scholarly journals The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
João Castelhano ◽  
Gisela Lima ◽  
Marta Teixeira ◽  
Carla Soares ◽  
Marta Pais ◽  
...  

There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g., LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.

2020 ◽  
Author(s):  
Mei Yan Melody Chan ◽  
Yvonne M.Y. Han

Abstract Background Impaired imitation has been found to be an important factor contributing to social communication deficits in individuals with autism spectrum disorder (ASD). It has been hypothesized that the neural correlates of imitation, the mirror neuron system (MNS), are dysfunctional in ASD, resulting in imitation impairment as one of the key behavioral manifestations in ASD. Previous MNS studies produced inconsistent results, leaving the debate of whether mirror neurons are “broken” in ASD unresolved.Methods This meta-analysis aimed to explore the differences in MNS activation patterns between typically developing (TD) and ASD individuals when they observe/imitate biological motions with/without emotional components. Effect-size signed differential mapping (ES-SDM) was adopted to synthesize the available fMRI data. Results The MNS is dysfunctional in ASD; not only the brain regions containing mirror neurons were affected, the brain regions supporting MNS functioning were also impaired. Second, MNS dysfunction in ASD is modulated by task complexity; differential activation patterns during the presentation of “cold” and “hot” stimuli might be a result of atypical functional connectivity in ASD. Third, MNS dysfunction in ASD individuals is modulated by age. MNS regions were found to show delayed maturation; abnormal lateralization development in some of the brain regions also contributed to the atypical development of the MNS in ASD. Limitations We have attempted to include a comprehensive set of original data for this analysis. However, whole brain analysis data were not obtainable from some of the published papers, these studies could not be included as a result. Moreover, the results indicating the age effect on MNS in ASD could only be generalized to individuals aged 11-37, as MNS activation remains unstudied for populations beyond this age range. Also, the ES-SDM linear regression modelling might not be ideal to illustrate the associations between age and MNS activation; the meta-regression results should be treated with caution. Conclusion There is a “global” rather than a “local” network dysfunction, which may underlie the imitation impairments in individuals with ASD. Task complexity and age modulate the functioning of the MNS, which may explain the previous peculiar results contributing to the unresolved “broken mirror neuron” debate.


2005 ◽  
Vol 187 (6) ◽  
pp. 500-509 ◽  
Author(s):  
Amélie M. Achim ◽  
Martin Lepage

BackgroundNumerous studies have examined the neural correlates of episodic memory deficits in schizophrenia, yielding both consistencies and discrepancies in the reported patterns of results.AimsTo identify in schizophrenia the brain regions in which activity is consistently abnormal across imaging studies of memory.MethodData from 18 studies meeting the inclusion criteria were combined using a recently developed quantitative meta-analytic approach.ResultsRegions of consistent differential activation between groups were observed in the left inferior prefrontal cortex, medial temporal cortex bilaterally, left cerebellum, and in other prefrontal and temporal lobe regions. Subsequent analyses explored memory encoding and retrieval separately and identified between-group differences in specific prefrontal and medial temporal lobe regions.ConclusionsBeneath the apparent heterogeneity of published findings on schizophrenia and memory, a consistent and robust pattern of group differences is observed as a function of memory processes.


Author(s):  
Jack M. Gorman

Although some functions, like speech and vision, can be linked to single, specific locations in the brain, complex emotions and behaviors usually involve complex interactions among brain regions. As our brains mature, these connections are shaped by our lived experiences. Scientists in basic neuroscience laboratories have traced the pathways and networks necessary for the acquisition, expression, and extinction of one emotion: fear. Brain imaging studies have shown that these same connected brain regions are activated by fear and anxiety in humans. The “fear network” includes the amygdala, hippocampus, and prefrontal cortex. Abnormalities in activity and strength of connections in the fear network are present in children and adults with anxiety disorders and depression. Brain networks that are necessary for other emotions and behaviors have been identified, so that today we look to how our brains are connected to understand our actions and emotions.


2021 ◽  
Author(s):  
Pavithra Elumalai ◽  
Yasharth Yadav ◽  
Nitin Williams ◽  
Emil Saucan ◽  
Jürgen Jost ◽  
...  

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders that pose a significant global health burden. Measures from graph theory have been used to characterise ASD-related changes in resting-state fMRI functional connectivity networks (FCNs), but recently developed geometry-inspired measures have not been applied so far. In this study, we applied geometry-inspired graph Ricci curvatures to investigate ASD-related changes in resting-state fMRI FCNs. To do this, we applied Forman-Ricci and Ollivier-Ricci curvatures to compare networks of ASD and healthy controls (N = 1112) from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset. We performed these comparisons at the brain-wide level as well as at the level of individual brain regions, and further, determined the behavioral relevance of region-specific differences with Neurosynth meta-analysis decoding. We found brain-wide ASD-related differences for both Forman-Ricci and Ollivier-Ricci curvatures. For Forman-Ricci curvature, these differences were distributed across 83 of the 200 brain regions studied, and concentrated within the Default Mode, Somatomotor and Ventral Attention Network. Meta-analysis decoding identified the brain regions showing curvature differences as involved in social cognition, memory, language and movement. Notably, comparison with results from previous non-invasive stimulation (TMS/tDCS) experiments revealed that the set of brain regions showing curvature differences overlapped with the set of brain regions whose stimulation resulted in positive cognitive or behavioural outcomes in ASD patients. These results underscore the utility of geometry-inspired graph Ricci curvatures in characterising disease-related changes in ASD, and possibly, other neurodevelopmental disorders.


2021 ◽  
Author(s):  
Rahat Hasan ◽  
Jack Humphrey ◽  
Conceicao Bettencourt ◽  
Tammaryn Lashley ◽  
Pietro Fratta ◽  
...  

Frontotemporal lobar degeneration (FTLD) is a group of heterogeneous neurodegenerative disorders affecting the frontal and temporal lobes of the brain. Nuclear loss and cytoplasmic aggregation of the RNA-binding protein TDP-43 represents the major FTLD pathology, known as FTLD-TDP. To date, there is no effective treatment for FTLD-TDP due to an incomplete understanding of the molecular mechanisms underlying disease development. Here we compared post-mortem tissue RNA-seq transcriptomes from the frontal cortex, temporal cortex and cerebellum between 28 controls and 30 FTLD-TDP patients to profile changes in cell-type composition, gene expression and transcript usage. We observed downregulation of neuronal markers in all three regions of the brain, accompanied by upregulation of microglia, astrocytes, and oligodendrocytes, as well as endothelial cells and pericytes, suggesting shifts in both immune activation and within the vasculature. We validate our estimates of neuronal loss using neuropathological atrophy scores and show that neuronal loss in the cortex can be mainly attributed to excitatory neurons, and that increases in microglial and endothelial cell expression are highly correlated with neuronal loss. All our analyses identified a strong involvement of the cerebellum in the neurodegenerative process of FTLD-TDP. Altogether, our data provides a detailed landscape of gene expression alterations to help unravel relevant disease mechanisms in FTLD.


2020 ◽  
Author(s):  
Bryony Goulding Mew ◽  
Darije Custovic ◽  
Eyal Soreq ◽  
Romy Lorenz ◽  
Ines Violante ◽  
...  

AbstractFlexible behaviour requires cognitive-control mechanisms to efficiently resolve conflict between competing information and alternative actions. Whether a global neural resource mediates all forms of conflict or this is achieved within domainspecific systems remains debated. We use a novel fMRI paradigm to orthogonally manipulate rule, response and stimulus-based conflict within a full-factorial design. Whole-brain voxelwise analyses show that activation patterns associated with these conflict types are distinct but partially overlapping within Multiple Demand Cortex (MDC), the brain regions that are most commonly active during cognitive tasks. Region of interest analysis shows that most MDC sub-regions are activated for all conflict types, but to significantly varying levels. We propose that conflict resolution is an emergent property of distributed brain networks, the functional-anatomical components of which place on a continuous, not categorical, scale from domain-specialised to domain general. MDC brain regions place towards one end of that scale but display considerable functional heterogeneity.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xueyan Fu ◽  
Will Patterson ◽  
Gregory Dolnikowski ◽  
Bess Dawson-Hughes ◽  
Martha Morris ◽  
...  

Abstract Objectives Very little is known about the forms of vitamin D and vitamin K in the human brain. The objective of this study is to evaluate concentrations of vitamin D and vitamin K forms in human brain and their correlations across four human brain regions. Methods Vitamin D [D3, 25(OH)D and 1,25(OH)2D] and vitamin K [phylloquinone and menaquinone-4 (MK4)] concentrations were measured by LC/MS/MS and HPLC, respectively, in four brain regions from post-mortem samples obtained from participants in the Rush Memory and Aging Project (n = 130, mean age 82 yrs, 81% female). The brain regions analyzed were the mid-frontal cortex (MF) and mid-temporal cortex (MT) [two regions important for memory in Alzheimer's Disease (AD)], the cerebellum (CR, a region not affected by AD), and the anterior watershed white matter (AWS, a region associated with vascular disease). The correlations among the vitamin forms across brain regions were calculated using Spearman rank order correlation coefficients. Significance was set at P < 0.001. Results The average concentrations of vitamin D3, 25(OH)D and MK4 were 604 pg/g, 535 pg/g, and 3.4 pmol/g, respectively. 25(OH)D and MK4 were detected in >95% of the brain samples. Nearly 92% of 1,25(OH)2D and 80% of phylloquinone samples had concentrations below the limit of assay detection (LOD) 1,25(OH)2D = 20 ng/g, phylloquinone = 0.1 pmol/g). Vitamin D3 and 25(OH)D concentrations were positively correlated across all four regions (all Spearman r ≥ 0.78, P < 0.0001). The 1,25(OH)2D was significantly correlated between the MF and CR regions only (Spearman r = 0.30, P < 0.001, all other P ≥ 0.002). MK4 and PK were positively correlated across the four regions studied (MK4 all Spearman r ≥ 0.78, phylloquinone r ≥ 0.49, all P < 0.001). Conclusions To the best of our knowledge, this study is the first evaluation of the concentrations of vitamin D and vitamin K forms in multiple regions of the human brain. Overall, the vitamin D and vitamin K forms were each positively correlated across the four brain regions studied. Future studies are needed to clarify the roles of these nutrients in AD and dementia. Funding Sources National Institute of Aging.


Author(s):  
Jack M. Gorman

Some scientists now argue that humans are really not superior to other species, including our nearest genetic neighbors, chimpanzees and bonobos. Indeed, those animals seem capable of many things previously thought to be uniquely human, including a sense of the future, empathy, depression, and theory of mind. However, it is clear that humans alone produce speech, dominate the globe, and have several brain diseases like schizophrenia. There are three possible sources within the brain for these differences in brain function: in the structure of the brain, in genes coding for proteins in the brain, and in the level of expression of genes in the brain. There is evidence that all three are the case, giving us a place to look for the intersection of the human mind and brain: the expression of genes within neurons of the prefrontal cortex.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jonghan Shin ◽  
Vladimir Kepe ◽  
Gary W. Small ◽  
Michael E. Phelps ◽  
Jorge R. Barrio

The spatial correlations between the brain's default mode network (DMN) and the brain regions known to develop pathophysiology in Alzheimer's disease (AD) have recently attracted much attention. In this paper, we compare results of different functional and structural imaging modalities, including MRI and PET, and highlight different patterns of anomalies observed within the DMN. Multitracer PET imaging in subjects with and without dementia has demonstrated that [C-11]PIB- and [F-18]FDDNP-binding patterns in patients with AD overlap within nodes of the brain's default network including the prefrontal, lateral parietal, lateral temporal, and posterior cingulate cortices, with the exception of the medial temporal cortex (especially, the hippocampus) where significant discrepancy between increased [F-18]FDDNP binding and negligible [C-11]PIB-binding was observed. [F-18]FDDNP binding in the medial temporal cortex—a key constituent of the DMN—coincides with both the presence of amyloid and tau pathology, and also with cortical areas with maximal atrophy as demonstrated by T1-weighted MR imaging of AD patients.


2019 ◽  
Vol 375 (1791) ◽  
pp. 20190304 ◽  
Author(s):  
Ryan Calmus ◽  
Benjamin Wilson ◽  
Yukiko Kikuchi ◽  
Christopher I. Petkov

Understanding how the brain forms representations of structured information distributed in time is a challenging endeavour for the neuroscientific community, requiring computationally and neurobiologically informed approaches. The neural mechanisms for segmenting continuous streams of sensory input and establishing representations of dependencies remain largely unknown, as do the transformations and computations occurring between the brain regions involved in these aspects of sequence processing. We propose a blueprint for a neurobiologically informed and informing computational model of sequence processing (entitled: Vector-symbolic Sequencing of Binding INstantiating Dependencies, or VS-BIND). This model is designed to support the transformation of serially ordered elements in sensory sequences into structured representations of bound dependencies, readily operates on multiple timescales, and encodes or decodes sequences with respect to chunked items wherever dependencies occur in time. The model integrates established vector symbolic additive and conjunctive binding operators with neurobiologically plausible oscillatory dynamics, and is compatible with modern spiking neural network simulation methods. We show that the model is capable of simulating previous findings from structured sequence processing tasks that engage fronto-temporal regions, specifying mechanistic roles for regions such as prefrontal areas 44/45 and the frontal operculum during interactions with sensory representations in temporal cortex. Finally, we are able to make predictions based on the configuration of the model alone that underscore the importance of serial position information, which requires input from time-sensitive cells, known to reside in the hippocampus and dorsolateral prefrontal cortex. This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.


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