Home alone : A population neuroscience investigation of brain morphology substrates

As a social species, ready exchange with peers is a pivotal asset - our “social capital”. Yet, single-person households have come to pervade metropolitan cities worldwide, with unknown consequences in the long run. Here, we systematically explore the morphological manifestations associated with singular living in ∼40,000 UK Biobank participants. The uncovered population-level signature spotlights the highly associative default mode network, in addition to findings such as in the amygdala central, cortical and corticoamygdaloid nuclei groups, as well as the hippocampal fimbria and dentate gyrus. Both positive effects, equating to greater gray matter volume associated with living alone, and negative effects, which can be interpreted as greater gray matter associations with not living alone, were found across the cortex and subcortical structures Sex-stratified analyses revealed male-specific neural substrates, including somatomotor, saliency and visual systems, while female-specific neural substrates centered on the dorsomedial prefrontal cortex. In line with our demographic profiling results, the discovered neural pattern of living alone is potentially linked to alcohol and tobacco consumption, anxiety, sleep quality as well as daily TV watching. The persistent trend for solitary living will require new answers from public-health decision makers

On the relationship between the “default mode network” and the “social brain”

The default mode network (DMN) of the brain consists of areas that are typically more active during rest than during active task performance. Recently however, this network has been shown to be activated by certain types of tasks. Social cognition, particularly higher-order tasks such as attributing mental states to others, has been suggested to activate a network of areas at least partly overlapping with the DMN. Here, we explore this claim, drawing on evidence from meta-analyses of functional MRI data and recent studies investigating the structural and functional connectivity of the social brain. In addition, we discuss recent evidence for the existence of a DMN in non-human primates. We conclude by discussing some of the implications of these observations

Linking actions to outcomes in the frontal lobe

Behaviour is guided by accumulated experience, valuation and comparison. While many aspects associated with these functions are mediated by the frontal lobes, the precise contribution from particular regions remains debated. This thesis will deal with how an organism comes to select an option and will specifically focus on the role of the orbitofrontal cortex (OFC) in two mechanisms in this process: learning of outcome specificities and selecting between multiple options based on their expected values. Despite evidence emphasizing anatomical and connective heterogeneity within this structure, the OFC is often regarded as a uniform region. This thesis aims to resolve some of this uncertainty by assuming that the medial and lateral regions of the OFC contribute differentially to learning and decision-making. Two distinct methodologies were used in these investigations. First, the contribution of the medial OFC to social and emotional processing was examined. The findings from this study disprove previously held beliefs that the medial regions of the OFC guide social and emotional behaviours, but indicted a role for this region in value-guided decision-making. The second study examined functional differences between the lateral and medial OFC by making circumscribed lesions to either region in macaque monkeys. The animals performed a number of 3-armed bandit tasks which were designed to investigate different aspects of value assignment and comparison. The results show that while lateral OFC was required for "credit assignment" – the correct assignment of values to visual cues – medial OFC was critical for comparison of the cues' values during decision-making. In unchanging probabilistic environments, mOFC lesions induced decision-making impairments when value comparison was difficult without affecting credit assignment and associative learning. By contrast, lateral OFC lesions caused the opposite pattern of impairment. The final study used human-neuroimaging techniques to investigate the differential representation of outcome-specific contingency learning and found not only that the expectation of a unique outcome facilitated learning and memory recall but that this was supported by a neural network which included the lateral regions of the OFC and the anterior cingulate cortex. Activity in the mOFC did not correlate with outcome-specific contingency learning but instead reflected both the value associated with the receipt and expectation of a reward. Taken together, the results from this thesis suggest that specific parts of the OFC make markedly different contributions to these very different cognitive functions.</p

Linking actions to outcomes in the frontal lobe

Behaviour is guided by accumulated experience, valuation and comparison. While many aspects associated with these functions are mediated by the frontal lobes, the precise contribution from particular regions remains debated. This thesis will deal with how an organism comes to select an option and will specifically focus on the role of the orbitofrontal cortex (OFC) in two mechanisms in this process: learning of outcome specificities and selecting between multiple options based on their expected values. Despite evidence emphasizing anatomical and connective heterogeneity within this structure, the OFC is often regarded as a uniform region. This thesis aims to resolve some of this uncertainty by assuming that the medial and lateral regions of the OFC contribute differentially to learning and decision-making. Two distinct methodologies were used in these investigations. First, the contribution of the medial OFC to social and emotional processing was examined. The findings from this study disprove previously held beliefs that the medial regions of the OFC guide social and emotional behaviours, but indicted a role for this region in value-guided decision-making. The second study examined functional differences between the lateral and medial OFC by making circumscribed lesions to either region in macaque monkeys. The animals performed a number of 3-armed bandit tasks which were designed to investigate different aspects of value assignment and comparison. The results show that while lateral OFC was required for "credit assignment" – the correct assignment of values to visual cues – medial OFC was critical for comparison of the cues' values during decision-making. In unchanging probabilistic environments, mOFC lesions induced decision-making impairments when value comparison was difficult without affecting credit assignment and associative learning. By contrast, lateral OFC lesions caused the opposite pattern of impairment. The final study used human-neuroimaging techniques to investigate the differential representation of outcome-specific contingency learning and found not only that the expectation of a unique outcome facilitated learning and memory recall but that this was supported by a neural network which included the lateral regions of the OFC and the anterior cingulate cortex. Activity in the mOFC did not correlate with outcome-specific contingency learning but instead reflected both the value associated with the receipt and expectation of a reward. Taken together, the results from this thesis suggest that specific parts of the OFC make markedly different contributions to these very different cognitive functions.This thesis is not currently available via ORA

Characterisation of structural and functional network organisation after focal prefrontal lesions in humans in proof of principle study

Lesion research classically maps behavioral effects of focal damage to the directly injured brain region. However, such damage can also have distant effects that can be assessed with modern imaging methods. Furthermore, the combination and comparison of imaging methods in a lesion model may shed light on the biological basis of structural and functional networks in the healthy brain. We characterized network organization assessed with multiple MRI imaging modalities in 13 patients with chronic focal damage affecting either superior or inferior frontal gyrus (SFG, IFG) and 18 demographically matched healthy Controls. We first defined structural and functional network parameters in Controls and then investigated grey matter (GM) and white matter (WM) differences between patients and Controls. Finally, we examined the differences in functional coupling to large-scale resting state networks (RSNs). The results suggest lesions are associated with widespread within-network GM loss at distal sites, yet leave WM and RSNs relatively preserved. Lesions to either prefrontal region also had a similar relative level of impact on structural and functional networks. The findings provide initial evidence for causal contributions of specific prefrontal regions to brain networks in humans that will ultimately help to refine models of the human brain

Contrasting effects of medial and lateral orbitofrontal cortex lesions on credit assignment and decision making in humans

The orbitofrontal cortex is critical for goal-directed behavior. Recent work in macaques has suggested the lateral orbitofrontal cortex (lOFC) is relatively more concerned with assignment of credit for rewards to particular choices during value-guided learning, whereas the medial orbitofrontal cortex (often referred to as ventromedial prefrontal cortex in humans; vmPFC/mOFC) is involved in constraining the decision to the relevant options. We examined whether people with damage restricted to subregions of prefrontal cortex showed the patterns of impairment observed in prior investigations of the effects of lesions to homologous regions in macaques. Groups of patients with either lOFC (predominantly right hemisphere), mOFC/vmPFC, or dorsomedial prefrontal (DMF), and a comparison group of healthy age- and education-matched controls performed a probabilistic 3-choice decision-making task. We report anatomically specific patterns of impairment. We found that credit assignment, as indexed by the normal influence of contingent relationships between choice and reward, is reduced in lOFC patients compared with Controls and mOFC/vmPFC patients. Moreover, the effects of reward contingency on choice were similar for patients with lesions in DMF or mOFC/vmPFC, compared with Controls. By contrast, mOFC/vmPFC-lesioned patients made more stochastic choices than Controls when the decision was framed by valuable distracting alternatives, suggesting that value comparisons were no longer independent of irrelevant options. Once again, there was evidence of regional specialization: patients with lOFC lesions were unimpaired relative to Controls. As in macaques, human lOFC and mOFC/vmPFC are necessary for contingent learning and value-guided decision-making, respectively

Local and global reward learning in the lateral frontal cortex show differential development during human adolescence.

Funder: Wellcome TrustReward-guided choice is fundamental for adaptive behaviour and depends on several component processes supported by prefrontal cortex. Here, across three studies, we show that two such component processes, linking reward to specific choices and estimating the global reward state, develop during human adolescence and are linked to the lateral portions of the prefrontal cortex. These processes reflect the assignment of rewards contingently to local choices, or noncontingently, to choices that make up the global reward history. Using matched experimental tasks and analysis platforms, we show the influence of both mechanisms increase during adolescence (study 1) and that lesions to lateral frontal cortex (that included and/or disconnected both orbitofrontal and insula cortex) in human adult patients (study 2) and macaque monkeys (study 3) impair both local and global reward learning. Developmental effects were distinguishable from the influence of a decision bias on choice behaviour, known to depend on medial prefrontal cortex. Differences in local and global assignments of reward to choices across adolescence, in the context of delayed grey matter maturation of the lateral orbitofrontal and anterior insula cortex, may underlie changes in adaptive behaviour

Frontal Cortex and Reward-Guided Learning and Decision-Making

Reward-guided decision-making and learning depends on distributed neural circuits with many components. Here we focus on recent evidence that suggests four frontal lobe regions make distinct contributions to reward-guided learning and decision-making: the lateral orbitofrontal cortex, the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex, anterior cingulate cortex, and the anterior lateral prefrontal cortex. We attempt to identify common themes in experiments with human participants and with animal models, which suggest roles that the areas play in learning about reward associations, selecting reward goals, choosing actions to obtain reward, and monitoring the potential value of switching to alternative courses of action