Measures of brain activation (e.g., changes in scalp electrical potentials) have become the most popular method for inferring brain function. However, examining brain disruption (e.g., examining behavior after brain injury) can complement activation studies. Activation techniques identify regions involved with a task, whereas disruption techniques are able to discover which regions are crucial for a task. Voxel-based lesion mapping can be used to determine relationships between behavioral measures and the location of brain injury, revealing the function of brain regions. Lesion mapping can also correlate the effectiveness of neurosurgery with the location of brain resection, identifying optimal surgical targets. Traditionally, voxel-based lesion mapping has employed the chi-square test when the clinical measure is binomial and the Student's t test when measures are continuous. Here we suggest that the Liebermeister approach for binomial data is more sensitive than the chi-square test. We also suggest that a test described by Brunner and Munzel is more appropriate than the t test for nonbinomial data because clinical and neuropsychological data often violate the assumptions of the t test. We test our hypotheses comparing statistical tests using both simulated data and data obtained from a sample of stroke patients with disturbed spatial perception. We also developed software to implement these tests (MRIcron), made freely available to the scientific community.

Spatial normalization reshapes an individual’s 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.mccauslandcenter.sc.edu/CRNL/tools/spm8-scripts).

In most cases, aphasia is caused by strokes involving the left hemisphere, with more extensive damage typically being associated with more severe aphasia. The classical model of aphasia commonly adhered to in the Western world is the Wernicke-Lichtheim model. The model has been in existence for over a century, and classification of aphasic symptomatology continues to rely on it. However, far more detailed models of speech and language localization in the brain have been formulated. In this regard, the dual stream model of cortical brain organization proposed by Hickok and Poeppel is particularly influential. Their model describes two processing routes, a dorsal stream and a ventral stream, that roughly support speech production and speech comprehension, respectively, in normal subjects. Despite the strong influence of the dual stream model in current neuropsychological research, there has been relatively limited focus on explaining aphasic symptoms in the context of this model. Given that the dual stream model represents a more nuanced picture of cortical speech and language organization, cortical damage that causes aphasic impairment should map clearly onto the dual processing streams. Here, we present a follow-up study to our previous work that used lesion data to reveal the anatomical boundaries of the dorsal and ventral streams supporting speech and language processing. Specifically, by emphasizing clinical measures, we examine the effect of cortical damage and disconnection involving the dorsal and ventral streams on aphasic impairment. The results reveal that measures of motor speech impairment mostly involve damage to the dorsal stream, whereas measures of impaired speech comprehension are more strongly associated with ventral stream involvement. Equally important, many clinical tests that target behaviours such as naming, speech repetition, or grammatical processing rely on interactions between the two streams. This latter finding explains why patients with seemingly disparate lesion locations often experience similar impairments on given subtests. Namely, these individuals' cortical damage, although dissimilar, affects a broad cortical network that plays a role in carrying out a given speech or language task. The current data suggest this is a more accurate characterization than ascribing specific lesion locations as responsible for specific language deficits.awx363media15705668782001.

Background and Purpose Despite being the gold standard technique for stroke assessment, conventional diffusion magnetic resonance imaging (dMRI) provides only partial information about tissue microstructure. Diffusional kurtosis imaging (DKI) is an advanced dMRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis (K), which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics (WMM). The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WMM. Methods We performed a retrospective review of clinical and DKI data of forty-four acute/subacute ischemic stroke patients. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. ROI analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared to the contralateral hemisphere. Results K maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient (ADC) maps. K metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WMM reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared to extra-axonal (De) diffusion microenvironment of the ischemic WM lesion. Conclusions The well-known decrease in the ADC of WM following ischemia is found to be mainly driven by a significant drop in Da. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.