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Godfrey D Pearlson

Publications and source records attributed to Godfrey D Pearlson.

At least 19 recordsLinked to original sources
PubMed2006

A virtual reality apartment as a measure of medication management skills in patients with schizophrenia: a pilot study.

Performance on a novel, virtual reality (VR) assessment of medication management skills, the Virtual Reality Apartment Medication Management Assessment (VRAMMA), was investigated in 25 patients with schizophrenia and 18 matched healthy controls. The VRAMMA is a virtual 4-room apartment consisting of a living room with an interactive clock and TV, a bedroom, a kitchen, and a bathroom with an interactive medicine cabinet. After an exploratory phase, participants were given a mock prescription regimen to be taken 15 minutes later from pill bottles located in the medicine cabinet in the bathroom of the virtual environment. The VRAMMA was administered with a validated measure of medication management skills, several neurocognitive tests, and a symptom scale. Results revealed that (1) schizophrenic patients made significantly more quantitative errors in the number of pills taken, were less accurate at taking the prescribed medications at the designated time, and checked the interactive clock less frequently than healthy controls; (2) in patients with schizophrenia, there was significant agreement in classification of adherence vs nonadherence between a validated measure of medication management skills and the VRAMMA; and (3) in patients with schizophrenia, years of education and a measure of verbal learning and memory were linked to quantitative errors on the VRAMMA, while positive symptoms, specifically delusional symptoms, were inversely linked to distance traveled within the VRAMMA. This is the first study, to our knowledge, to provide evidence for the utility of VR technology in the assessment of instrumental role functioning in patients with schizophrenia.

Adult↗
PubMed2006

Neural correlates of the object-recall process in semantic memory.

The recall of an object from features is a specific operation in semantic memory in which the thalamus and pre-supplementary motor area (pre-SMA) are integrally involved. Other higher-order semantic cortices are also likely to be involved. We used the object-recall-from-features paradigm, with more sensitive scanning techniques and larger sample size, to replicate and extend our previous results. Eighteen right-handed healthy participants performed an object-recall task and an association semantic task, while undergoing functional magnetic resonance imaging. During object-recall, subjects determined whether words pairs describing object features combined to recall an object; during the association task they decided if two words were related. Of brain areas specifically involved in object recall, in addition to the thalamus and pre-SMA, other regions included the left dorsolateral prefrontal cortex, inferior parietal lobule, and middle temporal gyrus, and bilateral rostral anterior cingulate and inferior frontal gyri. These regions are involved in semantic processing, verbal working memory and response-conflict detection and monitoring. The thalamus likely helps to coordinate activity of these different brain areas. Understanding the circuit that normally mediates this process is relevant for schizophrenia, where many regions in this circuit are functionally abnormal and semantic memory is impaired.

Adult↗
PubMed2006

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

BACKGROUND: Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. METHODS: We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. RESULTS: Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. CONCLUSIONS: Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

Adult↗
PubMed2006

DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking.

A versatile resource program was developed for diffusion tensor image (DTI) computation and fiber tracking. The software can read data formats from a variety of MR scanners. Tensor calculation is performed by solving an over-determined linear equation system using least square fitting. Various types of map data, such as tensor elements, eigenvalues, eigenvectors, diffusion anisotropy, diffusion constants, and color-coded orientations can be calculated. The results are visualized interactively in orthogonal views and in three-dimensional mode. Three-dimensional tract reconstruction is based on the Fiber Assignment by Continuous Tracking (FACT) algorithm and a brute-force reconstruction approach. To improve the time and memory efficiency, a rapid algorithm to perform the FACT is adopted. An index matrix for the fiber data is introduced to facilitate various types of fiber bundles selection based on approaches employing multiple regions of interest (ROIs). The program is developed using C++ and OpenGL on a Windows platform.

Algorithms↗
PubMed2006

A method for multitask fMRI data fusion applied to schizophrenia.

It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel-by-voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are "coupled" together by a shared loading parameter. We first compute an activation map for each task and each individual as "features," which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate "decreased" connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate "more similarly" for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less-unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them.

Adult↗
PubMed2006

Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality.

INTRODUCTION: Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving. OBJECTIVE: We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center. METHODS: Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA. RESULTS: Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined. CONCLUSION: In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.

Automobile Driving↗
PubMed2005

Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.

BACKGROUND: The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. METHOD: Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. RESULTS: Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. CONCLUSIONS: Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.

Adult↗
PubMed2005

Diffusion tensor imaging in schizophrenia.

BACKGROUND: Diffusion tensor imaging (DTI) is a relatively new neuroimaging technique that can be used to examine the microstructure of white matter in vivo. A systematic review of DTI studies in schizophrenia was undertaken to test the hypothesis that DTI can detect white matter differences between schizophrenia patients and normal control subjects. METHODS: EMBASE, PubMed, Medline, and PsychInfo were searched online and key journals were searched manually for studies comparing anisotropy (a measure of white matter integrity) between patients and control subjects. Nineteen articles were systematically reviewed. RESULTS: Though 16 studies found differences, methodological and data differences prevented a meta-analysis. Fourteen studies found reduced anisotropy in patients; two studies found only a loss of normal asymmetry. The region of investigation varied across studies, however, and when the same region (for example, the cingulum) was examined in different studies, as many failed to find a difference as found one. These inconsistencies may be the result of small sample sizes and differences in methodology. CONCLUSIONS: Diffusion tensor imaging has yet to provide consistent findings of white matter abnormalities in schizophrenia. Its potential as a means of examining anatomical connectivity may be realized with the study of larger, more homogenous groups of subjects and with ongoing improvements in image analysis.

Adult↗
PubMed2005

Decreased frontal white-matter volume in chronic substance abuse.

There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.

Adult↗
PubMed2005

Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia.

Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used "region of interest" (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem.

Adult↗
PubMed2005

Hippocampal and ventricular volumes in psychotic and nonpsychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study.

BACKGROUND: Previous reports of ventricular and hippocampal volumes in patients with bipolar disorder (BP) have been inconsistent in their findings. One possibility is that volumetric abnormalities are determined by disease subtype. Prior evidence suggests that psychotic (PBP) and nonpsychotic (NPBP) forms of BP are two subtypes that might differ in pathophysiology. METHODS: We investigated ventricular and hippocampal volumes in 38 adults with clearly defined PBP (n = 23) and NPBP subtypes, compared with 33 persons with schizophrenia (SZ) and 44 healthy community control subjects (HC). Ventricular and hippocampal volumes were reliably measured on high-resolution anatomic magnetic resonance imaging scans. We used a multivariate analysis of covariance to compare volumes across groups, covarying for total brain volume. Potential effects of BP illness features were explored, contrasting PBP and NPBP. RESULTS: For ventricular but not hippocampal regions, we found significant volume difference in PBP but not NPBP compared with HC (p < .005). We also observed nonsignificantly smaller left hippocampal volumes in PBP versus HC. Schizophrenic subjects had significantly larger ventricular and smaller left hippocampal volumes than HC. CONCLUSIONS: These results suggest that PBP but not NPBP is associated with increased ventricle volumes and a trend toward smaller left hippocampal volumes, as observed in SZ.

Adult↗
PubMed2005

Source density-driven independent component analysis approach for fMRI data.

Independent component analysis (ICA) has become a popular tool for functional magnetic resonance imaging (fMRI) data analysis. Conventional ICA algorithms including Infomax and FAST-ICA algorithms employ the underlying assumption that data can be decomposed into statistically independent sources and implicitly model the probability density functions of the underlying sources as highly kurtotic or symmetric. When source data violate these assumptions (e.g., are asymmetric), however, conventional ICA methods might not work well. As a result, modeling of the underlying sources becomes an important issue for ICA applications. We propose a source density-driven ICA (SD-ICA) method. The SD-ICA algorithm involves a two-step procedure. It uses a conventional ICA algorithm to obtain initial independent source estimates for the first-step and then, using a kernel estimator technique, the source density is calculated. A refitted nonlinear function is used for each source at the second step. We show that the proposed SD-ICA algorithm provides flexible source adaptivity and improves ICA performance. On SD-ICA application to fMRI signals, the physiologic meaningful components (e.g., activated regions) of fMRI signals are governed typically by a small percentage of the whole-brain map on a task-related activation. Extra prior information (using a skewed-weighted distribution transformation) is thus additionally applied to the algorithm for the regions of interest of data (e.g., visual activated regions) to emphasize the importance of the tail part of the distribution. Our experimental results show that the source density-driven ICA method can improve performance further by incorporating some a priori information into ICA analysis of fMRI signals.

Adult↗
PubMed2005

fMRI hippocampal activity during a virtual radial arm maze.

Numerous studies have shown that the hippocampus is critical for spatial memory. Within nonhuman research, a task often used to assess spatial memory is the radial arm maze. Because of the spatial nature of this task, this maze is often used to assess the function of the hippocampus. Our goal was to extrapolate this task to humans and examine whether healthy undergraduates utilize their hippocampus while performing a virtual reality version of the radial arm maze task. Thirteen undergraduates performed a virtual radial arm maze during functional magnetic resonance imaging. The brain maps of activity reveal bilateral hippocampal BOLD signal changes during the performance of this task. However, paradoxically, this BOLD signal change decreases during the spatial memory component of the task. Additionally, we note frontal cortex activity reflective of working memory circuits. These data reveal that, as predicted by the rodent literature, the hippocampus is involved in performing the virtual radial arm maze in humans. Hence, this virtual reality version may be used to assess the integrity of hippocampus so as to predict risk or severity in a variety of psychiatric disorders.

Adolescent↗
PubMed2005

The use of word-reading to estimate "premorbid" ability in cognitive domains other than intelligence.

Diagnostic neuropsychological assessment requires the clinician to estimate a patient's premorbid abilities. Word reading tests, such as the National Adult Reading Test-Revised (NART-R), provide reasonably accurate estimates of premorbid IQ, but their capacity to benchmark other premorbid cognitive abilities remains unclear. In this extension of an earlier report, we administered the NART-R, an abbreviated Wechsler Adult Intelligence Scale (WAIS-R or WAIS-III), and 26 other cognitive measures to 322 reasonably healthy adults. While NART-R performance correlated robustly (rs > or = .72) with concurrent Verbal and Full Scale IQ, its correlation with all other cognitive measures was significantly lower. Thus, while it is appealing to use word reading as a proxy for premorbid functioning in other cognitive domains, the NART-R has limited utility for this because it does not predict current performance on other cognitive tests as well as it predicts IQ in healthy adults.

Adolescent↗
PubMed2004

Functional MRI study of a serial reaction time task in Huntington's disease.

The aim of this study was to investigate pathophysiological changes at an early stage of clinical Huntington's disease (HD) using a functional magnetic resonance imaging (fMRI) study and a serial reaction time task paradigm. Mildly affected and presymptomatic HD subjects (n = 8) and healthy normal controls (NC, n = 12) were studied. A group behavioral effect of implicit learning was seen only in the control population. Individual statistical parametric mapping (SPM) analysis showed more consistent activation of the caudate nucleus and putamen in the NC group. In the HD group, the group average SPM showed significant activation in the right head of caudate nucleus, as well as bilateral thalami, left middle temporal, right superior temporal, right superior frontal, right middle and inferior frontal and right postcentral gyri. In the comparison of between-group differences (NC-HD), reduced activation in the HD group relative to NC was observed in the right middle frontal, left middle occipital, left precuneus, and left middle frontal gyri. The variable striatal activity in the Huntington's group suggests early functional loss possibly associated with previously demonstrated early atrophy of these same neural structures.

Adult↗
PubMed2004

Aberrant localization of synchronous hemodynamic activity in auditory cortex reliably characterizes schizophrenia.

BACKGROUND: Among the most prominent features of schizophrenic brains are abnormalities in auditory cortex structure and function, particularly in the superior temporal gyrus (STG). In this study, we attempted to examine auditory cortex function using an intrinsic, task-uncorrelated measure. METHODS: Using functional magnetic resonance imaging data, we calculated synchronous hemodynamic independent maps (SHIMs) of auditory cortex in patients with schizophrenia and matched healthy control subjects while they performed an auditory oddball task. RESULTS: Patient SHIMs revealed greater synchrony in ventral and medial STG regions (including auditory association Brodmann area [BA] 42); control SHIMs had greater synchrony in dorsal and lateral STG regions (which did not include BA 42). A within-participant subtractive comparison of these two sets of regions differentiated schizophrenic from healthy control subjects with 97% accuracy initially (further validated by a retest of the healthy control subjects) and performed with 94% accuracy in a confirmatory study of new subjects scanned at a different site. CONCLUSIONS: These results shed new light on STG functional differences in schizophrenia, suggest that aberrant patterns of coherence in temporal lobe cortical regions are a cardinal abnormality in schizophrenia, and have the potential to provide a powerful, quantitative clinical tool for the assessment of schizophrenia.

Acoustic Stimulation↗
PubMed2004

Functional brain changes in presymptomatic Huntington's disease.

Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.

Adult↗