Sensation-seeking is related to functional connectivities of the medial orbitofrontal cortex with the anterior cingulate cortex

Sensation-seeking is a multifaceted personality trait with components that include experience-seeking, thrill and adventure seeking, disinhibition, and susceptibility to boredom, and is an aspect of impulsiveness. We analysed brain regions involved in sensation-seeking in a large-scale study with 414 participants and showed that the sensation-seeking score could be optimally predicted from the functional connectivity with typically (in different participants) 18 links between brain areas (measured in the resting state with fMRI) with correlation r ​= ​0.34 (p ​= ​7.3 ​× ​10−13) between the predicted and actual sensation-seeking score across all participants. Interestingly, 8 of the 11 links that were common for all participants were between the medial orbitofrontal cortex and the anterior cingulate cortex and yielded a prediction accuracy r ​= ​0.30 (p ​= ​4.8 ​× ​10−10). We propose that this important aspect of personality, sensation-seeking, reflects a strong effect of reward (in which the medial orbitofrontal cortex is implicated) on promoting actions to obtain rewards (in which the anterior cingulate cortex is implicated). Risk-taking was found to have a moderate correlation with sensation-seeking (r ​= ​0.49, p ​= ​3.9 ​× ​10−26), and three of these functional connectivities were significantly correlated (p ​< ​0.05) with the overall risk-taking score. This discovery helps to show how the medial orbitofrontal and anterior cingulate cortices influence behaviour and personality, and indicate that sensation-seeking can involve in part the medial orbitofrontal cortex reward system, which can thereby become associated with risk-taking and a type of impulsiveness

Risk-taking in humans and the medial orbitofrontal cortex reward system

Risk-taking differs between humans, and is associated with the personality measures of impulsivity and sensation-seeking. To analyse the brain systems involved, self-report risk-taking, resting state functional connectivity, and related behavioral measures were analyzed in 18,740 participants of both sexes from the UK Biobank. Functional connectivities of the medial orbitofrontal cortex, ventromedial prefrontal cortex (VMPFC), and the parahippocampal areas were significantly higher in the risk-taking group (p < 0.001, FDR corrected). The risk-taking measure was validated in that it was significantly associated with alcohol drinking amount (r = 0.08, p = 5.1×10 ), cannabis use (r = 0.12, p = 6.0×10 ), and anxious feelings (r = -0.12, p = 7.6× ). The functional connectivity findings were cross-validated in two independent datasets. The higher functional connectivity of the medial orbitofrontal cortex and VMPFC included higher connectivity with the anterior cingulate cortex, which provides a route for these reward-related regions to have a greater influence on action in risk-taking individuals. In conclusion, the medial orbitofrontal cortex, which is involved in reward value and pleasure, was found to be related to risk-taking, which is associated with impulsivity. An implication is that risk-taking is driven by specific orbitofrontal cortex reward systems, and is different for different rewards which are represented differently in the brains of different individuals. This is an advance in understanding the bases and mechanisms of risk-taking in humans, given that the orbitofrontal cortex, VMPFC and anterior cingulate cortex are highly developed in humans, and that risk-taking can be reported in humans. [Abstract copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

The neural correlates of risk propensity in males and females using resting-state fMRI

Men are more risk prone than women, but the underlying basis remains unclear. To investigate this question, we developed a trait-like measure of risk propensity which we correlated with resting-state functional connectivity to identify sex differences. Specifically, we used short- and long-range functional connectivity densities to identify associated brain regions and examined their functional connectivities in resting-state functional magnetic resonance imaging (fMRI) data collected from a large sample of healthy young volunteers. We found that men had a higher level of general risk propensity (GRP) than women. At the neural level, although they shared a common neural correlate of GRP in a network centered at the right inferior frontal gyrus, men and women differed in a network centered at the right secondary somatosensory cortex, which included the bilateral dorsal anterior/middle insular cortices and the dorsal anterior cingulate cortex. In addition, men and women differed in a local network centered at the left inferior orbitofrontal cortex. Most of the regions identified by this resting-state fMRI study have been previously implicated in risk processing when people make risky decisions. This study provides a new perspective on the brain-behavioral relationships in risky decision making and contributes to our understanding of sex differences in risk propensity.Yuan Zhou, Shu Li, John Dunn, HuandongLi, Wen Qin, Maohu Zhu, Li-Lin Rao, Ming Song, Chunshui Yu and Tianzi Jian

Orbitofrontal cortex connectivity is associated with food reward and body weight in humans

The aim was to investigate with very large scale analyses whether there are underlying functional connectivity differences between humans that relate to food reward; and whether these in turn are associated with being overweight. In 37,286 humans from the UK Biobank resting state functional connectivities of the orbitofrontal cortex, especially with the anterior cingulate cortex, were positively correlated with the liking for sweet foods (FDR p < 0.05). They were also positively correlated with the body mass index (BMI) (FDR p < 0.05). Moreover, in a sample of 502,492 people, the 'liking for sweet foods' was correlated with their BMI (r=0.06, p<10-125). In a cross-validation with 545 participants from the Human Connectome Project, higher functional connectivity involving the orbitofrontal cortex relative to other brain areas was associated with high BMI (≥30) compared to a mid-BMI group (22-25; p=6x10-5); and low orbitofrontal cortex functional connectivity was associated with low BMI (≤20.5; p<0.024). It is proposed that high BMI relates to increased efficacy of orbitofrontal cortex food reward systems, and low BMI to decreased efficacy. This was found with no stimulation by food, so may be an underlying individual difference in brain connectivity that is related to food reward and BMI. [Abstract copyright: © The Author(s) 2021. Published by Oxford University Press.

Attractor cortical neurodynamics, schizophrenia, and depression

The local recurrent collateral connections between cortical neurons provide a basis for attractor neural networks for memory, attention, decision-making, and thereby for many aspects of human behavior. In schizophrenia, a reduction of the firing rates of cortical neurons, caused for example by reduced NMDA receptor function or reduced spines on neurons, can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention in the prefrontal cortex, contributing to the cognitive symptoms. Reduced NMDA receptor function in the orbitofrontal cortex by reducing firing rates may produce negative symptoms, by reducing reward, motivation, and emotion. Reduced functional connectivity between some brain regions increases the temporal variability of the functional connectivity, contributing to the reduced stability and more loosely associative thoughts. Further, the forward projections have decreased functional connectivity relative to the back projections in schizophrenia, and this may reduce the effects of external bottom-up inputs from the world relative to internal top-down thought processes. Reduced cortical inhibition, caused by a reduction of GABA neurotransmission, can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. In depression, the lateral orbitofrontal cortex non-reward attractor network system is over-connected and has increased sensitivity to non-reward, providing a new approach to understanding depression. This is complemented by under-sensitivity and under-connectedness of the medial orbitofrontal cortex reward system in depression

Exploring the impact of health and lifestyle factors on brain function in humans : insights from large-scale neuroimaging data

This thesis performs investigations with data analysis methods and modelling approaches with large-scale neuroimaging data, and applies them to brain-wide association studies to investigate the brain systems associated with human behaviours such as memory decline, food preferences, and lifestyle habits. This thesis utilises data from the largest neuroimaging dataset by far, the UK Biobank, which is the most detailed and extensive multi-modal human dataset with over 500,000 participants. The large number of participants is helpful to mine datasets so that we can investigate brain function in health and disease. In addition to the large sample size to improve the reproducibility of results, the replication method based on independent large datasets is used to evaluate the robustness of these big data analysis methods and models. The large number of participants for analysis and replication presented a significant challenge to computational technology, necessitating data cleaning, preprocessing, feature extraction, data analysis, and modelling. As the basis for all studies in this thesis, normalised whole brain functional connectivity is measured for each individual based on the timeseries signals at the voxel level of the brain, which are divided into brain regions with a selected brain atlas and reflects the strength of interactions between each pair of brain regions. The large number of functional connectivity links and the number of statistical comparisons create a high risk of false discoveries. So, methods were implemented that correct for multiple comparisons. In a large-scale investigation of human memory decline, a standard structural equation model and a mediation model was developed. The mediation model was used to identify the brain regions that mediate between memory impairment and hypertension and is used in this particular application for the first time in this study. Lower functional connectivity of the hippocampus was found to mediate the association between poor prospective memory performance and hypertension, as indicated by a significant (11.5%) mediation effect. Clinically, this is the first time that the mediator role of the hippocampus in memory loss related to hypertension has been identified, confirming that it is the primary region associated with human memory in a large data set with approximately 20,000 participants. In addition, an extensive neuroimaging investigation of decision-making was conducted using an innovative methodology. The novel method employs association patterns of the functional connectivity of a network of brain regions with behaviour, instead of using the conventional method's individual links. In this study, the "liking for sweet foods" was significantly correlated with individuals’ body mass index (BMI) (False Discovery Rate (FDR) corrected, P<0.05). Further, functional connectivity in the orbitofrontal cortex (OFC) was positively correlated with a higher BMI (FDR corrected, P<0.05), compared to the functional connectivity involved in the whole brain, which had a significantly negative association with a higher BMI (FDR corrected, P<0.05). This research demonstrated an association between the OFC functional connectivity and obesity that was related to food preferences. Finally, the relationships between seven lifestyle factors, nine mental health measures, brain structure, and cortical functional connectivity were investigated using large datasets containing numerous behaviour measures. These findings highlight the extensive association between lifestyle risk and a broad spectrum of mental health problems in later life. In addition, they provide insight into the neural mechanisms associated with daily habits, including brain regions involved in motor, auditory, decision-making, emotion, face processing, and memory functions (Bonferroni corrected, P<0.05). Overall, by exploring computational methods and modelling approaches on large-scale neuroimaging data for analyses of brain function and behavioural measures, efficient and reliable models have been developed. Moreover, significant progress has been made in applying the big data analysis methods to understanding the brain regions involved in memory decline, dietary preference and obesity, and human lifestyle behaviour

The orbitofrontal cortex, food reward, body weight and obesity

In primates including humans, the orbitofrontal cortex is the key brain region representing the reward value and subjective pleasantness of the sight, smell, taste and texture of food. At stages of processing before this, in the insular taste cortex and inferior temporal visual cortex, the identity of the food is represented, but not its affective value. In rodents, the whole organisation of reward systems appears to be different, with reward value reflected earlier in processing systems. In primates and humans, the amygdala is overshadowed by the great development of the orbitofrontal cortex. Social and cognitive factors exert a top-down influence on the orbitofrontal cortex, to modulate the reward value of food that is represented in the orbitofrontal cortex. Recent evidence shows that even in the resting state, with no food present as a stimulus, the liking for food, and probably as a consequence of that body mass index, is correlated with the functional connectivity of the orbitofrontal cortex and ventromedial prefrontal cortex. This suggests that individual differences in these orbitofrontal cortex reward systems contribute to individual differences in food pleasantness and obesity. Implications of how these reward systems in the brain operate for understanding, preventing and treating obesity are described

Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala

The orbitofrontal cortex and amygdala are involved in emotion and in motivation, but the relationship between these functions performed by these brain structures is not clear. To address this, a unified theory of emotion and motivation is described in which motivational states are states in which instrumental goal-directed actions are performed to obtain rewards or avoid punishers, and emotional states are states that are elicited when the reward or punisher is or is not received. This greatly simplifies our understanding of emotion and motivation, for the same set of genes and associated brain systems can define the primary or unlearned rewards and punishers such as sweet taste or pain. Recent evidence on the connectivity of human brain systems involved in emotion and motivation indicates that the orbitofrontal cortex is involved in reward value and experienced emotion with outputs to cortical regions including those involved in language, and is a key brain region involved in depression and the associated changes in motivation. The amygdala has weak effective connectivity back to the cortex in humans, and is implicated in brainstem-mediated responses to stimuli such as freezing and autonomic activity, rather than in declarative emotion. The anterior cingulate cortex is involved in learning actions to obtain rewards, and with the orbitofrontal cortex and ventromedial prefrontal cortex in providing the goals for navigation and in reward-related effects on memory consolidation mediated partly via the cholinergic system

The Effect of Appetite on Pain

Hunger and pain are powerful homeostatic drives, which compete for a behavioural response when experienced simultaneously. This thesis set out to explore neural mechanisms underpinning this competition, and how appetitive visual and olfactory stimuli may modulate the effect of homeostatic energy manipulations on pain. Using well-established techniques including EEG source analysis and resting state fMRI, we consistently employed a within-subjects fasting vs. satiation paradigm to investigate the effects of appetite on subjective pain perception and neural pain processing. Pain stimuli which selectively activated nociceptive Aδ fibres were presented concurrently with appetitive stimuli, and the neural nociceptive responses were mapped with high-density (128-channel) EEG recordings and fMRI functional connectivity. Based on the results of previous research, we hypothesised that fasting would suppress subjective and neural pain processing, and that visual and olfactory appetitive stimuli may augment this effect. We first found that a relatively short overnight fast was sufficient to induce significant changes in resting state functional connectivity in areas that underlie both hunger / satiety and pain: insula cortex, hypothalamus, and regions of prefrontal cortex. Source analysis of EEG data revealed a small group of brain regions whose pain-related activation was suppressed by hunger and / or appetitive stimuli: anterior cingulate cortex, operculo-insular cortex, parahippocampal cortex, and cerebellum. Functional connectivity analysis of fMRI data further uncovered a widely-distributed network of brain areas whose pain-induced connectivity was enhanced by fasting or satiety. Of particular interest was a small network of areas involved in stimulus saliency processing (anterior insula, anterior cingulate cortex, and prefrontal cortex), which was stronger during fasting; presumably advantageous when searching for food. Lastly, in an experiment using a bread odour, we found that the suppressive effect of appetitive stimuli on nociception is not just confined to the visual modality. Brief, strong pain can also be suppressed by an appetitive odour during fasting. We conclude that fasting reliably interferes with pain processing, and that ambient appetitive stimuli might be of use in situations where short-lasting pain is likely to occur