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Value, drug addiction and the brain

Loganathan K, Ho ETW

Addict Behav, 2021 05;116:106816.
PMID: 33453587 DOI: 10.1016/j.addbeh.2021.106816

Over the years, various models have been proposed to explain the psychology and biology of drug addiction, built primarily around the habit and compulsion models. Recent research indicates drug addiction may be goal-directed, motivated by excessive valuation of drugs. Drug consumption may initially occur for the sake of pleasure but may transition to a means of escaping withdrawal, stress and negative emotions. In this hypothetical paper, we propose a value-based neurobiological model for drug addiction. We posit that during dependency, the value-based decision-making system in the brain is not inactive but has instead prioritized drugs as the reward of choice. In support of this model, we consider the role of valuation in choice, its influence on pleasure and punishment, and how valuation is contrasted in impulsive and compulsive behaviours. We then discuss the neurobiology of value, beginning with the dopaminergic system and its relationship with incentive salience before moving to brain-wide networks involved in valuation, control and prospection. These value-based neurobiological components are then integrated into the cycle of addiction as we consider the development of drug dependency from a valuation perspective. We conclude with a discussion of cognitive interventions utilizing value-based decision-making, highlighting not just advances in recalibrating the valuation system to focus on non-drug rewards, but also areas for improvement in refining this approach.
Associations Between Delay Discounting and Connectivity of the Valuation-control System in Healthy Young Adults

Loganathan K, Lv J, Cropley V, Ho ETW, Zalesky A

Neuroscience, 2021 01 01;452:295-310.
PMID: 33242540 DOI: 10.1016/j.neuroscience.2020.11.026

The process of valuation assists in determining if an object or course of action is rewarding. Delay discounting is the observed decay of a rewards' subjective value over time. Encoding the subjective value of rewards across a spectrum has been attributed to brain regions belonging to the valuation and executive control systems. The valuation system (VS) encodes reward value over short and long delays, influencing reinforcement learning and reward representation. The executive control system (ECS) becomes more active as choice difficulty increases, integrating contextual and mnemonic information with salience signals in the modulation of decision-making. Here, we aimed to identify resting-state functional connectivity-based patterns of the VS and ECS correlated with value-setting and delay discounting (outside-scanner paradigm) in a large (n = 992) cohort of healthy young adults from the Human Connectome Project (HCP). Results suggest the VS may be involved in value-setting of small, immediate rewards while the ECS may be involved in value-setting and delay discounting for large and small rewards over a range of delays. We observed magnitude sensitive connections involving the posterior cingulate cortex, time-sensitive connections with the ventromedial and lateral prefrontal cortex while connections involving the posterior parietal cortex appeared both magnitude- and time-sensitive. The ventromedial prefrontal cortex and posterior parietal cortex could act as "comparator" regions, weighing the value of small rewards against large rewards across various delay duration to aid in decision-making.
Valuation system connectivity is correlated with poly-drug use in young adults

Loganathan K, Lv J, Cropley V, Zalesky A, Ho ETW

Neurosci Res, 2021 Dec;173:114-120.
PMID: 34214618 DOI: 10.1016/j.neures.2021.06.006

Poly-drug consumption contributes to fatal overdose in more than half of all poly-drug users. Analyzing decision-making networks may give insight into the motivations behind poly-drug use. We correlated average functional connectivity of the valuation system (VS), executive control system (ECS) and valuation-control complex (VCC) in a large population sample (n = 992) with drug use behaviour. VS connectivity is correlated with sedative use, ECS connectivity is separately correlated with hallucinogens and opiates. Network connectivity is also correlated with drug use via two-way interactions with other substances including alcohol and tobacco. These preliminary findings can contribute to our understanding of the common combinations of substance co-use and associated neural patterns.
Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use

Singh D, Narayanan S, Müller CP, Vicknasingam B, Yücel M, Ho ETW, et al.

J Psychoactive Drugs, 2018 12 15;51(1):19-27.
PMID: 30556488 DOI: 10.1080/02791072.2018.1555345

Kratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (≤3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.
Fulltext Conversational Task Increases Heart Rate Variability of Individuals Susceptible to Perceived Social Isolation

Feng YX, Roslan NS, Izhar LI, Abdul Rahman M, Faye I, Ho ETW

Int J Environ Res Public Health, 2021 09 18;18(18).
PMID: 34574777 DOI: 10.3390/ijerph18189858

Studies showed that introversion is the strongest personality trait related to perceived social isolation (loneliness), which can predict various complications beyond objective isolation such as living alone. Lonely individuals are more likely to resort to social media for instantaneous comfort, but it is not a perpetual solution. Largely negative implications including poorer interpersonal relationship and depression were reported due to excessive social media usage. Conversational task is an established intervention to improve verbal communication, cognitive and behavioral adaptation among lonely individuals. Despite that behavioral benefits have been reported, it is unclear if they are accompanied by objective benefits underlying physiological changes. Here, we investigate the physiological signals from 28 healthy individuals during a conversational task. Participants were ranked by trait extraversion, where greater introversion is associated with increased susceptibility to perceived social isolation as compared to participants with greater extraversion as controls. We found that introverts had a greater tendency to be neurotic, and these participants also exhibited significant differences in task-related electrodermal activity (EDA), heart rate (HR) and HR variability (HRV) as compared to controls. Notably, resting state HRV among individuals susceptible to perceived loneliness was below the healthy thresholds established in literature. Conversational task with a stranger significantly increased HRV among individuals susceptible to isolation up to levels as seen in controls. Since HRV is also elevated by physical exercise and administration of oxytocin hormone (one form of therapy for behavioral isolation), conversational therapy among introverts could potentially confer physiological benefits to ameliorate social isolation and loneliness. Our findings also suggest that although the recent pandemic has changed how people are interacting typically, we should maintain a healthy dose of social interaction innovatively.
Fulltext Towards Multiplex Molecular Diagnosis-A Review of Microfluidic Genomics Technologies

Basha IHK, Ho ETW, Yousuff CM, Hamid NHB

Micromachines (Basel), 2017 Aug 30;8(9).
PMID: 30400456 DOI: 10.3390/mi8090266

Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity.
Fulltext Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.

PLoS One, 2020;15(7):e0236826.
PMID: 32730314 DOI: 10.1371/journal.pone.0236826

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.
Fulltext Working Memory Performance under a Negative Affect Is More Susceptible to Higher Cognitive Workloads with Different Neural Haemodynamic Correlates

Feng YX, Kiguchi M, Ung WC, Dass SC, Mohd Hani AF, Tang TB, et al.

Brain Sci, 2021 Jul 15;11(7).
PMID: 34356169 DOI: 10.3390/brainsci11070935

The effect of stress on task performance is complex, too much or too little stress negatively affects performance and there exists an optimal level of stress to drive optimal performance. Task difficulty and external affective factors are distinct stressors that impact cognitive performance. Neuroimaging studies showed that mood affects working memory performance and the correlates are changes in haemodynamic activity in the prefrontal cortex (PFC). We investigate the interactive effects of affective states and working memory load (WML) on working memory task performance and haemodynamic activity using functional near-infrared spectroscopy (fNIRS) neuroimaging on the PFC of healthy participants. We seek to understand if haemodynamic responses could tell apart workload-related stress from situational stress arising from external affective distraction. We found that the haemodynamic changes towards affective stressor- and workload-related stress were more dominant in the medial and lateral PFC, respectively. Our study reveals distinct affective state-dependent modulations of haemodynamic activity with increasing WML in n-back tasks, which correlate with decreasing performance. The influence of a negative effect on performance is greater at higher WML, and haemodynamic activity showed evident changes in temporal, and both spatial and strength of activation differently with WML.
Assessment of gonadotropins and testosterone hormone levels in regular Mitragyna speciosa (Korth.) users

Singh D, Murugaiyah V, Hamid SBS, Kasinather V, Chan MSA, Ho ETW, et al.

J Ethnopharmacol, 2018 Jul 15;221:30-36.
PMID: 29626673 DOI: 10.1016/j.jep.2018.04.005

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) also known as kratom, is a native medicinal plant of Southeast Asia with opioid-like effects. Kratom tea/juice have been traditionally used as a folk remedy and for controlling opiate withdrawal in Malaysia. Long-term opioid use is associated with depletion in testosterone levels.
AIM OF THE STUDY: Since kratom is reported to deform sperm morphology and reduce sperm motility, we aimed to clinically investigate the testosterone levels following long-term kratom tea/juice use in regular kratom users.
METHODS: A total of 19 regular kratom users were recruited for this cross-sectional study. A full-blood test was conducted including determination of testosterone level, follicle stimulating hormone (FSH) and luteinizing hormone (LH) profile, as well as hematological and biochemical parameters of participants.
RESULTS: We found long-term kratom tea/juice consumption with a daily mitragynine dose of 76.23-94.15 mg did not impair testosterone levels, or gonadotrophins, hematological and biochemical parameters in regular kratom users.
CONCLUSION: Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans.
Fulltext Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis

Choy SW, Bagarinao E, Watanabe H, Ho ETW, Maesawa S, Mori D, et al.

Hum Brain Mapp, 2020 08 15;41(12):3198-3211.
PMID: 32304267 DOI: 10.1002/hbm.25008

White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.
Correction to: A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility

Abrams MB, Bjaalie JG, Das S, Egan GF, Ghosh SS, Goscinski WJ, et al.

Neuroinformatics, 2021 Apr 13.
PMID: 33851344 DOI: 10.1007/s12021-021-09522-x
Fulltext A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility

Abrams MB, Bjaalie JG, Das S, Egan GF, Ghosh SS, Goscinski WJ, et al.

Neuroinformatics, 2022 Jan;20(1):25-36.
PMID: 33506383 DOI: 10.1007/s12021-020-09509-0

There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.

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