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Robert Freedman

Publications and source records attributed to Robert Freedman.

43 records · Page 3Linked to original sources
PubMed2002

Input dysfunction, schizotypy, and genetic models of schizophrenia.

Peter Venables proposed that an input dysfunction, which causes the brain to lose its ability to control the flood of sensory information into its higher level processing areas, might be an important pathophysiological mechanism in schizophrenia. The hypothesis was part of his general belief that even the most severe psychopathology arises from aberrations in normal brain psychophysiology. Neurobiological and genetic investigations based on his initial observations include the demonstration that diminished inhibition of the auditory-evoked response to repeated stimuli is a genetically determined deficit, linked to one of the chromosomal loci that is also responsible for the part of the genetically transmitted risk for schizophrenia. Increasing evidence that schizophrenia is a multigenetic illness prompts reconsideration of the nature of schizotypy. Individual genes that convey part of the risk for schizophrenia may be quite common in the general population and cause relatively subtle changes in psychophysiology. Thus, as predicted by Venables, the substrates of schizotypy and schizophrenia may arise from variants in normal brain function.

Adult↗
PubMed2002

Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia.

BACKGROUND: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) has been implicated as a candidate gene for schizophrenia, and for an auditory sensory processing deficit found in the disease, by both genetic linkage at 15q14 and biochemical data. The expression of CHRNA7 is reduced in several brain regions in schizophrenic subjects compared with control subjects. This study presents DNA sequence analysis of the core promoter region for CHRNA7 in schizophrenic and control subjects. METHODS: Single-strand conformation polymorphism analysis and DNA sequencing were used for mutation screening of the core promoter in the CHRNA7 gene. The sample included subjects from 166 schizophrenic families and 165 controls. Controls had no evidence of current or past psychosis and had auditory evoked potentials recorded. RESULTS: Multiple polymorphic patterns were identified in the CHRNA7 core promoter in both schizophrenic and control subjects. Functional analysis of polymorphisms indicated that transcription was reduced. The prevalence of functional promoter variants was statistically greater in schizophrenic subjects than in the controls. Presence of an alpha7 promoter polymorphism in controls was associated with failure to inhibit the P50 auditory evoked potential response. CONCLUSIONS: Although linkage disequilibrium with other genetic alterations cannot be excluded, the CHRNA7 core promoter variants, found in this study, may contribute to a common pathophysiologic feature of schizophrenia.

Auditory Perceptual Disorders↗
PubMed2002

Monitoring eye movements during fMRI tasks with echo planar images.

Verifying task compliance during functional magnetic resonance imaging (fMRI) experiments is an essential component of experimental design. To date, studies of oculomotor tasks such as smooth pursuit eye movements have either measured task performance outside the magnet and assumed similar performance during functional neuroimaging, or have used MR-compatible eye movement recording devices, which can be costly and technically difficult to use. We describe a simple method to visualize and quantify eye movements during an imaging experiment using the gradient echo images. We demonstrate that local eye movements will influence whole-head motion correction procedures, resulting in inaccurate movement parameters and potentially lowering the sensitivity to detect activations.

Adult↗
PubMed2002

Comparison of detrending methods for optimal fMRI preprocessing.

Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.

Adult↗
PubMed2002

Brain activation during smooth-pursuit eye movements.

A potential application of studying eye movements with functional MRI (fMRI) is to examine patient populations with known eye movement dysfunction, but the reliability with which normal subjects demonstrate activity in specific brain regions has not been established. To date, fMRI studies of smooth-pursuit eye movements have used relatively small numbers of subjects and have been restricted to fixed-effects analyses. We extend these studies to whole brain imaging at 1.5 T, properly accounting for intersubject variation using random effects analysis. Smooth-pursuit eye movements elicited activation consistently in dorsal cortical eye fields and cerebellum. Subcortical activation was greatly attenuated, but not eliminated, with the random-effects second-level analysis. In addition, session-dependent changes in activation were greater in some regions than others and may indicate areas of brain, such as the supplementary eye fields, that are sensitive to attentional modulation of eye movements.

Adult↗
PubMed2002

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes.

Abnormalities during a smooth pursuit eye movement task (SPEM) are common in schizophrenic patients and their relatives. This study assessed various components of SPEM performance in first-degree unaffected relatives of schizophrenic patients. One hundred individuals with schizophrenia, 137 unaffected first-degree relatives, and 69 normal controls completed a 16.7 degrees/s SPEM task. Smooth pursuit gain, catch-up saccades (CUS), large anticipatory saccades, and leading saccades (LS) were identified. Groups were compared with parametric and admixture analyses. Schizophrenic patients performed more poorly than unaffected relatives and normals on gain, CUS, and LS. Unaffected relatives were more frequently impaired than normals only on gain and LS. Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset schizophrenia.

Adolescent↗