Biomedical subjects

Ruben C Gur

Publications and source records attributed to Ruben C Gur.

At least 37 records · Page 2Linked to original sources

PubMed2005

Symptoms versus neurocognitive test performance as predictors of psychosocial status in schizophrenia: a 1- and 4-year prospective study.

In recent years, a growing body of literature has highlighted the significance of neurocognitive deficits as markers for subsequent psychosocial deficits in patients with schizophrenia. Relatively few studies, however, have directly compared symptoms and neurocognitive test performance as predictors of psychosocial status in a prospective design. In two studies with schizophrenia patients, we investigated the relationship between symptom dimensions (psychomotor poverty, disorganization, reality distortion) and neurocognitive measures (problem solving, attention, verbal learning and memory) obtained at study entry, and psychosocial status measured at a 1- and 4-year followup. Results from the 1-year followup (n = 70) revealed that psychomotor poverty, symptoms of disorganization, and performance on measures of card-sorting and visual vigilance were related to psychosocial status. Results from the 4-year followup (n = 26) revealed a similar pattern of findings with the exception of verbal learning, which emerged as a predictor of psychosocial status only at the 4-year followup. Stepwise regression revealed that performance on measures of visual vigilance and psychomotor poverty symptoms explained the largest amount of variance in psychosocial status at both followup intervals. The significance of these findings for the development and assessment of novel treatment interventions for schizophrenia is discussed.

Adult↗

PubMed2005

Quantification of facial expressions using high-dimensional shape transformations.

We present a novel methodology for quantitative analysis of changes in facial display as the intensity of an emotion evolves from neutral to peak expression. The face is modeled as a combination of regions and their boundaries. An expression change in a face is characterized and quantified through a combination of non-rigid (elastic) deformations, i.e., expansions and contractions of these facial regions. After elastic interpolation, this yields a geometry-based high-dimensional 2D shape transformation, which is used to register regions defined on subjects (i.e., faces with expression) to those defined on the reference template face (a neutral face). This shape transformation produces a vector-valued deformation field and is used to define a scalar valued regional volumetric difference (RVD) function, which characterizes and quantifies the facial expression. The approach is applied to a standardized database consisting of single images of professional actors expressing emotions at predefined intensities. We perform a detailed analysis of the deformations generated and the regional volumetric differences computed for expressions. We were able to quantify subtle changes in expression that can distinguish the intended emotions. A model for the average expression of specific emotions was also constructed using the RVD maps. This method can be applied in basic and clinical investigations of facial affect and its neural substrates.

Adolescent↗

PubMed2005

Anger and depression in cocaine addiction: association with the orbitofrontal cortex.

The high prevalence of anger, impulsivity and violence in cocaine addiction implicates chronic cocaine use in the compromise of higher-order inhibitory control neurocognitive processes. We used the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) anger content scale as a personality measure of inhibitory control and examined its association with glucose metabolism in the lateral orbitofrontal gyrus (LOFG) at rest as measured by positron emission tomography with 2-deoxy-2[(18)F]fluoro-D-glucose (PET (18)FDG) in 17 recently abstinent cocaine-dependent subjects and 16 comparison subjects. Three additional variables--the MMPI-2 depression content scale, metabolism in the medial orbitofrontal gyrus (MOFG) and the anterior cingulate (AC) gyrus--were inspected. When level of education was statistically controlled for, the LOFG was significantly associated with anger within the cocaine group. No other region was associated with anger within the cocaine-dependent group, and the LOFG did not correlate with depression within any of the study groups. The present study confirms earlier reports in demonstrating a positive association between relative metabolism at rest in the LOFG and cognitive-behavioral and personality measures of inhibitory control in drug addiction: the higher the metabolism, the better the inhibitory control.

Adult↗

PubMed2005

Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities.

CONTEXT: Neuroanatomic abnormalities in schizophrenia may underlie behavioral manifestations. Characterization of such abnormalities is required for interpreting functional data. Frontotemporal abnormalities have been documented by using predetermined region-of-interest approaches, but deformation-based morphometry permits examination of the entire brain. OBJECTIVES: To perform whole-brain analyses of structural differences between patients with schizophrenia and controls, to examine sex and medication effects, and to apply a high-dimensional nonlinear pattern classification technique to quantify the degree of separation between patients and controls, thereby testing the potential of this new technique as an aid to diagnostic procedures. DESIGN: Whole-brain morphologic analysis using high-dimensional shape transformations. SETTING: Schizophrenia Research Center, University of Pennsylvania Medical Center. PARTICIPANTS: Neuroleptic-naïve and previously treated patients with DSM-IV schizophrenia (n = 69) and sociodemographically matched controls (n = 79). MAIN OUTCOME MEASURES: Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the brain. RESULTS: Magnetic resonance images showed reduced gray matter and increased ventricular cerebrospinal fluid volumes in patients with schizophrenia in the whole brain and in specific foci: the hippocampus and adjacent white matter, the cingulate and orbitofrontal cortex, the frontotemporal and parietotemporal areas, and the occipital areas near the lingual gyrus. The classifier had a mean classification accuracy of 81.1% for men and women combined (82% for women and 85% for men, when each group was treated separately), determined via cross-validation. CONCLUSIONS: This study confirms previous findings of reduced frontotemporal volumes and suggests new hypotheses, especially involving occipital association and speech production areas. It also suggests finer localization of volume reduction in the hippocampus and other limbic structures and in the frontal lobe. Pattern classification showed high sensitivity and specificity for the diagnosis of schizophrenia, suggesting the potential utility of magnetic resonance imaging as a diagnostic aid.

Adult↗

PubMed2005

Telling truth from lie in individual subjects with fast event-related fMRI.

Deception is a clinically important behavior with poorly understood neurobiological correlates. Published functional MRI (fMRI) data on the brain activity during deception indicates that, on a multisubject group level, lie is distinguished from truth by increased prefrontal and parietal activity. These findings are theoretically important; however, their applied value will be determined by the accuracy of the discrimination between single deceptive and truthful responses in individual subjects. This study presents the first quantitative estimate of the accuracy of fMRI in conjunction with a formal forced-choice paradigm in detecting deception in individual subjects. We used a paradigm balancing the salience of the target cues to elicit deceptive and truthful responses and determined the accuracy of this model in the classification of single lie and truth events. The relative salience of the task cues affected the net activation associated with lie in the superior medial and inferolateral prefrontal cortices. Lie was discriminated from truth on a single-event level with an accuracy of 78%, while the predictive ability expressed as the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 85%. Our findings confirm that fMRI, in conjunction with a carefully controlled query procedure, could be used to detect deception in individual subjects. Salience of the task cues is a potential confounding factor in the fMRI pattern attributed to deception in forced choice deception paradigms.

Adolescent↗

PubMed2005

Brain maturation and its relevance to understanding criminal culpability of juveniles.

The purpose of this review is to summarize current understanding of the process of maturation in human brains during the juvenile period to young adulthood. We describe the methods used in such investigations, and outline the main findings regarding the course of brain development. There is much that we do not know about brain maturation, but there is congruence of evidence indicating that brain maturation is not complete until young adulthood (approximately age 21 years). Furthermore, the main index of maturation, which is rate of myelination, points to large variability in the rate of maturation among brain regions. Generally, maturation of association cortex is not complete by late adolescence, and within this cortex the prefrontal regions are last to mature. The review concludes by discussing the behavioral implications of these findings. The role of myelination is to focus and refine the operation of neural networks regulating behavior, and the frontal lobes specifically modulate and inhibit impulses, shaping behavior within the context of the environment in relation to planned action and long-term goals. Because the brain anatomy data indicate that people are not biologically prepared to exercise mature executive control required for full criminal intent until they reach adulthood, juveniles have diminished capacity in this regard and should not be eligible for the most severe punishment available for their crime.

Brain↗

PubMed2005

Neural synchrony and gray matter variation in human males and females: integration of 40 Hz gamma synchrony and MRI measures.

Coherent cognition requires activity to be brought together across diverse brain networks. Synchronous, in-phase oscillations in the high-frequency (40 Hz) Gamma range are thought to be one mechanism underlying the functional integration of brain networks. While sex differences have been observed across a range of cognitive functions, their role in normal cortical synchronization has not been elucidated. We recorded Gamma phase synchrony in 500 male and 500 female subjects during an auditory oddball task, which taps discrimination of task-relevant signals. Results revealed a marked sex-linked dissociation in the spatio-temporal pattern of cortical synchronization. Females showed increased Gamma synchrony in the frontal brain, while males showed enhanced synchrony in the parieto-occipital region. These differences were not accounted for by sex differences in whole brain MRI volume. However, there were positive associations between Gamma synchrony and gray matter for females, while these relationships were negative for males. Sex differences in the profile of cortical synchronization may reflect distinct aspects of evolutionary advantage.

Adult↗

PubMed2005

Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition.

OBJECTIVE: Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. METHOD: Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. RESULTS: Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. CONCLUSIONS: Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies.

Adult↗

PubMed2005

Face recognition memory deficits and visual object memory performance in patients with schizophrenia and their relatives.

OBJECTIVE: Face recognition memory deficits in schizophrenia are attributed to frontotemporal dysfunction. Biological relatives of patients have similar deficits, suggesting genetic susceptibility. Because the impairment may reflect generalized object memory deficits, the authors evaluated both face and visual object recognition. METHOD: The Penn Face Memory Test and Visual Object Learning Test were given to 102 patients with schizophrenia, 60 of their biological relatives, and 135 healthy comparison subjects. RESULTS: Significant immediate and delayed face recognition deficits were observed in patients and their relatives. Although patients were more impaired in visual object memory than comparison subjects, relatives were not. CONCLUSIONS: Face recognition deficits in patients with schizophrenia and their families are not secondary to generalized object memory deficits and may be an endophenotype reflecting frontotemporal impairment.

Adult↗

PubMed2004

Differences in facial expressions of four universal emotions.

The facial action coding system (FACS) was used to examine recognition rates in 105 healthy young men and women who viewed 128 facial expressions of posed and evoked happy, sad, angry and fearful emotions in color photographs balanced for gender and ethnicity of poser. Categorical analyses determined the specificity of individual action units for each emotion. Relationships between recognition rates for different emotions and action units were evaluated using a logistic regression model. Each emotion could be identified by a group of action units, characteristic to the emotion and distinct from other emotions. Characteristic happy expressions comprised raised inner eyebrows, tightened lower eyelid, raised cheeks, upper lip raised and lip corners turned upward. Recognition of happy faces was associated with cheek raise, lid tightening and outer brow raise. Characteristic sad expressions comprised furrowed eyebrow, opened mouth with upper lip being raised, lip corners stretched and turned down, and chin pulled up. Only brow lower and chin raise were associated with sad recognition. Characteristic anger expressions comprised lowered eyebrows, eyes wide open with tightened lower lid, lips exposing teeth and stretched lip corners. Recognition of angry faces was associated with lowered eyebrows, upper lid raise and lower lip depression. Characteristic fear expressions comprised eyes wide open, furrowed and raised eyebrows and stretched mouth. Recognition of fearful faces was most highly associated with upper lip raise and nostril dilation, although both occurred infrequently, and with inner brow raise and widened eyes. Comparisons are made with previous studies that used different facial stimuli.

Adolescent↗

PubMed2004

Facial recognition deficits and cognition in schizophrenia.

Previous investigations have found impaired recognition of facial affect and cognition in schizophrenia. We compared patients with schizophrenia and healthy control volunteers on computerized tasks of emotion recognition, to determine whether emotion processing deficits were correlated with neurocognitive performance. A Computerized Neuropsychological Test Battery (CNP) was administered to 40 patients (25 male, 15 female, mean age+/-S.D. 30.4+/-8.1) with schizophrenia (DSM-IV, 15 first episode and 25 chronically ill patients) treated with atypical neuroleptics and 43 healthy volunteers. A German version of the PENN Facial Discrimination, Differentiation and Memory Test, including happy, sad and neutral faces was used. Additionally, all patients were tested with a standard neuropsychological battery and rated for positive and negative symptoms. Patients with schizophrenia performed worse than control subjects on all emotion recognition tasks (p<0.01). We found higher error rates for discrimination of emotion in happy (p<0.02) and happy female faces (p<0.01), for differentiation of sad versus happy faces (p<0.001) and for facial memory (p<0.04). Poorer performance in emotion discrimination and facial memory correlated with severity of negative symptoms, abstraction-flexibility (p<0.001), verbal memory (p<0.01) and language processing (p<0.001). The study did not reveal a specific deficit for emotion recognition in schizophrenia. These findings lend support to the notion that difficulties in emotion recognition are associated in schizophrenia with key cognitive deficits.

Adult↗

PubMed2004

Symptom and demographic profiles in first-episode schizophrenia.

First-episode schizophrenia (FE-SZP) presents a diagnostic challenge because of symptomatic overlap between the various causes of psychosis. An early and accurate diagnosis is important for the implementation of appropriate treatment, for determining prognosis and for identifying research participants. In an effort to facilitate early diagnosis, we followed a group of first-episode psychosis patients with a presumptive diagnosis of schizophrenia who were subsequently diagnosed at 6-month follow-up with either schizophrenia (n=104) or other psychiatric diagnoses (n=19). The two groups-first-episode schizophrenia and first-episode non-schizophrenia-were compared on measures of demographics, symptoms, quality of life, premorbid adjustment and lateral dominance. Odds ratios were calculated for each variable and all significant variables were entered into a multivariate prediction model. The model showed that higher levels of anhedonia and hallucinations increased the odds of a final diagnosis of schizophrenia. This predictive model was validated in a smaller group of patients.

Adolescent↗

PubMed2004

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-naïve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.

Adult↗

PubMed2004

The Penn Conditional Exclusion Test: a new measure of executive-function with alternate forms of repeat administration.

Studies of change in neuropsychological function over time in both healthy and diseased populations have been hindered by the absence of alternate forms of most commonly used neuropsychological tests. The Penn Conditional Exclusion Test (PCET) was developed as a new cognitive instrument to assess "executive" functioning with four alternate forms. In Study 1, the PCET was administered in counterbalanced order to 80 healthy young adults to establish equivalent test difficulty. Results revealed that the four versions were related on categories achieved, total number of errors and total number of trials. In Study 2, the PCET was administered to 25 healthy adults of a wide age range with a battery of computerized neuropsychological tests to assess construct validity. Convergent validity was confirmed by positive correlations between the PCET and a measure of abstraction. Divergent validity was established through low, nonsignificant correlations between the PCET and measures of facial emotion recognition, word and face memory, visuospatial function, and verbal reasoning.

Adolescent↗

PubMed2004

Recognition of facial emotions in neuropsychiatric disorders.

Recognition of facial emotions represents an important aspect of interpersonal communication and is governed by select neural substrates. We present data on emotion recognition in healthy young adults utilizing a novel set of color photographs of evoked universal emotions. In addition, we review the recent literature on emotion recognition in psychiatric and neurologic disorders, and studies that compare different disorders.

Affect↗

PubMed2004

Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine.

The introduction of surgically implantable medication delivery systems provides psychiatric patients with reversible, uninterrupted access to medication for up to 14 months. This study designed and administered a survey to assess patients' attitudes and beliefs towards illness, medication, and this potential new treatment method. The survey included questions about demographics, insight and attitudes towards illness, current and past medication adherence, attitudes towards psychiatric and nonpsychiatric medications, and understanding and attitudes towards surgical implants. The sample of 206 psychiatric patients was almost equally split between favorably and unfavorably considering implants. Patients favorable towards implants ascribed forgetting and failure to refill medication on time as the reasons for missing doses, recognized the benefits of medication in general, and understood that the implant would be inserted under the skin. Favorable consideration of implants was positively correlated with the desire to avoid adverse consequences of missing medicine, stay well, avoid the need for daily oral medications, and decrease family burden. Unfavorable consideration of implants was related to a preference to take medication orally, concern about feeling controlled, unwillingness to try something new, and not understanding that the implant would be placed under the skin. Demographic variables, past/current medications, specific diagnosis, and illness severity did not influence the decision. This survey elucidates patients' attitudes and beliefs towards illness, medication, and surgical implants. The results indicate that a significant proportion of patients recognize the difficulties of medication adherence and the need for better methods to attain therapeutic response. Thus, the study provides impetus for future work in this area.

Adult↗

PubMed2004

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia.

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.

Adult↗

PubMed2004

Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol.

OBJECTIVE: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. RESULTS: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. CONCLUSIONS: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Adolescent↗