Biomedical subjects

C Richard Clark

Publications and source records attributed to C Richard Clark.

At least 19 recordsLinked to original sources

PubMed2007

Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysiology.

Adolescence to early adulthood is a period of dramatic transformation in the healthy human brain. However, the relationship between the concurrent structural and functional changes remains unclear. We investigated the impact of age on both neuroanatomy and neurophysiology in the same healthy subjects (n = 138) aged 10 to 30 years using magnetic resonance imaging (MRI) and resting electroencephalography (EEG) recordings. MRI data were segmented into gray and white matter images and parcellated into large-scale regions of interest. Absolute EEG power was quantified for each lobe for the slow-wave, alpha and beta frequency bands. Gray matter volume was found to decrease across the age bracket in the frontal and parietal cortices, with the greatest change occurring in adolescence. EEG activity, particularly in the slow-wave band, showed a similar curvilinear decline to gray matter volume in corresponding cortical regions. An inverse pattern of curvilinearly increasing white matter volume was observed in the parietal lobe. We suggest that the reduction in gray matter primarily reflects a reduction of neuropil, and that the corresponding elimination of active synapses is responsible for the observed reduction in EEG power.

Adolescent↗

PubMed2006

Standardized assessment of cognitive functioning during development and aging using an automated touchscreen battery.

This study examined the effects of age, gender and education on subjects spanning nine decades on a new cognitive battery of 12 tests. One thousand and seven participants between 6 and 82 completed the battery under standardized conditions using an automated, computerized touchscreen. Sensitive indicators of change were obtained on measures of attention and working memory, learning and memory retrieval, and language, visuospatial function, sensori-motor and executive function. Improvement tended to occur through to the third and fourth decade of life, followed by gradual decrement and/or stabilized performance thereafter. Gender differences were obtained on measures of sustained attention, verbal learning and memory, visuospatial processing and dexterity. Years of education in adults was reflected in performance on measures of verbal function. Overall, the test battery provided sensitive indicators on a range of cognitive functions suitable for the assessment of abnormal cognition, the evaluation of treatment effects and for longitudinal case management.

Adolescent↗

PubMed2006

Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei.

BACKGROUND: Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. METHOD: 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. RESULTS: Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. CONCLUSIONS: Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.

Adolescent↗

PubMed2006

Regional white matter and neuropsychological functioning across the adult lifespan.

BACKGROUND: The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning. METHODS: One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups. RESULTS: The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory. CONCLUSIONS: The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter.

Adult↗

PubMed2006

Cognitive status of young and older cigarette smokers: data from the international brain database.

Previous studies that have examined the impact of cigarette smoking on cognition have revealed mixed results; some studies report no impact and others report detrimental effects, especially in older individuals. Few studies, however, have examined the effects of cigarette smoking on both young and old healthy individuals using highly robust and standardized methods of cognitive assessment. This study draws on an international database to contrast cognitive differences between younger and older individuals who regularly smoke cigarettes and non-smokers. Data were sampled from 1000 highly screened healthy individuals free of medical or psychiatric health complications. A cohort of 62 regular smokers (n = 45 < 45 years of age; n = 1745 years) with a Fagerstrom nicotine dependency score of 1 or more were identified and matched to a cohort of 62 healthy nonsmokers (n = 43 < 45 years; n = 1945 years) on demographic variables and estimated intelligence. Performances on cognitive measures of attention, reaction time, cognitive flexibility, psychomotor speed, and memory were considered for analysis. As a group, smokers performed more poorly than nonsmokers on one measure of executive function. A significant age and smoking status interaction was identified with older smokers performing more poorly than older nonsmokers and younger smokers on a measure of long-delayed recall of new information. Cigarette smoking is associated with isolated and subtle cognitive difficulties among very healthy individuals.

Adult↗

PubMed2006

The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan.

OBJECTIVE: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan. METHODS: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance. RESULTS: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function. CONCLUSIONS: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.

Adult↗

PubMed2006

Integrative assessment of brain function in PTSD: brain stability and working memory.

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

Adult↗

PubMed2006

Predicting severity of non-clinical depression: preliminary findings using an integrated approach.

INTRODUCTION: Depression is characterized by disturbances in affect, cognition, brain and body function, yet studies have tended to focus on single domains of dysfunction. An integrated approach may provide a more complete profile of the range of deficits characterized by depressed individuals, but it is unclear whether this approach is able to predict depression severity over and above that predicted by single tasks or domains of function. In this study, we examined the value of combining multiple domains of function in predicting depression severity. METHODS: Participants contained in the International Brain Database, (http://www.brainresource.com) had completed three testing components including a web-based questionnaire of Personal History, the Brain Resource Cognition battery of Neuropsychological tests, Personality assessment and Psychophysiological testing. Two hundred and sixty six of these participants were able to be classified as either non-depressed, mild-moderately or severely (non-clinically) depressed, based on a depression screening questionnaire. Analysis of variance identified variables on which the categorized participants differed. Significant variables were then entered into a series of stepwise regressions to examine their ability to predict depression scores. RESULTS: An integrated model including measures of affect (increased Neuroticism; decreased Emotional Intelligence), cognition (increased variability of reaction time during a working memory task; decreased "name the word component score" in the verbal interference task), brain (decreased left-lateralized P150 ERP component during a working memory task) and body function (increased negative skin conductance level gradient) were found to predict more of the variation in depression severity than any single domain of function. DISCUSSION: On the basis of behavioral as well as Psychophysiological findings reported in this study, it was suggested that deficits in subclinically depressed individuals are more pronounced during automatic stages of stimulus processing, and that performance in these individuals may improve (to the level displayed by controls) when task demands are increased. Findings also suggest that it is important to consider disturbances across different domains of function in order to elucidate depression severity. Each domain may contribute unique explanatory information consistent with an integrative model of depression, taking into account the role of both behavior and underlying neural changes.

Acoustic Stimulation↗

PubMed2006

Distractibility in AD/HD predominantly inattentive and combined subtypes: the P3a ERP component, heart rate and performance.

The current study aimed to investigate whether children and adolescents diagnosed with Attention Deficit/Hyperactivity Disorder Predominantly Inattentive (AD/HD-in; Child n = 24, Adolescent n = 33) and Combined (AD/HD-com; Child n = 30, Adolescent n = 42) subtypes were more distractible than controls (Child n = 54; Adolescents n = 75), by assessing event-related potential (ERP), performance and peripheral arousal measures. All AD/HD groups displayed smaller amplitudes and/or shorter latencies of the P3a ERP component - thought to reflect involuntary attention switching - following task-deviant novel stimuli (checkerboard patterns) embedded in a Working Memory (WM) task. The P3a results suggested that both AD/HD-in and AD/HD-com subtypes ineffectively evaluate deviant stimuli and are hence more "distractible". These abnormalities were most pronounced over the central areas. AD/HD groups did not display any abnormalities in averaged heart rate over the WM task, a measure of peripheral arousal. They did display abnormalities in performance measures from the task, but these were unrelated to P3a abnormalities. AD/HD groups also displayed a number of deficits on Switching of Attention and Verbal Memory tasks, however, the pattern of abnormality mostly reflected general cognitive deficits rather than resulting from distraction.

Adolescent↗

PubMed2005

Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder.

This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.

Brain Mapping↗

PubMed2005

Preservation of limbic and paralimbic structures in aging.

Patterns of gray matter (GM) loss were measured in 223 healthy subjects spanning eight decades. We observed significant clusters of accelerated loss in focal regions of the frontal and parietal cortices, including the dorsolateral frontal cortex, pre- and postcentral gyrus, and the inferior and superior parietal lobes. The rate of loss in these clusters was approximately twice that of the global average. By contrast, clusters of significant GM preservation were found in limbic and paralimbic structures, including the amygdala, hippocampus, thalamus, and the cingulate gyrus. In these clusters, GM loss was attenuated significantly relative to the global rate. The preservation of these structures is consistent with the functional importance of the thalamo-limbic circuits in sensory integration, arousal, emotion, and memory, and lends credence to the idea that later-maturing cortical regions are more vulnerable to age-related morphologic changes. Moreover, the limbic findings act as a frame of reference to explore further the effects of stress and learning on these structures in an evidence-based manner across age.

Adolescent↗

PubMed2005

Source localisation in a real human head.

Neural activity within the human brain produces electrical potentials that are transmitted through the various tissues of the head to the scalp. A three-dimensional finite difference model has been applied to simulate this process and used as the basis for an inverse model, wherein known potentials on the scalp are used to locate sources of neural activity within the brain. The inverse model uses linear and nonlinear response functions, together with nonlinear regression to determine the source location. The model has been applied to three different simulations, and in each case was able to locate the source using a combination of linear and nonlinear response functions.

Algorithms↗

PubMed2005

Clozapine improves working memory updating in schizophrenia.

This study investigated the effect of clozapine on working memory in 15 subjects with schizophrenia, using an event related potential paradigm designed to separate components reflecting working memory updating from components related to target detection and response. Compared to matched controls and prior to treatment with clozapine, subjects with schizophrenia had N1, P3 and Late Slow Wave abnormalities indicating impairment in early stimulus evaluation and subsequent working memory functions. Treatment with clozapine was associated with normalization of the P3 and Late Slow Waves, indicating improvement in working memory updating and executive processing. There was also a partial normalization of N1 amplitude, suggesting improvement in early stimulus evaluation.

Adult↗

PubMed2005

Toward an integrated profile of depression: evidence from the brain resource international database.

Clinical depression is one of the most common psychiatric disorders in adults, yet non-clinical depression in the community may go unnoticed, despite high prevalence rates and significant psychosocial impairment. The aim of the current study was to classify 1,226 individuals from a community sample on the basis of depression scores (using the Depression Anxiety Stress Scales, DASS) and to determine whether depression in a non-clinical sample differed significantly from healthy controls on a profile of multimodal measures. The data analyzed in this study included personality, emotional intelligence, cognition and psychophysiology. It was predicted that non-clinically depressed participants would differ from healthy controls on measures of personality (increased neuroticism; decreased extraversion), emotional intelligence (decreased), cognition (impairments in executive dysfunction and memory impairment), psychophysiology (increased resting-state, right-frontal activation; diminished skin conductance) after controlling for gender, age, handedness and years of education. Findings provide support for the majority of hypotheses, though no evidence was found for memory impairment or frontal hemispheric asymmetry. Longitudinal studies are needed to determine the extent to which of these findings will have utility for the prediction of depression onset and treatment response/non-response.

Adult↗

PubMed2005

Age-dependent change in executive function and gamma 40 Hz phase synchrony.

Decline in cognitive function is well recognized, yet few neurophysiological correlates of age-related cognitive decline have been identified. In this study we examined the impact of age on neurocognitive function and Gamma phase synchrony among 550 normal subjects (aged 11-70). Gamma phase synchrony was acquired to targets in the auditory oddball paradigm. The two tasks of executive function were switching of attention and an electronic maze. Subjects were divided into four age groups, which were balanced for sex. We hypothesized that reduced cognitive performance among older healthy individuals would be associated with age-related changes in gamma phase synchrony. Results showed a significant decrease in executive function in the oldest (51-70 years) age group. ANOVAs of age-by-frontal Gamma synchrony also showed a significant effect of age on Gamma phase synchrony in the left frontal region that corresponded modestly to the age effect found on executive task performance, with reduced performance associated with increased gamma synchrony. The results indicate that age-related changes in cognitive function evident among elderly individuals may in part be related to decreased ability to integrate information and this may be reflected as a compensatory increase in gamma synchrony in frontal regions of the brain.

Adolescent↗

PubMed2005

Integrative assessment of brain and cognitive function in post-traumatic stress disorder.

The present study combined neuropsychological and electrophysiological measures to obtain a comprehensive profile of the everyday attentional and memory dysfunction reported in PTSD. The event-related potential (ERP) literature has consistently found abnormalities in late components (N2, P3) reflecting working memory (WM) function. However, the neuropsychological profile reported in the literature has considerable variation. The present study examined ERP activity in 33 PTSD participants and matched controls during a standard two-tone auditory oddball task. Neuropsychological assessment was carried out using a task battery assessing a wide range of cognitive functions. Consistent with previous work, the PTSD group showed delayed N2 latency and reduced P3 target amplitude, together with slower and less accurate target detection. Scalp topography provided evidence of widespread abnormality during WM function, but with strongest effects broadly over the left hemisphere. Neuropsychological testing found concomitant difficulties on factorial measures of verbal memory retention/access and sustained attention but enhanced performance on measures of immediate recall. This integrative pattern of effects reflects a specific impairment in the operation of working memory systems that guide ongoing, planned behavior and that facilitate the acquisition and retention of new memories.

Adult↗

PubMed2005

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

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

Adult↗

PubMed2005

The dose-dependent effect of methylphenidate on performance, cognition and psychophysiology.

The effects of methylphenidate (MPH) on 32 healthy human male volunteers (aged 18 to 25 years, mean age=22.26) were examined using a within-subject design. Each participant attended six testing periods, held once per week. Within each testing period, three repeat testing sessions were undertaken: pre-medication, on-medication and two hours post-medication. In these sessions, dose was manipulated (placebo, 5 mg, 15 mg or 45 mg) according a double-blind placebo design. In this report, we focus on behavioral, autonomic arousal (heart rate, skin conductance) and psychophysiological (ERP) data acquired during the working memory task. We found increased autonomic arousal (heart rate, skin conductance and blood pressure) with MPH. A linear reduction in reaction time, omission errors and target P3 latency, and a corresponding increase in background P3 amplitude was observed with increased MPH dose. The relationship between these measures supported an increase in performance and underlying brain function with MPH. To our knowledge, this is the first paper to use behavioral, arousal and electrophysiological measures in an integrative approach to study the effects of MPH on healthy adults.

Adolescent↗