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Habeas corpus : from England to empire
We call habeas corpus the 'Great Writ of Liberty' but it was actually a writ of power. In a work based on an unprecedented study of thousands of cases across more than 500 years, Paul Halliday provides a sweeping revisionist account of the world's most revered legal device.
Book
Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour
Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson’s disease.
Osugo et al show in healthy humans that sustained dopamine D2/D3 receptor antagonism impairs motivated behaviour, hedonic experience, and emotional expression, and that this is related to blunted striatal reward response following D2/D3 antagonism.
Journal Article
Making habeas work : a legal history
Eric M. Freedman \"Making Habeas Work: A Legal History\" explores habeas corpus, a judicial order that requires a person under arrest to be brought before an independent judge or into court. In his book, Freedman critically discusses habeas corpus as a common law writ, as a legal remedy and as an instrument of checks and balances.
Book
High-frequency neuromodulation improves obsessive–compulsive behavior
Nearly one billion people worldwide suffer from obsessive–compulsive behaviors
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,
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, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive–compulsive behaviors as maladaptive habit learning
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,
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, which may be associated with abnormal beta–gamma neurophysiology of the orbitofrontal–striatal circuitry during reward processing
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,
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. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta–gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive–compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive–compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive–compulsive behavior, suggest a unifying functional role of rhythms in the beta–gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.
Selective and personalized neuromodulation of orbitofrontal beta–gamma rhythms in humans, achieved with an alternating current, robustly attenuates obsessive–compulsive behavior for 3 months.
Journal Article
Striatal dopamine can enhance both fast working memory, and slow reinforcement learning, while reducing implicit effort cost sensitivity
Associations can be learned incrementally, via reinforcement learning (RL), or stored instantly in working memory (WM). While WM is fast, it is also capacity-limited and effortful. Striatal dopamine may promote WM, by facilitating WM updating and effort exertion and also RL, by boosting plasticity. Yet, prior studies have failed to distinguish between the effects of dopamine manipulations on RL versus WM. N = 100 participants completed a paradigm isolating these systems in a double-blind study measuring dopamine synthesis with [
18
F]-FDOPA PET imaging and manipulating dopamine with methylphenidate and sulpiride. We find that learning is enhanced among high synthesis capacity individuals and by methylphenidate, but impaired by sulpiride. Methylphenidate also blunts implicit effort cost learning. Computational modeling reveals that individuals with higher dopamine synthesis capacity rely more on WM, while methylphenidate boosts their RL rates. The D2 receptor antagonist sulpiride reduces accuracy due to diminished WM involvement and faster WM decay. We conclude that dopamine enhances both slow RL, and fast WM, by promoting plasticity and reducing implicit effort sensitivity. This work was completed as part of a registered trial with the Overview of Medical Research in the Netherlands (NL-OMON43196).
Striatal dopamine signaling accelerates reinforcement learning while also boosting reliance on working memory and making working memory less effortful as revealed in this pharmaco-PET study of healthy young adults.
Journal Article
Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment
Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.
Journal Article
Modals and quasi-modals in English
\"Modals and Quasi-modals in English reports the findings of a corpus-based study of the modals and a set of semantically-related 'quasi-modals' in English. The study is informed by recent developments in the study of modality, including grammaticalization and recent diachronic change. The selection of the parallel corpora used, representing British, American and Australian English, was designed to facilitate the exploration of both regional and stylistic variation.\"--Jacket.
Book
Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity
Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [ ¹¹C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral (“self-reports” for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [ ¹¹C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BP ND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BP ND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.
Journal Article