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1.  Language, perception, and the schematic representation of spatial relations 
Brain and Language  2011;120(3):226-236.
Schemas are abstract nonverbal representations that parsimoniously depict spatial relations. Despite their ubiquitous use in maps and diagrams, little is known about their neural instantiation. We sought to determine the extent to which schematic representations are neurally distinguished from language on the one hand, and from rich perceptual representations on the other. In patients with either left hemisphere damage or right hemisphere damage, a battery of matching tasks depicting categorical spatial relations was used to probe for the comprehension of basic spatial concepts across distinct representational formats (words, pictures, and schemas). Left hemisphere patients underperformed right hemisphere patients across all tasks. However, focused residual analyses using VLSM (voxel-based lesion-symptom mapping) suggest that (1) left hemisphere deficits in the representation of categorical spatial relations are difficult to distinguish from deficits in naming these relations and (2) the right hemisphere plays a special role in extracting schematic representations from richly textured pictures.
doi:10.1016/j.bandl.2011.09.007
PMCID: PMC3299879  PMID: 22070948
semantics; spatial cognition; hemispheric specialization; lesion studies
2.  Direct Comparison of FDG-PET and ASL-MRI in Alzheimer’s Disease 
BACKGROUND
The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer’s Disease (AD) diagnosis is well established. Recently, measurement of cerebral blood flow using arterial spin labeling MRI (ASL-MRI) has shown diagnostic potential in AD, though it has never been directly compared to FDG-PET.
METHODS
We employed a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched controls. Paired FDG-PET and ASL-MRI images from 19 controls and 15 AD patients were included for qualitative analysis, while paired images 18 controls and 13 AD patients were suitable for quantitative analyses.
RESULTS
The combined imaging protocol was well tolerated. Both modalities revealed very similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD following visual review by two expert readers. Interobserver agreement was better for FDG-PET (kappa 0.75, SE 0.12) than ASL-MRI (kappa 0.51, SE 0.15), intermodality agreement was moderate to strong (kappa 0.45-0.61), and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral FDG uptake (FDG-PET) or whole brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under ROC curves of 0.90 for FDG-PET (95% CI 0.79-0.99) and 0.91 for ASL-MRI (95% CI 0.80-1.00).
CONCLUSIONS
Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.
doi:10.1016/j.jalz.2011.06.003
PMCID: PMC3264701  PMID: 22018493
ASL; FDG; PET; MRI; Alzheimer’s disease; spin label; fluorodeoxyglucose; dementia
3.  The neural basis of reversible sentence comprehension: Evidence from voxel-based lesion-symptom mapping in aphasia 
Journal of Cognitive Neuroscience  2011;24(1):212-222.
We explored the neural basis of reversible sentence comprehension in a large group of aphasic patients (N=79). Voxel-based lesion-symptom mapping revealed a significant association between damage in temporoparietal cortex and impaired sentence comprehension. This association remained after we controlled for phonological working memory. We hypothesize that this region plays an important role in the thematic or what-where processing of sentences. In contrast, we detected weak or no association between reversible sentence comprehension and the ventrolateral prefrontal cortex, which includes Broca’s area, even for syntactically complex sentences. This casts doubt on theories that presuppose a critical role for this region in syntactic computations.
doi:10.1162/jocn_a_00118
PMCID: PMC3389786  PMID: 21861679
Broca’s area; Prefrontal; Temporoparietal; Thematic Roles; Syntax
4.  Support for Anterior Temporal Involvement in Semantic Error Production in Aphasia: New Evidence from VLSM 
Brain and language  2010;117(3):110-122.
Semantic errors in aphasia (e.g., naming a horse as “dog”) frequently arise from faulty mapping of concepts onto lexical items. A recent study by our group used voxel-based lesion-symptom mapping (VLSM) methods with 64 patients with chronic aphasia to identify voxels that carry an association with semantic errors. The strongest associations were found in the left anterior temporal lobe (L-ATL), in the mid- to anterior MTG region. The absence of findings in Wernicke’s area was surprising, as were indications that ATL voxels made an essential contribution to the post-semantic stage of lexical access. In this follow-up study, we sought to validate these results by re-defining semantic errors in a manner that was less theory dependent and more consistent with prior lesion studies. As this change also increased the robustness of the dependent variable, it made it possible to perform additional statistical analyses that further refined the interpretation. The results strengthen the evidence for a causal relationship between ATL damage and lexically-based semantic errors in naming and lend confidence to the conclusion that chronic lesions in Wernicke’s area are not causally implicated in semantic error production.
doi:10.1016/j.bandl.2010.09.008
PMCID: PMC3037437  PMID: 20961612
aphasia; voxel-based lesion-symptom mapping; naming; semantic; errors
5.  Inappropriate usage of the Brunner-Munzel test in recent voxel-based lesion-symptom mapping studies 
Neuropsychologia  2010;48(1):341-343.
Voxel-based lesion symptom mapping (VLSM) techniques have been important in elucidating structure-function relationships in the human brain. Rorden, Karnath & Bonilha (2007b) introduced the nonparametric Brunner-Munzel rank order test as an alternative to parametric tests often used in VLSM analyses. However, the Brunner-Munzel statistic produces inflated z scores when used at any voxel where there are less than ten subjects in either the lesion or no lesion groups. Unfortunately, a number of recently published VLSM studies using this statistic include relatively small patient populations, such that most (if not all) examined voxels do not meet the necessary criteria. We demonstrate the effects of inappropriate usage of the Brunner-Munzel test using a dataset included with MRIcron, and find large Type I errors. To correct for this we suggest that researchers use a permutation-derived correction as implemented in current versions of MRIcron when using the Brunner-Munzel test.
doi:10.1016/j.neuropsychologia.2009.09.016
PMCID: PMC2795086  PMID: 19766664
voxel-based lesion symptom mapping; VLSM; brain-lesion mapping; lesion; voxel; structure-function
6.  Anterior temporal involvement in semantic word retrieval: voxel-based lesion-symptom mapping evidence from aphasia 
Brain  2009;132(12):3411-3427.
Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernicke's area.
doi:10.1093/brain/awp284
PMCID: PMC2792374  PMID: 19942676
aphasia; voxel-based lesion-symptom mapping; naming; semantic; errors
7.  Acute functional recovery of cerebral blood flow after forebrain ischemia in rat 
After complete cerebral ischemia, the postischemic blood flow response to functional activation is severely attenuated for several hours. However, little is known about the spatial and temporal extent of the blood flow response in the acute postischemic period after incomplete cerebral ischemia. To investigate the relative cerebral blood flow (rCBF) response in the somatosensory cortex of rat to controlled vibrissae stimulation after transient incomplete ischemia (15-min bilateral common carotid artery occlusion + hypotension), we employed laser speckle imaging combined with statistical parametric mapping. We found that the ischemic insult had a significant impact on the baseline blood flow (P < 0.005) and the activation area in response to functional stimulation was significantly reduced after ischemia (P < 0.005). The maximum rCBF response in the activation area determined from the statistical analysis did not change significantly up to 3 h after ischemia (P > 0.1). However, the time when rCBF response reached its maximum was significantly delayed (P < 0.0001) from 2.4 ± 0.2 secs before ischemia to 3.6 ± 0.1 secs at 20 mins into reperfusion (P < 0.001); the delay was reduced gradually to 2.9 ± 0.2 secs after 3 h, which was still significantly greater than that observed before the insult (P = 0.04).
doi:10.1038/jcbfm.2008.21
PMCID: PMC2771551  PMID: 18382471
cerebral blood flow; cerebral ischemia; functional activation; functional recovery; laser speckle imaging; statistical parametric map

Results 1-7 (7)