Electrocorticographic (ECoG) spectral patterns obtained during language tasks from 12 epilepsy patients (age: 12-44 years) were analysed in order to identify and characterize cortical language areas. ECoG from 63 subdural electrodes (500 Hz/channel) chronically implanted over frontal, parietal and temporal lobes were examined. Two language tasks were performed. During the first language task, patients listened to a series of 50 words preceded by warning tones, and were asked to repeat each word. During a second memory task, subjects heard the 50 words from the first task randomly mixed with 50 new words and were asked to repeat the word only if it was a new word. Increases in ECoG gamma power (70-100 Hz) were observed in response to hearing tones (primary auditory cortex), hearing words (posterior temporal and parietal cortex) and repeating words (lateral frontal and anterior parietal cortex). These findings were compared to direct electrical stimulation and separate analysis of ECoG gamma changes during spontaneous inter-personal conversations. The results indicate that high-frequency ECoG reliably differentiates cortical areas associated with receptive and expressive speech processes for individual patients. Compared to listening to words, greater frontal lobe and decreased temporal lobe gamma activity was observed while speaking. The data support the concept of distributed functionally specific language modules interacting to serve receptive and expressive speech, with frontal lobe 'corollary discharges' suppressing low-level receptive cortical language areas in the temporal lobe during speaking.
We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimer's disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness.
Patients with Alzheimer's disease (AD) were asked to name pictures and perform a multiplechoice word-picture matching task with verbs and nouns. AD patients were significantly more impaired with verbs than nouns for both naming and word-picture matching, and their patterns of semantic naming errors differed for verbs and nouns. One subgroup of AD patients was compromised on both naming and word-picture matching consistent with a semantic memory deficit. Naming was worse for verbs than for nouns in these patients, and they produced significantly fewer hierarchically related semantic substitutions for verbs than for nouns. Other AD patients without semantic memory difficulty did not demonstrate these form class-sensitive patterns. The investigators hypothesize that form class-specific effects in AD patients' naming are due in part to differences in processing verbs and nouns in semantic memory.
Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a five-year period with serial neurological exams, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first two years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease.
Background
Functional magnetic resonance imaging (fMRI) time series are subject to corruption by many noise sources, especially physiological noise and motion. Researchers have developed many methods to reduce physiological noise, including RETROICOR, which retroactively removes cardiac and respiratory waveforms collected during the scan, and CompCor, which applies principal components analysis (PCA) to remove physiological noise components without any physiological monitoring during the scan.
New Method
We developed four variants of the CompCor method. The optimized CompCor method applies PCA to time series in a noise mask, but orthogonalizes each component to the BOLD response waveform and uses an algorithm to determine a favorable number of components to use as "nuisance regressors." Whole brain component correction (WCompCor) is similar, except that it applies PCA to time-series throughout the whole brain. Low-pass component correction (LCompCor) identifies low-pass filtered components throughout the brain, while high-pass component correction (HCompCor) identifies high-pass filtered components. Comparison with existing method: We compared the new methods with the original CompCor method by examining the resulting functional contrast-to-noise ratio (CNR), sensitivity, and specificity.
Results
1) the optimized CompCor method increased the CNR and sensitivity compared to the original CompCor method and 2) the application of WCompCor yielded the best improvement in the CNR and sensitivity.
Conclusions
The sensitivity of the optimized CompCor, WCompCor, and LCompCor methods exceeded that of the original CompCor method. However, regressing noise signals showed a paradoxical consequence of reducing specificity for all noise reduction methods attempted.
We investigated phonologic production in patients with mild to moderate Alzheimer's disease (AD) on a repetition task. AD patients produced significantly more speech errors than age-matched controls. AD patients' errors, unlike those of controls, resulted in the transformation of real words into pseudowords, occurred disproportionately in word-initial positions, and were not influenced by the phonologic environment. This pattern of errors suggests a lexical phonologic retrieval deficit in AD.
Brain metastases occur in up to 25–55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood–brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).
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