Dissecting Neural Responses to Temporal Prediction, Attention, and Memory: Effects of Reward Learning and Interoception on Time Perception.

Temporal prediction (TP) is needed to anticipate future events and is essential for survival. Our sense of time is modulated by emotional and interoceptive (corporal) states that are hypothesized to rely on a dopamine (DA)-modulated "internal clock" in the basal ganglia. However, the neurobiological substrates for TP in the human brain have not been identified. We tested the hypothesis that TP involves DA striato-cortical pathways, and that accurate responses are reinforcing in themselves and activate the nucleus accumbens (NAc). Functional magnetic resonance imaging revealed the involvement of the NAc and anterior insula in the temporal precision of the responses, and of the ventral tegmental area in error processing. Moreover, NAc showed higher activation for successful than for unsuccessful trials, indicating that accurate TP per se is rewarding. Inasmuch as activation of the NAc is associated with drug-induced addictive behaviors, its activation by accurate TP could help explain why video games that rely on TP can trigger compulsive behaviors.

Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic rates including hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes in basal ganglia metabolism offer potential insight into targeting strategies for therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions.

Methylphenidate's effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls.

Methylphenidate (MPH) is a first line treatment for ADHD and is also misused as a purported cognitive enhancer, yet its effects on brain function are still poorly understood. Recent functional magnetic resonance imaging (fMRI) studies showed that MPH altered cortico-striatal resting functional connectivity (RFC). Here we investigated the effects of MPH in thalamic connectivity since the thalamus modulates striato-cortical signaling. We hypothesized that MPH would increase thalamic connectivity and metabolism, and that this response would be blunted in cannabis abusers. For this purpose, we measured RFC in seven thalamic nuclei using fMRI and brain glucose metabolism using positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) in sixteen healthy controls and thirteen participants with cannabis use disorder (CUD) twice after placebo and after MPH (0.5 mg/kg, iv). MPH significantly increased thalamo-cerebellar connectivity and cerebellar metabolism to the same extent in both groups. Group comparisons revealed that in CUD compared to controls, metabolism in nucleus accumbens was lower for the placebo and MPH measures, that MPH-induced increases in thalamic metabolism were blunted, and that enhanced negative connectivity between thalamus and accumbens in CUD was normalized by MPH (reducing negative connectivity). Our findings identify the thalamus as a target of MPH, which increased its metabolism and connectivity. The reduced metabolism in nucleus accumbens and the disrupted thalamo-accumbens connectivity (enhanced negative connectivity) in CUD is consistent with impaired reactivity of the brain reward's circuit. MPH's normalization of thalamo-accumbens connectivity (reduced negative connectivity) brings forth its potential therapeutic value in CUD, which merits investigation.

Fluorine-18-fluorodihydroxyphenylalanine Positron-emission Tomography Scans of Neuroendocrine Tumors (Carcinoids and Pheochromocytomas).

OBJECTIVES: Conventional methods of imaging neuroendocrine tumors with computed tomography, magnetic resonance imaging, indium-111-octreotide, or radiolabeled metaiodobenzilguanidine scintigraphy have limitations. This pilot study tried to improve the localization of these tumors with fluorine-18-fluorodihydroxyphenylalanine (F-DOPA) positron-emission tomography (PET) scanning. MATERIALS AND METHODS: We studied 22 patients, the majority of whom were referred with clinical diagnosis or suspicion of carcinoid (n = 11), neuroendocrine tumors (n = 7) or pheochromocytoma/paraganglioma (PGL) (n = 4). The comparison was made with the prior conventional imaging. RESULTS: The F-DOPA findings were compared with the results of subsequent surgery (2), endoscopy (1), or a long-term follow-up (mean duration, 49 months) for 17 patients. Two patients were lost to follow-up. Foci of F-DOPA deposition were detected in eight patients (final diagnosis of carcinoid in six, of neuroendocrine tumors in one, and of PGL in another). Comparison with the final diagnoses revealed concordance in 16 of the 22 patients. F-DOPA results appeared superior to those obtained with conventional imaging. Despite the small number and diagnostic heterogeneity, in a substantial fraction of patients F-DOPA PET added information relevant to clinical management. CONCLUSION: F-DOPA scanning added prognostic value, particularly when multiple abnormal foci versus a negative examination were considered.

Chemotherapy-induced pericarditis on F-18 FDG positron emission tomography scan.

F-18 FDG positron emission tomography (PET) is a highly valuable imaging tool in evaluation and follow up of lymphoma and many other malignancies. Constrictive or effusive constrictive pericarditis is an uncommon complication of chemotherapy. The authors report a case in which pericardial FDG uptake was seen on a whole-body PET scan performed for posttreatment follow-up evaluation for a mantle cell lymphoma.