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Adams RA, Pinotsis D, Tsirlis K, Unruh L, Mahajan A, Montero Horas A, Convertino L, Summerfelt A, Sampath H, Du XM, Kochunov P, Ji JL, Repovs G, Murray JD, Friston KJ, Hong E, Anticevic A (2022): Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia. Biol Psychiatry 91:202-15.

This paper (also given as a talk) was a finalist for the Somerfeld-Ziskind Research Award, for best paper published in Biological Psychiatry in 2022. I used biophysical modelling of neural circuits to show that – across one fMRI and three EEG experiments – people with schizophrenia have evidence of reduced excitatory (pyramidal) cell excitability, but psychotic symptoms like hallucinations correlate with reduced inhibitory interneuron activity. This suggests that interneuron downregulation in schizophrenia may be compensating for a primary excitatory neuron dysfunction, rather than being the fundamental pathology (as was previously supposed). This has major implications for treatments targeting glutamate receptors on these neurons, because effective treatments will need to target the neurons containing the primary pathology and not the brain’s compensatory response. 

Adams RA*, Vincent P*, Benrimoh D, Friston KJ, Parr T (2022): Everything is connected: Inference and attractors in delusions. Schizophr Res 245:5-22.

This paper was the first to demonstrate how a computational (Bayesian) model of the brain could produce fully delusional beliefs: i.e. beliefs that are immune to substantial amounts of counterevidence. They are modelled as 'failure modes' of the system which occur because loss of precision in the mapping between sensory inputs and cognitive representations (known as the 'likelihood' in Bayesian inference) makes cognition less influenced by evidence and more vulnerable to feedback loops involving affective states, cognitive 'habits' and dopaminergic effects on confidence. These self-reinforcing loops (known as 'attractor states') can produce beliefs that get 'stuck' and cannot easily be updated.

Adams RA*, Bush D*, Zheng F*, Meyer SM, Kaplan R, Orfanos S, Marques TR, Howes OD, Burgess N (2020): Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia. Brain 143:1261-77.

In this paper we investigated frontotemporal brain connectivity in people with schizophrenia using magnetoencephalography (MEG). We showed that during memory retrieval (in a virtual reality-based spatial memory task), hippocampus and frontal cortex oscillate in phase with each other at theta (1-8Hz) frequency in controls but not in the schizophrenia group. These parallel oscillations, known as ‘phase coupling’, allow distant brain areas to communicate with each other. We also showed that the area of hippocampus that showed a loss of phase coupling with frontal cortex in schizophrenia is also deficient in GABAa5 receptors (using positron emission tomography), demonstrating a potential drug target for the strengthening of hippocampal theta oscillations and treatment of memory problems in people with schizophrenia. These data were re-analysed by Laura Convertino and Dan Bush, who found that the schizophrenia group showed reduced evidence of grid cell firing in their right temporal lobe (these cells usually aid spatial navigation).

Adams RA*, Napier G*, Roiser JP, Mathys C, Gilleen J (2018): Attractor-like dynamics in belief updating in schizophrenia. J Neurosci 38:9471-85.

In this paper we found behavioural evidence for a decade old theory of neural circuit dysfunction in schizophrenia: the ‘unstable attractor’ hypothesis. This hypothesis proposes that NMDA receptor dysfunction and interneuron disinhibition in schizophrenia lead to unstable firing patterns (‘attractors’) in cortical circuits. It was a prominent hypothesis for schizophrenia but little evidence had been found for it. We used computational modelling of a behavioural probabilistic inference task (guessing which jar a sequence of beads was coming from) to show that the beliefs of people with schizophrenia in this task are unstable in the same way that one might expect if they were encoded by neural circuits that also show unstable dynamics. This work was recently replicated by another group (Hauke et al, 2022, Schiz Bull), who also showed that the belief instability inferred by my model could predict the outcome of cognitive treatment for the disorder. 

Adams RA, Stephan KE, Brown HR, Frith CD, Friston KJ (2013): The computational anatomy of psychosis. Front Psychiatry 4:47.

This paper from my PhD used computational modelling to demonstrate that many phenomena in people with schizophrenia can be explained by a loss of precision of neural coding in higher order brain regions such as hippocampus and frontal cortex. In modelling terms, this equates to a loss of influence of prior beliefs over incoming sensory evidence in a Bayesian model. This can explain many classic findings in schizophrenia, including abnormalities of smooth pursuit eye movements, reduced oddball responses in EEG, connectivity changes in higher order and primary sensory cortices in rsfMRI and improved ‘force-matching’ task performance and resistance to visual illusions. 

All publications

Fradkin I, Adams RA, Siegelman N, Moran R, Dolan RJ (2024): Latent mechanisms of language disorganization relate to specific dimensions of psychopathology. Nat Mental Health (in press). See PDF

Limanowski J, Adams RA, Kilner J, Parr T (2024): The many roles of precision in action. Entropy 26:790. See PDF

Adams RA*, Zor C*, Mihalik A, Tsirlis K, Brudfors M, Chapman J, Ashburner J, Paulus MP, Mourão-Miranda J (2024): Voxel-wise sparse multivariate analysis of adolescents’ brain and psychosocial data yields six distinct modes of variation in cognition and psychopathology. Biol Psych CNNI 9:915-27. See PDF

Hauke DJ, Wobmann M, Andreou C, Mackintosh AJ, de Bock R, Karvelis P, Adams RA, Sterzer P, Borgwardt, Roth V, Diaconescu AO (2024): Altered perception of environmental volatility during social learning in emerging psychosis. Comput Psychiatry 8:1-22. See PDF

Hua L, Adams RA, Grent-‘t-Jong T, Gajwani R, Gross J, Gumley AI, Krishnadas R, Lawrie SM, Schultze-Lutter F, Schwannauer M,  Uhlhaas P (2023): Thalamo-Cortical Circuits during Sensory Attenuation in Emerging Psychosis: A Combined MEG and Dynamic Causal Modelling Study. Schizophrenia 9:25. See PDF

Knolle F, Sterner E, Moutoussis M, Adams RA, … NSPN Consortium, Goodyer IM, Fletcher PC, Murray GK (2022): Action selection in early stages of psychosis: an active inference approach. J Psychiatry Neurosci 48:E78-89. See PDF

Convertino L*, Bush D*, Zheng F, Adams RA, Burgess N (2022): Reduced grid-like theta modulation in schizophrenia. Brain 146:2191-8. See PDF

Neacsu V, Mirza MB, Adams RA, Friston KJ (2022): Structure learning enhances concept formation in synthetic Active Inference agents. PLoS One 17:e0277199. See PDF

Mihalik A, Chapman J, Adams RA, … Mourão-Miranda J, ADNI (2022): Canonical Correlation Analysis and Partial Least Squares for Identifying Brain-Behavior Associations: A Tutorial and a Comparative Study. Biol Psych CNNI 7:1055-67. See PDF

Hauke DJ, Roth V, Karvelis P, Adams RA, Moritz S, Borgwardt S, Diaconescu AO, Andreou C (2022): Increased belief instability in psychotic disorders predicts treatment response to metacognitive training. Schiz Bull 48:826-38. See PDF

Ferreira FS, Mihalik A, Adams RA, Ashburner J, Mourão-Miranda J (2022): A hierarchical Bayesian model to find brain-behaviour associations in incomplete data sets. Neuroimage 249:118854. See PDF

Croft J, Teufel C, Heron J, Fletcher PC, David AS, Lewis G, Moutoussis M, FitzGerald THB, Linden DEJ, Thompson A, Jones PB, Cannon M, Holmans P, Adams RA, Zammit S (2022): A computational analysis of abnormal belief-updating processes and their association with psychotic experiences and childhood trauma in a UK birth cohort. Biol Psych CNNI 7:725-34. See PDF

Adams RA, Pinotsis D, Tsirlis K, Unruh L, Mahajan A, Montero Horas A, Convertino L, Summerfelt A, Sampath H, Du XM, Kochunov P, Ji JL, Repovs G, Murray JD, Friston KJ, Hong E, Anticevic A (2022): Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia. Biol Psychiatry 91:202-15. See PDF

Adams RA*, Vincent P*, Benrimoh D, Friston KJ, Parr T (2022): Everything is connected: Inference and attractors in delusions. Schizophr Res 245:5-22. See PDF

Adams RA*, Gu X* (2021): Editorial: 2021, A New Chapter. Comput Psychiatr 5:1-3. See PDF

Bhat A, Irizar H, Thygesen JH, Kuchenbaecker K, Pain O, Adams RA, …, Friston K, Hong E, Hall M, Bramon E (2021): Transcriptome-wide association study reveals two genes that influence mismatch negativity. Cell Reports 34:108868. See PDF

Hua L, Recasens M, Grent-‘t-Jong T, Adams RA, Gross J, Uhlhaas PJ (2020): Investigating cortico-subcortical circuits during auditory sensory attenuation: A combined MEG and dynamic causal modelling study. Hum Brain Mapp 41:4419-30. See PDF

Howes OD, Hird EJ, Adams RA, Corlett PR, McGuire P (2020): Aberrant salience, information processing and dopaminergic signalling in people at clinical risk for psychosis. Biol Psychiatry 88:304-14. See PDF

FitzGerald THB, Penny WD, Bonnici HM, Adams RA (2020): Retrospective inference as a form of bounded rationality, and its beneficial influence on learning. Front Artif Intell 3:2. See PDF

Mihalik A*, Adams RA*, Huys QJM (2020): Canonical correlation analysis for identifying biotypes of depression. Biol Psychiatry CNNI 5:478-80. See PDF

Fradkin I, Adams RA, Parr T, Roiser JP, Huppert JD (2020): Searching for an anchor in an unpredictable world: A computational model of obsessive compulsive disorder. Psychol Rev 127:672-99. See PDF

Adams RA*, Bush D*, Zheng F*, Meyer SM, Kaplan R, Orfanos S, Marques TR, Howes OD, Burgess N (2020): Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia. Brain 143:1261-77. See PDF

Adams RA, Moutoussis M, Nour MM, Dahoun T, Lewis D, Illingworth B, Veronese M, Mathys C, De Boer L, Guitart-Masip M, Friston KJ, Howes OD, Roiser JP (2020): Variability in action selection relates to striatal dopamine 2/3 receptor availability in humans: a PET study of reinforcement learning and active inference. Cereb Cortex 30:3573-89. See PDF

Mihalik A, Ferreira FS, Moutoussis M, Ziegler G, Adams RA, … Mourão-Miranda J (2020): Multiple hold-outs with stability: improving the generalizability of machine learning analyses of brain-behaviour relationships. Biol Psychiatry 87:368-76. See PDF

Dahoun T, … Adams RA, Bloomfield M, Howes OD (2019): The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study. Transl Psychiatry 9:287. See PDF

Mirza MB, Parr T, Adams RA, Friston K (2019): Introducing a Bayesian model of selective attention based on active inference. Sci Reports 9:13915. See PDF

Benrimoh D, Parr T, Adams RA, Friston K (2019): Hallucinations both in and out of context: an active inference account. PLoS One 14:e0212379. See PDF

Mihalik A, Ferreira FS, Rosa MJ, Moutoussis M, Ziegler G, Monteiro JM, Portugal L, Adams RA, … Dolan RJ, Mourão-Miranda J (2019): Brain-behaviour modes of covariation in healthy and clinically depressed young people. Sci Reports 9:11536. See PDF

Zarkali A, Adams RA, Psarras S, Leyland L-A, Rees G, Weil RS (2019): Increased weighting on prior knowledge in Lewy Body-associated visual hallucinations. Brain Comms 1:fcz007. See PDF

Dahoun T, Nour MM, Adams RA, Trossbach S, Korth C, Howes OD (2019): Disrupted-in-Schizophrenia 1 (DISC1) functional polymorphisms and D2/D3 receptor availability: a [11C]-(+)-PHNO imaging study. Genes Brain Behav 18:e12596. See PDF

Nour MM, Dahoun T, McCutcheon RA, Adams RA, Wall MB, Howes OD (2019): Task-induced functional brain connectivity mediates the relationship between striatal D2/3 receptors and working memory. eLife 8:e45045. See PDF

Mirza MB, Adams RA, Parr T, Friston K (2019): Impulsivity and active inference. J Cog Neurosci 31:202-20. See PDF

Humpston CS, Adams RA, …, Linden DEJ (2019): From computation to the first-person: auditory-verbal hallucinations and delusions of thought interference in schizophrenia-spectrum psychoses. Schiz Bull 45(Supp 1):S56-66. See PDF

Benrimoh D, Parr T, Vincent P, Adams RA, Friston K (2018): Precise beliefs, imprecise evidence: active inference and auditory hallucinations. Comput Psychiatr 2:183-204. See PDF

McCutcheon RA, Nour MM, …, Adams RA, Turkheimer F, Mehta M, Howes OD (2018): Mesolimbic dopamine function is related to salience network connectivity: an integrative PET and MR study. Biol Psychiatry 85:368-78. See PDF

Nour MM, Dahoun T, Schwartenbeck P, Adams RA, FitzGerald THB, Coello C, Wall MB, Dolan RJ, Howes OD (2018): A dopaminergic basis for signalling belief updates, but not surprise, and the link to paranoia. PNAS 115:E10167-76. See PDF

Adams RA*, Napier G*, Roiser JP, Mathys C, Gilleen J (2018): Attractor-like dynamics in belief updating in schizophrenia. J Neurosci 38:9471-85. See PDF

Sterzer P, Adams RA, Fletcher P, Frith C, …, Uhlhaas P, Voss M, Corlett PR (2018): The predictive-coding account of psychosis. Biol Psychiatry 84:634-43. See PDF

Mirza MB, Adams RA, Mathys CD, Friston KJ (2018): Human visual exploration reduces uncertainty about the sensed world. PLoS One 13:e0190429. See PDF

Díez A, Ranlund S, Pinotsis D, …, Friston KJ, Adams RA*, Bramon E* (2017): Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives. Hum Brain Mapp 38:3262-3276. See PDF

Mirza MB, Adams RA, Mathys CD, Friston KJ (2016): Scene construction, visual foraging and active inference. Front Comput Neurosci 10:56. See PDF

Rutledge RB, …, Adams RA, Lindenberger U, Dayan P, Dolan RJ (2016): Risk taking for potential rewards decreases across the lifespan. Curr Biol 26:1634-9. See PDF

Adams RA, Pinotsis D, Bauer M, Friston K (2016): Dynamic causal modelling of eye movements during pursuit: confirming precision-encoding in V1 using MEG. Neuroimage 132:175-89. See PDF

Adams RA, Huys QJM, Roiser JP (2016): Computational Psychiatry – towards a mathematically informed understanding of mental illness. JNNP 87:53-63. See PDF

Ranlund S, Adams RA, …, Bramon E (2016): Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity. Hum Brain Mapp 37:351-65. See PDF

Smittenaar P, Rutledge RB, Zeidman P, Adams RA, …, Dolan RJ (2015): Proactive and reactive response inhibition across the lifespan. PLoS One 10:e0140383. See PDF

McNab F, Zeidman P, Rutledge RB, …, Adams RA, Dolan RJ (2015): Age-related changes in working memory and the ability to ignore distraction. PNAS 112:6515-8. See PDF

Adams RA, Aponte E, …, Friston KJ (2015): Active inference and oculomotor pursuit: dynamic causal modelling of eye movements. J Neurosci Methods 242:1-14. See PDF

Moran R, Jones MW, Blockeel A, Adams RA, Stephan K, Friston K (2015): Losing control under ketamine: suppressed cortico-hippocampal drive following acute ketamine in rats. Neuropsychopharm 40:268-77. See PDF

Vossel S, Bauer M, Mathys C, Adams RA, Dolan R, Stephan KE, Friston K (2014): Cholinergic stimulation enhances Bayesian belief updating in the deployment of spatial attention. J Neurosci 34:15735-42. See PDF

Pareés I, Brown HR, Nuruki A, Adams RA, Davare M, Bhatia KP, Friston KJ, Edwards MJ (2014): Loss of sensory attenuation in patients with functional (psychogenic) movement disorders. Brain 137:2916-21. See PDF

Perrinet LU, Adams RA, Friston KF (2014): Active inference, eye movements and oculomotor delays. Biol Cybern 108:777-801. See PDF

Brown HR, …, Adams RA, McNab F, Rutledge RB & Dolan RJ (2014): Crowd-sourcing for cognitive science: the utility of smartphones. PLoS One 9:e100662. See PDF

Shipp S, Adams RA, Friston KJ (2013): Reflections on agranular architecture: predictive coding in the motor cortex. Trends Neurosci 36:706-16. See PDF

Adams RA, Stephan KE, Brown HR, Frith CD, Friston KJ (2013): The computational anatomy of psychosis. Front Psychiatry 4:47. See PDF

Brown H, Adams RA, Pareés I, Edwards M, Friston K (2013): Active inference, sensory attenuation and illusions. Cognitive Processing 14:411-27. See PDF

Adams RA, Shipp S & Friston KJ (2013): Predictions, not commands: active inference in the motor system. Brain Struct Funct 218:611-43. See PDF

Bastos AM, Usrey WM, Adams RA, Mangun GR, Fries P & Friston KJ (2012): Canonical microcircuits for predictive coding. Neuron 76:695-711. See PDF

Friston K, Adams R, Montague R (2012): What is value – accumulated reward or evidence? Front Neurorobot 6:11. See PDF

Adams RA, Perrinet LU & Friston K (2012): Smooth pursuit and visual occlusion: active inference and oculomotor control in schizophrenia. PLoS One 7:e47502. See PDF

Friston K, Adams RA, Perrinet L & Breakspear M (2012): Perceptions as hypotheses: saccades as experiments. Front Psychol 3:151. See PDF

Edwards MJ*, Adams RA*, Brown H, Pareés I, Friston KJ (2012): A Bayesian account of ‘hysteria’. Brain 135:3495-512. See PDF

Friston KJ, …, Adams R, Brown H, Dolan RJ, Stephan KE, Bestmann S (2012): Dopamine, affordance and active inference. PLoS Comput Biol 8:e1002327. See PDF

Adams R & David AS (2007): Patterns of anterior cingulate activation in schizophrenia: a selective review. Neuropsychiatry Dis Treat 3:87-101. See PDF

*equal contribution