion-symptom mapping in a large cohort of 410 acute ischemic stroke patients. Montreal Cognitive Assessment at three to six months after stroke was used to assess global cognitive functioning and cognitive domains (memory, language, attention, executive and visuospatial function). The relation between infarct location and cognition was assessed in multivariate analyses at the voxel-level and the level of regions of interest using support vector regression. These two assumption-free analyses consistently identified the left angular gyrus, left basal ganglia structures and the white matter around the left basal ganglia as strategic structures for global cognitive impairment after stroke. A strategic network involving several overlapping and domain-specific cortical and subcortical structures was identified for each of the cognitive domains. Future studies should aim to develop even more comprehensive infarct location-based models for post-stroke cognitive impairment through multicenter studies including thousands of patients.

Mapping Common Aphasia Assessments to Underlying Cognitive Processes and Their Neural Substrates

Background. Understanding the relationships between clinical tests, the processes they measure, and the brain networks underlying them, is critical in order for clinicians to move beyond aphasia syndrome classification toward specification of individual language process impairments. Objective. To understand the cognitive, language, and neuroanatomical factors underlying scores of commonly used aphasia tests. Methods. Twenty-five behavioral tests were administered to a group of 38 chronic left hemisphere stroke survivors and a high-resolution magnetic resonance image was obtained. Test scores were entered into a principal components analysis to extract the latent variables (factors) measured by the tests. Multivariate lesion-symptom mapping was used to localize lesions associated with the factor scores. Results. The principal components analysis yielded 4 dissociable factors, which we labeled Word Finding/Fluency, Comprehension, Phonology/Working Memory Capacity, and Executive Function. While many tests loaded onto the factors in predictable ways, some relied heavily on factors not commonly associated with the tests. Lesion symptom mapping demonstrated discrete brain structures associated with each factor, including frontal, temporal, and parietal areas extending beyond the classical language network. Specific functions mapped onto brain anatomy largely in correspondence with modern neural models of language processing. Conclusions. An extensive clinical aphasia assessment identifies 4 independent language functions, relying on discrete parts of the left middle cerebral artery territory. A better understanding of the processes underlying cognitive tests and the link between lesion and behavior may lead to improved aphasia diagnosis, and may yield treatments better targeted to an individual’s specific pattern of deficits and preserved abilities.

Functional activation independently contributes to naming ability and relates to lesion site in post-stroke aphasia.

Language network reorganization in aphasia may depend on the degree of damage in critical language areas, making it difficult to determine how reorganization impacts performance. Prior studies on remapping of function in aphasia have not accounted for the location of the lesion relative to critical language areas. They rectified this problem by using a multimodal approach, combining multivariate lesion-symptom mapping and fMRI in chronic aphasia to understand the independent contributions to naming performance of the lesion and the activity in both hemispheres. Activity was examined during two stages of naming: covert retrieval, and overt articulation. Regions of interest were drawn based on over- and under-activation, and in areas where activity had a bivariate relationship with naming. Regressions then tested whether activation of these regions predicted naming ability, while controlling for lesion size and damage in critical left hemisphere naming areas, as determined by lesion-symptom mapping. Engagement of the right superior temporal sulcus (STS) and disengagement of the left dorsal pars opercularis (dPOp) during overt naming was associated with better than predicted naming performance. Lesions in the left STS prevented right STS engagement and resulted in persistent left dPOp activation. In summary, changes in activity during overt articulation independently relate to naming outcomes, controlling for stroke severity. Successful remapping relates to network disruptions that depend on the location of the lesion in the left hemisphere. Hum Brain Mapp 38:2051-2066, 2017. © 2017 Wiley Periodicals, Inc.

Successful Self-Monitoring of Speech Errors Depends on Frontal White Matter Tracts

Successful Self-Monitoring of Speech Errors Depends on Frontal White Matter Tracts

Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke.

Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

Subjective experience of inner speech in aphasia: Preliminary behavioral relationships and neural correlates

Many individuals with aphasia describe anomia with comments like “I know it but I can’t say it.” The exact meaning of such phrases is unclear. We hypothesize that at least two discrete experiences exist: the sense of (1) knowing a concept, but failing to find the right word, and (2) saying the correct word internally but not aloud (successful inner speech, sIS). We propose that sIS reflects successful lexical access; subsequent overt anomia indicates post-lexical output deficits. In this pilot study, we probed the subjective experience of anomia in 37 persons with aphasia. Self-reported sIS related to aphasia severity and phonological output deficits. In multivariate lesion-symptom mapping, sIS was associated with dorsal stream lesions, particularly in ventral sensorimotor cortex. These preliminary results suggest that people with aphasia can often provide meaningful insights about their experience of anomia and that reports of sIS relate to specific lesion locations and language deficits.

Depression Symptoms in Chronic Left Hemisphere Stroke Are Related to Dorsolateral Prefrontal Cortex Damage.

Damage to the brain's mood regulation systems may contribute to poststroke depression. This study examines relationships between depression symptoms and psychosocial factors and then uses multivariate lesion-symptom mapping to localize depression symptoms in people with chronic left hemisphere stroke. Depression symptoms relate inversely to education and directly to physical disability. Damage in the left dorsolateral prefrontal cortex is associated with greater depression symptoms. These results demonstrate a neurological contribution to depression symptoms in chronic left hemisphere stroke and provide evidence of convergent biological mechanisms for poststroke depression symptoms and major depression with regard to left dorsolateral prefrontal cortex dysfunction.

Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter volumes in these clusters related to verbal working memory capacity, but not other cognitive functions. Further, grey matter volumes in these areas were greater in stroke survivors than healthy control subjects. To confirm this result, 10 chronic left hemisphere stroke survivors with no history of aphasia were identified. Grey matter volumes in right temporoparietal clusters were greater in stroke survivors with aphasia compared to those without history of aphasia. These findings suggest that the grey matter structure of right hemisphere posterior dorsal stream language homologues independently contributes to language production abilities in chronic left hemisphere stroke, and that these areas may undergo hypertrophy after a stroke causing aphasia.

Support Vector Regression-based Multivariate Lesion Symptom Mapping

Support Vector Regression-based Multivariate Lesion Symptom Mapping

Support vector regression based multivariate lesion-symptom mapping.

A novel multivariate lesion-symptom mapping (LSM) methodology was developed in this study. Lesion analysis is a classic model for studying brain functions. Using lesion data, focal brain-behavior associations have been widely assessed using the massive voxel-based lesion symptom mapping (VLSM) method. Assessing each voxel independently, VLSM suffers from low sensitivity after correcting for the enormous number of comparisons. It is also incapable for assessing a spatially distributed association pattern though the brain-behavior associations generally involve a collection of functionally related voxels. To solve these two outstanding problems, we carried out the first multivariate lesion symptom mapping (MLSM) in this study using support vector regression (SVR). In the so dubbed SVR-LSM, the symptom relation to the entire lesion map rather than each isolated voxel is modeled using a non-linear function, so the inter-voxel correlations are intrinsically considered, resulting in a potentially more sensitive way to examine lesion-symptom relationships. Evaluations using synthetic data and real data showed that SVR-LSM gained a much better performance (in terms of sensitivity and specificity) for detecting brain-behavior relations than VLSM. While the method was designed for lesion analysis, extending it to neuroimaging data will be straightforward.

A single-season prospective study of respiratory viral infections in lung transplant recipients

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.