What is mood? A computational perspective

“However, modern accounts of brain function reject the classical notion of the brain as a passive organ in favour of theories of embodiment and self-organisation (Friston, 2010; Seth, 2013; Corlett & Fletcher, 2014).”

“However, they also showed that methylation rates rapidly declined in rodents who were maternally groomed and nurtured while rates remained elevated in neglected pups (Weaver et al. 2004).”

“This hierarchical minimisation of prediction errors allows allostatic control over homoeostatic reflexes (Sterling & Eyer, 1988; McEwen, 1998; Ramsay & Woods, 2014).”

“Mood disorders are heterogeneous and complex and depend upon the interplay of several neuromodulator systems and genetic and epigenetic factors (Hirschfeld, 2000; Holsboer, 2000; Nestler & Carlezon, 2006; Nutt et al. 2007; Dowlati et al. 2010; Möhler, 2012).”

“Similarly, it has been argued that pharmacotherapy may work via its effects on neurogenesis and synaptic plasticity (Santarelli et al. 2003; Anacker et al. 2011; Castrén & Hen, 2013) and that stressors may leave an indelible scar on key neurobiological systems that disrupts their structure and/or…”

“In this regard, active inference may explain the established finding that childhood trauma poses a risk for various psychopathologies (Bernet & Stein, 1999; Heim & Nemeroff, 2001; Heim et al. 2008).”

“In current predictive coding formulations of the Bayesian brain, expectation and prediction error units are thought to occupy deep and superficial pyramidal layers of cortex, respectively (Friston & Kiebel, 2009; Bastos et al. 2012; Shipp et al. 2013); such that predictions generated, from expectations, at one level o…”

“Mood disorders are heterogeneous and complex and depend upon the interplay of several neuromodulator systems and genetic and epigenetic factors (Hirschfeld, 2000; Holsboer, 2000; Nestler & Carlezon, 2006; Nutt et al. 2007; Dowlati et al. 2010; Möhler, 2012).”

“Although speculative, this provides a potential framework that can be modelled in terms of active inference and is entirely consistent with theories based upon allostasis (McEwen, 2000; Radley et al. 2011; Braithwaite et al. 2015).”

“surprise is minimised and uncertainty resolved (Friston, 2009).”

“We argue that progress may be facilitated by an appreciation of the dynamic and selforganising nature of neurobiological systems (Seth, 2013; Fotopoulou, 2015; Clark et al. 2016).”

“In this way, a self-regulating embodied loop of circular causality is constructed in which the brain constructs the external environment (and internal milieu) it expects to encounter, which in turn rein-forces its predictions (Seth, 2014; Barrett & Simmons, 2015).”

“In this regard, active inference may explain the established finding that childhood trauma poses a risk for various psychopathologies (Bernet & Stein, 1999; Heim & Nemeroff, 2001; Heim et al. 2008).”

“…hypotheses propose that the neurobiological underpinnings of a variety of disorders arise from structural or functional abnormalities in the brain consequent on a combination of environmental stress and genetic vulnerabilities (Videbech & Ravnkilde, 2004; Ota & Duman, 2013; Duman, 2014).”

“It is thought that expectations (and subsequent predictions) are encoded by synaptic activity, while precision, or uncertainty, is encoded by the extent to which this activity is attenuated or amplified (Friston & Kiebel, 2009), e.g. through careful synaptic efficacy or gain control.”

“First, expectations can be updated (by changing neuronal activity) so that predictions provide a better explanation for sensory inputs (Friston et al. 2006).”

“Indeed it has been shown that patients with post-traumatic stress disorder (PTSD) have heightened HPA axis drive originating at the amygdala (Shin et al. 2006) and PVN (Kasckow et al.”

“Our ideas also explain why epigenetic variability tends to occur at critical periods of development (Heim & Binder, 2012).”

“Recent theoretical arguments have converged on the idea that emotional states reflect changes in the uncertainty about the somatic consequences of action (Joffily & Coricelli, 2013; Wager et al. 2015; Seth & Friston, 2016).”

“This means predictable environmental outcomes elsewhere can act as a buffer against the detrimental effects of trauma (Southwick & Charney, 2012).”

“In this setting, negative emotions contextualise events that induce expectations of unpredictability, while positive emotions refer to events that resolve uncertainty and confer a feeling of control (Barrett & Satpute, 2013; Gu et al. 2013).”

“In depression there is increased paraventricular nucleus (PVN) drive and CRH production (Raadsheer et al. 1994; Gao et al. 2013) and resistance to glucocorticoid receptor (GR) mediated negative feed-back (Holsboer et al. 1982; Sher et al. 2013).”

“The active minimisation of free energy is known as active inference , which means the brain can selectively sample from data that concur with its current expectations (Friston et al. 2011; Pezzulo, 2012).”

“This explains the finding of lower cortisol levels in certain testing conditions only (Meewisse et al. 2007).”

“This means that allostatic control is precluded – and is replaced by low-level homoeostatic responses (Barrett et al. 2016; Stephan et al. 2016; Peters et al. 2017).”

“…pre-empt the need for homoeostasis [e.g. in a hypogly-caemic state, by attenuating the precision of prediction errors reporting hypoglycaemia, we can suspend the reflex mobilisation of glucose and act on the world (by eating) to fulfil and maintain higher level predictions] (Pezzulo et al. 2015).”

“Mood disorders are heterogeneous and complex and depend upon the interplay of several neuromodulator systems and genetic and epigenetic factors (Hirschfeld, 2000; Holsboer, 2000; Nestler & Carlezon, 2006; Nutt et al. 2007; Dowlati et al. 2010; Möhler, 2012).”

“As precision enforces prediction-fulfilling action, maladaptive behaviours may therefore be conceptualised as an aberrant action-perception cycle that is self-reinforcing – or self-evidencing (Hohwy, 2016).”

“Conversely, depressed patients show a reward hyposensitivity in line with overly precise prior prediction of a negative outcome and subsequent aversion to positive bottom-up (interoceptive) signals (Eshel & Roiser, 2010).”

“This has clear and important ramifications for preventive strategies – and may also explain why traumatic experiences are not invariably associated with the onset of psychopathology despite biologic effects (Carpenter et al. 2007).”

“This means that allostatic control is precluded – and is replaced by low-level homoeostatic responses (Barrett et al. 2016; Stephan et al. 2016; Peters et al. 2017).”

“have thus proposed that a negative emotional bias is a core feature of depression and is the psychological target of antidepressant medication (Harmer et al. 2009; Harmer & Cowen, 2013) and correspondingly that modulating attentional bias can provide therapeutic benefit (Browning et al.”

“2001) and decreased inhibitory input from the hippocampus (Smith, 2005), although they show increased sensitivity to dexamethasone suppression test (Yehuda et al. 1993).”

“Crucially, GRs are found in the hippocampus and amygdala (Morimoto et al. 1996); regions that send descending predictions to the paraventricular nucleus (Herman et al. 2002).”

“This means that allostatic control is precluded – and is replaced by low-level homoeostatic responses (Barrett et al. 2016; Stephan et al. 2016; Peters et al. 2017).”

“Similarly, it has been argued that pharmacotherapy may work via its effects on neurogenesis and synaptic plasticity (Santarelli et al. 2003; Anacker et al. 2011; Castrén & Hen, 2013) and that stressors may leave an indelible scar on key neurobiological systems that disrupts their structure and/or function.”

“2001) and decreased inhibitory input from the hippocampus (Smith, 2005), although they show increased sensitivity to dexamethasone suppression test (Yehuda et al.”

“Mood disorders are heterogeneous and complex and depend upon the interplay of several neuromodulator systems and genetic and epigenetic factors (Hirschfeld, 2000; Holsboer, 2000; Nestler & Carlezon, 2006; Nutt et al. 2007; Dowlati et al. 2010; Möhler, 2012).”

“This hierarchical minimisation of prediction errors allows allostatic control over homoeostatic reflexes (Sterling & Eyer, 1988; McEwen, 1998; Ramsay & Woods, 2014).”

“This has interesting parallels with theories of optimal con-trol and reinforcement learning in which a link between action (e.g. pushing a button) and outcome (e.g. losing money) reinforce avoidance behaviour – a phenomenon which is absent or impaired in mania (see below) (Bach & Dolan, 2012).”

“Recent theoretical arguments have converged on the idea that emotional states reflect changes in the uncertainty about the somatic consequences of action (Joffily & Coricelli, 2013; Wager et al. 2015; Seth & Friston, 2016).”

“…in two studies, showing reduced top-down dorsolateral prefrontal modulation of amygdala response to negative images in bipolar depression (Radaelli et al. 2015) with a converse pattern of increased orbitomedial – amygdala connectivity when viewing positive faces (de Almeida et al. 2009).”

“2013) and resistance to glucocorticoid receptor (GR) mediated negative feedback (Holsboer et al. 1982; Sher et al. 2013).”

“Although speculative, this provides a potential framework that can be modelled in terms of active inference and is entirely consistent with theories based upon allostasis (McEwen, 2000; Radley et al. 2011; Braithwaite et al. 2015).”

“A more recent and promising psychological model of depression stems from the demonstration of attentional bias in patients towards negative facial expressions (Duque & Vázquez, 2015).”

“Crucially, GRs are found in the hippocampus and amygdala (Morimoto et al. 1996); regions that send descending predictions to the paraventricular nucleus (Herman et al. 2002).”

“Recent theoretical arguments have converged on the idea that emotional states reflect changes in the uncertainty about the somatic consequences of action (Joffily & Coricelli, 2013; Wager et al. 2015; Seth & Friston, 2016).”

“…shown that positive prediction errors (receiving more food than expected), show a strong positive correlation with dopaminergic change in the nucleus accumbens (Hart et al. 2014) with corresponding changes in functional brain activity in humans during a financial reward task (Rutledge et al. 2010).”

“…it has been argued that pharmacotherapy may work via its effects on neurogenesis and synaptic plasticity (Santarelli et al. 2003; Anacker et al. 2011; Castrén & Hen, 2013) and that stressors may leave an indelible scar on key neurobiological systems that disrupts their structure and/or function.”

“…error units are thought to occupy deep and superficial pyramidal layers of cortex, respectively (Friston & Kiebel, 2009; Bastos et al. 2012; Shipp et al. 2013); such that predictions generated, from expectations, at one level of the cortical hierarchy descend to form prediction errors in…”

“…hypotheses propose that the neurobiological underpinnings of a variety of disorders arise from structural or functional abnormalities in the brain consequent on a combination of environmental stress and genetic vulnerabilities (Videbech & Ravnkilde, 2004; Ota & Duman, 2013; Duman, 2014).”

“Indeed it has been shown that patients with post-traumatic stress disorder (PTSD) have heightened HPA axis drive originating at the amygdala (Shin et al. 2006) and PVN (Kasckow et al. 2001) and decreased inhibitory input from the hippocampus (Smith, 2005), although they show increased sensitivity to dexamethasone supp…”

“2009; Harmer & Cowen, 2013) and correspondingly that modulating attentional bias can provide therapeutic benefit (Browning et al. 2012).”

“…al. have thus proposed that a negative emotional bias is a core feature of depression and is the psychological target of antidepressant medication (Harmer et al. 2009; Harmer & Cowen, 2013) and correspondingly that modulating attentional bias can provide therapeutic benefit (Browning et al. 2012).”

“A corollary of this is that patients with low mood (low prior precision) should show a hypersensitivity to interoceptive cues (high sensory precision) and a failure of sensory attenuation (Badcock et al. 2017) – of the sort associated with stress responses (please see below).”

“…this regard (Friston et al. 2003) and could prove a fruitful tool for further investigation – specifically in examining the task-dependent coupling between hierarchical levels of neuromodula-tor control (Schlosser et al. 2008; Lu et al. 2012; Radaelli et al. 2015; Vai et al. 2015; Vai et al. 2016).”

“Similarly, it has been shown that signal change in the anterior insula is significantly related to the magnitude of prediction error (Bossaerts, 2010).”

“…increased activation in orbitofrontal cortex and amygdala when viewing emotional faces (Sladky et al. 2012), but furthermore, in controls this network shows top-down modulation – which is reversed in patients – orbitofrontal cortex drives greater activation in amygdala (Sladky et al. 2015).”

“Although speculative, this provides a potential framework that can be modelled in terms of active inference and is entirely consistent with theories based upon allostasis (McEwen, 2000; Radley et al. 2011; Braithwaite et al. 2015).”

“…this regard (Friston et al. 2003) and could prove a fruitful tool for further investigation – specifically in examining the task-dependent coupling between hierarchical levels of neuromodula-tor control (Schlosser et al. 2008; Lu et al. 2012; Radaelli et al. 2015; Vai et al. 2015; Vai et al. 2016).”

“D, depression; M, Mania; Ax, anxious depression. harm-aversion, while levodopa made individuals more likely to harm themselves than others (Crockett et al. 2015).”

“This is perhaps best exemplified by the risk posed for PTSD by acute and extreme episodes of trauma (Sullivan et al. 2006).”

“This accords with the findings from recent studies (Watson et al. 2014) though not others.”

“This has been demonstrated using self-report measures of behavioural drive (Van der Gucht et al. 2009) and response time analyses to financial reward cues (Singh et al. 2013).”

“…trials (Chekroud, 2015) and represents a potentially important approach; however, it may be possible to go one step further and replace the search for a biomarker with a computational signature (Nitsche et al. 2010; Huys et al. 2011; Barch et al. 2012; Montague et al. 2012; Wang & Krystal, 2014).”

“…this regard (Friston et al. 2003) and could prove a fruitful tool for further investigation – specifically in examining the task-dependent coupling between hierarchical levels of neuromodula-tor control (Schlosser et al. 2008; Lu et al. 2012; Radaelli et al. 2015; Vai et al. 2015; Vai et al. 2016).”

“However, modern accounts of brain function reject the classical notion of the brain as a passive organ in favour of theories of embodiment and self-organisation (Friston, 2010; Seth, 2013; Corlett & Fletcher, 2014).”

“Accordingly, manic individuals lose the capacity to appreciate the unpredictable consequences of their actions and will engage in overconfident, high-risk behaviours (Mason et al. 2017).”

“This has been demonstrated using self-report measures of behavioural drive (Van der Gucht et al. 2009) and response time analyses to financial reward cues (Singh et al. 2013).”

“…hypotheses propose that the neurobiological underpinnings of a variety of disorders arise from structural or functional abnormalities in the brain consequent on a combination of environmental stress and genetic vulnerabilities (Videbech & Ravnkilde, 2004; Ota & Duman, 2013; Duman, 2014).”

“showed that patients with social anxiety disorder demonstrated increased activation in orbitofrontal cortex and amygdala when viewing emotional faces (Sladky et al. 2012), but furthermore, in controls this network shows top-down modulation – which is reversed in patients – orbitofrontal cortex drives greater activatio…”

“…trials (Chekroud, 2015) and represents a potentially important approach; however, it may be possible to go one step further and replace the search for a biomarker with a computational signature (Nitsche et al. 2010; Huys et al. 2011; Barch et al. 2012; Montague et al. 2012; Wang & Krystal, 2014).”

“This ties emotional states to the resolution of uncertainty and, through the biophysical encoding of precision, to neuromodulation and cortical gain control (Brown & Friston, 2012).”

“The active minimisation of free energy is known as active inference , which means the brain can selectively sample from data that concur with its current expectations (Friston et al. 2011; Pezzulo, 2012).”

“Epigenetics has emerged as a major field of enquiry in recent years, specifically in relation to methylation of the NR3C1 gene, which encodes GR (Nantharat et al. 2015; Smart et al. 2015; Palma-Gudiel et al. 2016).”

“We argue that progress may be facilitated by an appreciation of the dynamic and selforganising nature of neurobiological systems (Seth, 2013; Fotopoulou, 2015; Clark et al. 2016).”

“One recent and novel study has employed machine-learning techniques to predict treatment outcome in clinical trials (Chekroud, 2015) and represents a potentially important approach; however, it may be possible to go one step further and replace the search for a biomarker with a computational signature (Nitsche et al.”

“This notion has gained traction as an explanation for autism and schizophrenia in the exteroceptive (perceptual) domain (Lawson et al. 2014; Corlett, 2017; Krystal et al. 2017).”

“Epigenetics has emerged as a major field of enquiry in recent years, specifically in relation to methylation of the NR3C1 gene, which encodes GR (Nantharat et al. 2015; Smart et al. 2015; Palma-Gudiel et al. 2016).”

“…this regard (Friston et al. 2003) and could prove a fruitful tool for further investigation – specifically in examining the task-dependent coupling between hierarchical levels of neuromodula-tor control (Schlosser et al. 2008; Lu et al. 2012; Radaelli et al. 2015; Vai et al. 2015; Vai et al. 2016).”

“Accordingly patients also show a failure to learn from punishing cues (Mueller et al. 2010).”

“Mania is less well studied but there are reports of underactive HPA axis drive being particularly related to euphoria (Valiengo et al. 2012).”

“…trials (Chekroud, 2015) and represents a potentially important approach; however, it may be possible to go one step further and replace the search for a biomarker with a computational signature (Nitsche et al. 2010; Huys et al. 2011; Barch et al. 2012; Montague et al. 2012; Wang & Krystal, 2014).”

“In depression there is increased paraventricular nucleus (PVN) drive and CRH production (Raadsheer et al. 1994; Gao et al. 2013) and resistance to glucocorticoid receptor (GR) mediated negative feed-back (Holsboer et al. 1982; Sher et al. 2013).”

“2013) and resistance to glucocorticoid receptor (GR) mediated negative feedback (Holsboer et al. 1982; Sher et al. 2013).”

“We argue that progress may be facilitated by an appreciation of the dynamic and selforganising nature of neurobiological systems (Seth, 2013; Fotopoulou, 2015; Clark et al. 2016).”

“This notion has gained traction as an explanation for autism and schizophrenia in the exteroceptive (perceptual) domain (Lawson et al. 2014; Corlett, 2017; Krystal et al. 2017).”

“Epigenetics has emerged as a major field of enquiry in recent years, specifically in relation to methylation of the NR3C1 gene, which encodes GR (Nantharat et al. 2015; Smart et al. 2015; Palma-Gudiel et al. 2016).”

“We also propose that these pathologic beliefs are ascribed excessive precision, weight, or influence in many psychiatric disorders (Clark et al., 2018).”

“Clark and colleagues similarly emphasize precision, associating major depression with being certain about encountering uncertain environments, thereby precluding effective allostatic regulation [83].”

“In other contexts, it has been suggested that action model precision updates (what we have labeled AC ) could be used to inform selective attention (e.g., Clark et al., 2018; Palacios, Razi, Parr, Kirchhoff, & Friston, 2019).”