Neural substrates of the interaction between effort-expenditure reward decision-making and outcome anticipation.

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.

Perceptual confidence of visual stimulus features is associated with duration perception.

It has been shown that the perceived duration of an object in the subsecond range is closely associated with its nontemporal perceptual properties, the mechanism under which remains unclear. Previous studies have revealed a modulatory effect of early visual feature processing on the apparent duration. Here, we further examined the relationship between perceptual confidence and subjective time by asking participants to simultaneously perform temporal and nontemporal perceptual judgments. The results revealed a significant effect on confidence levels. When participants' confidence in judging the coherent motion direction or relative dot numerosity increases, their perceived duration of the stimulus also appears longer. These results are discussed in the context of perceptual evidence accumulation and evaluation for the decision-making of perceptual properties. They suggest a profound contribution of object processing to the computation of subjective time and provide further insights into the mechanism of event timing.

Humour processing deficits in individuals with social anhedonia.

Humour processing comprises the humour comprehension and the humour appreciation phases. Patients with schizophrenia have impaired humour processing. However, it is unclear whether such deficits affect subclinical populations such as individuals with social anhedonia. Our study recruited forty-eight individuals with high levels of social anhedonia (HSA, screened by the Revised Chapman Social Anhedonia Scale) and 50 individuals with low levels of social anhedonia (LSA). Participants completed behavioural tasks which tapped into humour comprehension and appreciation, and a set of questionnaires assessing their sense of humour, humour styles and subjective experiential pleasure. Using signal detection theory analysis, the d' and ß values were generated to measure the detection of humour signal in the comprehension phase and the inner criteria of the humour appreciation respectively. The results showed that the HSA and LSA groups did not differ in humour signal detection (d') but the HSA group had significantly higher inner criteria of humour appreciation (ß) than the LSA group. The ß value was correlated with experiential anticipatory pleasure in all participants. The HSA group had significantly lower within-group coherence than the LSA group when processing humour. Our findings suggested that individuals with social anhedonia have impaired humour processing.

Delay discounting and affective priming in individuals with negative schizotypy.

Previous studies have demonstrated that patients with schizophrenia and individuals with schizotypy experience decreased anticipatory pleasure. However, it is unclear whether this decrease is contributed by altered reward processing at the proximal or distal future. In order to investigate the preference for receiving rewards in the proximal or distal future for individuals with schizophrenia spectrum disorders, individuals with either high or low levels of negative schizotypy performed a delay discounting task under positive, neutral and negative affective priming conditions. Compared with individuals with low levels of negative schizotypy, individuals with high levels of schizotypy exhibited increased delay discounting, preferring to choose immediate but smaller rewards instead of delayed but larger rewards across all three affective priming conditions. Negative affective priming elevated discounting for both groups compared with both the positive and neutral affective conditions. After dividing delayed temporal distance into the proximal and distal future, the results showed that individuals with high levels of negative schizotypy exhibited more preference for immediate but smaller rewards in the distal instead of proximal future compared with controls. Our results suggest that individuals with high levels of negative schizotypy have altered anticipatory reward processing, which is mainly attributed to alterations in representing rewards in the distal future. These findings extend the alterations in representing reward values from schizophrenia patients to schizotypal individuals, and suggest that diminished anticipatory pleasure in schizophrenia spectrum disorders may be due to changes in processing anticipatory rewards in the distal future.

Tongxinluo inhibits cyclooxygenase-2, inducible nitric oxide synthase, hypoxia-inducible factor-2α/vascular endothelial growth factor to antagonize injury in hypoxia-stimulated cardiac microvascular endothelial cells.

BACKGROUND: Endothelial dysfunction is considered as the initiating process and pathological basis of cardiovascular disease. Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS), inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) are key enzymes with opposing actions in inflammation and oxidative stress, which are believed to be the major driver of endothelial dysfunction. And in hypoxia (Hx), Hx-inducible factor (HIF)-1α and HIF-2α are predominantly induced to activate vascular endothelial growth factor (VEGF), resulting in abnormal proliferation. Whether and how Tongxinluo (TXL) modulates COX-2, PGIS, iNOS, eNOS, HIF-1α, HIF-2α, and VEGF in Hx-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been clarified. METHODS: HCMEC were treated with CoCl 2 to mimic Hx and the mRNA expressions of COX-2, PGIS, iNOS, eNOS, HIF-1α, HIF-2α, and VEGF were first confirmed, and then their mRNA expression and protein content as well as the cell pathological alterations were evaluated for TXL treatment with different concentrations. In addition, the effector molecular of inflammation prostaglandin E 2 (PGE 2 ) and the oxidative marker nitrotyrosine (NT) was adopted to reflect HCMEC injury. RESULTS: Hx could induce time-dependent increase of COX-2, iNOS, HIF-2α, and VEGF in HCMEC. Based on the Hx-induced increase, TXL could mainly decrease COX-2, iNOS, HIF-2α, and VEGF in a concentration-dependent manner, with limited effect on the increase of PGIS and eNOS. Their protein contents verified the mRNA expression changes, which was consistent with the cell morphological alterations. Furthermore, high dose TXL could inhibit the Hx-induced increase of PGE 2 and NT contents, attenuating the inflammatory and oxidative injury. CONCLUSIONS: TXL could inhibit inflammation-related COX-2, oxidative stress-related iNOS, and HIF-2α/VEGF to antagonize Hx-induced HCMEC injury.