Biomedical subjects

J Daniel Ragland

Publications and source records attributed to J Daniel Ragland.

At least 19 recordsLinked to original sources

PubMed2007

Hemodynamic responses in neural circuitries for detection of visual target and novelty: An event-related fMRI study.

The oddball paradigm examines attentional processes by establishing neural substrates for target detection and novelty. Event-related functional imaging enables characterization of hemodynamic changes associated with these processes. We studied 36 healthy participants (17 men) applying a visual oddball event-related design at 4 Tesla, and performed an unbiased determination of the hemodynamic response function (HRF). Targets were associated with bilateral, albeit leftward predominant changes in frontal-parietal temporal and occipital cortices, and limbic and basal ganglia regions. Activation to novelty was more posteriorly distributed, and frontal activation occurred only on the right, while robust activation was seen in occipital regions bilaterally. Overlapping regions were left thalamus, caudate and cuneus and right parietal precuneus. While robust HRFs characterized most regions, target detection was associated with a negative HRF in the right parietal precuneus and a biphasic HRF in thalamus, basal ganglia, and all occipital regions. Both height of the HRF and longer time to peak in the right cingulate were associated with slower response time. Sex differences were observed, with higher HRF peaks for novelty in men in right occipital regions, and longer time to peak in the left hemisphere. Age was associated with reduced peak HRF in left frontal region. Thus, indices of the HRF can be used to better understand the relationship between hemodynamic changes and performance and can be sensitive to individual differences.

Adolescent↗

PubMed2006

Project among African-Americans to explore risks for schizophrenia (PAARTNERS): recruitment and assessment methods.

The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia.

Adult↗

PubMed2006

Functional magnetic resonance imaging of internal source monitoring in schizophrenia: recognition with and without recollection.

Patients with schizophrenia tend to have impaired source monitoring and intact item recognition, suggesting an over-reliance of familiarity effects. We previously demonstrated that providing patients with a levels-of-processing (LOP) semantic encoding strategy normalized source monitoring. The current blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) study tests the hypothesis that patients will have abnormally increased fronto-temporal activation despite intact performance. fMRI was measured in 13 patients and 13 demographically matched healthy controls during a LOP source monitoring paradigm. SPM2 was used for standard pre-processing and statistical analyses, with a corrected significance threshold of p<.05. Examination of accuracy and speed measures did not reveal any group differences in task performance. Regardless of source retrieval success both groups activated expected prefrontal and parietal regions, with no areas of relatively greater control versus patient activation. In support of the hypothesis, patients showed abnormally increased activation in temporolimbic areas including middle and superior temporal gyrus, thalamus, and parahippocampal gyrus. Activation in these areas was associated with worse positive and negative symptoms, but did not correlate with performance, suggesting inefficient rather than compensatory activation.

Adolescent↗

PubMed2006

A comparison of cognitive structure in schizophrenia patients and healthy controls using confirmatory factor analysis.

There is evidence that cognitive task performance breaks down into the same broad domains in schizophrenia as in healthy populations. However, this does not mean that the domains are independent of one another or that the interrelationships among domains are the same between groups. We used confirmatory factor analysis (CFA) to compare the latent structure of a broad neuropsychological battery in schizophrenia patients (n = 148) and healthy controls (n = 157). Main analyses examined the fit of a hierarchical six-factor model, in which associations among the factors were assumed to reflect their strong shared relationship to a general cognitive ability factor. The model incorporated the factors of verbal comprehension, perceptual organization, verbal memory, spatial memory, processing speed, and executive/working memory. The hierarchical model provided a good overall fit to data from both groups. However multiple groups CFA revealed significant differences in factor loadings between groups, reflecting a more generalized latent structure of cognitive ability in schizophrenia. This was also evident in higher bivariate correlations among cognitive domain composite scores calculated from the observed test data. Cognitive ability, as reflected in test performance, appears to be more unitary in schizophrenia than in healthy subjects. This finding may have measurement and treatment implications.

Adult↗

PubMed2006

Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures.

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 follow-up. 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.

Adolescent↗

PubMed2006

Levels-of-processing effect on internal source monitoring in schizophrenia.

BACKGROUND: Recognition can be normalized in schizophrenia by providing patients with semantic organizational strategies through a levels-of-processing (LOP) framework. However, patients may rely primarily on familiarity effects, making recognition less sensitive than source monitoring to the strength of the episodic memory trace. The current study investigates whether providing semantic organizational strategies can also normalize patients' internal source-monitoring performance. METHOD: Sixteen clinically stable medicated patients with schizophrenia and 15 demographically matched healthy controls were asked to identify the source of remembered words following an LOP-encoding paradigm in which they alternated between processing words on a 'shallow' perceptual versus a 'deep' semantic level. A multinomial analysis provided orthogonal measures of item recognition and source discrimination, and bootstrapping generated variance to allow for parametric analyses. LOP and group effects were tested by contrasting recognition and source-monitoring parameters for words that had been encoded during deep versus shallow processing conditions. RESULTS: As in a previous study there were no group differences in LOP effects on recognition performance, with patients and controls benefiting equally from deep versus shallow processing. Although there were no group differences in internal source monitoring, only controls had significantly better performance for words processed during the deep encoding condition. Patient performance did not correlate with clinical symptoms or medication dose. CONCLUSIONS: Providing a deep processing semantic encoding strategy significantly improved patients' recognition performance only. The lack of a significant LOP effect on internal source monitoring in patients may reflect subtle problems in the relational binding of semantic information that are independent of strategic memory processes.

Adult↗

PubMed2006

Sex differences in clustering and switching in verbal fluency tasks.

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study, the clustering and switching components of semantic and phonemic verbal fluency tests were examined in 40 healthy men and 40 healthy women. Possible sex differences in the influence of cognitive factors such as speed of information processing, word knowledge, and/or verbal long-term memory on these verbal fluency factors were also assessed. The results showed that women switched more often between categories in the phonemic fluency test, whereas men showed a trend toward a larger cluster size leading to a smaller total number of words generated. Additionally, higher performance on the Digit Symbol test was associated with better performance on the semantic and phonemic verbal fluency test in men, whereas in women, better memory performance was associated with better performance on these verbal fluency tests. Our data indicate that men and women are using different processing strategies for phonemic verbal fluency tests to optimize verbal fluency task performance. In the current study, women adopted a more successful strategy of balancing clustering and switching in the phonemic fluency task.

Cognition↗

PubMed2006

Prognostic variables at intake and long-term level of function in schizophrenia.

OBJECTIVE: This study assessed the relationship between symptoms and cognitive measures at intake and functional outcome 2-8 years later (average 3 years) in first-episode and previously treated schizophrenia patients. METHOD: A composite cognitive score was assessed at intake to determine the influence of cognition on later functional outcome. At intake and follow-up, positive and negative symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and affective symptoms were assessed with the Hamilton Depression Rating Scale. Level of function in seven domains (social function, occupational function, independent living, symptom severity, fullness of life, extent of psychiatric hospitalization, and overall level of function) at intake and follow-up was assessed with the Strauss-Carpenter Level of Function scale. The contributions of sex, education, and duration of illness to functional outcome were also examined. RESULTS: The results indicated that symptoms at intake had distinct patterns of prognostic significance for functional outcome in previously treated patients, compared with first-episode patients. In addition, male and female patients differed in the degree to which initial symptoms were correlated with later function. CONCLUSIONS: Initial level of function, symptoms, sex, education, and duration of illness are all important predictors for functional outcome in patients with schizophrenia.

Activities of Daily Living↗

PubMed2005

Organization of semantic category exemplars in schizophrenia.

Semantic memory was investigated in 27 individuals with schizophrenia and 30 healthy controls using an animal similarity judgment and organization test with reduced retrieval demands. Participants arranged 12 common animal names according to similarity on a computer screen and provided verbal descriptions of organizational strategies. Distance between each animal pair was compared to the number of shared semantic attributes between the pairs (e.g., size, diet, habitat). The three primary organizational strategies included single animals not related to other exemplars, isolated clusters of animals that shared a single strategic relationship (e.g., pets), and overlapping clusters that combined more than one strategic relationship (e.g., cats and mammals). A strong negative correlation was observed between distance ratings and number of shared semantic attributes, confirming that semantic features related to visual distances in both groups. Animal pairs that shared few semantic attributes were placed in closer proximity in the schizophrenia group, whereas the groups placed animal pairs sharing more features equidistantly. Analyses of clustering strategies revealed a double dissociation, with patients relying on isolated, non-overlapping clusters and controls producing more overlapping semantic clusters. Results suggest that performance differences on semantic tasks with limited retrieval demands in schizophrenia relate to difficulties utilizing higher-order categorization strategies.

Adult↗

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

Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia.

Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia.

Brain↗

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

The effects of geometric distortion correction on motion realignment in fMRI.

RATIONALE AND OBJECTIVES: Subject motion is well recognized as a significant impediment to resolution and sensitivity in functional magnetic resonance imaging (fMRI). A parallel confounder to fMRI data quality is geometric image distortion, particularly at high field strengths, due to susceptibility-induced magnetic field inhomogeneity. Consequently, many high-field echo-planar imaging methods incorporate a post-processing distortion correction by acquiring a field map of the sample prior to the fMRI measurement. However, field mapping methods impose a spatial mask on the data, since field information is only obtainable from regions with adequate signal-to-noise ratio (SNR). This masking, when applied to subsequent images in the fMRI time series, can clip the effects of motion, resulting in inaccurate estimation and correction of motion-based changes in the images. MATERIALS AND METHODS: The effects of geometric distortion correction on automated realignment (motion correction) of fMRI data are investigated from data acquired at 4 T. The results of image realignment with and without prior application of distortion correction are compared, using the estimated motion parameters and overall image realignment as metrics. RESULTS: The application of field-map-based distortion correction prior to image realignment reduces the amount of motion detected by a standard motion correction algorithm. Moreover, motion correction applied before distortion correction is shown to result in superior realignment of motion-correction images. CONCLUSION: It is preferable to perform motion realignment prior to correcting for geometric distortion.

Humans↗

PubMed2004

Images of desire: food-craving activation during fMRI.

Food craving (defined as an intense desire to eat a specific food) is of interest because it is extremely common and because it influences obesity or nutritional status. It has also been suggested that food craving may be the evolutionary source for cravings of all kinds including cravings for drugs and alcohol. Yet, little is known about the functional neuroanatomy of food craving. We report here the first functional magnetic resonance imaging (fMRI) study to explicitly examine food craving. A two-part technique was used to produce the food cravings. Threshold was reduced through a diet manipulation (monotonous diet) and cravings were triggered during blood oxygenation level-dependent (BOLD) fMRI sessions by having subjects imagine the sensory properties of favorite foods (a cue-induction technique). Subjects were also asked to imagine the monotonous diet (which they did not crave). Diet condition had an activating effect on both behavioral (reports of craving) and fMRI measures. Craving-related changes in fMRI signal were identified in the hippocampus, insula, and caudate, three areas reported to be involved in drug craving. Thus, this work supports the common substrate hypothesis for food and drug cravings.

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

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

Normative data for the symbol cancellation test in young healthy adults.

Mesulam's (1985) symbol cancellation test (SCT) provides a measure of neglect, organizational process, and attention. Although the SCT lends itself to qualitative interpretation, normative data would be helpful for interpreting errors and time to complete this test. SCT normative data are provided for healthy young adults and the contribution of age, education, ethnicity, and gender to SCT performance is examined. Results were as follows: Age was significant (p < .05) and education approached significance (p = .06) as predictors of SCT performance, but percentile ranks revealed an unstable performance pattern across age and education. Thus, normative data for the SCT are provided for the entire sample (n = 136). Conclusions are as follows: Healthy young adults make few errors and complete the SCT in under 2 min, consistent with general findings (Mesulam, 1985). In addition, a relation likely exists between SCT performance and age and education, but a larger sample seems warranted to reliably model the pattern.

Adult↗