OPEN Foundation

Day: 27 September 2018

Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD

September 27, 2018 / Neuroscience, Other subjects, Other substances, Papers, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

Understanding the underlying mechanisms of the human brain in health and disease will require models with necessary and sufficient details to explain how function emerges from the underlying anatomy and is shaped by neuromodulation. Here, we provide such a detailed causal explanation using a whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical data from diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) with neurotransmitter data obtained with positron emission tomography (PET) of the detailed serotonin 2A receptor (5-HT2AR) density map. This allowed us to model the resting state (with and without concurrent music listening) and mechanistically explain the functional effects of 5-HT2AR stimulation with lysergic acid diethylamide (LSD) on healthy participants. The whole-brain model used a dynamical mean-field quantitative description of populations of excitatory and inhibitory neurons as well as the associated synaptic dynamics, where the neuronal gain function of the model is modulated by the 5-HT2AR density. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to (1) the underlying anatomical connectivity, (2) the modulation by the specific brainwide distribution of neurotransmitter receptor density, and (3) the non-linear interactions between the two. Taking neuromodulatory activity into account when modeling global brain dynamics will lead to novel insights into human brain function in health and disease and opens exciting possibilities for drug discovery and design in neuropsychiatric disorders.

Deco, G., Cruzat, J., Cabral, J., Knudsen, G. M., Carhart-Harris, R. L., Whybrow, P. C., … & Kringelbach, M. L. (2018). Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD. Current biology, 28(19), 3065-3074., 10.1016/j.cub.2018.07.083

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Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression

September 27, 2018 / Creativity, Ketamine, Medicine, Neuroscience, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression.

METHODS:

Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion.

RESULTS:

Significant improvements were found on speed of processing ( F=9.344, p<0.001) and verbal learning ( F=5.647, p=0.004) in a linear mixed model. The Sobel test showed significant indirect effects between time and improvement in speed of processing (Sobel test=3.573, p<0.001) as well as improvement in verbal learning (Sobel test=6.649, p<0.001), which were both significantly mediated by change in depressive symptoms. Logistic regression analysis showed ketamine responders had better visual learning at baseline than non-responders (B=0.118, p<0.001).

CONCLUSIONS:

Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.

Zhou, Y., Zheng, W., Liu, W., Wang, C., Zhan, Y., Li, H., … & Ning, Y. (2018). Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. Journal of Psychopharmacology, 32(10), 1118-1126, 10.1177/0269881118798614
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Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy

September 27, 2018 / Mystical experiences, Other subjects, Other substances, Papers, Phenomenology, Psychology, Psychopharmacology, Psychotherapy, Publications, Spirituality / By /

Abstract

A psychological model of classic psychedelic-assisted psychotherapy informed by contemporary scientific data is presented in this paper. It is suggested that classic psychedelic-occasioned mystical experience is characterized by profound awe, a discrete emotion experienced in the presence of a vast stimulus requiring accommodation of mental structures. Awe, in turn, promotes the small self, a construct that, in the extreme, is analogous to those of unitive experience and ego dissolution. The small self is conceptualized as key to understanding the downstream effects of mystical experience occasioned in the context of classic psychedelic-assisted psychotherapy. With this novel theoretical framework in mind, a number of clinical implications and recommendations are provided so as to advance this incipient field of study.
Hendricks, P. S. (2018). Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. International Review of Psychiatry, 30(4), 331-342., 10.1080/09540261.2018.1474185
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30 April - Q&A with Rick Strassman

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