Laetitia L. Thompson

Prefrontal Cortex Activity is Reduced in Gambling and Nongambling Substance Users During Decision-Making

Objective: Poor decision‐making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision‐making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance‐dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance‐dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems. Method: 18 controls, 14 substance‐dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT. Result: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision‐making. Controls showed the greatest activity, followed by SDPG, followed by SD. Conclusion: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision‐making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance‐dependent individuals. Hum Brain Mapp, 2007.

Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals.

BACKGROUND Chronic exposure to drugs of addiction induces cellular adaptations in orbitofrontal cortex (OFC) and associated limbic-prefrontal pathways that might underlie abuse-related behavior. A propensity to make risky decisions in spite of substantial negative consequences might be mediated by medial OFC dysfunction in substance-dependent individuals (SDI). We tested the hypothesis that medial OFC gray matter (GM) volume would be lower in SDI compared with control subjects. METHODS Nineteen SDI and 20 control subjects participated. The SDI were dependent on two or more substances, most often cocaine, amphetamine, and alcohol, with mean duration of abstinence 4.7, 2.4, and 3.2 years, respectively. High-resolution T1-weighted images were acquired on a 3-T magnetic resonance system. Image processing and analyses were conducted with voxel-based morphometry (VBM) implemented in Statistical Parametric Mapping (SPM) 5. Differences in regional GM volume were tested with an analysis of covariance model, co-varying for global GM and age. Statistical maps were set at p < .05, corrected for multiple comparisons. Medial OFC GM volume was correlated with behavioral performance on a modified gambling task. RESULTS There was lower GM volume specifically in bilateral medial OFC in SDI compared with control subjects. There was a small but significant correlation between medial OFC GM and persistence of playing high-risk decks on a modified gambling task. CONCLUSIONS This is the first study to use VBM with whole brain correction for multiple comparisons in SDI after prolonged abstinence. Reduced medial OFC GM might reflect long-term adaptations within the reward-learning circuit underlying pathological decision-making in substance dependence.

Intensive speech treatment for patients with Parkinson's disease Short- and long-term comparison of two techniques

The purpose of this study was to evaluate the long-term (12 months) effects of two forms of speech treatment on the speech and voice deficits that occur in Parkinsons disease. Thirty-five patients with idiopathic Parkinsons disease were assigned to one of two speech treatment groups: voice and respiration (The Lee Silverman Voice Treatment [LSVT]) or placebo (respiration) treatment. Vocal intensity data from before, immediately after, and at 6 and 12 months after speech treatment revealed statistically significant differences between the treatment groups. Only subjects in the LSVT group improved or maintained vocal intensity above pretreatment levels by 12 months after treatment. The placebo group had statistically significant deterioration of vocal intensity levels from before to 12 months after treatment during conversational monologue. The LSVT group did not deteriorate to levels below pretreatment in vocal intensity over the 12-month period. This study is the first to document the short- and long-term effects of intensive speech treatment (LSVT), which focuses on the voice, for patients with Parkinsons disease compared with a placebo speech treatment group. NEUROLOGY 1996;47: 1496-1504

Influences on adolescent substance dependence: conduct disorder, depression, attention deficit hyperactivity disorder, and gender

OBJECTIVE In adolescents, conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), and depression are frequently comorbid with substance dependence (SD). We hypothesized that the prevalence and severity of CD, major depressive disorder (MDD), and ADHD would differ by gender, and that these conditions would associate differentially with severity of SD in males and females. METHODS We examined these issues, using standardized diagnostic interviews, in 285 male and 82 female adolescents referred for comorbid CD and SD. RESULTS Males and females did not differ significantly in severity of substance involvement, MDD, or ADHD, but males had more severe CD. MDD severity was the only variable significantly associated with SD severity for females, while for males, severity of CD combined with MDD and ADHD was significantly associated with SD severity. CONCLUSIONS Among referred adolescents, CD, MDD, and ADHD may all be important concomitants of SD in males, while in females, depression may be the primary variable related to SD.

Contribution of ADHD symptoms to substance problems and delinquency in conduct-disordered adolescents

We examined adolescents with conduct disorder (CD) and substance problems to determine if those with attention deficit hyperactivity disorder (ADHD) symptomatology had more severe delinquency and substance involvement. ADHD symptomatology was assessed in two ways: (1) by self-reports using the Diagnostic Interview Schedule for Children (DISC) and (2) by use of DISC plus reports of others (parents, program staff, and program teacher). We divided boys into three ADHD groups based on DISC: those who met criteria, those who reported at least eight current symptoms, and those who reported fewer than eight symptoms. We also divided the same boys into two groups: those with reports of ADHD by two or more sources and those without this multisource ADHD. Examining these definitions of ADHD revealed that boys with either self- or multisource ADHD had more CD symptoms, earlier age of CD onset, more substance dependence diagnoses, and more comorbid depression and anxiety.

Discriminability of the Wisconsin Card Sorting Test using the standardization sample.

The four neurological patient groups and the normals from the Wisconsin Card Sorting Test (WCST) standardization sample were used to examine the discriminability of the WCSTs indices. Results reveal consistent differentiation of normals from the patient groups on all WCST variables, with classification rates averaging 71% accuracy. However, patient groups with frontal, diffuse, and nonfrontal lesions were not consistently discriminable from each other. The results suggest that the WCST is most usefully conceptualized as a measure of executive abilities that involves the frontal lobes, but should not be considered solely as a marker of isolated frontal lobe pathology.

Evaluation of the general sensitivity of the Wisconsin card sorting test among younger and older children

Although the Wisconsin Card Sorting Test (WCST) has been widely used to evaluate the cognitive effects of cerebral dysfunction, particularly of the frontal lobes, among adult populations, it has received little attention among children. To evaluate the general sensitivity of the WCST in this group, the present study compared the WCST performances of a heterogeneous sample (n = 77) of younger children (94 to 119 months of age) and older children (120 to 189 months of age) who were referred for neuropsychological evaluation on clinical grounds with the WCST performances of age‐appropriate controls (n = 80). Five measures derived from the standard WCST were examined, and the results revealed significant (p < .005) main effects of group and age for each of the WCST variables; no interactions were observed. These findings suggest that although WCST performance is age‐dependent, its sensitivity is not restricted by age; that is, it is still possible to identify differences in level of skill at older and younger...

Do patients with Parkinson’s disease benefit from embryonic dopamine cell transplantation?

Abstract.Embryonic dopamine cell transplants survive in nearly all patients regardless of age and without immunosuppression. Transplants can improve Parkinson “off” symptoms up to the best effects of L-dopa observed preoperatively. They cannot improve the “best on” state. Transplants appear to survive indefinitely. In 10 to 15% of patients, transplants can reproduce the dyskinetic effects of L-dopa even after discontinuing all L-dopa. Neurotransplantation should be tried earlier in the clinical course of Parkinson’s to see if earlier intervention can prevent progression of the disease, particularly the dyskinetic responses seen after longterm L-dopa treatment.

Reduced cortical gray matter volume in male adolescents with substance and conduct problems

UNLABELLED Boys with serious conduct and substance problems (Antisocial Substance Dependence (ASD)) repeatedly make impulsive and risky decisions in spite of possible negative consequences. Because prefrontal cortex (PFC) is involved in planning behavior in accord with prior rewards and punishments, structural abnormalities in PFC could contribute to a persons propensity to make risky decisions. METHODS We acquired high-resolution structural images of 25 male ASD patients (ages 14-18 years) and 19 controls of similar ages using a 3T MR system. We conducted whole-brain voxel-based morphometric analysis (p<0.05, corrected for multiple comparisons at whole-brain cluster-level) using Statistical Parametric Mapping version-5 and tested group differences in regional gray matter (GM) volume with analyses of covariance, adjusting for total GM volume, age, and IQ; we further adjusted between-group analyses for ADHD and depression. As secondary analyses, we tested for negative associations between GM volume and impulsivity within groups and separately, GM volume and symptom severity within patients using whole-brain regression analyses. RESULTS ASD boys had significantly lower GM volume than controls in left dorsolateral PFC (DLPFC), right lingual gyrus and bilateral cerebellum, and significantly higher GM volume in right precuneus. Left DLPFC GM volume showed negative association with impulsivity within controls and negative association with substance dependence severity within patients. CONCLUSIONS ASD boys show reduced GM volumes in several regions including DLPFC, a region highly relevant to impulsivity, disinhibition, and decision-making, and cerebellum, a region important for behavioral regulation, while they showed increased GM in precuneus, a region associated with self-referential and self-centered thinking.

Three-word recall as a measure of memory

Clinical examination of memory functions often includes the administration of simple free recall tasks, such as the recall of several words following a few minutes. Little is known, however, about the normative parameters or psychometric properties of such procedures, and such techniques have rarely been compared with more comprehensive, well-standardized memory indices. To address these issues, two three-word recall tasks were administered to a large group of carefully selected healthy subjects over the age of 50 years. The Mini-Mental State Examination (MMSE) was obtained as an index of global cognitive status, and the California Verbal Learning Test (CVLT) was used to exclude subjects with abnormal memory abilities. Significant but modest relationships were found between two three-word recall tasks and CVLT results. Substantial variability was seen on three-word recall, with a significant proportion of normal subjects recalling zero or one word. Results suggest using caution in interpreting simple recall performance as an index of memory, as great variability in results is seen among healthy (particularly older) individuals.