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Adams, R. A.

Publications and source records attributed to Adams, R. A..

10 recordsLinked to original sources

Measuring excitation/inhibition balance through field potentials

Several electroencephalography-based metrics have been proposed to index excitation/inhibition balance (E/I). We used single-unit and local field potential recordings from rat medial prefrontal and orbitofrontal cortex and mouse visual cortex and hippocampus to evaluate four candidate metrics against empirically-measured E/I. While 1/f slope and gamma oscillations showed region and context dependencies, broadband (6-80 Hz) and high gamma (80-150 Hz) power consistently correlated with E/I, supporting their use as proxy measures. If at least 30 minutes' data from medial prefrontal cortex were used per animal, broadband power could rank the animals by their E/I ratio, suggesting it could be used as an individual differences measure.

neuroscience↗

Fronto-Temporal Dysconnectivity and Cortical Excitability in High Schizotypy: Associations with Symptom Dimensions

BackgroundPsychosis has been conceptualised as a continuum extending from healthy individuals with psychotic-like experiences to clinical populations with schizophrenia. It is unclear which biological mechanisms found in chronic schizophrenia extend across the psychosis continuum to healthy individuals with high positive schizotypy (HS). In this study, we used computational modeling to test whether changes in effective connectivity and excitation/inhibition (E/I) balance reported in schizophrenia are also found in HS. MethodsA total of 2425 individuals from the general population were screened for HS. A subset (N=141) was invited for in-depth phenotyping. Resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1H-MRS) were recorded in n=69 HS individuals and n=72 group-matched controls with low schizotypy (LS). We used dynamic causal modeling to estimate effective connectivity between bilateral primary auditory cortex (A1), superior temporal gyrus (STG), and inferior frontal gyrus (IFG). ResultsBilateral backward connectivity from IFG to STG was significantly reduced in HS compared to LS. Widespread cortical disinhibition in the auditory cortex-IFG network correlated with more severe positive schizotypy scores and impulsive nonconformity. Reduced excitability in the same network was correlated with stronger cognitive disorganisation. ConclusionsOur results favour a psychosis-continuum hypothesis, suggesting that reduced top-down drive from frontal cortex and compensatory allostatic upregulation of cortical excitability, as observed in chronic schizophrenia, also extend to groups with sub-clinical psychotic symptoms. Frontal cortex dysfunction may serve as a biologically interpretable biomarker of psychosis risk and a target for preventative interventions.

neuroscience↗

The Semantic Underpinnings of Speech Disorganization in Schizophrenia

Effective communication relies on shared semantic representations and their context-sensitive retrieval. Accordingly, difficulties in communicating coherently, as seen in some patients with schizophrenia, may reflect impairments at the level of semantic structure or the retrieval process operating on this structure. Disentangling these components is challenging. Here, we address this problem using a word association task and magnetoencephalography (MEG), allowing us to examine behavioral markers of semantic structure and retrieval as well as semantic representation in the brain. For the latter, we detail an approach that contrasts the brains encoding of concepts as predicted by generic versus personalized semantic models. In so doing, we provide converging evidence for semantic structure idiosyncrasy in patients with schizophrenia who also exhibit speech disorganization. The findings advance our understanding of the semantic underpinnings of speech disorganization in schizophrenia, while also revealing the potential of using personalized semantic models to explain neural representation and behavior.

neuroscience↗

A Canonical Microcircuit for Estimating Excitation/Inhibition (E/I) Balance

Excitation/inhibition (E/I) balance is crucial for maintaining healthy brain function and can be disrupted in various neurological and psychiatric disorders. Despite its importance, there are few tools to study E/I balance non-invasively in humans. Here, we propose a canonical microcircuit model to estimate E/I balance from non-invasive magneto- and electroencephalography (M/EEG) recordings by parameterising global pyramidal and inhibitory cell excitability. We first establish that E/I parameters are identifiable and recoverable. We then explore the effects of these new parameters and their interaction with other parameters in a series of simulations. To highlight the clinical relevance of this new model, we simulate changes in E/I balance and their impact on event-related potentials (ERPs) derived from paired-click, passive and active oddball paradigms, which are among the most robust clinical biomarkers of schizophrenia. Our simulations show that a loss of pyramidal cell excitability can explain reduced ERP amplitudes across all three paradigms, mirroring empirical findings in schizophrenia. This method may serve as a computational assay for estimating synaptopathy and E/I balance from non-invasive M/EEG recordings across various clinical conditions thereby advancing efforts to develop personalised interventions to restore E/I balance.

neuroscience↗

Normative models reveal distinct cortical abnormalities to dimensions of psychopathologies in preadolescents

BackgroundEvidence suggests a non-specific mapping between psychiatric disorders and underlying neurobiological substrates. A dimensional psychopathology framework may prove useful for organizing observed neurobiological alterations along broad psychopathological dimensions. MethodsWe applied latent class analysis, with an additional constraint on classification uncertainty, to identify clinical cohorts of symptomatic homogeneity to represent the high-risk end of specific psychopathological dimensions (i.e., internalizing/externalizing, p-factor), using baseline data (N = 11860) from the Adolescent Brain and Cognitive Development (ABCD) Study. These cohorts were compared against neurotypical individuals in deviations from the normality of cortical development, quantified using autoencoder-based normative models, to reveal cortical abnormalities. ResultsWe identified cortical thickness related to psychopathologies in the ABCD data, particularly to externalizing syndromes, and revealed distinct structural abnormalities to broad psychopathological dimensions. ConclusionThis study highlights the value of person-centered analytic techniques, combined with normative modeling, to complement traditional associational methodologies in revealing neurobiological correlates of dimensional psychopathologies.

neuroscience↗

Computational neurodevelopment: infant decision-making in changing environments

In recognition of the fact that most psychiatric conditions have neurodevelopmental origins, there is an increasing interest in applying the methodological and conceptual approaches from computational psychiatry to developmental cohorts. However, the challenge of acquiring and modelling behavioural responses in very young infants has thus far proven difficult to overcome. To address this we developed a novel gaze-contingent, cued-reversal paradigm that allowed 6-10 month old infants to make overt behavioural responses to assess learning of expectations and updating of behaviour in response to change. We then fit computational models to infant behaviour and, for the first time, were able to validate the winning model to the same standards as would be expected of adults (e.g. good parameter recoverability, model identifiability and simulated behavioural responses). Similar to prior findings in adults, model-based prediction error measures correlated with post-switch increases in pupil size; consistent with noradrenalines hypothesised role in learning about change. Data-driven clustering based on model parameters revealed two infant behavioural subtypes hidden within the data; one with a perseverating profile and the other with a more exploratory decision-making pattern. This approach sheds new light on the classic finding that all infants under 12 months tend to perseverate. Crucially, there were no significant differences in age between the clusters, but differences in terms of adaptive skills and temperament measured via gold-standard developmental assessments. These results prime the field for infant computational psychiatry, demonstrating that we can reliably fit models to infant data and that the parameters from such models can identify subgroups with distinct cognitive profiles that are superior to those derived from the behavioural data alone.

neuroscience↗

Forest characteristics predict tri-colored bat activity within novel Colorado habitats

Climate change and other anthropogenic pressures are altering species distributions. Several studies have indicated that tri-colored bats (Perimyotis subflavus) are extending their distributional range westward in the United States. Montane and subalpine habitats consist of a mosaic of forest types including lodgepole pine woodlands and montane meadows, which provide an opportunity to study how a newly arriving species, typically associated with lowland riparian systems, is adapting to novel environmental conditions. The objective of this study is to document tri-colored bat activity in these novel habitats using acoustic surveys and to quantify what factors are influencing activity patterns in habitats and at elevations not previously documented. We selected sites at 2700m elevation that differed in stand structure, driven primarily by beetle kill outbreaks, and were in various stages of secondary succession. We used acoustic monitoring to model habitat activity patterns using nonparametric multiplicative regression. Results showed that tri-colored bats used meadows and lodgepole pine stands undergoing secondary succession following bark beetle outbreaks. Activity was highest in meadows and early time-since-kill (TSK) forests in the beginning of the survey period, and tri-colored bats had increased activity in late TSK forest habitats at the end of the survey period in early August. Temporally, activity was lowest during the middle of the survey period (mid-July) indicating that tri-colored bats moved away from our study area. However, activity significantly returned by the end of the survey. Our study demonstrates that tri-colored bats are not restricting their activity to lower elevation riparian areas in the Colorado foothills, but instead appear to be using high elevation habitat types in areas dominated by lodgepole pine and subalpine meadows. We hope this study will support conservation efforts for this species following the proposed U.S. Fish and Wildlife Service listing.

ecology↗

Retrospective inference as a form of bounded rationality, and its beneficial influence on learning

Probabilistic models of cognition typically assume that agents make inferences about current states by combining new sensory information with fixed beliefs about the past, an approach known as Bayesian filtering. This is computationally parsimonious, but, in general, leads to suboptimal beliefs about past states, since it ignores the fact that new observations typically contain information about the past as well as the present. This is disadvantageous both because knowledge of past states may be intrinsically valuable, and because it impairs learning about fixed or slowly changing parameters of the environment. For these reasons, in offline data analysis it is usual to infer on every set of states using the entire time series of observations, an approach known as (fixed-interval) Bayesian smoothing. Unfortunately, however, this is impractical for real agents, since it requires the maintenance and updating of beliefs about an ever-growing set of states. We propose an intermediate approach, finite retrospective inference (FRI), in which agents perform update beliefs about a limited number of past states. (Formally, this represents online fixed-lag smoothing with a sliding window.) This can be seen as a form of bounded rationality in which agents seek to optimise the accuracy of their beliefs subject to computational and other resource costs. We show through simulation that this approach has the capacity to significantly increase the accuracy of both inference and learning, using a simple variational scheme applied to both randomly generated Hidden Markov models (HMMs), and a specific application of the HMM, in the form of the widely used probabilistic reversal task. Our proposal thus constitutes a theoretical contribution to normative accounts of bounded rationality, which makes testable empirical predictions that can be explored in future work.

neuroscience↗

Hallucinations both in and out of context: An Active Inference Account

Hallucinations, including auditory verbal hallucinations (AVH), occur in both the healthy population and in psychotic conditions such as schizophrenia (often developing after a prodromal period). In addition, hallucinations can be in-context (they can be consistent with the environment, such as when one hallucinates the end of a sentence that has been repeated many times), or out-of-context (such as the bizarre hallucinations associated with schizophrenia). In previous work, we introduced a model of hallucinations as false (positive) inferences based on a (Markov decision process) formulation of active inference. In this work, we extend this model to include content - to disclose the computational mechanisms behind in- and out-of-context hallucinations. In active inference, sensory information is used to disambiguate alternative hypotheses about the causes of sensations. Sensory information is balanced against prior beliefs, and when this balance is tipped in the favor of prior beliefs, hallucinations can occur. We show that in-context hallucinations arise when (simulated) subjects cannot use sensory information to correct prior beliefs about hearing a voice, but beliefs about content (i.e. the sequential order of a sentence) remain accurate. When hallucinating subjects also have inaccurate beliefs about state transitions, out-of-context hallucinations occur; i.e. their hallucinated speech content is disordered. Furthermore, subjects with inaccurate beliefs about state transitions but an intact ability to use sensory information do not hallucinate and are reminiscent of prodromal patients. This work demonstrates the different computational mechanisms that may underlie the spectrum of hallucinatory experience - from the healthy population to psychotic states.

neuroscience↗

Brain-behaviour modes of covariation in healthy and clinically depressed young people

Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.

neuroscience↗