Ben J. Harrison

• PhD
• Principal Investigator at University of Melbourne

Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis....

Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understoo...

Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances in the function and connectivity of brain corticostriatal networks, or "loops." Although neuroimaging studies of patients have supported this network model of OCD, very few have applied measurements that are sensitive to brain connectivity features. Using resting-s...

The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants we exami...

The notion of a “default mode of brain function” has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consisten...

Self-related cognitions are integral to personal identity and psychological wellbeing. Persistent engagement with negative self-cognitions can precipitate mental ill health; whereas the ability to restructure them is protective. Here, we leverage ultra-high field 7T fMRI and dynamic causal modelling to characterise a negative self-cognition network...

Across species, stress drives alterations in feeding behaviour, including heightened food-seeking and the overconsumption of palatable foods. The bed nucleus of the stria terminalis (BNST) acts as a neural hub linking stress and reward circuits. However, its role in human food cue and taste processing under stress remains unclear. Here, using 7-Tes...

Importance: Major depressive disorder (MDD) is highly heterogeneous, with marked individual differences in clinical presentation and neurobiology, which may obscure identification of structural brain abnormalities in MDD. To explore this, we used normative modeling to index regional patterns of variability in cortical thickness (CT) across individu...

Background Major depressive disorder (MDD) is marked by significant changes to the local synchrony of spontaneous neural activity across various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of...

Aims Adults with attention‐deficit/hyperactivity disorder (ADHD) often exhibit heightened risk‐taking behavior due to disadvantageous decision‐making. This study investigates the influence of preceding unconscious and affectively driven processes on this behavior, with a focus on sex‐specific effects. Methods Functional magnetic resonance imaging...

Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine’s antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less...

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, c...

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial‐and‐error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning‐based methods that predict individual‐level pharmacotherapeutic treatment response using cortical morphometry from multis...

Self-related cognitions are integral to personal identity and psychological wellbeing. Persistent engagement with negative self-cognitions can precipitate mental ill health; whereas the ability to restructure them is protective. Here, we leverage ultra-high field 7T fMRI and dynamic causal modelling to characterise a negative self-cognition network...

Altered connectivity both within and between the default mode and salience networks have been observed across depressive and anxiety disorders. Recent work has highlighted the importance of subcortical regions, including subdivisions of the basal forebrain, in coordinating activity of these networking. However, the influence of specific basal foreb...

Background Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the...

Safety learning involves associating stimuli with the absence of threats, enabling the inhibition of fear and anxiety. Despite growing interest in psychology, psychiatry, and neuroscience, safety learning lacks a formal consensus definition, leading to inconsistent methodologies and varied results. Conceptualized as a form of inhibitory learning (c...

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age model...

Major depressive disorder (MDD) is marked by altered processing of emotional stimuli, including facial expressions. Recent neuroimaging research has attempted to investigate how these stimuli alter the directional interactions between brain regions in those with MDD; however, methodological heterogeneity has made identifying consistent effects diff...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitat...

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) – an extensively connected hub region of the default mode network – has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to c...

The brain’s default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, particularly social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during...

Major depressive disorder (MDD) is marked by significant changes to the coupling of spontaneous neural activity within various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations...

Major depressive disorder (MDD) is marked by significant changes to the coupling of spontaneous neural activity within various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations...

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case–control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditi...

Background: Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how they relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cogniti...

The brain's default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, including social anxiety disorder (SAD). This study aimed to clarify alterations to network dynamics present during self-appraisal i...

Background Adult attention-deficit/hyperactivity disorder (ADHD) is often associated with risky decision-making behavior. However, current research studies are often limited by the ability to adequately reflect daily behavior in a laboratory setting. Over the lifespan impairments in cognitive functions appear to improve, whereas affective functions...

Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence f...

Objective: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method: Here, we examine this issue through two approaches: (a) an...

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep l...

Core regions of the salience network (SN), including the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), coordinate rapid adaptive changes in attentional and autonomic processes in response to negative emotional events. In doing so, the SN incorporates bottom-up signals from subcortical brain regions, such as the amygdala and pe...

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy i...

Suppression of the brain’s default mode network (DMN) during external goal-directed cognitive tasks has been consistently observed in neuroimaging studies. However, emerging insights suggest the DMN is not a monolithic “task-negative” network but is comprised of subsystems that show functional heterogeneity. Despite considerable research interest,...

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associ...

Safety learning creates associations between conditional stimuli and the absence of threat. Studies of human fear conditioning have accumulated evidence for the neural signatures of safety over various paradigms, aligning on several common brain systems. While these systems are often interpreted as underlying safety learning in a generic sense, the...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders based on brain patterns. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, w...

Fear conditioning paradigms are critical to understanding anxiety-related disorders, but studies use an inconsistent array of methods to quantify the same underlying learning process. We previously demonstrated that selection of trials from different stages of experimental phases and inconsistent use of average compared to trial-by-trial analysis c...

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task...

Utilitarian actions involve aversive or harmful act be performed in order to achieve outcomes perceived as benefits to ‘the greater good’. Humans are often averse to such actions when they involve inflicting direct harm to others, regardless of the positive outcomes that are achieved. Predominant theory proposes that anti-utilitarian biases stem fr...

The substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy cont...

Negative self-beliefs are a core feature of psychopathology. Despite this, we have a limited understanding of the brain mechanisms by which negative self-beliefs are cognitively restructured. Using a novel paradigm, we had participants use Socratic questioning techniques to restructure negative beliefs during ultra-high resolution 7-Tesla functiona...

Background Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/peri-natal period may be reflected in individual variations in cortical surface area. Methods Inter-regional profiles of grou...

The ‘core’ regions of the default mode network (DMN) – the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) – show consistent involvement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswe...

Background Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-...

The brain's "default mode network" (DMN) enables flexible switching between internally and externally focused cognition. Precisely how this modulation occurs is not well understood, although it may involve key subcortical mechanisms, including hypothesized influences from the basal forebrain (BF) and mediodorsal thalamus (MD). Here, we used ultra-h...

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviours. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition tas...

The rostral anterior cingulate cortex (rACC) is consistently implicated in the neurobiology of depression. While the functional connectivity of the rACC has been previously associated with treatment response, there is a paucity of work investigating the specific directional interactions underpinning these associations. We compared the fMRI resting-...

The brain's 'default mode network' (DMN) enables flexible switching between internally and externally focused cognition. Precisely how this modulation occurs is not well understood, although may involve key subcortical mechanisms, including hypothesized influences from the basal forebrain (BF) and mediodorsal thalamus (MD). Here, we used ultra-high...

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an...

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep l...

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined...

Objective A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behaviour. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method Here, we examine this issue through two approaches: (i) an e...

Objective Research suggests abnormalities in reward‐based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time‐dependent processes in the ventral striatum (VS) during social feedback in AN using...

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling bra...

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical an...

Negative self-beliefs are a core feature of psychopathology. Despite this, we have a limited understanding of the brain mechanisms by which negative self-beliefs are cognitively restructured. Using a novel paradigm, we had participants use Socratic questioning techniques to restructure self-beliefs during ultra-high resolution 7-Tesla functional ma...

Background Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate...

Brain-derived neurotropic factor (BDNF) is a potent regulator of memory processes and is believed to influence the consolidation of fear extinction memories. No previous human study has tested the effect of unstimulated BDNF on fear extinction recall, and no study has tested the association between plasma BDNF levels and psychophysiological respond...

Background The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. Methods This study examined the role of genetic endocannab...

Safety learning occurs when an otherwise neutral stimulus comes to signal the absence of threat, allowing organisms to use safety information to inhibit fear and anxiety in nonthreatening environments. Although it continues to emerge as a topic of relevance in biological and clinical psychology, safety learning remains inconsistently defined and un...

The processing of emotional facial expressions is underpinned by the integration of information from a distributed network of brain regions. Despite investigations into how different emotional expressions alter the functional relationships within this network, there remains limited research examining which regions drive these interactions. This stu...

Objective Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD working group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depr...

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,07...

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resource...

Obsessive-compulsive disorder (OCD) is a symptomatically heterogeneous disease. Symptoms of OCD can be grouped into a six-factor structure including washing, checking, neutralizing, obsessing, ordering and hoarding. These different symptom profiles might be one of the critical factors contributing to the inconsistent neuroanatomical findings in OCD...

Shame and guilt are moral emotions that play an important role in social functioning. There is limited knowledge about the neural underpinnings of these emotions, particularly in young people. In the current study, 36 healthy females (mean age 18.8 ± 1.9 years) underwent functional Magnetic Resonance Imaging, during which they reflected on their de...

Deficient safety learning has been implicated in the pathogenesis of anxiety disorders. Despite increased translational interest, there has been limited research on the basis of safety learning in humans. Here, we examined safety learning in seventy-three healthy participants via a modified Pavlovian conditioned inhibition paradigm, featuring a con...

Most biological brains, as well as artificial neural networks, are capable of performing multiple tasks [1]. The mechanisms through which simultaneous tasks are performed by the same set of units are not yet entirely clear. Such systems can be modular or mixed selective through some variables such as sensory stimulus [2,3]. Based on simple tasks st...

Social anxiety disorder (SAD) has been linked to maladaptive forms of fear regulation, including flexibly distinguishing between learned threat and safety signals. Few studies have examined this in young, unmedicated SAD patients, including its neural basis. We aimed to characterize the neural, subjective, and autonomic correlates of reversal learn...

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international da...

The cognitive reappraisal of emotion is hypothesized to involve frontal regions modulating the activity of subcortical regions such as the amygdala. However, the pathways by which structurally disparate frontal regions interact with the amygdala remains unclear. In this study, 104 healthy young people completed a cognitive reappraisal task. Dynamic...

Impulsivity and compulsivity are traits relevant to a range of mental health problems and have traditionally been conceptualised as distinct constructs. Here, we reconceptualised impulsivity and compulsivity as partially overlapping phenotypes using a bifactor modelling approach and estimated heritability for their shared and unique phenotypic vari...

Impulsivity and compulsivity are behavioural traits that underlie many aspects of decision-making and form the characteristic symptoms of Obsessive Compulsive Disorder (OCD) and Gambling Disorder (GD). The neural underpinnings of aspects of reward and avoidance learning under the expression of these traits and symptoms are only partially understood...

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling bra...

Background: Suicidal behavior is highly heterogeneous and complex. A better understanding of its biological substrates and mechanisms could inform the design of more effective suicide prevention and intervention strategies. Neuroimaging studies of suicidality have so far been conducted in small samples, prone to biases and false-positive associatio...

Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thi...