Julius Fridriksson

Using Transcranial Direct-Current Stimulation to Treat Stroke Patients With Aphasia

Background and Purpose— Recent research suggests that increased left hemisphere cortical activity, primarily of the left frontal cortex, is associated with improved naming performance in stroke patients with aphasia. Our aim was to determine whether anodal transcranial direct-current stimulation (tDCS), a method thought to increase cortical excitability, would improve naming accuracy in stroke patients with aphasia when applied to the scalp overlying the left frontal cortex. Methods— Ten patients with chronic stroke-induced aphasia received 5 days of anodal tDCS (1 mA for 20 minutes) and 5 days of sham tDCS (for 20 minutes, order randomized) while performing a computerized anomia treatment. tDCS positioning was guided by a priori functional magnetic resonance imaging results for each individual during an overt naming task to ensure that the active electrode was placed over structurally intact cortex. Results— Results revealed significantly improved naming accuracy of treated items (F[1,9]=5.72, P<0.040) after anodal tDCS compared with sham tDCS. Patients who demonstrated the most improvement were those with perilesional areas closest to the stimulation site. Crucially, this treatment effect persisted at least 1 week after treatment. Conclusions— Our findings suggest that anodal tDCS over the left frontal cortex can lead to enhanced naming accuracy in stroke patients with aphasia and, if proved to be effective in larger studies, may provide a supplementary treatment approach for anomia.

Age-specific CT and MRI templates for spatial normalization

Spatial normalization reshapes an individuals brain to match the shape and size of a template image. This is a crucial step required for group-level statistical analyses. The most popular standard templates are derived from MRI scans of young adults. We introduce specialized templates that allow normalization algorithms to be applied to stroke-aged populations. First, we developed a CT template: while this is the dominant modality for many clinical situations, there are no modern CT templates and popular algorithms fail to successfully normalize CT scans. Importantly, our template was based on healthy individuals with ages similar to what is commonly seen in stroke (mean 65 years old). This template allows studies where only CT scans are available. Second, we derived a MRI template that approximately matches the shape of our CT template as well as processing steps that aid the normalization of scans from older individuals (including lesion masking and the ability to generate high quality cortical renderings despite brain injury). The benefit of this strategy is that the resulting templates can be used in studies where mixed modalities are present. We have integrated these templates and processing algorithms into a simple SPM toolbox (http://www.mricro.com/clinical-toolbox/spm8-scripts).

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy

Purpose:  Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE.

Preservation and Modulation of Specific Left Hemisphere Regions is Vital for Treated Recovery from Anomia in Stroke

The location and extent of brain changes that support recovery in chronic stroke is probably related to the structural integrity of the remaining cortex. However, little is known about the specifics of this relationship and how it influences treatment outcome in chronic stroke. To examine this issue, the current study examined frank brain damage and changes in cortical activation as predictors of language-treatment outcome in patients with chronic aphasia caused by stroke. Twenty-six patients received multiple MRI sessions before and after 30 h of aphasia treatment targeting anomia, an impairment in the ability to name common objects. Improved naming was associated with increased brain activation in the anterior and posterior regions of the left hemisphere, whereas damage to the posterior portion of the left middle temporal lobe and the temporal-occipital junction had a particularly negative effect on treatment outcome. Specifically, patients whose brain damage included regions commonly associated with lexical retrieval and phonological processing (e.g., Brodmanns areas 37 and 39) were less likely to show treatment-related improvement in correct naming compared with cases where the same areas were intact. These findings suggest that brain changes associated with improved naming ability in chronic aphasia rely on preservation and recruitment of eloquent cortex in the left hemisphere. In general, it seems likely that a similar relationship between cortical preservation and recruitment may also pertain to recovery from other functional impairments in chronic stroke.

Left Hemisphere Plasticity and Aphasia Recovery

A recent study by our group revealed a strong relationship between functional brain changes in the left hemisphere and anomia treatment outcome in chronic stroke patients (N=26) with aphasia (Fridriksson, 2010). The current research represents a continuation of this work in which we have refined our methods and added data from four more patients (for a total sample size of 30) to assess where in the left hemisphere treatment-related brain changes occur. Unlike Fridriksson (2010) which only focused on changes in correct naming as a marker of treatment outcome, the current study examined the relationship between changes in left hemisphere activity and changes in correct naming, semantic paraphasias, and phonemic paraphasias following treatment. We also expanded on the work by Fridriksson by examining whether neurophysiological measures taken at baseline (defined henceforth as the time-point before the start of anomia treatment) predict treatment outcome. Our analyses revealed that changes in activation in perilesional areas predicted treatment-related increases in correct naming in individuals with chronic aphasia. This relationship was most easily observed in the left frontal lobe. A decrease in the number of semantic and phonemic paraphasias was predicted by an activation change in the temporal lobe involving cortical areas that were shown to be active during picture naming in 14 normal subjects. In contrast, a far less certain relationship was found between baseline neurophysiological measures and anomia treatment outcome. Our findings suggest that improved naming associated with behavioral anomia treatment in aphasia is associated with modulation of the left frontal lobe whereas a reduction in naming errors is mediated by left posterior regions that classically are thought to be involved in language processing.

An evaluation of traditional and novel tools for lesion behavior mapping

Kinkingnéhun et al. (Kinkingnéhun, S., Volle, E., Pélégrini-Issac, M., Golmard, J.L., Lehéricy, S., du Boisguéheneuc, F., Zhang-Nunes, S., Sosson, D., Duffau, H., Samson, Y., Levy, R., Dubois, B., 2007. A novel approach to clinical-radiological correlations: Anatomo-Clinical Overlapping Maps (AnaCOM): method and validation. NeuroImage 37: 1237-1249.) have recently described a novel approach for lesion-behavior mapping (LBM), referred to as Anatomo-Clinical Overlapping Maps (AnaCOM). Conventional voxelwise LBM tools apply statistics to contrast behavioral performance of patients with lesions that encompass given voxels to control patients where these voxels are spared. In contrast, AnaCOM contrasts performance of patients with injury involving given voxels to the performance of neurologically healthy participants. The authors correctly note that their procedure can offer substantially more statistical power than conventional LBM methods. We compared AnaCOM to conventional LBM techniques by examining hemiparesis (a common consequence of stroke) as the behavior of interest. We found that AnaCOM detected many regions of the middle cerebral artery territory not associated with the motor system. We suggest that conventional LBM techniques detect regions that are damaged in patients with a deficit while spared in those without a deficit, while AnaCOM detects regions that are associated with a deficit. Therefore, this new measure may offer poor specificity. Furthermore, on theoretical grounds we suggest that permutation-based thresholding will be a more sensitive method for controlling familywise error than the method of counting lesion-overlap clusters used by AnaCOM. Finally, we note that the within group variability tends to be smaller for neurologically healthy controls than in neurological patients, due to ceiling effects. Therefore, we suggest that nonparametric measures or the Welchs t-test are more appropriate than the conventional pooled variance t-test used by AnaCOM.

Neural Correlates of Phonological and Semantic Based Anomia Treatment in Aphasia

Most naming treatments in aphasia either assume a phonological or semantic emphasis or a combination thereof. However, it is unclear whether semantic or phonological treatments recruit the same or different cortical areas in chronic aphasia. Employing three persons with aphasia, two of whom were non-fluent, the present study compared changes in neural recruitment associated with phonologic and semantic-based naming treatments. The participants with non-fluent aphasia were able to name more items following both treatment approaches. Although this was not the case for the participant who had fluent aphasia, her naming errors decreased considerably following treatment. Post-treatment fMRI revealed similar changes in neural activity bilaterally in the precuneus among the two non-fluent participants--increased activity was noted in the right entorhinal cortex and posterior thalamus on post-treatment scans for the third participant. These findings imply that cortical areas not traditionally related to language processing may support anomia recovery in some patients with chronic aphasia.

Activity in Preserved Left Hemisphere Regions Predicts Anomia Severity in Aphasia

Understanding the neural mechanism that supports preserved language processing in aphasia has implications for both basic and applied science. This study examined brain activation associated with correct picture naming in 15 patients with aphasia. We contrasted each patients activation to the activation observed in a neurologically healthy control group, allowing us to identify regions with unusual activity patterns. The results revealed that increased activation in preserved left hemisphere areas is associated with better naming performance in aphasia. This relationship was linear in nature; progressively less cortical activation was associated with greater severity of anomia. These findings are consistent with others who suggests that residual language function following stroke relies on preserved cortical areas in the left hemisphere.

Neural recruitment associated with anomia treatment in aphasia

The purpose of this study was to investigate changes in the spatial distribution of cortical activity associated with anomia treatment in three persons with aphasia. Participants underwent three fMRI sessions before and after a period of intensive language treatment focused on object naming. The results revealed bilateral hemispheric recruitment associated with improved ability to name items targeted in treatment. This is the first study to employ multiple pre- and post-treatment fMRI sessions in the study of treatment-induced recovery from aphasia and has implications for future studies of brain plasticity in stroke.

Functional communication and executive function in aphasia.

The purpose of this exploratory study was to investigate the relationship between functional communication and executive function ability in aphasia. Twenty‐five participants with aphasia underwent examination with an extensive test battery including measures of functional communication, executive function ability, and language impairment. Compared to published norms, most participants did not perform within normal limits on the executive function tests. As expected, the correlation between severity of language impairment and functional communication ratings exceeded that among the executive functioning and functional communication measures. Eight of ten correlation coefficients for the relationship between executive functioning and functional communication reached statistical significance suggesting a clear relationship between scores on the executive functioning measures and functional communication ability. Based on these results, it appears that decreased executive functioning ability may coincide with decreased functional communication ability in persons with aphasia.