Edmund T Rolls

• MA, DPhil, DSc, Hon DSc
• Manager at Oxford Centre for Computational Neuroscience, Oxford, UK. http://www.oxcns.org/publications

A unified theory of emotion and motivation is updated in which motivational states are states in which instrumental goal-directed actions are performed to obtain anticipated rewards or avoid punishers, and emotional states are states that are elicited when the (conditioned or unconditioned) instrumental reward or punisher is or is not received. Thi...

Task-fMRI analyses typically focus on localized activation contrasts between stimuli, neglecting the dynamic hierarchy of the brain. We introduce Brain Diffusion Transformer (Brain-DiT), a deep generative model capturing recurrent processing underlying individualized neurocognitive state transitions via functional networks. Without prior assumption...

To understand the neural mechanism of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to investigate individuals at an early stage with brain, behavioural and also genetic measures, but such research is still lacking. Here, using the cross-sectional sMRI data of...

Two key series of discoveries about the hippocampus are described. One is the discovery of hippocampal spatial view cells in primates. This discovery opens the way to a much better understanding of human episodic memory, for episodic memory prototypically involves a memory of where people or objects or rewards have been seen in locations “out there...

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial pa...

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brain’s emotion processing system to environmental stresses. Analyzing brain’s responses to angry faces in a longitudinally large-scal...

A key question for understanding the function of the hippocampus in memory is how information is recalled from the hippocampus to the neocortex. This was investigated in a neuronal network model of the hippocampal system in which “What” and “Where” neuronal firing rate vectors were applied to separate neocortical modules, which then activated entor...

The primate including the human hippocampus implicated in episodic memory and navigation represents a spatial view, very different from the place representations in rodents. To understand this system in humans, and the computations performed, the pathway for this spatial view information to reach the hippocampus was analysed in humans. Whole-brain...

Suicide is a global public health challenge, yet considerable uncertainty remains regarding the associations of both behaviour-related and physiological factors with suicide attempts (SA). Here we first estimated polygenic risk scores (PRS) for SA in 334,706 UK Biobank participants and conducted phenome-wide association analyses considering 2,291 f...

A computational neuroscience approach to the symptoms, mechanisms of, and treatments for schizophrenia and depression is described. The approach is based on a stochastic neurodynamical framework in which the stability of attractor networks in the brain is analyzed. The stability is influenced by statistical fluctuations in populations of neurons ca...

Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by measuring selective fMRI activations and functional connectivity increases to stationary visual stimuli of faces, scenes, body parts and tools from 956 HCP participants. Faces activate...

Generative Artificial Intelligence foundation models (for example Generative Pre-trained Transformer – GPT – models) can generate the next token given a sequence of tokens. How can this ‘generative AI’ be compared with the ‘real’ intelligence of the human brain, when for example a human generates a whole memory in response to an incomplete retrieva...

We describe evidence for dissociable roles of the medial and lateral orbitofrontal cortex (OFC) in major depressive disorder (MDD) from structure, functional activation, functional connectivity, metabolism, and neurochemical systems. The reward-related medial orbitofrontal cortex has lower connectivity and less reward sensitivity in MDD associated...

To understand the neural mechanisms of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to include brain, behavioural and also genetic measures and to investigate individuals at an early age, but such research is still lacking. Here, using structural MRI of 1030...

To understand the neural mechanism of autism spectrum disorder (ASD) concurrent with developmental delay/intellectual disability (DD/ID), it is essential to comprehensively take genetic, brain, and behavioural measurements as a whole and focus on subjects at early age. However, such research is still lacking. Here, using the sMRI data of 1030 child...

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Pro...

The abnormal maturation of white matter microstructure in autism spectrum disorder (ASD) compared with typical developing (TD) and developmental delay/intellectual disorder (DD/ID) during early childhood and their associations with clinical implications remain unclear. Here, we characterized spatial and temporal patterns of white matter development...

The hierarchical organization between 25 ventral stream visual cortical regions and 180 cortical regions was measured with magnetoencephalography using the Human Connectome Project Multimodal Parcellation atlas in 83 Human Connectome Project participants performing a visual memory task. The aim was to reveal the hierarchical organization using a wh...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

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...

A commentary is provided on issues raised in the Special Issue of Hippocampus (2023) on hippocampal system view representations. First, the evidence for hippocampal and parahippocampal spatial view cells in primates including humans shows that the allocentric representations provided by at least some of these cells are very useful for human memory...

Some lifestyle factors are related to health and brain function and structure, but the brain systems involved are incompletely understood. A general linear model was used to test the associations of the combined and separate lifestyle risk measures of alcohol use, smoking, diet, amounts of physical activity, leisure activity, and mobile phone use,...

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, wheth...

To understand auditory cortical processing, the effective connectivity between 15 auditory cortical regions and 360 cortical regions was measured in 171 Human Connectome Project participants, and complemented with functional connectivity and diffusion tractography. 1. A hierarchy of auditory cortical processing was identified from Core regions (inc...

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi‐modal neuroimaging analyses on a group of patients with low‐grade gliomas to localize cortical regions and white matter tracts responsible for audit...

Background Hearing impairment was recently identified as the most prominent risk factor for dementia. However, the mechanisms underlying the link between hearing impairment and dementia are still unclear. Methods We investigated the association of hearing performance with cognitive function, brain structure and cerebrospinal fluid (CSF) proteins i...

The evidence about the association of smoking with both brain structure and cognitive functions remains inconsistent. Using structural magnetic resonance imaging from the UK Biobank (n = 33,293), we examined the relationships between smoking status, dosage, and abstinence with total and 166 regional brain gray matter volumes (GMV). The relationship...

Background Gestational age (GA) is associated with later cognition and behavior. However, it is unclear how specific cognitive domains and brain structural development varies with the stepwise change of gestational duration. Methods This large-scale longitudinal cohort study analyzed 11,878 early adolescents’ brain volume maps at 9–10 years (basel...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

The amygdala and orbitofrontal cortex have been implicated in emotion. To understand these regions better in humans, their effective connectivity with 360 cortical regions was measured in 171 humans from the Human Connectome Project, and complemented with functional connectivity and diffusion tractography. The human amygdala has effective connectiv...

Effective connectivity, functional connectivity, and tractography were measured between 57 cortical frontal and somatosensory regions and the 360 cortical regions in the Human Connectome Project (HCP) multimodal parcellation atlas for 171 HCP participants. A ventral somatosensory stream connects from 3b and 3a via 1 and 2 and then via opercular and...

The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, a...

Hippocampal and parahippocampal gyrus spatial view neurons in primates respond to the spatial location being looked at. The representation is allocentric, in that the responses are to locations "out there" in the world, and are relatively invariant with respect to retinal position, eye position, head direction, and the place where the individual is...

Background Considerable uncertainty remains regarding associations of multiple risk factors with Alzheimer’s disease (AD). We aimed to systematically screen and validate a wide range of potential risk factors for AD. Methods and Materials Among 502,493 participants from the UK Biobank (UKB), baseline data were extracted for 4171 factors spanning t...

The effective connectivity between 21 regions in the human posterior parietal cortex, and 360 cortical regions was measured in 171 Human Connectome Project (HCP) participants using the HCP atlas, and complemented with functional connectivity and diffusion tractography. Intraparietal areas LIP, VIP, MIP, and AIP have connectivity from early cortical...

The effective connectivity between 55 visual cortical regions and 360 cortical regions was measured in 171 HCP participants using the HCP-MMP atlas, and complemented with functional connectivity and diffusion tractography. A Ventrolateral Visual “What” Stream for object and face recognition projects hierarchically to the inferior temporal visual co...

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, wheth...

The human ventromedial prefrontal cortex (vmPFC) / anterior cingulate cortex is implicated in reward and emotion, but also in memory. It is shown how the human orbitofrontal cortex connecting with the vmPFC and anterior cingulate cortex provide a route to the hippocampus for reward and emotional value to be incorporated in episodic memory, enabling...

Although sleep, physical activity and sedentary behavior have been found to be associated with dementia risk, findings are inconsistent and their joint relationship remains unclear. This study aimed to investigate independent and joint associations of these three modifiable behaviors with dementia risks. A total of 431,924 participants (median foll...

Objective To investigate the independent associations of social isolation and loneliness with incident dementia and to explore the potential neurobiological mechanisms. Methods We utilized the UK Biobank cohort to establish Cox proportional hazard models with social isolation and loneliness as separate exposures. Demographic (sex, age and ethnicity...

Background Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset. Methods Leveraging the geneti...

To advance understanding of brain networks involved in language, the effective connectivity between 26 cortical regions implicated in language by a community analysis and 360 cortical regions was measured in 171 humans from the Human Connectome Project, and complemented with functional connectivity and diffusion tractography, all using the HCP mult...

Background: Childhood traumatic events are risk factors for psychopathology, but large-scale studies of how childhood traumatic events relate to mental health and cognition in adulthood, and how the brain is involved, are needed. Methods: The associations between childhood traumatic events (such as abuse and neglect, and defined by the 'Childhoo...

A modified and extended version, HCPex, is provided of the surface-based Human Connectome Project-MultiModal Parcellation atlas of human cortical areas (HCP-MMP v1.0, Glasser et al. 2016). The original atlas with 360 cortical areas has been modified in HCPex for ease of use with volumetric neuroimaging software, such as SPM, FSL, and MRIcroGL. HCPe...

The human orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex are involved in reward processing and thereby in emotion but are also implicated in episodic memory. To understand these regions better, the effective connectivity between 360 cortical regions and 24 subcortical regions was measured in 172 humans f...

Objective To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children. Method Data with children aged 9–11 of 8709 mothers with parental age 15–45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the pa...

Effective connectivity measurements in the human hippocampal memory system based on the resting-state blood oxygenation-level dependent signal were made in 172 participants in the Human Connectome Project to reveal the directionality and strength of the connectivity. A ventral "what" hippocampal stream involves the temporal lobe cortex, perirhinal...

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 connectivi...

Flavor reflects taste, olfactory, and oral texture inputs, and can be influenced by the sight of food, cognitive descriptions, and attention. This chapter shows how flavor is built by the appropriate combinations of these different sensory inputs and modulatory processes in the primate including human brain. Complementary neuronal recordings, and f...

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large-scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamic...

The cortical connections of the human hippocampal memory system are fundamental to understanding its operation in health and disease, especially in the context of the great development of the human cortex. The functional connectivity of the human hippocampal system was analyzed in 172 participants imaged at 7T in the Human Connectome Project. The h...

Neocortical pyramidal cells have three key classes of excitatory input: forward inputs from the previous cortical area (or thalamus); recurrent collateral synapses from nearby pyramidal cells; and backprojection inputs from the following cortical area. The neocortex performs three major types of computation: (1) unsupervised learning of new categor...

Low sleep duration in adults is correlated with psychiatric and cognitive problems. We performed for the first time a large-scale analysis of sleep duration in children, and how this relates to psychiatric problems including depression, to cognition, and to brain structure. Structural MRI was analyzed in relation to sleep duration, and psychiatric...

A neuroscience-based approach has recently been proposed for the relation between the mind and the brain. The proposal is that events at the sub-neuronal, neuronal, and neuronal network levels take place simultaneously to perform a computation that can be described at a high level as a mental state, with content about the world. It is argued that a...

First, neurophysiological evidence for the learning of invariant representations in the inferior temporal visual cortex is described. This includes object and face representations with invariance for position, size, lighting, view and morphological transforms in the temporal lobe visual cortex; global object motion in the cortex in the superior tem...

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 wit...

Children’s behavioral problems have been associated with their family environments. Here, we investigate whether specific features of brain structures could relate to this link. Using structural magnetic resonance imaging of 8756 children aged 9-11 from the Adolescent Brain Cognitive Developmental study, we show that high family conflict and low pa...

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 neu...

The human hippocampus is involved in forming new memories: damage impairs memory. The dual stream model suggests that object “what” representations from ventral stream temporal cortex project to the hippocampus via the perirhinal and then lateral entorhinal cortex, and spatial “where” representations from the dorsal parietal stream via the parahipp...

Objective: Increased anxiety in response to the COVID-19 pandemic has been widely noted. The purpose of this study was to test whether the prepandemic functional connectome predicted individual anxiety induced by the pandemic. Methods: Anxiety scores from healthy undergraduate students were collected during the severe and remission periods of th...

The relation between mental states and brain states is important in computational neuroscience, and in psychiatry in which interventions with medication are made on brain states to alter mental states. The relation between the brain and the mind has puzzled philosophers for centuries. Here a neuroscience approach is proposed in which events at the...

We describe advances in the understanding of brain dynamics that are important for understanding the operation of the cerebral cortex in health and disease. Peaks in the resting state fMRI BOLD signal in many different brain areas can become synchronized. In data from 1,017 participants from the Human Connectome Project, we show that early visual a...

We describe advances in the understanding of brain dynamics that are important for understanding the operation of the cerebral cortex in health and disease. In data from 1017 participants from the Human Connectome Project, we show that early visual and connected areas have low temporal variability of their functional connectivity. We show that a lo...

Emotions can be defined as states elicited by rewards or punishments, and indeed the neurology of emotional disorders can be understood in terms of this foundation. The orbitofrontal cortex in humans and other primates is a critical area in emotion processing, determining the value of stimuli and whether they are rewarding or nonrewarding. The cort...

The anatomical structure of the human brain varies widely, as does individual cognitive behavior. It is important and interesting to study the relationship between brain structure and cognitive behavior. There has however been little previous work on the relationship between inhibitory control and brain structure. The goal of this study was to eluc...

Humans and other primates can reverse their choice of stimuli in one trial when the rewards delivered by the stimuli change or reverse. Rapidly changing our behavior when the rewards change is important for many types of behavior, including emotional and social behavior. It is shown in a one-trial rule-based Go-NoGo deterministic visual discriminat...

The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not obtaining an expected reward. Cortical processing before the orbitofrontal cortex is about the identity of stimuli, i.e. ′what′ is present, and not about reward value. There is evidence tha...

Background The objective was a large-scale analysis of the relation between hypertension, memory problems, and brain function. Methods The study design was to measure the association between a history of hypertension, and the functional connectivity between 94 brain regions, and prospective and numeric memory, in 19,507 participants from the UK Bi...

Background: Two studies have suggested that severe prolonged nausea and vomiting during pregnancy is associated with emotional and behavioral problems in offspring, with smaller sample size and short-term follow-up. Moreover, little information is available on the role of the brain structure in the associations. Methods: In a US-based cohort, th...

Background The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. Methods Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140)...

Objective: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression. Methods: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314...

The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate c...

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-seeki...

Background The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dep...

The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 when unmedicated) and 254 controls, using FDR correction p < 0.05 for pairs of voxe...

Cognitive Changes and the Aging Brain - edited by Kenneth M. Heilman December 2019

Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal...

A theory and model of spatial coordinate transforms in the dorsal visual system through the parietal cortex that enable an interface via posterior cingulate and related retrosplenial cortex to allocentric spatial representations in the primate hippocampus is described. First, a new approach to coordinate transform learning in the brain is proposed,...

Motivation: Advances in neuroimaging and sequencing techniques provide an unprecedented opportunity to map the function of brain regions and identify the roots of psychiatric diseases. However, the results from most neuroimaging studies, i.e. activated clusters/regions or functional connectivities between brain regions, frequently cannot be conven...

Two systems in the brain that are involved in emotional and economic decision-making are described. The first is an evolutionarily old emotion-based system that operates on rewards defined by the genes such as food, warmth, social reputation, and having children. Such decisions are often based on heuristics, such as being highly sensitive to losses...

The aim was to go beyond functional connectivity, by measuring in the first large‐scale study differences in effective, that is directed, connectivity between brain areas in autism compared to controls. Resting‐state functional magnetic resonance imaging was analyzed from the Autism Brain Imaging Data Exchange (ABIDE) data set in 394 people with au...

Following a first version AAL of the automated anatomical labeling atlas (Tzourio-Mazoyer et al., 2002), a second version (AAL2) (Rolls et al., 2015) was developed that provided an alternative parcellation of the orbitofrontal cortex following the description provided by Chiavaras, Petrides, and colleagues. We now provide a third version, AAL3, whi...

Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of...

To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly diff...

A new approach to understanding the interaction between cortical areas is provided by a mathematical analysis of biased competition, which describes many interactions between cortical areas, including those involved in top-down attention. The analysis helps to elucidate the principles of operation of such cortical systems, and in particular the par...

In a group of 831 participants from the general population in the Human Connectome Project, smokers exhibited low overall functional connectivity, and more specifically of the lateral orbitofrontal cortex which is associated with non-reward mechanisms, the adjacent inferior frontal gyrus, and the precuneus. Participants who drank a high amount had...