Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.

Background: Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. As intranasal oxytocin has been shown to modulate activation of the brain's reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. Methods: In this randomized, double-blind, placebo-controlled, crossover functional magnetic resonance imaging study, we examined effects of a 24-IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Results: Nonsignificant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. Conclusions: Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD.

Brain Damage With Heart Failure: Cardiac Biomarker Alterations and Gray Matter Decline.

RATIONALE: Heart failure (HF) following heart damage leads to a decreased blood flow due to a reduced pump efficiency of the heart muscle. A consequence can be insufficient oxygen supply to the organism including the brain. While HF clearly shows neurological symptoms, such as fatigue, nausea, and dizziness, the implications for brain structure are not well understood. Few studies show regional gray matter decrease related to HF; however, the underlying mechanisms leading to the observed brain changes remain unclear. OBJECTIVE: To study the relationship between impaired heart function, hampered blood circulation, and structural brain change in a case-control study. METHODS AND RESULTS: Within a group of 80 patients of the Leipzig Heart Center, we investigated a potential correlation between HF biomarkers and the brain's gray matter density (GMD) obtained by magnetic resonance imaging. We observed a significant positive correlation between cardiac ejection fraction and GMD across the whole frontal and parietal medial cortex reflecting the consequence of HF onto the brain's gray matter. Moreover, we also obtained a relationship between GMD and the NT-proBNP (N-terminal prohormone of brain natriuretic peptide)-a biomarker that is used for screening, diagnosis, and prognosis of HF. Here, we found a significant negative correlation between NT-proBNP and GMD in the medial and posterior cingulate cortex but also in precuneus and hippocampus, which are key regions implicated in structural brain changes in dementia. CONCLUSIONS: We obtained significant correlations between brain structure and markers of heart failure including ejection fraction and NT-proBNP. A diminished GMD was found with decreased ejection fraction and increased NT-proBNP in wide brain regions including the whole frontomedian cortex as well as hippocampus and precuneus. Our observations might reflect structural brain damage in areas that are related to cognition; however, whether these structural changes facilitate the development of cognitive alterations has to be proven by further longitudinal studies.

Cortical laminar resting-state signal fluctuations scale with the hypercapnic blood oxygenation level-dependent response.

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level-dependent (BOLD) response. This is achieved by scaling, using information from a perfusion-sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath-hold task. In this work, we seek for a validation of the use of the resting-state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth-dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia-induced signal changes (tSDhc ) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc ( R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M ( R2 = 0.62 ± 0.19). Laminar profiles of RSFA-normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.

tDCS modulates cortical nociceptive processing but has little to no impact on pain perception.

Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. In this double-blind, randomized, cross-over, sham controlled study, we examined the effects of anodal, cathodal, and sham stimulation of the left motor cortex in 16 healthy volunteers using functional imaging during an acute heat pain paradigm as well as pain thresholds, pain intensity ratings, and quantitative sensory testing. tDCS was applied at 1 mA for 15 minutes. Neither cathodal nor anodal tDCS significantly changed brain activation in response to nociceptive stimulation when compared with sham stimulation. However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.

Structural brain changes in chronic pain reflect probably neither damage nor atrophy.

Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD) years, 10 female) before hip joint endoprosthetic surgery (pain state) and monitored brain structural changes up to 1 year after surgery: 6-8 weeks, 12-18 weeks and 10-14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC), insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA). We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.

Brain gray matter decrease in chronic pain is the consequence and not the cause of pain.

Recently, local morphologic alterations of the brain in areas ascribable to the transmission of pain were reported in patients suffering from chronic pain. Although some authors discussed these findings as damage or loss of brain gray matter, one of the key questions is whether these structural alterations in the cerebral pain-transmitting network precede or succeed the chronicity of pain. We investigated 32 patients with chronic pain due to primary hip osteoarthritis and found a characteristic gray matter decrease in patients compared with controls in the anterior cingulate cortex (ACC), right insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC), amygdala, and brainstem. We then investigated a subgroup of these patients (n = 10) 6 weeks and 4 months after total hip replacement surgery, monitoring whole brain structure. After surgery, all 10 patients were completely pain free and we observed a gray matter increase in the DLPFC, ACC, amygdala, and brainstem. As gray matter decrease is at least partly reversible when pain is successfully treated, we suggest that the gray matter abnormalities found in chronic pain do not reflect brain damage but rather are a reversible consequence of chronic nociceptive transmission, which normalizes when the pain is adequately treated.