Jane B. Allendorfer

Recovered vs. not-recovered from post-stroke aphasia: the contributions from the dominant and non-dominant hemispheres.

PURPOSE Several adult studies have documented the importance of the peri-stroke areas to aphasia recovery. But, studies examining the differences in patterns of cortical participation in language comprehension in patients who have (LMCA-R) or have not recovered (LMCA-NR) from left middle cerebral artery infarction have not been performed up to date. METHODS In this study, we compare cortical correlates of language comprehension using fMRI and semantic decision/tone decision task in 9 LMCA-R and 18 LMCA-NR patients matched at the time of stroke for age and handedness. We examine the cortical correlates of language performance by correlating intra- and extra-scanner measures of linguistic performance with fMRI activation and stroke volumes. RESULTS Our analyses show that LMCA-R at least 1 year after stroke show a return to typical fMRI language activation patterns and that there is a compensatory reorganization of language function in LMCA-NR patients with shifts to the right hemispheric brain regions. Further, with increasing strength of the left-hemispheric fMRI signal shift there are associated improvements in performance as tested with standardized linguistic measures. A negative correlation between the size of the stroke and performance on some of the linguistic tests is also observed. CONCLUSIONS This right-hemispheric shift as a mechanism of post-stroke recovery in adults appears to be an ineffective mode of language function recovery with increasing right-hemispheric shift associated with lower language performance. Thus, normalization of the post-stroke language activation patterns is needed for better language performance while shifts of the activation patterns to the non-dominant (right) hemisphere and/or large stroke size are associated with decreased linguistic abilities after stroke.

Uncinate fasciculus connectivity in patients with psychogenic nonepileptic seizures: A preliminary diffusion tensor tractography study

The amygdala, hippocampus, and medial prefrontal cortex are limbic brain regions connected by the uncinate fasciculus (UF) and implicated in emotion regulation. The aim of this study was to assess the connectivity characteristics of the UF in patients with psychogenic nonepileptic seizures (PNES) and matched healthy controls. We hypothesized that white matter connectivity of the UF in patients with PNES would differ from that in healthy controls. Eight patients with PNES and eight age- and sex-matched healthy controls underwent 3T MRI and 32-direction diffusion tensor imaging (DTI). Computation of DTI indices including fractional anisotropy (FA) and diffusion tensor tractography was performed. Two regions of interest were defined to manually trace the UF in each hemisphere for each subject. Fractional anisotropy and the number of reconstructed streamlines for the left and right hemispheres of the UF and the degree of asymmetry for each measure were compared between groups. Correlations between UF measures and clinical variables were also performed. Patients with PNES exhibited a significantly greater number of UF streamlines in the right hemisphere tract than in the left hemisphere (p=0.031), with such difference not observed in controls (p=0.81). This was reflected in a significant group difference in the asymmetry index (AI) for the number of streamlines, with more rightward asymmetry in patients with PNES (p=0.021). Average FA of the UF was similar between groups and between hemispheres for each group (all p>0.05). Age at illness onset was correlated with the AI for FA (r=-0.87; p=0.0045). Previously observed differences in emotion processing between controls and patients with PNES may be related to the differences in the rightward asymmetry in the number of UF streamlines in patients with PNES. Age at PNES onset appears to also have a role in the FA asymmetry of the UF. This is the first study to investigate the structural connectivity in these regions involved in emotional regulation in patients with PNES; further research is necessary to clarify the complex relationships between clinical measures and DTI characteristics.

Voxel-based Gaussian naïve Bayes classification of ischemic stroke lesions in individual T1-weighted MRI scans.

BACKGROUND Manual lesion delineation by an expert is the standard for lesion identification in MRI scans, but it is time-consuming and can introduce subjective bias. Alternative methods often require multi-modal MRI data, user interaction, scans from a control population, and/or arbitrary statistical thresholding. NEW METHOD We present an approach for automatically identifying stroke lesions in individual T1-weighted MRI scans using naïve Bayes classification. Probabilistic tissue segmentation and image algebra were used to create feature maps encoding information about missing and abnormal tissue. Leave-one-case-out training and cross-validation was used to obtain out-of-sample predictions for each of 30 cases with left hemisphere stroke lesions. RESULTS Our method correctly predicted lesion locations for 30/30 un-trained cases. Post-processing with smoothing (8mm FWHM) and cluster-extent thresholding (100 voxels) was found to improve performance. COMPARISON WITH EXISTING METHOD Quantitative evaluations of post-processed out-of-sample predictions on 30 cases revealed high spatial overlap (mean Dice similarity coefficient=0.66) and volume agreement (mean percent volume difference=28.91; Pearsons r=0.97) with manual lesion delineations. CONCLUSIONS Our automated approach agrees with manual tracing. It provides an alternative to automated methods that require multi-modal MRI data, additional control scans, or user interaction to achieve optimal performance. Our fully trained classifier has applications in neuroimaging and clinical contexts.

White matter diffusion abnormalities in patients with psychogenic non-epileptic seizures.

The purpose of this study was to conduct a preliminary investigation of the white matter characteristics in patients with psychogenic non-epileptic seizures (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3T in 16 patients with PNES and 16 age- and sex-matched healthy controls (HC). All patients with PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid neurological or psychiatric conditions. DTI indices including fractional anisotropy (FA), and mean diffusivity (MD) were calculated and compared between patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS). Significantly higher FA values were observed in patients with PNES in the left corona radiata, left internal and external capsules, left superior temporal gyrus, as well as left uncinate fasciculus (UF) (P<0.05; corrected for multiple comparisons). There was no significant change in other indices between patients with PNES and HCs. These findings suggest that patients with PNES have significantly altered white matter structural connectivity when compared to age- and sex-matched HCs. These abnormalities are present in left hemispheric regions associated with emotion regulation and motor pathways. While the relationship between the pathophysiology of PNES and these abnormalities is not entirely clear, this work provides an initial basis to guide future prospective studies.

Age at stroke determines post-stroke language lateralization

PURPOSE To determine how age at the time of left middle cerebral artery stroke affects language lateralization in a combined sample of subjects with perinatal, childhood, and adult stroke. METHODS 19 participants who had perinatal stroke (<1 month of age), 32 with later stroke, and 51 sex-/age-matched healthy controls (HCs) received fMRI of language using verb generation task (VGT). RESULTS Percent lesion volumes were not different between groups (perinatal vs. late stroke) when taking brain volume into account (p = 0.084). Perinatal stroke group showed bilateral signal increases compared to more left-lateralized signals in matched HCs; late stroke group and HCs both showed left-hemispheric signal increases. LIs in the stroke groups were consistently more bilateral than in HCs (all p < 0.008) except for the late groups posterior LI (p = 0.080). There was greater proportion of leftward language lateralization in HCs compared to their respective stroke groups (78.9% vs. 31.6% in perinatal; 87.5% vs. 59.4% in late stroke; p = 0.004) and a larger proportion of leftward lateralization in late compared to perinatal stroke (p = 0.039). The age of stroke occurrence showed significant positive associations with global and frontal LI (both p ≤ 0.007). CONCLUSION As expected, the age of stroke occurrence affects subsequent verb generation lateralization. Greater cortical plasticity is observed in earlier stroke while later stroke is associated with reliance on the repair of the previously damaged left-hemispheric networks.

Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — A pilot cross-sectional fMRI study

Stress is commonly reported as a seizure precipitant in individuals with poorly controlled seizures including temporal lobe epilepsy. The aim of the study was to assess the neural and physiologic correlates of psychosocial stress response during functional magnetic resonance imaging (fMRI) and their relationship with seizure occurrence in patients with left temporal lobe epilepsy (LTLE). We enrolled 23 patients with LTLE and 23 age- and sex-matched healthy controls (HCs); all underwent fMRI with control math task (CMT) and stress math task (SMT) and pre-/post-fMRI salivary cortisol analysis (acute stress reactivity calculated as % reduction from post-stress to recovery baseline; dCORT). The Beck Depression Inventory-II (BDI-II) and Perceived Stress Scale (PSS-10) were administered. T-tests of performance and cortisol variables were performed. Processing and single-subject modeling of fMRI response to CMT positive feedback and SMT negative feedback, group comparisons, and whole-brain correlation of seizure occurrence and fMRI response in patients with poorly controlled LTLE were performed. Patients with LTLE and healthy controls were similar in demographics, math performance, heart rate, and PSS-10 scores (all p>0.05). Patients with LTLE exhibited greater dCORT (p=0.048) and lower BDI-II scores (p=0.016) compared with HCs. Patients with poorly controlled LTLE showed a positive association between seizure frequency and dCORT (r=0.73, p=0.016). Functional MRI activation to feedback was similar between groups, including midfrontal, temporal, parietal, and occipital regions. Regression analyses revealed no group differences to positive feedback, but, compared with HCs, patients with LTLE showed decreased activation to negative feedback in the left cerebellum/middle occipital/fusiform gyri, left hippocampus/parahippocampus, bilateral medial frontal/cingulate/superior frontal gyri, right postcentral gyrus/inferior parietal lobule, and right insula/postcentral gyrus (p<0.05, corrected). Patients with poorly controlled LTLE showed negative association between seizure frequency and activation in the bilateral subgenual anterior cingulate (p<0.05, corrected). This study is the first to characterize the cortical and physiologic responses to acute psychosocial stress and to show a significant relationship between seizure control in LTLE and both the hypothalamic-pituitary-adrenal axis and fMRI signal reactivity to acute psychosocial stress. These findings extend our understanding of the complex interplay between stress, physiologic stress markers, and seizures/epilepsy.

Constraint-Induced Aphasia Therapy for Treatment of Chronic Post-Stroke Aphasia: A Randomized, Blinded, Controlled Pilot Trial

Background Few studies have documented the possibility of treatment-induced improvements in language functions 12 months or longer after stroke. The purpose of the current study was to provide a preliminary estimate of efficacy of constraint-induced aphasia therapy (CIAT) when compared to no-intervention in patients with chronic (>1 year) post-stroke aphasia in order to provide the data needed to design an appropriately powered trial. Material/Methods This was a randomized, controlled, single-blinded, pilot trial. We identified 32 patients with chronic post-stroke aphasia. Of these, 27 were offered participation, and 24 were randomized (CONSORT diagram): 14 to CIAT and to 10 to no-intervention. CIAT groups received up to 4 hours/day of intervention for 10 consecutive business days (40 hours of therapy). Outcomes were assessed within 1 week of intervention and at 1 and 12 weeks after intervention and included several linguistic measures and a measure of overall subjective communication abilities (mini-Communicative Abilities Log (mini-CAL)). To maintain blinding, clinicians treating patients (CIAT group) did not communicate with other team members and the testing team members were blinded to treatment group assignment. Results Overall, the results of this pilot trial support the results of previous observational studies that CIAT may lead to improvements in linguistic abilities. At 12 weeks, the treatment group reported better subjective communication abilities (mini-CAL) than the no-intervention group (p=0.019). Other measures trended towards better performance in the CIAT group. Conclusions In this randomized, controlled, and blinded pilot study, intensive language therapy (CIAT) led to an improvement in subjective language abilities. The effects demonstrated allow the design of a definitive trial of CIAT in patients with a variety of post-stroke aphasia types. In addition, our experiences have identified important considerations for designing subsequent trial(s) of CIAT or other interventions for post-stroke aphasia.

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.

The canonical semantic network supports residual language function in chronic post-stroke aphasia: Canonical Networks Support Aphasia Recovery

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long‐term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post‐stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22%–33% of the variance in language test scores. Whole‐brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemispheric damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. Hum Brain Mapp 38:1636–1658, 2017.

Arcuate fasciculus asymmetry has a hand in language function but not handedness

The importance of relationships between handedness, language lateralization and localization, and white matter tracts for language performance is unclear. The goal of the study was to investigate these relationships by examining arcuate fasciculus (AF) structural asymmetry (DTI) and functional asymmetry (fMRI) in language circuits, handedness, and linguistic performance. A large sample of right‐handed (n = 158) and atypical‐handed (n = 82) healthy adults underwent DTI at 3 T to assess number of streamlines and fractional anisotropy (FA) of the AF, and language fMRI. Language functions were assessed using standard tests of vocabulary, naming, verbal fluency, and complex ideation. Laterality indices (LIs) illustrated degree of asymmetry and lateralization patterns for the AF (streamlines and FA) and verb generation fMRI. Both handedness groups showed leftward lateralization bias for streamline and fMRI LIs and symmetry for FA LI. The proportion of subjects with left, right, or symmetric lateralization were similar between groups if based on AF LIs, but differed if based on fMRI LIs (p = 0.0016). Degree of right‐handedness was not associated with AF lateralization, but was associated with fMRI language lateralization (p = 0.0014). FA LI was not associated with performance on language assessments, but streamline LI was associated with better vocabulary and complex ideation performance in atypical‐handed subjects (p = 0.022 and p = 0.0098, respectively), and better semantic fluency in right‐handed subjects (p = 0.047); however, these did not survive multiple comparisons correction. We provide evidence that AF asymmetry is independent of hand preference, and while degree of right‐handedness is associated with hemispheric language lateralization, the majority of atypical‐handed individuals are left‐lateralized for language. Hum Brain Mapp 37:3297–3309, 2016.