Human social interactions depend on the ability to resolve uncertainty about the mental states of others. The context in which social interactions take place is crucial for mental state attribution ...as sensory inputs may be perceived differently depending on the context. In this paper, we introduce a mental state attribution task where a target-face with either an ambiguous or an unambiguous emotion is embedded in different social contexts. The social context is determined by the emotions conveyed by other faces in the scene. This task involves mental state attribution to a target-face (either happy or sad) depending on the social context. Using active inference models, we provide a proof of concept that an agent's perception of sensory stimuli may be altered by social context. We show with simulations that context congruency and facial expression coherency improve behavioural performance in terms of decision times. Furthermore, we show through simulations that the abnormal viewing strategies employed by patients with schizophrenia may be due to (i) an imbalance between the precisions of local and global features in the scene and (ii) a failure to modulate the sensory precision to contextualise emotions.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor encoded by
NFE2L2
. Under oxidative stress, Nrf2 does not undergo its normal cytoplasmic degradation but instead travels ...to the nucleus, where it binds to a DNA promoter and initiates transcription of anti-oxidative genes. Nrf2 upregulation is associated with increased cellular levels of glutathione disulfide, glutathione peroxidase, glutathione transferases, thioredoxin and thioredoxin reductase. Given its key role in governing the cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder and schizophrenia, which are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide and peroxynitrite. These processes lead to extensive lipid peroxidation, protein oxidation and carbonylation, and oxidative damage to nuclear and mitochondrial DNA. Intake of
N
-acetylcysteine, coenzyme Q
10
and melatonin is accompanied by increased Nrf2 activity.
N
-acetylcysteine intake is associated with improved cerebral mitochondrial function, decreased central oxidative and nitrosative stress, reduced neuroinflammation, alleviation of endoplasmic reticular stress and suppression of the unfolded protein response. Coenzyme Q
10
, which acts as a superoxide scavenger in neuroglial mitochondria, instigates mitohormesis, ameliorates lipid peroxidation in the inner mitochondrial membrane, activates uncoupling proteins, promotes mitochondrial biogenesis and has positive effects on the plasma membrane redox system. Melatonin, which scavenges mitochondrial free radicals, inhibits mitochondrial nitric oxide synthase, restores mitochondrial calcium homeostasis, deacetylates and activates mitochondrial SIRT3, ameliorates increased permeability of the blood-brain barrier and intestine and counters neuroinflammation and glutamate excitotoxicity.
Impulsivity and Active Inference Mirza, M. Berk; Adams, Rick A.; Parr, Thomas ...
Journal of cognitive neuroscience,
02/2019, Letnik:
31, Številka:
2
Journal Article
Recenzirano
Odprti dostop
This paper characterizes impulsive behavior using a patch-leaving paradigm and active inference—a framework for describing Bayes optimal behavior. This paradigm comprises different environments ...(patches) with limited resources that decline over time at different rates. The challenge is to decide when to leave the current patch for another to maximize reward. We chose this task because it offers an operational characterization of impulsive behavior, namely, maximizing proximal reward at the expense of future gain. We use a Markov decision process formulation of active inference to simulate behavioral and electrophysiological responses under different models and prior beliefs. Our main finding is that there are at least three distinct causes of impulsive behavior, which we demonstrate by manipulating three different components of the Markov decision process model. These components comprise (i) the depth of planning, (ii) the capacity to maintain and process information, and (iii) the perceived value of immediate (relative to delayed) rewards. We show how these manipulations change beliefs and subsequent choices through variational message passing. Furthermore, we appeal to the process theories associated with this message passing to simulate neuronal correlates. In future work, we will use this scheme to identify the prior beliefs that underlie different sorts of impulsive behavior—and ask whether different causes of impulsivity can be inferred from the electrophysiological correlates of choice behavior.
Objective
We aimed to review clinical features and biological underpinnings related to neuroprogression in bipolar disorder (BD). Also, we discussed areas of controversy and future research in the ...field.
Method
We systematically reviewed the extant literature pertaining to neuroprogression and BD by searching PubMed and EMBASE for articles published up to March 2016.
Results
A total of 114 studies were included. Neuroimaging and clinical evidence from cross‐sectional and longitudinal studies show that a subset of patients with BD presents a neuroprogressive course with brain changes and unfavorable outcomes. Risk factors associated with these unfavorable outcomes are number of mood episodes, early trauma, and psychiatric and clinical comorbidity.
Conclusion
Illness trajectories are largely variable, and illness progression is not a general rule in BD. The number of manic episodes seems to be the clinical marker more robustly associated with neuroprogression in BD. However, the majority of the evidence came from cross‐sectional studies that are prone to bias. Longitudinal studies may help to identify signatures of neuroprogression and integrate findings from the field of neuroimaging, neurocognition, and biomarkers.
Bora E, Yücel M, Pantelis C, Berk M. Meta‐analytic review of neurocognition in bipolar II disorder.
Objective: The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD ...I) is not clear‐cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls.
Method: Meta‐analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls.
Results: Individuals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains.
Conclusion: Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness.
Objective
To investigate whether continued use of non‐aspirin NSAID, low‐dose aspirin, high‐dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using ...Danish nationwide population‐based registers.
Methods
All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in‐patient or out‐patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants.
Results
A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low‐dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non‐aspirin NSAIDs as well as high‐dose aspirin were associated with an increased rate of incident depression.
Conclusion
The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population‐based registers to systematically identify drugs with repurposing potential.
The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological ...correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.
Protein ubiquitylation is an important posttranslational modification affecting a wide range of cellular processes. Due to the low abundance of ubiquitylated species in biological samples, ...considerable effort has been spent on methods to purify and detect ubiquitylated proteins. We have developed and characterized a novel tool for ubiquitin detection and purification based on OtUBD, a high-affinity ubiquitin-binding domain (UBD) derived from an
Orientia tsutsugamushi
deubiquitylase (DUB). We demonstrate that OtUBD can be used to purify both monoubiquitylated and polyubiquitylated substrates from yeast and human tissue culture samples and compare their performance with existing methods. Importantly, we found conditions for either selective purification of covalently ubiquitylated proteins or co-isolation of both ubiquitylated proteins and their interacting proteins. As proof of principle for these newly developed methods, we profiled the ubiquitylome and ubiquitin-associated proteome of the budding yeast
Saccharomyces cerevisiae
. Combining OtUBD affinity purification with quantitative proteomics, we identified potential substrates for the E3 ligases Bre1 and Pib1. OtUBD provides a versatile, efficient, and economical tool for ubiquitin research with specific advantages over certain other methods, such as in efficiently detecting monoubiquitylation or ubiquitin linkages to noncanonical sites.
Dynamic Causal Modelling of Active Vision Parr, Thomas; Mirza, M Berk; Cagnan, Hayriye ...
The Journal of neuroscience,
08/2019, Letnik:
39, Številka:
32
Journal Article
Recenzirano
Odprti dostop
In this paper, we draw from recent theoretical work on active perception, which suggests that the brain makes use of an internal (i.e., generative) model to make inferences about the causes of ...sensations. This view treats visual sensations as consequent on action (i.e., saccades) and implies that visual percepts must be actively constructed via a sequence of eye movements. Oculomotor control calls on a distributed set of brain sources that includes the dorsal and ventral frontoparietal (attention) networks. We argue that connections from the frontal eye fields to ventral parietal sources represent the mapping from "where", fixation location to information derived from "what" representations in the ventral visual stream. During scene construction, this mapping must be learned, putatively through changes in the effective connectivity of these synapses. Here, we test the hypothesis that the coupling between the dorsal frontal cortex and the right temporoparietal cortex is modulated during saccadic interrogation of a simple visual scene. Using dynamic causal modeling for magnetoencephalography with (male and female) human participants, we assess the evidence for changes in effective connectivity by comparing models that allow for this modulation with models that do not. We find strong evidence for modulation of connections between the two attention networks; namely, a disinhibition of the ventral network by its dorsal counterpart.
This work draws from recent theoretical accounts of active vision and provides empirical evidence for changes in synaptic efficacy consistent with these computational models. In brief, we used magnetoencephalography in combination with eye-tracking to assess the neural correlates of a form of short-term memory during a dot cancellation task. Using dynamic causal modeling to quantify changes in effective connectivity, we found evidence that the coupling between the dorsal and ventral attention networks changed during the saccadic interrogation of a simple visual scene. Intuitively, this is consistent with the idea that these neuronal connections may encode beliefs about "what I would see if I looked there", and that this mapping is optimized as new data are obtained with each fixation.
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