Mikolaj A. Pawlak

Neural substrates of visuospatial processing in distinct reference frames: Evidence from unilateral spatial neglect

There is evidence for different levels of visuospatial processing with their own frames of reference: viewer-centered, stimulus-centered, and object-centered. The neural locus of these levels can be explored by examining lesion location in subjects with unilateral spatial neglect (USN) manifest in these reference frames. Most studies regarding the neural locus of USN have treated it as a homogenous syndrome, resulting in conflicting results. In order to further explore the neural locus of visuospatial processes differentiated by frame of reference, we presented a battery of tests to 171 subjects within 48 hr after right supratentorial ischemic stroke before possible structural and/or functional reorganization. The battery included MR perfusion weighted imaging (which shows hypoperfused regions that may be dysfunctional), diffusion weighted imaging (which reveals areas of infarct or dense ischemia shortly after stroke onset), and tests designed to disambiguate between various types of neglect. Results were consistent with a dorsal/ventral stream distinction in egocentric/allocentric processing. We provide evidence that portions of the dorsal stream of visual processing, including the right supramarginal gyrus, are involved in spatial encoding in egocentric coordinates, whereas parts of the ventral stream (including the posterior inferior temporal gyrus) are involved in allocentric encoding.

Neural regions essential for reading and spelling of words and pseudowords

To identify dysfunctional brain regions critical for impaired reading/spelling of words/pseudowords by evaluating acute stroke patients on lexical tests and magnetic resonance imaging, before recovery or reorganization of structure–function relationships.

Posttreatment recurrence of malignant brain neoplasm: Accuracy of relative cerebral blood volume fraction in discriminating low from high malignant histologic volume fraction

PURPOSE To determine the accuracy of relative cerebral blood volume (rCBV) fraction for distinguishing high-grade recurrent neoplasm from treatment-related necrosis (TRN) in enhancing masses identified on surveillance magnetic resonance (MR) images following treatment for primary or secondary brain neoplasm. MATERIALS AND METHODS This institutional review board approved and HIPAA-compliant retrospective study included 30 patients undergoing resection of recurrent enhancing mass appearing after treatment with surgery and radiation, with or without chemotherapy. The enhancing mass volume was manually segmented on three-dimensional T1-weighted images. The rCBV maps were created by using T2-weighted dynamic susceptibility contrast perfusion MR imaging and registered to T1-weighted images, and the fraction of enhancing mass with rCBV above a range of thresholds was calculated. A receiver operating characteristic (ROC) curve was created by calculating sensitivity-specificity pairs at each threshold for rCBV fraction (< or = 20% or > 20%) by using percentage of malignant features at histologic evaluation as the reference criterion. Relationships between rCBV and probability of recurrence were estimated by using logistic regression analysis. RESULTS ROC analysis showed excellent discriminating accuracy of rCBV fraction (area under the ROC curve, 0.97 +/- 0.03 [standard error]) and high efficiency (93%) with an rCBV threshold of 1.8 times that of normal-appearing white matter. Logistic regression analysis showed that a unit increase of rCBV is associated with a 254-fold increase (95% confidence interval: 43, 1504, P < .001) of the odds that enhanced tissue is recurrence, adjusting for age, treatment, volume of enhancing tissue, and time to suspected recurrence. CONCLUSION The fraction of malignant histologic features in enhancing masses recurring after treatment for brain neoplasms can be predicted by using the rCBV fraction, with improved differentiation between recurrent neoplasm and TRN.

Speech and language functions that require a functioning Broca's area

A number of previous studies have indicated that Brocas area has an important role in understanding and producing syntactically complex sentences and other language functions. If Brocas area is critical for these functions, then either infarction of Brocas area or temporary hypoperfusion within this region should cause impairment of these functions, at least while the neural tissue is dysfunctional. The opportunity to identify the language functions that depend on Brocas area in a particular individual was provided by a patient with hyperacute stroke who showed selective hypoperfusion, with minimal infarct, in Brocas area, and acutely impaired production of grammatical sentences, comprehension of semantically reversible (but not non-reversible) sentences, spelling, and motor planning of speech articulation. When blood flow was restored to Brocas area, as demonstrated by repeat perfusion weighted imaging, he showed immediate recovery of these language functions. The identification of language functions that were impaired when Brocas area was dysfunctional (due to low blood flow) and recovered when Brocas area was functional again, provides evidence for the critical role of Brocas area in these language functions, at least in this individual.

Where (in the brain) do semantic errors come from

BACKGROUND Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone. METHODS A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmanns areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits. RESULTS Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37. CONCLUSION Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.

Middle cerebral artery vasospasm: transcranial color-coded duplex sonography versus conventional nonimaging transcranial Doppler sonography.

Objective:To prospectively compare accuracies of transcranial color-coded duplex sonography (TCCS) and transcranial Doppler sonography (TCD) in the diagnosis of middle cerebral artery (MCA) vasospasm. Design:Prospective blinded head-to-head comparison TCD and TCCS methods using digital subtraction angiography (DSA) as the reference standard. Setting:Department of Radiology in a tertiary university health center in a metropolitan area. Patients:Eighty-one consecutive patients (mean age, 53.9 ± 13.9 years; 48 women). The indication for DSA was subarachnoid hemorrhage in 71 patients (87.6%), stroke or transient ischemic attack in five patients (6.2%), and other reasons in five patients (6.2%). Interventions:The MCA was graded as normal, narrowed <50%, and >50% using DSA. The accuracy of ultrasound methods was estimated by total area (Az) under receiver operator characteristic curve. To compare sensitivities of ultrasound methods, McNemar’s test was used with mean velocity thresholds of 120 cm/sec for the detection of less advanced, and 200 cm/sec for the more advanced MCA narrowing. Measurements and Main Results:Angiographic MCA narrowing ≤50% was found in 21, and >50% in 10 of 135 arteries. Accuracy of TCCS was insignificantly higher than that of TCD in the detection of ≤50% and >50% narrowing, total Az for mean velocity being 0.83 ± 0.05, 0.77 ± 0.05, and 0.95 ± 0.02, 0.86 ± 0.08, respectively. Sensitivity of TCCS at commonly used threshold of 120 cm/sec for less advanced MCA spasm was significantly better than that of TCD at similar specificity, 55% vs. 39%, p = 0.038, whereas at a threshold of 200 cm/sec used for more advanced spasm, sensitivities and specificities of both methods were not different. Conclusion:The accuracy of TCCS and TCD is similar, but TCCS is more sensitive than TCD in the detection of MCA spasm. Sensitivity of both techniques in the detection of mild and more advanced spasm using 120 cm/sec and 200 cm/sec thresholds, respectively, is poor; however, a larger sample is required to increase precision of our sensitivity estimates.

Suitability of Temporal Bone Acoustic Window: Conventional TCD Versus Transcranial Color‐Coded Duplex Sonography

To determine whether the proportion of patients with suitable temporal bone acoustic windows is different for conventional transcranial Doppler sonography (TCD) and transcranial color‐coded duplex sonography (TCCS), based on a head‐to‐head comparison in the same population of patients.

Brain Morphometry and Intelligence Quotient Measurements in Children With Sickle Cell Disease

Objective: To verify the hypothesis that volume of regional gray matter accounts substantially for variability in intelligence quotient (IQ) score among children with sickle cell disease, who have no magnetic resonance visible infarcts. Methods: We studied 31 children with sickle cell disease, homozygous for hemoglobin S, with no history of stroke, no magnetic resonance signal-intensity abnormality, and transcranial Doppler velocities <170 cm/sec, with a T1-weighted magnetic resonance sequence and the Kaufman Brief Intelligence Test. On the basis of Kaufman Brief Intelligence Test, we classified these children into 2 groups: high and low IQ based on a median split. We then used an automated and novel Bayesian voxel-based morphometry technique, called Graphical-Model-Based Multivariate Analysis (GAMMA), to assess the probabilistic association between IQ score and regional gray matter volume. Results: GAMMA found 1 region linking low IQ with smaller cortical gray matter volume. In comparison with the children in the high-IQ group, children in the low-IQ group had smaller regional gray matter volume in both frontal lobes, both temporal lobes, and both parietal lobes. Conclusions: In children with sickle cell disease, we found a linear association between IQ and regional gray matter volume. This finding suggests that some variance in intellectual ability in children with sickle cell disease is accounted for by regional variability of gray matter volume, which is independent of neuroradiological evidence of infarct.

Voxelwise Bayesian lesion-deficit analysis

Relating cognitive deficits to the presence of lesions has been an important means of delineating structure-function associations in the human brain. We propose a voxel-based Bayesian method for lesion-deficit analysis, which identifies complex linear or nonlinear associations among brain-lesion locations, and neurological status. We validated this method using a simulated data set, and we applied this algorithm to data obtained from an acute-stroke study to identify associations among voxels with infarct or hypoperfusion, and impaired word reading. We found that a distributed region involving Brodmann areas (BA) 22, 37, 39, and 40 was implicated in word reading.

Sickle Cell Disease: Ratio of Blood Flow Velocity of Intracranial to Extracranial Cerebral Arteries—Initial Experience

PURPOSE To establish reference values of the ratios of flow velocity in the middle cerebral artery (V(MCA)) and the terminal portion of the internal carotid artery (V(tICA)) to flow velocity in the extracranial portion of internal carotid artery (V(ICA)) in children with sickle cell disease (SCD). MATERIALS AND METHODS Institutional ethics committee approval and parental informed consent were obtained for this prospective HIPAA-compliant study. Sixty-eight children (38 female; mean age, 7.7 years +/- 3.3; range, 2-14 years) with HbSS genotype, without neurologic deficits and no history of stroke, were enrolled. Final study population comprised 56 (mean age 8.0 +/- 3.3 years, 26 females) children who underwent magnetic resonance (MR) angiography, which excluded intracranial arterial narrowing, transcranial color-coded duplex ultrasonography (US), and carotid US to determine V(MCA)/V(ICA) and V(tICA)/V(ICA) ratios from angle-corrected and uncorrected velocities. Tolerance interval estimates were used to calculate reference ranges and linear regression was used to quantify associations of Doppler parameters with age adjusted for hemoglobin and hematocrit. RESULTS Reference ranges in centimeters per second for mean angle-corrected V(MCA) on the left and right sides were 62-198 and 69-153; those for V(tICA) were 30-196 and 36-175; and those for V(ICA) were 18-116 and 15-95, respectively. Reference ranges for mean angle-corrected V(MCA)/V(ICA) ratio on the left and right sides were 1.2-4.0 and 0.4-3.4 and those for V(tICA)/V(IC)(A) ratio were 0.5-2.9 and 0.5-2.7, respectively. V(MCA), V(tICA), and V(tICA)/V(ICA) ratio were not age dependent, contrary to V(ICA) and V(MCA)/V(ICA) ratio, after controlling for hematocrit and hemoglobin. CONCLUSION The study provides reference limits for V(MCA), V(tICA), V(ICA), and velocity ratios obtained from children with SCD.