Biomedical subjects

Leanne M Williams

Publications and source records attributed to Leanne M Williams.

At least 19 recordsLinked to original sources

PubMed2005

Trauma modulates amygdala and medial prefrontal responses to consciously attended fear.

Effective fear processing relies on the amygdala and medial prefrontal cortex (MPFC). Post-trauma reactions provide a compelling model for examining how the heightened experience of fear impacts these systems. Post-traumatic stress disorder (PTSD) has been associated with excessive amygdala and a lack of MPFC activity in response to nonconscious facial signals of fear, but responses to consciously processed facial fear stimuli have not been examined. We used functional MRI to elucidate the effect of trauma reactions on amygdala-MPFC function during an overt fear perception task. Subjects with PTSD (n = 13) and matched non-traumatized healthy subjects (n = 13) viewed 15 blocks of eight fearful face stimuli alternating pseudorandomly with 15 blocks of neutral faces (stimulus duration 500 ms; ISI 767 ms). We used random effects analyses in SPM2 to examine within- and between-group differences in the MPFC and amygdala search regions of interest. Time series data were used to examine amygdala-MPFC associations and changes across the first (Early) versus second (Late) phases of the experiment. Relative to non-traumatized subjects, PTSD subjects showed a marked bilateral reduction in MPFC activity (in particular, right anterior cingulate cortex, ACC), which showed a different Early-Late pattern to non-traumatized subjects and was more pronounced with greater trauma impact and symptomatology. PTSD subjects also showed a small but significant enhancement in left amygdala activity, most apparent during the Late phase, but reduction in Early right amygdala response. Over the time course, trauma was related to a distinct pattern of ACC and amygdala connections. The findings suggest that major life trauma may disrupt the normal pattern of medial prefrontal and amygdala regulation.

Adult↗

PubMed2005

Neurophysiological markers of contextual processing: the relationship between P3b and Gamma synchrony and their modulation by arousal, performance and individual differences.

The ability to identify and respond to significant events in the environment is a vital aspect of human cognition and yet is poorly understood as a dynamic neural process. While the response to a contextually-relevant stimulus involves a number of complimentary processes, including selective attention and neural binding, it is also subject to modulation by factors like arousal, age and sex. Adopting an integrative approach, we investigated contextual processing (as indexed by P3b and Gamma phase synchrony) in 120 healthy subjects performing an auditory oddball task while controlling for these other modulating factors. Results suggest a relationship between P3b and Gamma-2 synchrony in posterior regions only, with phasic anterior processing seemingly unrelated to that in posterior regions. However, only the P3b was significantly correlated to central and autonomic arousal. Further, while age and sex were associated with variation in individual measures, they did not strongly affect the relationship between the measures. We concluded that, in simple contextual processing, global and local elements of target stimuli are processed in parallel with little variation being shown between the sexes or resulting from increasing age.

Acoustic Stimulation↗

PubMed2005

Grey matter deficits and symptom profile in first episode schizophrenia.

Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.

Adult↗

PubMed2005

Distinct amygdala-autonomic arousal profiles in response to fear signals in healthy males and females.

The amygdala has a key role in regulating arousal and vigilance, and responds to both visual and vocal signals of fear, including facial expressions of fear. In this study, we used functional MRI to examine sex differences in the magnitude, extent, lateralization and time course of amygdala responses to facial signals of fear, in a relatively large sample of males and females. Skin conductance was recorded simultaneously with functional imaging to examine concomitant changes in emotional arousal, and to provide an independent index of response attenuation. Scanning and skin conductance recording was undertaken during perception of facial fear stimuli. Sex differences were apparent in the laterality and time course of fear perception. In males, the right amygdala and autonomic arousal attenuated over the late half of the experiment. By contrast, females showed persistent bilateral amygdala responses, with a tendency towards greater left amygdala engagement during the late phase. Females also showed a greater general extent of amygdala response. We suggest that distinct evolutionary pressures might contribute to a lower threshold for vigilance to signals of danger in females, reflected in a profile of sustained amygdala-arousal interaction.

Adult↗

PubMed2005

Neural networks of information processing in posttraumatic stress disorder: a functional magnetic resonance imaging study.

BACKGROUND: Neuroimaging studies report reduced medial prefrontal cortical (particularly anterior cingulate) but enhanced amygdala response to fear signals in posttraumatic Stress Disorder (PTSD). We investigated whether anterior cingulate-amygdala dysregulation in PTSD would generalize to salient, but nonthreat related signals. METHODS: Individuals with PTSD (n = 14) and age and sex-matched nontraumatized controls (n = 14) completed an auditory oddball paradigm adapted to functional magnetic resonance imaging at a 1.5-T field strength. RESULTS: Controls displayed bilateral activation in ventral anterior cingulate and amygdala networks, and PTSD subjects showed bilateral dorsal anterior cingulate and amygdala activation to targets relative to nontargets. Compared to controls, PTSD subjects showed enhanced responses to targets in the dorsal and rostral anterior cingulate, and left amygdala. Whole-brain analyses confirmed the expected pattern of distributed prefrontal-parietal responses to targets in the oddball task. Greater activity in posterior parietal somatosensory regions was observed in PTSD. CONCLUSIONS: Our findings of enhanced anterior cingulate responses in PTSD contrast with reports of reduced activity for threat stimuli, suggesting that the latter may be specific to processing of threat-related content. Activation in rostral and dorsal anterior cingulate, left amygdala and posterior parietal networks in response to salient, nonthreatening stimuli may reflect generalized hypervigilance.

Amygdala↗

PubMed2005

Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder.

BACKGROUND: We examined gray- and white-matter brain volumes in first episode psychosis (FEP) at initial presentation and at two-year follow-up. We predicted that FEP subjects would show longitudinal reductions in fronto-temporal gray- and white-matter volumes compared with controls. Furthermore, we expected groups to be differentiated by diagnosis-related reductions. METHODS: Twenty-five schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan at first presentation and 2 years later. Matched healthy subjects (n = 22) underwent a single identical scan. RESULTS: At initial presentation FEP subjects had significantly less gray- and white-matter than healthy subjects. Diagnostic dissociations were revealed both at first presentation and at follow-up. In schizophrenia patients, gray-matter deficits were observed in lateral and medial frontal regions and in bilateral posterior temporal lobe regions, with additional extensive losses over time in lateral fronto-temporal regions and left anterior cingulate gyrus. By contrast, gray matter deficit in bipolar patients was localized to bilateral inferior temporal gyri with additional loss over time observed only in the anterior cingulate cortex. CONCLUSIONS: The results are consistent with a dual process model of psychosis, in which the diagnosis-related gray matter loss is determined by neurodevelopmental gray-matter volumetric differences which predate symptom onset, and diagnosis-related neurodegenerative gray-matter loss over time.

Adolescent↗

PubMed2005

Pathways for fear perception: modulation of amygdala activity by thalamo-cortical systems.

Effective perception of fear signals is crucial for human survival and the importance of the amygdala in this process is well documented. Animal, lesion and neuroimaging studies indicate that incoming sensory signals of fear travel from thalamus to amygdala via two neural pathways: a direct subcortical route and an indirect pathway via the sensory cortex. Other lines of research have demonstrated prefrontal modulation of the amygdala. However, no study to date has examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in vivo. We used psychophysiological and physiophysiological interactions to examine the functional connectivity within thalamus, amygdala and sensory (inferior occipital, fusiform) cortices, and the modulation of these networks by the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) data were acquired for 28 healthy control subjects during a fear perception task, with neutral as the 'baseline' control condition. Main effect analysis, using a region of interest (ROI) approach, confirmed that these regions are part of a distributed neural system for fear perception. Psychophysiological interactions revealed an inverse functional connectivity between occipito-temporal visual regions and the left amygdala, but a positive connectivity between these visual region and the right amygdala, suggesting that there is a hemispheric specialization in the transfer of fear signals from sensory cortices to amygdala. Physiophysiological interactions revealed a dorsal-ventral division in ACC modulation of the thalamus-sensory cortex pathway. While the dorsal ACC showed a positive modulation of this pathway, the ventral ACC exhibited an inverse relationship. In addition, both the dorsal and ventral ACC showed an inverse interaction with the direct thalamus-amygdala pathway. These findings suggest that thalamo-amygdala and cortical regions are involved in a dynamic interplay, with functional differentiation in both lateralized and ventral/dorsal gradients. Breakdowns in these interactions may give rise to affect-related symptoms seen in a range of neuropsychiatric disorders.

Adult↗

PubMed2005

Sex differences in adolescent ADHD: findings from concurrent EEG and EDA.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) occurs more frequently in male children and adolescents than in females, with a ratio of approximately 3 to 1. We determined whether psychophysiological differences are associated with the expression of ADHD in males and females, using simultaneously recorded electroencephalography (EEG) and electrodermal activity (EDA). METHODS: Quantitative EEG and EDA measures were acquired simultaneously and continuously (2min) during an eyes closed resting condition for 70 ADHD adolescents (48 males, 22 females) and their age- and sex-matched controls. RESULTS: Males and females with ADHD were differentiated by both EEG theta activity and EDA. ADHD males showed increased theta (widespread), whereas ADHD females showed a localised frontal enhancement of theta with reduced rate of EDA decrement. These sex differences were unrelated to ADHD subtype. CONCLUSIONS: These findings suggest that different psychophysiological processes may underlie ADHD in each sex. The profile of theta enhancement in ADHD males is consistent with a developmental deviation model of ADHD, whereas ADHD in females may be better understood within an arousal model, which emphasizes both central and autonomic function. SIGNIFICANCE: These findings highlight the potential for concurrent EDA measures to inform EEG studies of ADHD, particularly in regard to sex differences.

Adolescent↗

PubMed2005

BOLD, sweat and fears: fMRI and skin conductance distinguish facial fear signals.

It is not known how the brain and autonomic systems interact during perception of facial signals of danger. We recorded blood-oxygen-level-dependent (BOLD) activity using fMRI and simultaneous skin conductance measures of autonomic arousal in healthy subjects. Distinct response profiles were elicited for fear (enhanced arousal with amygdala activity), anger (rapid onset, slow recovery arousal responses with anterior cingulate) and disgust (delayed arousal responses with insula and basal ganglia activity). The findings suggest that fear, anger and disgust perception involves specific interactions in the neural arousal systems for emotion and motivation.

Adult↗

PubMed2005

A direct brainstem-amygdala-cortical 'alarm' system for subliminal signals of fear.

We examined whether consciously undetected fear signals engage a collateral brainstem pathway to the amygdala and prefrontal cortex in the intact human brain, using functional neuroimaging. 'Blindsight' lesion patients can respond to visual fear signals independently from conscious experience, suggesting that these signals reach the amygdala via a direct pathway that bypasses the primary visual cortex. Electrophysiological evidence points to concomitant involvement of prefrontal regions in automatic orienting to subliminal signals of fear, which may reflect innervation arising from brainstem arousal systems. To approximate blindsight in 22 healthy subjects, facial signals of fear were presented briefly (16.7 ms) and masked such that conscious detection was prevented. Results revealed that subliminal fear signals elicited activity in the brainstem region encompassing the superior colliculus and locus coeruleus, pulvinar and amygdala, and in fronto-temporal regions associated with orienting. These findings suggest that crude sensory input from the superior colliculo-pulvinar visual pathway to the amygdala may allow for sufficient appraisal of fear signals to innervate the locus coeruleus. The engagement of the locus coeruleus could explain the observation of diffuse fronto-temporal cortical activity, given its role in evoking collateral ascending noradrenergic efferents to the subcortical amygdala and prefrontal cortex. This network may represent an evolutionary adaptive neural 'alarm' system for rapid alerting to sources of threat, without the need for conscious appraisal.

Adult↗

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

Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power.

The purpose of this study was to examine the impact of age, sex, and education on category and letter verbal fluency task performance. A secondary goal was to examine whether resting EEG theta power in bilateral frontal and temporal lobes impacts age-associated decline in verbal fluency task performance. A large sample (N = 471) of healthy, normal participants, age 21-82, was assessed for letter fluency (i.e., FAS), and for category fluency (i.e., Animal Naming), and with a 32-channel EEG system for 'eyes-open' resting theta power. The effects of age, sex, and education were examined using analyses of variance. Correlation analyses were used to test the impact of theta power on age and fluency performance by controlling for the effects of theta when examining the relationship between the other two variables. The results indicated that performance on both fluency tests declined linearly with age, but that the rate of decline was greater for category fluency. These age changes were not associated with education level, and there were no sex differences. While theta power was negatively associated with age and positively associated with Animal Naming performance, it did not moderate the relationship between the two. The differential age-associated decline between category and letter fluency suggests separate neurobiological substrates underlying the two domains of performance, which is not related to theta activity.

Adult↗

PubMed2005

Responses to methylphenidate in adolescent AD/HD: evidence from concurrently recorded autonomic (EDA) and central (EEG and ERP) measures.

This paper aims to examine the effects of methylphenidate (MPH) on integrated baseline and event-related psychophysiological measures in AD/HD. Thirty-four unmedicated AD/HD adolescents (11-17 years; 6 females) were first compared to 34 age- and sex-matched controls, and then re-tested at least 4 weeks after methylphenidate (MPH) medication. In each testing session, EDA was recorded simultaneously with EEG during a resting eyes open condition, and with ERPs during an auditory oddball task. Unmedicated AD/HD subjects were compared to controls and then AD/HD subjects were compared pre- and post-medication. Correlations between the change in EEG theta and the remaining psychophysiological variables were undertaken to provide information about post MPH treatment changes. In the unmedicated state, AD/HD was characterized by abnormally enhanced theta, across fronto-central sites, generally reduced P2 responses, with larger non-specific and oddball-elicited SCRs and poor behavioural performance on the oddball task. Following treatment, AD/HD showed a 'normalization' of theta activity (particularly in the right hemisphere), a reduction in the rate of decrement of EDA and a general increase in P3 amplitude. These findings suggest that methylphenidate is associated with a robust 'normalization' of low frequency EEG activity during the resting brain state, but has less impact on task-related brain activity or phasic changes in autonomic function. This dissociation of resting and task-related activity may prove to be useful in elucidating the effects of stimulant versus new non-stimulant medications in AD/HD.

Adolescent↗

PubMed2005

Resting EEG theta activity predicts cognitive performance in attention-deficit hyperactivity disorder.

Quantitative electroencephalography has contributed significantly to elucidating the neurobiologic mechanisms of attention-deficit hyperactivity disorder. The most consistent and robust electroencephalographic disturbance in attention-deficit hyperactivity disorder has been abnormally increased theta band during resting conditions. Separate research using attention-demanding tests has elucidated cognitive disturbances that differentiate attention-deficit hyperactivity disorder. This study attempts to integrate electroencephalographic and neuropsychological indices to determine whether cognitive performance is specifically related to increased theta. Theta activity was recorded during a resting condition for 46 children/adolescents with attention-deficit hyperactivity disorder and their sex- and age-matched control subjects. Accuracy and reaction time during an auditory oddball and a visual continuous performance test were then recorded. Compared with control subjects, the attention-deficit hyperactivity disorder group manifested significantly increased (primarily left) frontal theta. Furthermore, the attention-deficit hyperactivity disorder group scored significantly delayed reaction time and decreased accuracy in both tasks. Correlation analysis revealed a significant relationship between frontal (primarily left) theta and oddball accuracy for the attention-deficit hyperactivity disorder group compared with a significant relationship between posterior (primarily right) theta and reaction time in the continuous performance test for the control group. These results indicate that spatial neurophysiologic deficits in attention-deficit hyperactivity disorder may be related to disturbances in signal detection. This observation has important implications for the role of trait-like biologic deficits in attention-deficit hyperactivity disorder predicting performance in information processing.

Adolescent↗

PubMed2005

Preliminary validity of "integneuro": a new computerized battery of neurocognitive tests.

The purpose of this study was to examine the preliminary validity of a newly developed battery of computerized cognitive measures, IntegNeuro. This standardized and semi-automated computerized battery assesses sensori-motor function, attention, new learning and memory, language fluency, executive function, and estimated intelligence. A total of 50 healthy individuals (aged 22-80 years) were included in the study. Correlational analyses revealed highly significant associations between the two cognitive batteries. These results support the use of IntegNeuro as a computerized cognitive system. Additional studies are needed to examine the clinical utility of the battery.

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

Toward an integrated profile of emotional intelligence: introducing a brief measure.

Over the last decade, an increasing number of research studies have focused on the construct of Emotional Intelligence (EI), which may be broadly defined as the capacity to perceive and regulate emotions in oneself as well as those of others. Researchers have generally adopted an organizational or management focus to the study of EI, however studies which adopt a more integrated perspective by combining psychological with biological measures, may help in further elucidating this relatively abstract construct. The first objective of this paper was to report on the psychometric properties of a brief, self-report measure of EI (Brain Resource Inventory for Emotional intelligence Factors or BRIEF), comprising internal emotional capacity (IEC), external emotional capacity (EEC) and self concept (SELF). Second, we further explored the validity of the measure by assessing the relationships between the BRIEF and variables considered relevant to the understanding of EI (including gender, age, personality, cognitive intelligence and resting state electroencephalography, EEG). The BRIEF possessed sound psychometric properties (internal consistency, r=0.68-0.81; test-retest reliability, r=0.92; construct validity with the Self Report Emotional Intelligence Test, r=0.70). As hypothesized, females were found to score higher than males on EI. EI was associated more with personality than with cognitive ability, and EEG was found to explain a significant portion of the variance in EI scores. The finding that low EI is related to underarousal of the left-frontal cortex (increased theta EEG) is consistent with research on patients with depression, as well as attention deficit hyperactivity disorder. Although EI did not display age-related increases, this might relate to the exclusion of adolescents from our sample. In conclusion, examination of the way in which EI measures relate to a complementary range of psychological and biological measures may help to further elucidate this construct.

Adult↗

PubMed2005

The impact of early life stress on psychophysiological, personality and behavioral measures in 740 non-clinical subjects.

Early Life Stress (ELS) has been associated with a range of adverse outcomes in adults, including abnormalities in electrical brain activity [1], personality dimensions [40], increased vulnerability to substance abuse and depression [14]. The present study seeks to quantify these proposed effects in a large sample of non-clinical subjects. Data for the study was obtained from The Brain Resource International Database (six laboratories: two in USA, two in Europe, two in Australia). This study analyzed scalp electrophysiological data (EEG eyes open, closed and target auditory oddball data) and personality (NEO-FFI), history of addictive substance use and ELS) data that was acquired from 740 healthy volunteers. The ELS measures were collected via a self-report measure and covered a broad range of events from childhood sexual and physical abuse, to first-hand experience of traumatizing accidents and sustained domestic conflict [41]. Analysis of covariance, controlling for age and gender, compared EEG data from subjects exposed to ELS with those who were unexposed. ELS was associated with significantly decreased power across the EEG spectrum. The between group differences were strongest in the eyes closed paradigm, where subjects who experienced ELS showed significantly reduced beta (F1,405=12.37, p=.000), theta (F1,405=20.48, p=.000), alpha (F1,405=9.65, p=.002) and delta power (F1,450=36.22, p=.000). ELS exposed subjects also showed a significantly higher alpha peak frequency (F1,405=6.39, p=.012) in the eyes closed paradigm. Analysis of covariance on ERP components revealed that subjects who experienced ELS had significantly decreased N2 amplitude (F1,405=7.73, p=.006). Analyses of variance conducted on measures of personality revealed that subjects who experienced ELS had significantly higher levels of neuroticism (F1,264=13.39, p=.000) and openness (F1,264=17.11, p=.000), but lower levels of conscientiousness, than controls (F1,264=4.08, p=.044). The number of ELS events experienced was shown to be a significant predictor of scores on the DASS questionnaire [27], which rates subjects on symptoms of depression (F3,688=16.44, p=.000, R2=.07), anxiety (F3,688=14.32, p=.000, R2=.06) and stress (F3,688=20.02, p=.000, R2=.08). Each additional early life stressor was associated with an increase in these scores independent of age, gender and the type of stressor. Furthermore, the number of ELS experiences among smokers was also found to be a positive predictor of the nicotine dependency score (Faegstrom Test For Nicotine Dependence, [19]) (F3,104=10.99, p=.000, R2=.24), independent of age, gender and type of stressor. In conclusion, we highlight the impact of a history of ELS showed significant effects on brain function (EEG and ERP activity), personality dimensions and nicotine dependence.

Adolescent↗