C. Richard Clark

The Psychiatric Sequelae of Traumatic Injury

OBJECTIVE Traumatic injury affects millions of people each year. There is little understanding of the extent of psychiatric illness that develops after traumatic injury or of the impact of mild traumatic brain injury (TBI) on psychiatric illness. The authors sought to determine the range of new psychiatric disorders occurring after traumatic injury and the influence of mild TBI on psychiatric status. METHOD In this prospective cohort study, patients were drawn from recent admissions to four major trauma hospitals across Australia. A total of 1,084 traumatically injured patients were initially assessed during hospital admission and followed up 3 months (N=932, 86%) and 12 months (N=817, 75%) after injury. Lifetime psychiatric diagnoses were assessed in hospital. The prevalence of psychiatric disorders, levels of quality of life, and mental health service use were assessed at the follow-ups. The main outcome measures were 3- and 12-month prevalence of axis I psychiatric disorders, levels of quality of life, and mental health service use and lifetime axis I psychiatric disorders. RESULTS Twelve months after injury, 31% of patients reported a psychiatric disorder, and 22% developed a psychiatric disorder that they had never experienced before. The most common new psychiatric disorders were depression (9%), generalized anxiety disorder (9%), posttraumatic stress disorder (6%), and agoraphobia (6%). Patients were more likely to develop posttraumatic stress disorder (odds ratio=1.92, 95% CI=1.08-3.40), panic disorder (odds ratio=2.01, 95% CI=1.03-4.14), social phobia (odds ratio=2.07, 95% CI=1.03-4.16), and agoraphobia (odds ratio=1.94, 95% CI=1.11-3.39) if they had sustained a mild TBI. Functional impairment, rather than mild TBI, was associated with psychiatric illness. CONCLUSIONS A significant range of psychiatric disorders occur after traumatic injury. The identification and treatment of a range of psychiatric disorders are important for optimal adaptation after traumatic injury.

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.

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. Hum Brain Mapp, 2005.

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. Hum Brain Mapp, 2007.

Abnormal stimulus processing in posttraumatic stress disorder

This study investigated event-related potential (ERP) indices of information processing in sufferers of posttraumatic stress disorder (PTSD). ERPs were obtained from 18 PTSD patients and 20 controls while they performed a target discrimination task requiring the detection of infrequent target tones from a background sequence of frequent and infrequent distractor tones. A delayed N2 and an attenuated P3 that failed to differentiate target from distractor tones indicated that patients had abnormal difficulty distinguishing task stimuli of differing relevance. It is proposed that this difficulty is reflected behaviorally in the slowed reaction time by patients to target stimuli and may underlie the disturbed concentration and memory impairments found in PTSD. It may also be related to dysfunction in central noradrenaline function, which has been shown to be both crucial in selective attention and abnormal in PTSD.

Misinterpreting Emotional Expressions in Attention-Deficit/Hyperactivity Disorder: Evidence for a Neural Marker and Stimulant Effects

BACKGROUND In addition to cognitive impairment, there are disruptions to mood and emotion processing in attention-deficit/hyperactivity disorder (ADHD) but little is known about their neural basis. We examined ADHD disturbances in mood and emotion recognition and underlying neural systems before and after treatment with stimulant medication. METHODS Participants were 51 unmedicated ADHD adolescents and 51 matched healthy control subjects rated for depressed and anxious mood and accuracy for identifying facial expressions of basic emotion. Brain function was recorded using event-related potentials (ERPs) while subjects viewed these expressions. ADHD subjects were retested after 4 weeks, following treatment with methylphenidate (MPH). RESULTS ADHD subjects showed a profile of emotion-related impairment: higher depression and anxiety, deficits in identifying threat-related emotional expressions in particular, and alterations in ERPs. There was a pronounced reduction in occipital activity during the early perceptual analysis of emotional expression (within 120 msec), followed by an exaggeration of activity associated with structural encoding (120-220 msec) and subsequent reduction and slowing of temporal brain activity subserving context processing (300-400 msec). Methylphenidate normalized neural activity and produced some improvement of emotion recognition but had no impact on negative mood. Improvements in neural activity with MPH were consistent predictors of improvement in clinical features of emotional lability and hyperactivity. CONCLUSIONS Objective behavioral and brain function measures of emotion processing may provide a valuable addition to the clinical armamentarium for assessing emotional disturbances in ADHD and the efficacy of stimulants for treating these disturbances.

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.

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study.

BACKGROUND This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information. METHODS Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison. RESULTS Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally. CONCLUSIONS The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.

Thinking activates EMG in scalp electrical recordings.

OBJECTIVE Fast electrical rhythms in the gamma range (30-100Hz) in scalp (but not intracranial) recordings are predominantly due to electromyographic (EMG) activity. We hypothesized that increased EMG activity would be augmented by mental tasks in proportion to task difficulty and the requirement of these tasks for motor or visuo-motor output. METHODS EEG was recorded in 98 subjects whilst performing cognitive tasks and analysed to generate power spectra. In four other subjects, neuromuscular blockade was achieved pharmacologically providing EMG-free spectra of EEG at rest and during mental tasks. RESULTS In comparison to the paralysed condition, power of scalp electrical recordings in the gamma range varied in distribution, being maximal adjacent to cranial or cervical musculature. There were non-significant changes in mean gamma range activity due to mental tasks in paralysed subjects. In normal subjects, increases in scalp electrical activity were observed during tasks, without relationship to task difficulty, but with tasks involving limb- or eye-movement having higher power. CONCLUSIONS Electrical rhythms in the gamma frequency range recorded from the scalp are inducible by mental activity and are largely due to EMG un-related to cognitive effort. EMG varies with requirements for somatic or ocular movement more than task difficulty. SIGNIFICANCE Severe restrictions exist on utilizing scalp recordings for high frequency EEG.

Relationships between changes in symptom ratings, neuropsychological test performance and quality of life in schizophrenic patients treated with clozapine

This study examined the correlations between reduction in symptoms, changes in neuropsychological test performance and improved quality of life in 19 schizophrenic outpatients treated with clozapine. Reduction in both negative symptoms and general psychopathology was associated with a better quality of life. Some improvement in neuropsychological test performance was found, with a variable pattern of association with change in psychopathology. Improved verbal fluency was associated with reduction in negative symptoms, while improved verbal concept formation was associated with reduction in positive symptoms.