Lawrence H. Sweet

Delayed reward discounting and addictive behavior: a meta-analysis

RationaleDelayed reward discounting (DRD) is a behavioral economic index of impulsivity and numerous studies have examined DRD in relation to addictive behavior. To synthesize the findings across the literature, the current review is a meta-analysis of studies comparing DRD between criterion groups exhibiting addictive behavior and control groups.ObjectivesThe meta-analysis sought to characterize the overall patterns of findings, systematic variability by sample and study type, and possible small study (publication) bias.MethodsLiterature reviews identified 310 candidate articles from which 46 studies reporting 64 comparisons were identified (total N = 56,013).ResultsFrom the total comparisons identified, a small magnitude effect was evident (d = .15; p < .00001) with very high heterogeneity of effect size. Based on systematic observed differences, large studies assessing DRD with a small number of self-report items were removed and an analysis of 57 comparisons (n = 3,329) using equivalent methods and exhibiting acceptable heterogeneity revealed a medium magnitude effect (d = .58; p < .00001). Further analyses revealed significantly larger effect sizes for studies using clinical samples (d = .61) compared with studies using nonclinical samples (d = .45). Indices of small study bias among the various comparisons suggested varying levels of influence by unpublished findings, ranging from minimal to moderate.ConclusionsThese results provide strong evidence of greater DRD in individuals exhibiting addictive behavior in general and particularly in individuals who meet criteria for an addictive disorder. Implications for the assessment of DRD and research priorities are discussed.

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.

Differential functional magnetic resonance imaging response to food pictures in successful weight-loss maintainers relative to normal-weight and obese controls

BACKGROUND Prior research indicates that successful weight-loss maintainers (SWLs) work harder than people of normal weight to maintain their weight loss, including greater dietary restriction of fat and higher physical activity levels. However, little work to date has examined how SWLs differ biologically from normal-weight (NW) and obese controls. OBJECTIVE The objective was to compare the brain responses of SWLs to food pictures with those of NW and obese controls. DESIGN Blood oxygen level-dependent responses to high- and low-energy food pictures were measured in 18 NW controls, 16 obese controls, and 17 SWLs. RESULTS Group differences were identified in 4 regions, which indicated significant change in activation in response to the food pictures. SWLs showed greater activation in the left superior frontal region and right middle temporal region than did NW and obese controls-a pattern of results confirmed in exploratory voxel-wise analyses. Obese controls also showed greater activation in a bilateral precentral region. CONCLUSIONS These results suggest that SWLs show greater activation in frontal regions and primary and secondary visual cortices-a pattern consistent with greater inhibitory control in response to food cues and greater visual attention to the food cues. A greater engagement of inhibitory control regions in response to food cues as well as a greater monitoring of foods may promote control of food intake and successful weight-loss maintenance.

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers.

Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis

Multiple sclerosis (MS) patients frequently experience impaired verbal working memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify neural mechanisms underlying these deficits. Neuroimaging studies of healthy adults have characterized responses associated with increased VWM demands during the n‐Back task, suggesting that this experimental paradigm could help identify neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15 matched control participants completed the n‐Back during whole‐brain fMRI. Mean signal during adjacent 0‐Back blocks was subtracted, on a voxel‐wise basis, from mean signal observed during n‐Back blocks. Resulting difference scores for 1‐, 2‐, and 3‐Back were compared across groups and difficulty levels. Signal intensity was positively related to difficulty level in anterior regions, including premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients exhibited significantly greater intensity in these areas compared to controls during the 1‐Back, while portions of the left superior frontal gyrus, cingulate, and parahippocampal gyri were relatively less intense at more difficult levels. MS group responses were slower during the 1‐Back and tended to be slower during the 3‐Back; however, accuracy did not differ at any level. Lesion load was positively related to only 1‐Back activity and unrelated to any performance measure. Results suggest that compensatory activity occurs among MS patients matched on performance accuracy. Furthermore, compensatory activity occurs predominantly in regions associated with VWM, and this may decline relative to controls as task demands increase. These findings may help to explain why MS patient performance decreases as a function of effort on neuropsychological tests. Hum Brain Mapp, 2005.

Vascular and cognitive functions associated with cardiovascular disease in the elderly.

This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56–85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.

Cognitive impairment is independently associated with reduced instrumental activities of daily living in persons with heart failure

Background:Heart failure (HF) is a disabling disease that often affects instrumental activities of daily living (instrumental ADLs). Despite high rates of disability in this population, little is known about the effects of cognitive impairment on instrumental ADLs in this population. Objective:The current study examined whether cognitive functioning predicts instrumental ADL performance in persons with HF. Methods:Persons with HF (N = 122; 68.49 [SD, 9.43] years; 35.2% female) completed neuropsychological testing, fitness assessment, and self-reported instrumental and basic ADL function as part of a larger protocol. Neuropsychological tests included the Mini-Mental State Examination and Trail Making Tests A and B. The 2-minute step test estimated fitness. Instrumental and basic ADL function was based on self-report on the Lawton-Brody Activities of Daily Living Scale. Hierarchical regression analyses were used to determine the independent contribution of cognitive function to ADLs in HF. Results:Heart failure patients reported high rates of impairments in instrumental ADLs, but indicated requiring little or no assistance with basic ADLs. Cognitive function showed incremental predictive validity for driving (R2 change = .07, P = .03) and medication management (R2 change = .14, P < .001). In each case, poorer neuropsychological test performance was associated with poorer instrumental ADL function. Conclusion:In persons with HF, cognitive performance is an independent predictor of independence in driving and medication management. Strategies to maintain or improve cognitive functioning in HF may help patients remain functionally independent in their daily living.

Early Life Stress and Adult Emotional Experience: An International Perspective

Early life stress (ELS) has been linked to adult psychopathology, though few studies have examined the universality of specific adverse childhood events (ACEs) in healthy adults. We examined the co-occurrence of specific ACEs and their relationship to current emotional distress in an international sample of adults without psychopathology. Participants were 1659 men and women recruited for an international neurocognitive-neuroimaging database from sites in the United States, Australia, England, and the Netherlands. Participants had no current or prior diagnosis of major depression, anxiety, substance abuse, or neurological brain disorder. The occurrence and age on onset of 19 ACEs was assessed by a self-report questionnaire (ELSQ), and current symptoms of stress, depression, and anxiety by the Depression Anxiety Stress Scale (DASS). The relationship of specific ACEs to DASS symptoms was examined. Participants reported relatively high prevalence of ACEs. Only 27.6% of the sample reported no ACEs, while 39.5% reported one or two significant experiences and 32.9% reported more than two ACEs. Rates of most ACEs were quite similar across the three continents. Various ACEs were significantly associated with current DASS severity, particularly ACEs involving emotional abuse, neglect, and family conflict, violence, and breakup. Finding nearly one-third of the sample reported three or more ACEs suggest a high prevalence of ELS in otherwise healthy “normal” adults around the world. Associations between ELS and current emotional distress suggest that these events have functional relevance and deserve further investigation.

Emotional and personality changes following cingulotomy.

The effects of bilateral anterior cingulate cortex (ACC) lesions on emotional and personality functioning were studied. Patients undergoing cingulotomy for chronic intractable pain were assessed on the Minnesota Multiphasic Personality Inventory (MMPI), the Profile of Mood States (POMS), cognitive tests, and pain ratings, pre- and postsurgically. Patients with intractable pain, not treated with cingulotomy, served as controls. Cingulotomy patients experienced reductions in POMS-Tension, POMS-Anger, and MMPI Scale 7 (Psychasthenia) compared with baseline and the controls. POMS-Tension was significantly correlated with attention-intention performance. The results indicate that the ACC modulates emotional experience, related to self-perceived tension, and that there is relationship between the emotional and the attentional effects of cingulotomy.

Cerebral Perfusion is Associated With White Matter Hyperintensities in Older Adults With Heart Failure

Cognitive impairment is common in heart failure (HF) and believed to be the result of cerebral hypoperfusion and subsequent brain changes including white matter hyperintensities (WMHs). The current study examined the association between cerebral blood flow and WMHs in patients with HF and the relationship between WMHs and cognitive impairment. Sixty-nine patients with HF completed the Mini-Mental State Examination (MMSE) and underwent echocardiography, transcranial Doppler sonography for cerebral blood flow velocity of the middle cerebral artery, and brain magnetic resonance imaging. Multivariable hierarchical regression analyses controlling for medical and demographic characteristics as well as intracranial volume showed reduced cerebral blood flow velocity of the middle cerebral artery was associated with greater WMHs (β=-0.34, P=.02). Follow-up regression analyses adjusting for the same medical and demographic factors in addition to cerebral perfusion also revealed marginal significance between increased WMHs and poorer performance on the MMSE (β=-0.26, P=.05). This study suggests that reduced cerebral perfusion is associated with greater WMHs in older adults with HF. These findings support the widely proposed mechanism of cognitive impairment in HF patients and prospective studies are needed to confirm these results.