Mapping adolescent reward anticipation,receipt, and prediction error during the monetary incentive delay task

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward‐related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity.     

Altered cortisol awakening response in posttraumatic stress disorder

An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder (PTSD), although there is inconsistent empirical evidence. Only few studies examined the awakening cortisol response and a daytime profile in PTSD. Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with (N=29) and without PTSD (N=19) and in 15 non-exposed controls. While the three groups did not differ with respect to their first cortisol level immediately after awakening, the expected cortisol increase to awakening 15-60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls. This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis. A significant negative correlation between the overall cortisol secretion (AUC(G)) and overall PTSD symptomatology and hyper-arousal symptoms was found. The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD.     

Interferon γ quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis

PURPOSE: To assess the utility of interferon gamma (INF-gamma) levels in cerebrospinal fluid (CSF), for the diagnosis of tuberculous meningitis (TBM), and compare these results with aPCR technique. METHODS: We studied CSF samples from patients with proven or probable TBM and a control group, composed by patients with other causes of meningitis and without meningitis. INFgamma levels were measured by radioimmunoassay. A PCR technique was performed using IS6110 primers. RESULTS: Of the 127 patients studied, 20 (15.6%) had TBM, 59 (46%) had meningitis of another aetiology and 49 (38.4%) had were HIV and non-HIV patients with normal CSF. The area below the ROC curve for interferon gamma levels in the diagnosis of TBM was 0.94. A cut-off of 6.4 IU/mL yielded a sensitivity of 70% and a specificity of 94%. False positive results were observed in 7 of the 59 patients (11.8%) with non-TB meningitis, (patients with herpetic meningoencephalitis and meningitis due to intracellular microorganisms). INF-gamma sensitivity was higher than PCR (70% vs. 65%). Both tests performed together showed higher sensitivity (80%) and specificity (92.6%). CONCLUSION: CSF INF-gamma levels (> 6.4 IU/mL) are very valuable in TBM diagnosis. PCR and INF-gamma could be simultaneously used to increase the diagnostic yield.     

Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys

The DSM-IV diagnoses generated by the fully structured lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) in the WHO World Mental Health (WMH) surveys were compared to diagnoses based on follow-up interviews with the clinician-administered non-patient edition of the Structured Clinical Interview for DSM-IV (SCID) in probability subsamples of the WMH surveys in France, Italy, Spain, and the US. CIDI cases were oversampled. The clinical reappraisal samples were weighted to adjust for this oversampling. Separate samples were assessed for lifetime and 12-month prevalence. Moderate to good individual-level CIDI-SCID concordance was found for lifetime prevalence estimates of most disorders. The area under the ROC curve (AUC, a measure of classification accuracy that is not influenced by disorder prevalence) was 0.76 for the dichotomous classification of having any of the lifetime DSM-IV anxiety, mood and substance disorders assessed in the surveys and in the range 0.62-0.93 for individual disorders, with an inter-quartile range (IQR) of 0.71-0.86. Concordance increased when CIDI symptom-level data were added to predict SCID diagnoses in logistic regression equations. AUC for individual disorders in these equations was in the range 0.74-0.99, with an IQR of 0.87-0.96. CIDI lifetime prevalence estimates were generally conservative relative to SCID estimates. CIDI-SCID concordance for 12-month prevalence estimates could be studied powerfully only for two disorder classes, any anxiety disorder (AUC = 0.88) and any mood disorder (AUC = 0.83). As with lifetime prevalence, 12-month concordance improved when CIDI symptom-level data were added to predict SCID diagnoses. CIDI 12-month prevalence estimates were unbiased relative to SCID estimates. The validity of the CIDI is likely to be under-estimated in these comparisons due to the fact that the reliability of the SCID diagnoses, which is presumably less than perfect, sets a ceiling on maximum CIDI-SCID concordance.     

Knee model of hydrodynamic lubrication during the gait cycle and the influence of prosthetic joint conformity

Background  The influence of the total joint components’ elastic deformation on lubrication is generally accepted, but little is known about the influence of joint conformity under hydrodynamic lubrication based on fluid film interposition. The aim of this study was to evaluate induced pressure and stresses in the knee under fluid film lubrication during the stance phase of walking under various joint conformity conditions. Methods  A theoretical two-dimensional (2D) geometric model of knee prosthesis contact, with Dirichlet boundary conditions at both edges, and with a conformity index (CI) of 0, 0.3, 0.5, 0.6, 0.7, 0.8, 0.9, 0.92, 0.94, 0.96, 0.98, 0.99, 0.995, and 1.0, was used to calculate the spatiotemporal lubricant flow on a synovial fluid rheological model. With the instantaneous load as a source term, the Reynolds lubrication equation was subsequently solved following a finite volume approach in two dimensions and three dimensions. Results  Conformity strongly influenced the peak pressure, from 47 MPa with CI = 0 to 1.4 MPa with CI = 1, with a definite behavior change from CI = 0.96. The role of hydrodynamic lubrication was restricted to early steps of the stance phase. With CI < 0.96, there was a smooth maximum pressure decrease with increasing CI. In contrast, the maximum pressure fell abruptly with conformity > 0.96. Conclusion  The present model suggested the limited modifying effect of hydrodynamic lubrication in total knee replacement systems. However, its role during the early stance phase, coupled with high conformity, helps significantly to decrease compressive stresses on the polyethylene, fostering the beneficial effect of high conformity in a mixed lubrication regime. This beneficial effect may also be of great interest in total knee replacement systems based on materials with less deformation.     

Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving

OBJECTIVE: Alcohol and other drugs of abuse stimulate dopamine release in the ventral striatum, which includes the nucleus accumbens, a core region of the brain reward system, and reinforce substance intake. Chronic alcohol intake is associated with down-regulation of central dopamine D(2) receptors, and delayed recovery of D(2) receptor sensitivity after detoxification is positively correlated with high risk for relapse. Prolonged D(2) receptor dysfunction in the ventral striatum may interfere with a dopamine-dependent error detection signal and bias the brain reward system toward excessive attribution of incentive salience to alcohol-associated stimuli. METHOD: Multimodal imaging, with the radioligand [(18)F]desmethoxyfallypride and positron emission tomography as well as functional magnetic resonance imaging (fMRI), was used to compare 11 detoxified male alcoholics with 13 healthy men. The authors measured the association of D(2)-like dopamine receptors in the ventral striatum with alcohol craving and central processing of alcohol cues. RESULTS: Activation of the medial prefrontal cortex and striatum by alcohol-associated stimuli, relative to activation by neutral visual stimuli, was greater in the detoxified alcoholics than in the healthy men. The alcoholics displayed less availability of D(2)-like receptors in the ventral striatum, which was associated with alcohol craving severity and with greater cue-induced activation of the medial prefrontal cortex and anterior cingulate as assessed with fMRI. DISCUSSION: In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.     

D2 autoreceptor switches CB2 receptor effects on [3H]-dopamine release in the striatum

CB₂ receptors (CB₂R) are expressed in midbrain neurons. To evidence the control of dopamine release in dorsal striatum by CB₂R, we performed experiments of [³H]-dopamine release in dorsal striatal slices. We found a paradoxical increase in K⁺-induced [³H]-dopamine release by CB₂R activation with GW 833972A and JWH 133 two selective agonist. To understand the mechanism involved, we tested for a role of the D₂ autoreceptor in this effect; because in pallidal structures, the inhibitory effect of CB₁ receptors (CB₁R) on GABA release is switched to a stimulatory effect by D₂ receptors (D₂R). We found that the blockade of D₂ autoreceptors with sulpiride prevented the stimulatory effect of CB₂R activation; in fact, under this condition, CB₂R decreased dopamine release, indicating the role of the D₂ autoreceptor in the paradoxical increase. We also found that the effect occurs in nigrostriatal terminals, since lesions with 6-OH dopamine in the middle forebrain bundle prevented CB₂R effects on release. In addition, D₂–CB₂R interaction promoted cAMP accumulation, and the increase in [³H]-dopamine release was prevented by PKA blockade. D₂–CB₂R coprecipitation and proximity ligation assay studies indicated a close interaction of receptors that could participate in the observed effects. Finally, intrastriatal injection of CB₂R agonist induced contralateral turning in amphetamine-treated rats, which was prevented by sulpiride, indicating the role of the interaction in motor behavior. Thus, these data indicate that the D₂ autoreceptor switches, from inhibitory to stimulatory, the CB₂R effects on dopamine release, involving the cAMP → PKA pathway in nigrostriatal terminals.     

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI

Journal of Neurology - Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause...