Gender and aging moderate brain-behavior relationships. Advances in neuroscience enable integrati... more Gender and aging moderate brain-behavior relationships. Advances in neuroscience enable integration of neurobehavioral, neuroanatomic, and neurophysiology measures. Here we present neurobehavioral studies thai examine cognitive and emotion processing in healthy men and women and highlight the effects of sex differences and aqinq. Neuroanatomic studies with maqnetic resonance imaging (MRI) indicate that the progressive decrease in brain volume affects froniotemporal brain regions in men more than in Vi/omen, Functional imaging methods suggest sex differences in rate of blood flow, pattern of glucose metabolism, and receptor activity. The role of ovarian hormones is important in elucidating the observed relationships. A life span perspective on gender differences through the integration of available methodologies will advance understanding healthy people and the effects of brain disorders.
Ventral striatum (VS) is a critical brain region for reinforcement learning and motivation, and V... more Ventral striatum (VS) is a critical brain region for reinforcement learning and motivation, and VS hypofunction is implicated in psychiatric disorders including schizophrenia. Providing rewards or performance feedback has been shown to activate VS. Intrinsically motivated subjects performing challenging cognitive tasks are likely to engage reinforcement circuitry even in the absence of external feedback or incentives. However, such intrinsic reinforcement responses have received little attention, have not been examined in relation to behavioral performance, and have not been evaluated for impairment in neuropsychiatric disorders such as schizophrenia. Here we used fMRI to examine a challenging "old" vs. "new" visual recognition task in healthy subjects and patients with schizophrenia. Targets were unique fractal stimuli previously presented as salient distractors in a visual oddball task, producing incidental memory encoding. Based on the prediction error theory of reinforcement learning, we hypothesized that correct target recognition would activate VS in controls, and that this activation would be greater in subjects with lower expectation of responding correctly as indexed by a more conservative response bias. We also predicted these effects would be reduced in patients with schizophrenia. Consistent with these predictions, controls activated VS and other reinforcement processing regions during correct recognition, with greater VS activation in those with a more conservative response bias. Patients did not show either effect, with significant group differences suggesting hyporesponsivity in patients to internally generated feedback. These findings highlight the importance of accounting for intrinsic motivation and reward when studying cognitive tasks, and add to growing evidence of reward circuit dysfunction in schizophrenia that may impact cognition and function.
Impaired facial expressions of emotions have been described as characteristic symptoms of schizop... more Impaired facial expressions of emotions have been described as characteristic symptoms of schizophrenia. Previous investigations of dynamic facial expressions have reported on global assessment of positive and negative emotion expressions. In this study, we examined facial expression differences based on duration and frequencies of emotion expressions. 12 persons with stable schizophrenia and matched healthy controls underwent a standardized procedure for evoked facial expressions of five universal emotions, including happy, sad, anger, fear, and disgust expressions. Subjects completed self-ratings of their emotion experience. Reliable raters coded evoked facial expressions according to the Facial Expression Coding System. For each emotion, facial expressions were coded as target, non-target or neutral expressions. Logistic regression analyses examined group differences in duration and frequencies of facial expressions. Comparing overall duration of and frequencies of emotion expres...
In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal dif... more In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal different moral decision patterns as compared to healthy subjects and whether common social interaction difficulties in ASD are reflected in altered brain activation during different aspects of moral reasoning. 28 patients with high-functioning ASD and 28 healthy subjects matched for gender, age and education took part in an event-related functional magnetic resonance imaging study. Participants were confronted with textual dilemma situations followed by proposed solutions to which they could agree or disagree. On a neural level, moral decision making was associated with activation in anterior medial prefrontal regions, the temporo-parietal junction and the precuneus for both groups. However, while patients and healthy controls did not exhibit significant behavioral differences, ASD patients showed decreased activation in limbic regions, particularly the amygdala, as well as increased activation in the anterior and the posterior cingulate gyrus during moral reasoning. Alterations of brain activation in patients might thus indicate specific impairments in empathy. However, activation increases in brain regions associated with the default mode network and self-referential cognition also provide evidence for an altered way of patients cerebral processing with regard to decision making based on social information.
Schizophrenia patients display impaired performance and brain activity during facial affect recog... more Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.
Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests pr... more Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect. Studies have examined the perception, experience, and expression of emotions in schizophrenia and reported normal ratings of experience but impaired affect identification. However, the relation between flat affect and performance on facial affect identification and cognitive tasks has not been systematically examined in relation to premorbid adjustment and clinical outcome. We report a prospective study of 63 patients with at least moderate severity of flat affect and 99 patients without flat affect, who were compared on functional domains, emotion processing tasks, and neurocognitive measures. Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year followup. Patients overall performed more poorly on emotion processing tasks, one that required identification of happy and sad emotions and one that required differentiating among intensities within these emotions. They responded inaccurately yet faster than controls for the intensity differentiation task, suggesting a decomposition of the normal relation between accuracy and speed. Flat affect ratings, compared with other negative symptoms, uniquely predicted performance on emotion processing tasks. Patients with flat affect showed greater impairment in both emotion processing tasks, with the most pronounced impairment for the intensity differentiation task. However, the 2 patient groups did not differ in the neurocognitive profile except for verbal memory. We conclude that flat affect is an important clinical feature of schizophrenia that exacerbates the course of illness.
Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia ... more Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia from unaffected family members and healthy comparison subjects. These deficits in neurocognitive performance in patients with schizophrenia appear stable in the short-term. However, the duration of most, but not all, longitudinal studies is modest and the majority have relied on traditional average performance measures to examine stability. Using a computerized neurocognitive battery (CNB), we assessed mean performance (accuracy and speed) and intra-individual variability (IIV) in a longitudinal study aimed to examine neurocognitive stability in European-American multiplex families with schizophrenia. Thirty-four patients with schizophrenia, 65 unaffected relatives, and 45 healthy comparison subjects completed the same computerized neurocognitive assessment over approximately 5 years. Measures of mean performance showed that patients had stable accuracy performance but were slower in many neurocognitive domains over time as compared with unaffected family members and healthy subjects. Furthermore, patients and family members showed dissociable patterns of change in IIV for speed across cognitive domains: compared with controls, patients showed higher across-task IIV in performance compared with family members, who showed lower across-task IIV. Patients showed an increase in IIV over time, whereas family members showed a decrease. These findings suggest that measures of mean performance and IIV of speed during a CNB may provide useful information about the genetic susceptibility in schizophrenia.
Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the n... more Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the need for activation tasks that engage emotional processing and can be used during physiologic neuroimaging ("neurobehavioral probes"). The stimuli pictured professional actors and actresses who had been screened for asymmetric features. In experiment I, same-sex stimuli were used to examine the performance of normal subjects (24 men, I5 women) on the three tasks. Performance was better during the emotion-discrimination tasks than during the age-discrimination task, and males had higher sensitivity scores for the detection of sad emotion. However, experiment II showed that the sex of the stimulus interacts with the sex of the subject. Compared with female subjects, male subjects (n = IO) were selectively less sensitive to sad emotion in female faces. Female subjects (n = IO) were more sensitive overall to emotional expression in male faces than in female faces. Thus, men and women differed in performance depending on the sex of the facial stimulus.
The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wi... more The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophreniaspecific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.
The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. I... more The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n= 304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in midadolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.
Herpes Simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis.... more Herpes Simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis. The infection is life long, with sensory ganglia serving as reservoirs of latent infection. Recently, exposure to HSV-1 has also been repeatedly associated with reduced cognitive function among healthy individuals without prior encephalitis. Though HSV-1 does not elevate risk for schizophrenia (SZ) per se, exposure is likewise associated with impaired cognitive functions among SZ patients. The range of cognitive changes observed in HSV-1 exposed persons has not been investigated systematically, nor is it known whether interaction between HSV-1 exposure and SZ related factors contributes to the impairment among SZ patients. Persons with or without schizophrenia/schizophreniform disorder (N = 298 total, DSM IV criteria) were assessed for HSV-1 exposure using serum HSV-1 antibody titers. The Penn Computerized Neurocognitive battery was used to assess eight cognitive domains with respect to accuracy and speed. There were no significant case-control differences in HSV-1 exposure. The SZ/schizophreniform disorder cases were significantly impaired in all cognitive domains compared with the controls. HSV-1
Deficits in emotional expression are prominent in several neuropsychiatric disorders, including s... more Deficits in emotional expression are prominent in several neuropsychiatric disorders, including schizophrenia. Available clinical facial expression evaluations provide subjective and qualitative measurements, which are based on static 2D images that do not capture the temporal dynamics and subtleties of expression changes. Therefore, there is a need for automated, objective and quantitative measurements of facial expressions captured using videos. This paper presents a computational framework that creates probabilistic expression profiles for video data and can potentially help to automatically quantify emotional expression differences between patients with neuropsychiatric disorders and healthy controls. Our method automatically detects and tracks facial landmarks in videos, and then extracts geometric features to characterize facial expression changes. To analyze temporal facial expression changes, we employ probabilistic classifiers that analyze facial expressions in individual frames, and then propagate the probabilities throughout the video to capture the temporal characteristics of facial expressions. The applications of our method to healthy controls and case studies of patients with schizophrenia and Asperger's syndrome demonstrate the capability of the video-based expression analysis method in capturing subtleties of facial expression. Such results can pave the way for a video-based method for quantitative analysis of facial expressions in clinical research of disorders that cause affective deficits.
Journal of Clinical and Experimental Neuropsychology, 2013
Objective-The psychometric properties of the Penn Face Memory Test (PFMT; Gur et al., 1997) were ... more Objective-The psychometric properties of the Penn Face Memory Test (PFMT; Gur et al., 1997) were investigated in a large sample (4,236 participants) of U.S. Army Soldiers undergoing computerized neurocognitive testing. Data were drawn from the initial phase of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), a large-scale study directed towards identifying risk and resilience factors for suicidal behavior and other stress-related disorders in Army Soldiers. In this paper we report parallel psychometric and cognitive modeling analyses of the PFMT to determine whether ability estimates derived from the measure are precise and valid indicators of memory in the Army STARRS sample. Method-Single-sample cross-validation methodology combined with exploratory factor and multidimensional item response theory techniques were used to explore the latent structure of the PFMT. To help resolve rotational indeterminacy of the exploratory solution, latent constructs were aligned with parameter estimates derived from an unequal-variance signal detection model. Results-Analyses suggest that the PFMT measures two distinct latent constructs, one associated with memory strength and one associated with response bias, and that test scores are generally precise indicators of ability for the majority of Army STARRS participants. Conclusions-These findings support the use of the PFMT as a measure of major constructs related to recognition memory and have implications for further cognitive-psychometric model development.
Journal of Cerebral Blood Flow & Metabolism, 1987
Repeated applications of the 133Xe inhalation technique for measuring regional CBF (rCBF) were ma... more Repeated applications of the 133Xe inhalation technique for measuring regional CBF (rCBF) were made during consecutive resting conditions in a sample of young healthy subjects. Subjects were grouped by order and by sex [nine had resting studies as the initial two measurements in a series of four measurement (six men, three women) and six had these measurements later (two men, four women)]. Three flow parameters were examined: f1 (fast flow) and IS (initial slope) for gray matter CBF, and CBF-15 for mean CBF (gray and white matter over 15-min integration), as well as w1, the percentage of tissue with fast clearing characteristics. With all groups combined, there were no significant differences between the two resting measurements, and high test-retest correlations were obtained for the flow parameters and w1. Analyses by order and sex grouping revealed, for the flow parameters, significant interactions of test-retest difference with order. Repeated initial studies showed reduced CBF ...
The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indire... more The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indirect measurement of cortical metabolic activity. The utility of this method in longitudinal clinical studies depends on the stability and reproducibility of resting and activated flow measures. We evaluated CBF in a sample of 16 elderly normal subjects (aged 54–73 years) at rest and during task performance in two sessions separated by an average of 9 weeks. Resting global CBF was lower in the second session, a finding consistent with the known effects of habituation previously reported. Regionally specific activated CBF did not change with repeated measurements. The results provide evidence that the 133Xe technique is reliable and of potential utility in evaluating the effect of the natural course of brain disease, as well as the effects of therapeutic interventions on brain activity.
Journal of Cerebral Blood Flow & Metabolism, 1987
The relation between anxiety and cortical activity was compared in two samples of normal voluntee... more The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using 18Flurodeoxyglucose (18FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between a...
BackgroundDiffusion tensor magnetic resonance imaging studies in schizophrenia to date have been ... more BackgroundDiffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure.AimsTo determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure.MethodScans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups.ResultsWe found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients.ConclusionsThe finding of widespread fractional an...
Gender and aging moderate brain-behavior relationships. Advances in neuroscience enable integrati... more Gender and aging moderate brain-behavior relationships. Advances in neuroscience enable integration of neurobehavioral, neuroanatomic, and neurophysiology measures. Here we present neurobehavioral studies thai examine cognitive and emotion processing in healthy men and women and highlight the effects of sex differences and aqinq. Neuroanatomic studies with maqnetic resonance imaging (MRI) indicate that the progressive decrease in brain volume affects froniotemporal brain regions in men more than in Vi/omen, Functional imaging methods suggest sex differences in rate of blood flow, pattern of glucose metabolism, and receptor activity. The role of ovarian hormones is important in elucidating the observed relationships. A life span perspective on gender differences through the integration of available methodologies will advance understanding healthy people and the effects of brain disorders.
Ventral striatum (VS) is a critical brain region for reinforcement learning and motivation, and V... more Ventral striatum (VS) is a critical brain region for reinforcement learning and motivation, and VS hypofunction is implicated in psychiatric disorders including schizophrenia. Providing rewards or performance feedback has been shown to activate VS. Intrinsically motivated subjects performing challenging cognitive tasks are likely to engage reinforcement circuitry even in the absence of external feedback or incentives. However, such intrinsic reinforcement responses have received little attention, have not been examined in relation to behavioral performance, and have not been evaluated for impairment in neuropsychiatric disorders such as schizophrenia. Here we used fMRI to examine a challenging "old" vs. "new" visual recognition task in healthy subjects and patients with schizophrenia. Targets were unique fractal stimuli previously presented as salient distractors in a visual oddball task, producing incidental memory encoding. Based on the prediction error theory of reinforcement learning, we hypothesized that correct target recognition would activate VS in controls, and that this activation would be greater in subjects with lower expectation of responding correctly as indexed by a more conservative response bias. We also predicted these effects would be reduced in patients with schizophrenia. Consistent with these predictions, controls activated VS and other reinforcement processing regions during correct recognition, with greater VS activation in those with a more conservative response bias. Patients did not show either effect, with significant group differences suggesting hyporesponsivity in patients to internally generated feedback. These findings highlight the importance of accounting for intrinsic motivation and reward when studying cognitive tasks, and add to growing evidence of reward circuit dysfunction in schizophrenia that may impact cognition and function.
Impaired facial expressions of emotions have been described as characteristic symptoms of schizop... more Impaired facial expressions of emotions have been described as characteristic symptoms of schizophrenia. Previous investigations of dynamic facial expressions have reported on global assessment of positive and negative emotion expressions. In this study, we examined facial expression differences based on duration and frequencies of emotion expressions. 12 persons with stable schizophrenia and matched healthy controls underwent a standardized procedure for evoked facial expressions of five universal emotions, including happy, sad, anger, fear, and disgust expressions. Subjects completed self-ratings of their emotion experience. Reliable raters coded evoked facial expressions according to the Facial Expression Coding System. For each emotion, facial expressions were coded as target, non-target or neutral expressions. Logistic regression analyses examined group differences in duration and frequencies of facial expressions. Comparing overall duration of and frequencies of emotion expres...
In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal dif... more In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal different moral decision patterns as compared to healthy subjects and whether common social interaction difficulties in ASD are reflected in altered brain activation during different aspects of moral reasoning. 28 patients with high-functioning ASD and 28 healthy subjects matched for gender, age and education took part in an event-related functional magnetic resonance imaging study. Participants were confronted with textual dilemma situations followed by proposed solutions to which they could agree or disagree. On a neural level, moral decision making was associated with activation in anterior medial prefrontal regions, the temporo-parietal junction and the precuneus for both groups. However, while patients and healthy controls did not exhibit significant behavioral differences, ASD patients showed decreased activation in limbic regions, particularly the amygdala, as well as increased activation in the anterior and the posterior cingulate gyrus during moral reasoning. Alterations of brain activation in patients might thus indicate specific impairments in empathy. However, activation increases in brain regions associated with the default mode network and self-referential cognition also provide evidence for an altered way of patients cerebral processing with regard to decision making based on social information.
Schizophrenia patients display impaired performance and brain activity during facial affect recog... more Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.
Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests pr... more Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect. Studies have examined the perception, experience, and expression of emotions in schizophrenia and reported normal ratings of experience but impaired affect identification. However, the relation between flat affect and performance on facial affect identification and cognitive tasks has not been systematically examined in relation to premorbid adjustment and clinical outcome. We report a prospective study of 63 patients with at least moderate severity of flat affect and 99 patients without flat affect, who were compared on functional domains, emotion processing tasks, and neurocognitive measures. Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year followup. Patients overall performed more poorly on emotion processing tasks, one that required identification of happy and sad emotions and one that required differentiating among intensities within these emotions. They responded inaccurately yet faster than controls for the intensity differentiation task, suggesting a decomposition of the normal relation between accuracy and speed. Flat affect ratings, compared with other negative symptoms, uniquely predicted performance on emotion processing tasks. Patients with flat affect showed greater impairment in both emotion processing tasks, with the most pronounced impairment for the intensity differentiation task. However, the 2 patient groups did not differ in the neurocognitive profile except for verbal memory. We conclude that flat affect is an important clinical feature of schizophrenia that exacerbates the course of illness.
Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia ... more Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia from unaffected family members and healthy comparison subjects. These deficits in neurocognitive performance in patients with schizophrenia appear stable in the short-term. However, the duration of most, but not all, longitudinal studies is modest and the majority have relied on traditional average performance measures to examine stability. Using a computerized neurocognitive battery (CNB), we assessed mean performance (accuracy and speed) and intra-individual variability (IIV) in a longitudinal study aimed to examine neurocognitive stability in European-American multiplex families with schizophrenia. Thirty-four patients with schizophrenia, 65 unaffected relatives, and 45 healthy comparison subjects completed the same computerized neurocognitive assessment over approximately 5 years. Measures of mean performance showed that patients had stable accuracy performance but were slower in many neurocognitive domains over time as compared with unaffected family members and healthy subjects. Furthermore, patients and family members showed dissociable patterns of change in IIV for speed across cognitive domains: compared with controls, patients showed higher across-task IIV in performance compared with family members, who showed lower across-task IIV. Patients showed an increase in IIV over time, whereas family members showed a decrease. These findings suggest that measures of mean performance and IIV of speed during a CNB may provide useful information about the genetic susceptibility in schizophrenia.
Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the n... more Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the need for activation tasks that engage emotional processing and can be used during physiologic neuroimaging ("neurobehavioral probes"). The stimuli pictured professional actors and actresses who had been screened for asymmetric features. In experiment I, same-sex stimuli were used to examine the performance of normal subjects (24 men, I5 women) on the three tasks. Performance was better during the emotion-discrimination tasks than during the age-discrimination task, and males had higher sensitivity scores for the detection of sad emotion. However, experiment II showed that the sex of the stimulus interacts with the sex of the subject. Compared with female subjects, male subjects (n = IO) were selectively less sensitive to sad emotion in female faces. Female subjects (n = IO) were more sensitive overall to emotional expression in male faces than in female faces. Thus, men and women differed in performance depending on the sex of the facial stimulus.
The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wi... more The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophreniaspecific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.
The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. I... more The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n= 304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in midadolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.
Herpes Simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis.... more Herpes Simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis. The infection is life long, with sensory ganglia serving as reservoirs of latent infection. Recently, exposure to HSV-1 has also been repeatedly associated with reduced cognitive function among healthy individuals without prior encephalitis. Though HSV-1 does not elevate risk for schizophrenia (SZ) per se, exposure is likewise associated with impaired cognitive functions among SZ patients. The range of cognitive changes observed in HSV-1 exposed persons has not been investigated systematically, nor is it known whether interaction between HSV-1 exposure and SZ related factors contributes to the impairment among SZ patients. Persons with or without schizophrenia/schizophreniform disorder (N = 298 total, DSM IV criteria) were assessed for HSV-1 exposure using serum HSV-1 antibody titers. The Penn Computerized Neurocognitive battery was used to assess eight cognitive domains with respect to accuracy and speed. There were no significant case-control differences in HSV-1 exposure. The SZ/schizophreniform disorder cases were significantly impaired in all cognitive domains compared with the controls. HSV-1
Deficits in emotional expression are prominent in several neuropsychiatric disorders, including s... more Deficits in emotional expression are prominent in several neuropsychiatric disorders, including schizophrenia. Available clinical facial expression evaluations provide subjective and qualitative measurements, which are based on static 2D images that do not capture the temporal dynamics and subtleties of expression changes. Therefore, there is a need for automated, objective and quantitative measurements of facial expressions captured using videos. This paper presents a computational framework that creates probabilistic expression profiles for video data and can potentially help to automatically quantify emotional expression differences between patients with neuropsychiatric disorders and healthy controls. Our method automatically detects and tracks facial landmarks in videos, and then extracts geometric features to characterize facial expression changes. To analyze temporal facial expression changes, we employ probabilistic classifiers that analyze facial expressions in individual frames, and then propagate the probabilities throughout the video to capture the temporal characteristics of facial expressions. The applications of our method to healthy controls and case studies of patients with schizophrenia and Asperger's syndrome demonstrate the capability of the video-based expression analysis method in capturing subtleties of facial expression. Such results can pave the way for a video-based method for quantitative analysis of facial expressions in clinical research of disorders that cause affective deficits.
Journal of Clinical and Experimental Neuropsychology, 2013
Objective-The psychometric properties of the Penn Face Memory Test (PFMT; Gur et al., 1997) were ... more Objective-The psychometric properties of the Penn Face Memory Test (PFMT; Gur et al., 1997) were investigated in a large sample (4,236 participants) of U.S. Army Soldiers undergoing computerized neurocognitive testing. Data were drawn from the initial phase of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), a large-scale study directed towards identifying risk and resilience factors for suicidal behavior and other stress-related disorders in Army Soldiers. In this paper we report parallel psychometric and cognitive modeling analyses of the PFMT to determine whether ability estimates derived from the measure are precise and valid indicators of memory in the Army STARRS sample. Method-Single-sample cross-validation methodology combined with exploratory factor and multidimensional item response theory techniques were used to explore the latent structure of the PFMT. To help resolve rotational indeterminacy of the exploratory solution, latent constructs were aligned with parameter estimates derived from an unequal-variance signal detection model. Results-Analyses suggest that the PFMT measures two distinct latent constructs, one associated with memory strength and one associated with response bias, and that test scores are generally precise indicators of ability for the majority of Army STARRS participants. Conclusions-These findings support the use of the PFMT as a measure of major constructs related to recognition memory and have implications for further cognitive-psychometric model development.
Journal of Cerebral Blood Flow & Metabolism, 1987
Repeated applications of the 133Xe inhalation technique for measuring regional CBF (rCBF) were ma... more Repeated applications of the 133Xe inhalation technique for measuring regional CBF (rCBF) were made during consecutive resting conditions in a sample of young healthy subjects. Subjects were grouped by order and by sex [nine had resting studies as the initial two measurements in a series of four measurement (six men, three women) and six had these measurements later (two men, four women)]. Three flow parameters were examined: f1 (fast flow) and IS (initial slope) for gray matter CBF, and CBF-15 for mean CBF (gray and white matter over 15-min integration), as well as w1, the percentage of tissue with fast clearing characteristics. With all groups combined, there were no significant differences between the two resting measurements, and high test-retest correlations were obtained for the flow parameters and w1. Analyses by order and sex grouping revealed, for the flow parameters, significant interactions of test-retest difference with order. Repeated initial studies showed reduced CBF ...
The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indire... more The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indirect measurement of cortical metabolic activity. The utility of this method in longitudinal clinical studies depends on the stability and reproducibility of resting and activated flow measures. We evaluated CBF in a sample of 16 elderly normal subjects (aged 54–73 years) at rest and during task performance in two sessions separated by an average of 9 weeks. Resting global CBF was lower in the second session, a finding consistent with the known effects of habituation previously reported. Regionally specific activated CBF did not change with repeated measurements. The results provide evidence that the 133Xe technique is reliable and of potential utility in evaluating the effect of the natural course of brain disease, as well as the effects of therapeutic interventions on brain activity.
Journal of Cerebral Blood Flow & Metabolism, 1987
The relation between anxiety and cortical activity was compared in two samples of normal voluntee... more The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using 18Flurodeoxyglucose (18FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between a...
BackgroundDiffusion tensor magnetic resonance imaging studies in schizophrenia to date have been ... more BackgroundDiffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure.AimsTo determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure.MethodScans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups.ResultsWe found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients.ConclusionsThe finding of widespread fractional an...
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Papers by Ruben Gur