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Biomedical subjects

J D Ragland

Publications and source records attributed to J D Ragland.

At least 19 recordsLinked to original sources

Brain activity during simulated deception: an event-related functional magnetic resonance study.

TheGuilty Knowledge Test (GKT) has been used extensively to model deception. An association between the brain evoked response potentials and lying on the GKT suggests that deception may be associated with changes in other measures of brain activity such as regional blood flow that could be anatomically localized with event-related functional magnetic resonance imaging (fMRI). Blood oxygenation level-dependent fMRI contrasts between deceptive and truthful responses were measured with a 4 Tesla scanner in 18 participants performing the GKT and analyzed using statistical parametric mapping. Increased activity in the anterior cingulate cortex (ACC), the superior frontal gyrus (SFG), and the left premotor, motor, and anterior parietal cortex was specifically associated with deceptive responses. The results indicate that: (a) cognitive differences between deception and truth have neural correlates detectable by fMRI, (b) inhibition of the truthful response may be a basic component of intentional deception, and (c) ACC and SFG are components of the basic neural circuitry for deception.

Adult↗

Comparison of the continuous performance test with and without working memory demands in healthy controls and patients with schizophrenia.

The Penn Continuous Performance Test (PCPT), a measure of sustained visual attention developed for use in functional neuroimaging studies, was compared with a standard CPT developed by Gordon Diagnostic Systems (GDS; Vigilance subtest). The PCPT and the GDS CPT were administered with a standard neuropsychological battery to 68 healthy adults to assess reliability and construct validity. The test had adequate internal consistency, and convergent validity was established through significant correlations between measures of efficiency on the PCPT and the GDS CPT. With the exception of a significant correlation between efficiency measures on the GDS CPT and a measure of auditory sustained attention, neither version of the CPT correlated significantly with other measures in the battery. Factor analysis showed that the PCPT loaded with the GDS CPT. In 39 patients with schizophrenia and 39 matched, healthy controls, equivalent impairment was evident on the two CPT tasks. Neither version correlated significantly with symptom measurements. These results support previous conclusions that sustained visual attention in schizophrenia is a core information processing deficit, not directly related to symptomatology.

Adult↗

Computerized neurocognitive scanning: I. Methodology and validation in healthy people.

Neuropsychological testing batteries are applied in neurobehavioral evaluations of brain disorders, including neuropsychiatric populations. They are lengthy, require expert administrators and professional scorers, and are prone to data handling errors. We describe a brief computerized neurocognitive "scan" that assesses similar domains with adequate reliability. The scan and a traditional battery were administered to a sample of 92 healthy individuals (44 men, 48 women) in a counterbalanced order. Both approaches showed a significant "sex-typical" gradient, with women outperforming men in verbal memory relative to spatial tasks. Both methods also yielded similar profiles of sex differences, with the additional computerized measure of face memory showing better performance in women. Age effects were evident for both methods, but the computerized scan isolated the effects to speed rather than accuracy. Therefore, the computerized scan has favorable reliability and construct validity and can be applied efficiently to study healthy variability related to age and gender.

Adult↗

Computerized neurocognitive scanning: II. The profile of schizophrenia.

Cognitive dysfunction in schizophrenia is well established with neuropsychological batteries, which have assessed multiple domains indicating diffuse deficits especially in processing related to frontotemporal systems. Two studies are reported examining the feasibility of the computerized neurocognitive scan to assess differential deficits in schizophrenia. In Study 1, we tested 53 patients and 71 controls with the traditional and computerized assessments counterbalanced in order. Both showed comparable generalized impairment in schizophrenia with differential deficits in executive functions and memory. The profile was replicated in Study 2 in a new sample of 68 patients and 37 controls, receiving only the computerized scan. The combined sample showed robust correlations between performance on both speed and accuracy measures of the neurocognitive scan and clinical variables, including premorbid adjustment, onset age, illness duration, quality of life, and severity of negative symptoms. These correlations were higher and more prevalent in women than men, who showed correlations predominantly for speed rather than accuracy. Neuroleptic exposure was associated with poorer performance only for speed of memory processing, and in men, this association was seen only for typical neuroleptics. We conclude that the computerized neurocognitive scan can be applied reliably in people with schizophrenia, yielding data that support its construct and criterion validity.

Adult↗

Effect of schizophrenia on frontotemporal activity during word encoding and recognition: a PET cerebral blood flow study.

OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.

Adult↗

Neuropsychological differences among empirically derived clinical subtypes of schizophrenia.

Neuropsychological profile differences between empirically derived clinical subtypes of schizophrenia were examined. Two hundred five patients and 209 demographically matched controls were administered a neuropsychological battery examining 8 domains. Subtypes included negative, disorganized, paranoid, Schneiderian, and mild. All subtypes displayed a neuropsychological profile of generalized impairment with greater deficits in learning, memory, and attention. Results were suggestive of diffuse cognitive dysfunction in schizophrenia with more severe deficits in learning and memory relative to executive skills. This pattern of greater learning and memory impairment was pronounced for disorganized patients. In contrast, paranoid patients outperformed disorganized and negative patients in several domains. These findings reflect bilateral frontal-temporal dysfunction, particularly in disorganized and negative patients. Subtype differences highlight the importance of conceptualizing schizophrenia as a multifocal disorder.

Adolescent↗

Controlled and automatic processing during animal word list generation in schizophrenia.

Controlled and automatic aspects of semantic-associative functioning in schizophrenia were investigated by evaluating performance on animal word list generation (WLG). Responses from control (n = 47) and patient (n = 38) participants were subjected to multidimensional scaling (MDS), cluster analysis (CA), and indices on the basis of number of shared attributes (SA) between consecutive responses. Patient MDS results accounted for less variance and contained more error than control data. CA results yielded fewer and less clear animal-response subgroups among patients yet demonstrated intact associations among strongly related exemplars. The SA indices revealed better clustering and more effective switching among response clusters in controls than patients. Results suggest that animal WLG in schizophrenia is compromised both by aberrant automatic semantic-associative network activation and by controlled processes such as search, access, and selection. This pattern is consistent with prominent frontotemporal pathology evident in the disorder.

Adult↗

Working memory constrains abstraction in schizophrenia.

BACKGROUND: Abstraction has long been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients' poor performance on the Wisconsin Card Sorting Test (WCST). Yet, the complexity and multidimensional nature of the WCST increases the likelihood that several different cognitive processes, perhaps mediated by different neural systems, are being tapped. METHODS: In the current study, the Abstraction and Working Memory (AIM) task was designed to disentangle abstraction and working memory so that the effects of each cognitive domain could be independently analyzed. The AIM task and a battery of neuropsychological tests were administered to 62 patients with schizophrenia and 62 matched healthy volunteers. RESULTS: Whereas patients with schizophrenia demonstrated deficits in simple abstraction, they were disproportionately impaired with the addition of a minimal memory requirement. CONCLUSIONS: Group differences on WCST performance appear to be attributable to patients' inability to maintain information over a short delay, before that information is used for more complex cognitive operations.

Adolescent↗

Hemispheric activation of anterior and inferior prefrontal cortex during verbal encoding and recognition: a PET study of healthy volunteers.

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET (15)O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.

Adult↗

Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow.

Women have better verbal memory, and higher rates of resting regional cerebral blood flow (rCBF). This study examined whether there are also sex differences in the relationship between verbal episodic memory and resting rCBF. Twenty eight healthy right-handed volunteers (14 male, 14 female) underwent a neuropsychological evaluation and a Positron Emission Tomography (PET) (15)O-water study. Immediate and delayed recall was measured on the logical memory subtest of the Wechsler Memory Scale - Revised (WMS-R), and on the California Verbal Learning Test (CVLT). Resting rCBF (ml/100 g/min) was calculated for four frontal, four temporal, and four limbic regions of interest (ROIs). Women had better immediate recall on both WMS-R and CVLT tasks. Sex differences in rCBF were found for temporal lobe regions. Women had greater bilateral blood flow in a mid-temporal brain region. There were also sex differences in rCBF correlations with performance. Women produced positive correlations with rCBF laterality in the temporal pole. Greater relative CBF in the left temporal pole was associated with better WMS-R immediate and delayed recall in women only. These results suggest that trait differences in temporal pole brain-behavior relationships may relate to sex differences in verbal episodic memory.

Adolescent↗

Marchiafava-Bignami disease: literature review and case report.

OBJECTIVE: We postulated that disruption of callosal pathways as occurs in Marchiafava-Bignami disease (MBD) is associated with marked impairment in brain functioning as measured by cognitive assessment and neuroimaging. BACKGROUND: MBD is considered to be a rare and severe complication of chronic alcoholism. It is characterized by necrosis and subsequent atrophy of the corpus callosum, which is the major brain structure connecting corresponding areas of both hemispheres. METHODS: We review the existing literature on MBD with respect to conceptualization, theories of pathogenesis, forms of the disease, and neuroimaging and neuropsychological findings. We then present the case of a middle-aged man with MBD who underwent extensive clinical, neuropsychological, and neuroimaging studies. RESULTS: Neuropsychological evaluation revealed a pattern of severe global dementia. Magnetic resonance imaging showed moderate atrophy of anterior callosal regions and severe atrophy of posterior callosal regions in the setting of cortical and subcortical atrophy. Resting metabolism positron emission tomography revealed decreased glucose metabolism most pronounced in subcortical and mesial frontal regions. The differential diagnosis, function of the corpus callosum, and potential limitations of our case study are discussed. CONCLUSIONS: On account of the history, clinical presentation, and results of magnetic resonance imaging of the brain, we diagnosed our patient with chronic MBD.

Alcohol-Related Disorders↗

Neuropsychological laterality indices of schizophrenia: interactions with gender.

Neurobehavioral laterality indices were examined across motor, sensory, language versus spatial, and verbal memory versus spatial memory domains for 75 patients with schizophrenia (45 men, 30 women) and 75 demographically matched healthy controls. Patients were impaired across tasks, and laterality results varied by domain. There was no evidence for diagnosis by hemisphere interactions in motor, sensory, or memory tasks. However, patients were more impaired in language than in spatial domains, which suggests relatively greater left hemisphere dysfunction. This finding was mediated by the sex of the participant. While patients as a group showed greater language than spatial impairment, male patients showed expected superiority in spatial relative to language performance, whereas female patients performed the same on both functions. These results underscore the importance of examining sex differences in laterality effects. The findings also demonstrate that, although the left hemisphere model of schizophrenia may be partially supported by data on higher cognitive functions, this support does not extend to more basic motor and sensory domains.

Adult↗

Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: a positron emission tomography study.

Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 15O-water measures of rCBF. Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals.

Adult↗

Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study.

The stability of neuropsychological performance in schizophrenia and its relationship to clinical change was contrasted between 60 patients with schizophrenia (30 first-episode, 30 previously treated) and 38 healthy controls using a comprehensive neuropsychological battery and clinical scales administered at intake and at a 19-month follow-up. Consistent with the neurodevelopmental model of schizophrenia, patients demonstrated deficits in cognitive performance at initial testing and did not show decline at follow-up. There were no differences in neuropsychological performance over time between first-episode and previously treated patients, nor between male and female patients or controls. As expected, patients improved clinically with treatment with respect to both positive and negative symptoms. First-episode patients improved more on the positive symptoms of hallucination and delusion; male and female patients showed equivalent clinical improvement. Clinical improvement correlated positively with neuropsychological change, with improved negative symptomatology accounting for most of the significant correlations.

Adult↗

Lateralized changes in regional cerebral blood flow during performance of verbal and facial recognition tasks: correlations with performance and "effort".

Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional 133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET 15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks-using both absolute and relative (region/ whole brain) CBF. Replicating the 133Xenon clearance findings, CBF was "appropriately" lateralized during task performance (left-right for words > left-right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with "mental effort" indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.

Adult↗

PET regional cerebral blood flow change during working and declarative memory: relationship with task performance.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.

Adolescent↗

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test.

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 schizophrenia-specific 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.

Adult↗

Cerebral blood flow in schizophrenia: effects of memory processing on regional activation.

Regional cerebral blood flow (rCBF) was measured with the 133Xenon clearance technique and a high resolution (254 detectors) scanner during the performance of a verbal and a facial memory task in 18 patients with schizophrenia and 18 sociodemographically matched controls. Patients and controls had comparable resting rCBF, but differed in global and hemispheric rCBF changes induced by the memory tasks. Patients had less global increase, which was relatively higher in the left hemisphere, and this was more pronounced for the verbal task. Although controls showed appropriate laterality changes (L > R for verbal and R > L for facial memory) in the midtemporal region, patients failed to show such a focal pattern. They did not show appropriate laterality change in the midtemporal region, but instead showed such changes in other regions. Patients showed greatest impairment in specificity of verbal recognition performance, and this correlated with severity of hallucinations and delusions. This supports a model of left temporal lobe dysfunction in schizophrenia.

Adult↗