OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically ..."old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: 15Owater and 18Ffluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen-limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.
We describe the Fundamental Neutron Physics Beamline (FnPB) facility located at the Spallation Neutron Source at Oak Ridge National Laboratory. The FnPB was designed for the conduct of experiments ...that investigate scientific issues in nuclear physics, particle physics, astrophysics and cosmology using a pulsed slow neutron beam. We present a detailed description of the design philosophy, beamline components, and measured fluxes of the polychromatic and monochromatic beams.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
OBJECTIVE: Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not ...been fully characterized. METHOD: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial. RESULTS: Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents. CONCLUSIONS: The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.
The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients ...with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.
Background: Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been ...previously characterized.
Methods: Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment.
Results: Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes.
Conclusions: Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We examined whether specific neurocognitive deficits predicted specific domains of community outcome in 40 schizophrenic patients. Neuropsychological assessments were conducted before hospital ...discharge, and measures of functional outcome were obtained 1 to 3.5 years later. A priori hypotheses were generated based upon a recent review by Green ( What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153(3):321-330). As hypothesized, verbal memory predicted all measures of community outcome, vigilance predicted social outcomes, and executive functioning predicted work and activities of daily living (ADLs). However, in addition to the predicted relationships, many other associations were found between neuropsychological test scores and adaptive function. Furthermore, both cognitive and functional measures were intercorrelated. If deficits in adaptive functioning are neurocognitively multi-determined, utilizing compensatory strategies to bypass multiple areas of cognitive impairment may be more efficient than cognitive remediation in improving community outcomes.
The relationships between positive and negative symptomatology, cognitive function, and the ability to perform basic activities of daily living in patients with schizophrenia were examined in two ...studies. In study 1, 112 medicated patients were assessed utilizing the Brief Psychiatric Rating Scale (positive symptoms), the Negative Symptom Assessment (negative symptoms and cognitive function), and the Functional Needs Assessment (activities of daily living). Study 2 (
n = 41 ), utilized the same measures of symptomatology and added a comprehensive neuropsychological test battery. Regression analyses in both studies determined that symptomatology predicts a relatively small amount of the variance in the ability to perform basic activities of daily living. Cognitive function, whether assessed with the Cognition subscale of the Negative Symptom Assessment or a comprehensive neuropsychological test battery, predicted over 40% of the variance in scores on the Functional Needs Assessment. A path model in which cognition predicted both concurrent symptomatology and activities of daily living and where symptomatology had little direct impact upon activities of daily living fit the data. The importance of addressing cognitive deficits in psychosocial intervention programs is discussed.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside.
Inter-rater reliability testing and ...validation using inter-group comparisons across levels of care and measures of cognition and behavior.
Forty elderly subjects randomly selected across four levels of care.
Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community.
The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses.
Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79).
These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE.
Impairment of executive-frontal lobe functioning, affecting the planning, initiation and regulation of goal-directed behavior, is a common cognitive deficit in schizophrenia. However, it is unclear ...if deficits in these frontal-lobe-mediated abilities are differentially expressed across clinical subgroups. We analyzed executive-frontal abilities in relation to symptom expression in 53 hospitalized schizophrenic patients. Patients were assigned to one of three subgroups based on rank order analysis of Brief Psychiatric Rating Scale factors: Withdrawal-Retardation, Reality Distortion and Conceptual Disorganization. Executive-frontal tests included Visual Search, Verbal Fluency, Verbal Series Attention, Trail Making — Part B, Symbol Digit, Hopkins Verbal Learning, Digit Span, Wisconsin Card Sorting, Stroop Color-Word and Attentional Capacity. The schizophrenia group showed significant deficits relative to healthy control subjects (
n = 20) on all tests. Exploratory factor analysis of test scores revealed three factors: (i) Verbal Processing/Memory; (ii) Cognitive Flexibility/Attention; and (iii) Psychomotor Speed/Visual Scanning. The three symptom subgroups were differentially impaired on executive-frontal abilities: Withdrawal-Retardation on psychomotor speed, verbal fluency, working memory, visual search and cognitive flexibility; Conceptual Disorganization on attention; Reality Distortion on verbal memory. The results have implications for syndrome definition, pharmacological intervention and prediction of outcome in schizophrenia.
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10.
Age and Features of Movement Influence Motor Overflow Bodwell, Julie A.; Mahurin, Roderick K.; Waddle, Sally ...
Journal of the American Geriatrics Society (JAGS),
December 2003, Volume:
51, Issue:
12
Journal Article
Peer reviewed
Open access
Objectives: To measure the magnitude and prevalence of motor overflow to the arm at rest during attempted unilateral arm movements.
Design: Cross‐sectional assessment.
Setting: Motor physiology ...laboratory.
Participants: Healthy young (n=20) and elderly (n=20) adult subjects.
Measurements: Surface electromyography (EMG) was obtained from bilateral forearm muscles during performance of 12 different unilateral finger‐tapping tasks.
Results: For all subjects, faster movement rate (F=2.56–3.30, P<.05), cognitive distraction (F=4.09, P<.05), and fatigue (F=15.15, P<.001) were each associated with a significant increase in the magnitude of EMG in the arm intended to be at rest. In elderly subjects, tapping at maximum rate and fatigue were each associated with a further increase in motor overflow across the midline. In addition, better left hand dexterity correlated with greater motor overflow to the right hand during rapid left hand tapping (r=0.63, P<.005). Prevalence of motor overflow was also higher in older subjects for some tasks, for example during 1 Hz tapping by the right index finger (motor overflow present in 45%, vs 15% young subjects, P<.05).
Conclusion: Several behavioral variables increase motor overflow across the midline in young and elderly adults. Motor overflow was even greater in elderly subjects with the most demanding tasks and was greater in those with better motor status, suggesting that this form of motor system change is a compensatory event of normal aging rather than age‐related dysfunction. The results support the hypotheses that healthy aging is associated with an increase in the degree to which brain function is bilaterally organized.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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