Biomedical subjects

A Z Snyder

Publications and source records attributed to A Z Snyder.

16 recordsLinked to original sources

PubMed1999

Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier.

The blood-brain barrier and a blood-cerebrospinal-fluid (CSF) barrier function together to isolate the brain from circulating drugs, toxins, and xenobiotics. The blood-CSF drug-permeability barrier is localized to the epithelium of the choroid plexus (CP). However, the molecular mechanisms regulating drug permeability across the CP epithelium are defined poorly. Herein, we describe a drug-permeability barrier in human and rodent CP mediated by epithelial-specific expression of the MDR1 (multidrug resistance) P glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP). Noninvasive single-photon-emission computed tomography with 99mTc-sestamibi, a membrane-permeant radiopharmaceutical whose transport is mediated by both Pgp and MRP, shows a large blood-to-CSF concentration gradient across intact CP epithelium in humans in vivo. In rats, pharmacokinetic analysis with 99mTc-sestamibi determined the concentration gradient to be greater than 100-fold. In membrane fractions of isolated native CP from rat, mouse, and human, the 170-kDa Pgp and 190-kDa MRP are identified readily. Furthermore, the murine proteins are absent in CP isolated from their respective mdr1a/1b(-/-) and mrp(-/-) gene knockout littermates. As determined by immunohistochemical and drug-transport analysis of native CP and polarized epithelial cell cultures derived from neonatal rat CP, Pgp localizes subapically, conferring an apical-to-basal transepithelial permeation barrier to radiolabeled drugs. Conversely, MRP localizes basolaterally, conferring an opposing basal-to-apical drug-permeation barrier. Together, these transporters may coordinate secretion and reabsorption of natural product substrates and therapeutic drugs, including chemotherapeutic agents, antipsychotics, and HIV protease inhibitors, into and out of the central nervous system.

3T3 Cells↗

PubMed1999

Diminished regional cerebral blood flow response to vibration in patients with blepharospasm.

OBJECTIVE: To determine whether patients with blepharospasm have abnormal sensorimotor processing similar to patients with writer's cramp. BACKGROUND: Blepharospasm is a focal dystonia manifest by involuntary, excessive blinking and squeezing of the eyes. Altered sensorimotor processing may contribute to the development of dystonic movements. Previously the authors demonstrated decreased vibration-induced cortical blood flow responses in hand primary sensorimotor area (PSA) in patients with hand dystonia. METHODS: In this prospective, case-control study, seven patients with blepharospasm were compared with seven normal subjects. PET measurements of regional blood flow were obtained using bolus administration of H(2)15O at rest or during sequential vibration of either the left or the right hand or side of the mouth. RESULTS: PSA activation decreased significantly in the patients with blepharospasm both ipsilateral (-68%; p = 0.0004) and contralateral to the side of facial stimulation (-56%; p = 0.0009). Patients had a 31% lower mean contralateral PSA response to hand vibration and a 51% smaller right supplementary motor area response to left-hand vibration than normal subjects, but these differences did not reach statistical significance. CONCLUSIONS: Patients with blepharospasm have abnormal sensorimotor processing in response to lower face vibration. They may also have abnormal brain responses to stimulation of clinically uninvolved parts of the body, but this requires confirmation.

Aged↗

PubMed1998

Functional MRI studies of word-stem completion: reliability across laboratories and comparison to blood flow imaging with PET.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.

Adult↗

PubMed1998

Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding.

The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human long-term memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.

Adolescent↗

PubMed1998

A common network of functional areas for attention and eye movements.

Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.

Adolescent↗

PubMed1998

Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging.

PURPOSE: To establish quantitative standards for the directionally averaged water apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A sigma) of normal brains in newborns by using diffusion tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Diffusion tensor MR imaging was performed during the first 36 hours of life in 22 newborns (gestational age range, 31-41 weeks). Values of D and A sigma were measured in regions of interest chosen in the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei, thalami, internal capsules, and cerebellar hemispheres. RESULTS: The D values in the gray and white matter in newborns are considerably higher than those in adults. There is a striking correlation between gestational age and D, with D decreasing as gestational age increases. The A sigma values in the white matter in newborns are lower than those in adults. Values of A sigma show statistically significant correlations with gestational age only in the white matter of the centrum semiovale, in which A sigma values increase sharply near term. CONCLUSION: The D values primarily reflect overall brain water content. The A sigma values are more sensitive to tissue microstructure (e.g., white matter packing and myelination). The D and A sigma images reveal information and not apparent on T1- and T2-weighted images.

Adult↗

PubMed1997

Anatomic localization and quantitative analysis of gradient refocused echo-planar fMRI susceptibility artifacts.

Functional magnetic resonance imaging (fMRI) techniques, such as echo-planar imaging, can permit rapid, sensitive, whole-brain measurements of local blood flow-induced MR signal changes seen during cognitive paradigms. Changes in blood oxygenation due to mismatch of flow and oxygen metabolism cause dynamic variations in microscopic susceptibility effects, leading to the blood oxygenation level-dependent (BOLD) signal measured by fMRI techniques. A related static macroscopic susceptibility effect is known to cause artifacts that attenuate the MR signal, leading to "blind spots" in some regions of brain adjacent to bone and air sinuses. The anatomical location, spatial extent, and magnitude of signal loss artifact are quantitated for a common whole-brain fMRI technique. Resting gradient-echo EPI studies were obtained in four healthy volunteers. Signal loss was primarily localized to inferior frontal regions (medial orbital gyri and gyrus rectus) and to inferior lateral temporal lobe (including part of fusiform gyrus) bilaterally. Increased echo time (TE) uniformly produced larger artifacts. The orientation of acquired slices and choice of phase-encoding direction influenced the location, shape, and extent of the artifacts. Regions of the brain with severe artifact may have attenuated activation signal, with potential implications for the design and interpretation of fMRI studies targeting activations in these areas.

Adult↗

PubMed1995

Scalp electrical potentials reflect regional cerebral blood flow responses during processing of written words.

Functional brain imaging studies with positron emission tomography (PET) have identified blood flow changes in widely separated areas of the brain during the performance of word-related tasks. In the present study, we have utilized event-related electrical potentials (ERPs) to investigate the temporal relationships among cortical areas previously identified by PET to be differentially activated when performing a task involving generating the uses of visually presented nouns versus reading aloud. ERPs showed strong task-related differences over left and middle inferior frontal and left parietotemporal regions. Frontal and left parietotemporal channels revealed these differences around 200 and 700 msec, respectively, after word presentation. These results provide the time course for parts of the anatomical circuit involved in generating the meaning of a word. Our results also demonstrate how combining the spatial localization of PET with the temporal resolution of ERPs greatly enhances the capacity to understand the mechanisms involved in human cognition.

Adult↗

PubMed1995

Blood flow changes in human somatosensory cortex during anticipated stimulation.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Adult↗

PubMed1990

Activation of extrastriate and frontal cortical areas by visual words and word-like stimuli.

Visual presentation of words activates extrastriate regions of the occipital lobes of the brain. When analyzed by positron emission tomography (PET), certain areas in the left, medial extrastriate visual cortex were activated by visually presented pseudowords that obey English spelling rules, as well as by actual words. These areas were not activated by nonsense strings of letters or letter-like forms. Thus visual word form computations are based on learned distinctions between words and nonwords. In addition, during passive presentation of words, but not pseudowords, activation occurred in a left frontal area that is related to semantic processing. These findings support distinctions made in cognitive psychology and computational modeling between high-level visual and semantic computations on single words and describe the anatomy that may underlie these distinctions.

Adult↗

PubMed1990

Replication of a study of frequency analysis of the resting awake EEG in mild probable Alzheimer's disease.

In the resting EEG, the percentage power in the delta, theta, alpha, and beta bands and the mean frequency were computed in an occipital-vertex derivation for two samples of subjects. The original sample (n = 79) and the new sample (n = 43) each contained a mild probable Alzheimer's disease (SDAT) group and a healthy elderly control group. Group medians in both samples were higher in the SDAT than in the healthy subjects for percentage delta and theta, and were lower for percentage alpha and beta and for mean frequency. Percentage theta and mean frequency were consistent across the two samples in showing statistically significant differences between SDAT and healthy groups. The ability of each EEG measure to detect individual subjects with SDAT was assessed. The most effective measure, percentage theta, had only modest sensitivity (about 20%), but this was attained at a specificity of 100%. The accurate detection of an individual at the mild stage requires that the predictive value of a positive test be high to avoid misclassification of non-SDAT subjects as SDAT. This, in turn, requires a specificity of virtually 100% when the prevalence is low. The low sensitivity puts several constraints on the usefulness of the EEG. For this reason, when the dementia is at the mild stage the EEG would be a useful detector of probable Alzheimer's disease only under certain limiting conditions, including high prevalence, high specificity, and a willingness to accept a high rate of falsely negative tests.

Aged↗

PubMed1989

Representation of the fovea in the superior temporal sulcus of the macaque monkey.

The response properties of 633 neurons from striate and prestriate cortex were recorded in 3 hemispheres of two awake cynomolgus monkeys while they fixated or tracked a small spot of light. Of 254 penetrations located at 1 mm intervals, 39% were identifiable from visible electrolytic lesions or electrode tracks and were used to reconstruct the positions of all recording sites. A total of 226 cells were located in the superior temporal sulcus and 81 cells in area V1. The location and visuotopic organization of the foveal portion of the middle temporal (MT) visual area were determined in three hemispheres. MT was defined physiologically on the basis of direction-selectivity, receptive field size, and retinotopic organization. Of 170 MT neurons, most were motion sensitive, and 65% had a directionality index, (best-opposite)/best, of 0.6 or higher. MT was defined anatomically on the basis of myelin staining within the superior temporal sulcus (STS). On the posterior bank of the STS the physiologically defined border corresponded closely to a myelin border visible on our sections. Distinct myelin borders were not consistently identifiable on the anterior bank. The representation of the central fovea (eccentricities of 0-1 deg) was located partly on the floor, but mostly on the posterior bank of the STS at the extreme postero-lateral edge of MT. In all three hemispheres foveal MT extended onto the roof of a cleft formed between the posterior bank and a wide flattened area on the floor of the STS. This region lies 10-12 mm below the brain surface, measuring along a line normal to the surface at a point 2-3 mm antero-lateral to foveal V1. The area of MT was 6-9 mm2 for the central fovea (0-1 deg), 15-24 mm2 for the entire fovea (0-3 deg), and 28-40 mm2 including the fovea and parafovea (0-10 deg). A visuotopic map of central foveal V1 (0-1 deg) was obtained in one animal. The measured area of this representation was 116 mm2. Using published estimates of the total areas of cynomolgus MT and V1 (73 and 1200 mm2 respectively) the ratio of central foveal to total area was calculated to be 0.10 for both MT (7.5/73) and V1 (116/1200), indicating that the relative magnification of the foveal versus the peripheral visual field is preserved in the mapping of V1 onto MT. A separate representation of the central visual field was found immediately adjacent to foveal MT.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Orientation shift between upper and lower layers in monkey visual cortex.

Microelectrode penetrations nearly normal to the layers of foveal striate cortex in awake, behaving monkeys reveal a shift in orientation preference between cells in the upper and lower layers. Mean shift size for 57 penetrations is 54.8 degrees, with 70% of the penetrations showing shifts of 45-90 degrees. Marking lesions localize the shift to the border between layers 4C and 5. The data are suggestive of inhibition between the upper and lower layers within an "orientation column".

Animals↗

PubMed1981

Magnification factor and receptive field size in foveal striate cortex of the monkey.

Receptive field size and magnification have been studied in striate cortex of awake, behaving rhesus monkeys at visual eccentricities in the range of 5-160 min. The major findings that emerge are (1) magnification in the foveola achieves values in the range of 30 mm/deg, (2) mean field size is not proportional to inverse magnification in contrast with previous reports, and (3) the product, magnification X aggregate field size, is greater in central vision than in peripheral vision. Thus, a point of light projected onto foveal retina is "seen" by larger numbers of striate cortical cells than a point of light projected onto peripheral retina. Implications of these findings for visual localization and two-point discrimination are discussed.

Animals↗

PubMedDate not supplied

Dipole source localization in the study of EP generators: a critique.

(1) The decision to solve the inverse problem in terms of one or more localized generators implies the assumption of a particular generator model. This assumption permits carrying out inverse dipole estimation. However, it is perilous to justify the procedure on the basis of the result. (2) Goodness of fit is a necessary but not sufficient criterion of model adequacy. A particular quantitative inverse solution has meaning only if it is accompanied by consideration of sensitivity to small changes in all of the free modeling parameters and estimates of perturbing factors including noise and forward calculation uncertainties.

Brain Mapping↗

PubMedDate not supplied

Steady-state vibration evoked potentials: descriptions of technique and characterization of responses.

Steady-state scalp evoked potentials were recorded in response to amplitude modulated vibration applied to the fingers and palmar surface of one hand. Evoked response dependence on the frequency of amplitude modulation in the 2-40 Hz range was studied in a group of normal young adult volunteers. Response amplitude was greatest at low amplitude modulation frequencies. The greatest signal to EEG noise ratios were found at modulation frequencies near 26 Hz. At modulation frequencies near 26 Hz the steady-state response latency was found to be 58 +/- 14 msec. Inverse dipole modeling localized the steady-state evoked response generators in or near somatosensory cortex with the dipole moment orientation being predominantly in the anterior-posterior direction.

Adolescent↗