From fossils to mind.

Fossil endocasts record features of brains from the past: size, shape, vasculature, and gyrification. These data, alongside experimental and comparative evidence, are needed to resolve questions about brain energetics, cognitive specializations, and developmental plasticity. Through the application of interdisciplinary techniques to the fossil record, paleoneurology has been leading major innovations. Neuroimaging is shedding light on fossil brain organization and behaviors. Inferences about the development and physiology of the brains of extinct species can be experimentally investigated through brain organoids and transgenic models based on ancient DNA. Phylogenetic comparative methods integrate data across species and associate genotypes to phenotypes, and brains to behaviors. Meanwhile, fossil and archeological discoveries continuously contribute new knowledge. Through cooperation, the scientific community can accelerate knowledge acquisition. Sharing digitized museum collections improves the availability of rare fossils and artifacts. Comparative neuroanatomical data are available through online databases, along with tools for their measurement and analysis. In the context of these advances, the paleoneurological record provides ample opportunity for future research. Biomedical and ecological sciences can benefit from paleoneurology's approach to understanding the mind as well as its novel research pipelines that establish connections between neuroanatomy, genes and behavior.

Co-administration of alcohol and combination antiretroviral therapy (cART) in male Sprague Dawley rats: A study on testicular morphology, oxidative and cytokines perturbations.

Alcohol consumption alongside combination antiretroviral therapy (cART) has attracted research interest, especially because of increasing male infertility. This study investigated the combined effects of alcohol and cART on testicular morphology, biomarkers of oxidative stress, inflammation, and apoptosis. Rats, weighing 330-370 g, were divided into four groups of six animals each; control, alcohol treated (A), cART, and alcohol plus cART treated (A+cART). Following 90 days treatment period, animals were euthanized, testis extracted, and routinely processed for histology and immunohistochemical analysis. Significantly decreased epithelial area fraction, increased luminal and connective tissue area fractions, and reduction of epithelial height and spermatocyte number, were recorded in the treated groups compared to control. Extensive seminiferous epithelial lesions including widened intercellular space, karyolysis, and sloughing of germinal epithelium were recorded in all the treated groups. Furthermore, upregulation of inducible nitric oxide synthase and 8-hydroxydeoxyguanosine, interleukin-6, and caspase 3 recorded in treated animals, was more significant in A+cART group. Also, the levels of interleukin-1ß and tumor necrosis factor-α were more elevated in A and cART treated groups than in A+cART, while MDA was significantly elevated in cART and A+cART treated groups compared to control group. Altogether, the results indicate testicular toxicity of the treatments. It is concluded that consuming alcohol or cART induces oxidative stress, inflammation, and apoptosis in testis of rats, which lead to testicular structural and functional derangements, which are exacerbated when alcohol and cART are consumed concurrently. The result will invaluably assist clinicians in management of reproductive dysfunctions in male HIV/AIDS-alcoholic patients on cART.

Fronto-temporal cortical atrophy in 'nyaope' combination heroin and cannabis use disorder.

Sub-Saharan Africa is one of the top three regions with the highest rates of opioid-related premature mortality. Nyaope is the street name for what is believed to be a drug cocktail in South Africa although recent research suggests that it is predominantly heroin. Nyaope powder is most commonly smoked together with cannabis, a drug-use pattern unique to the region. Due to the increasing burden of this drug in low-income communities and the absence of human structural neuroimaging data of combination heroin and cannabis use disorder, we initiated an important cohort study in order to identify neuroanatomical sequelae. Twenty-eight male nyaope users and thirty healthy, matched controls were recruited from drug rehabilitation centers and the community, respectively. T1-weighted MRI images were obtained using a 3 T General Electric Discovery and cortical thickness was examined and compared. Nyaope users displayed extensive grey matter atrophy in the right hemispheric medial orbitofrontal, rostral middle frontal, superior temporal, superior frontal, and supramarginal gyri (two-sided t-test, p < 0.05, corrected for multiple comparisons). Our findings indicate cortical abnormality in nyaope users in regions involved in impulse control, decision making, social- and self-perception, and working memory. Importantly, affected brain regions show large overlap with the pattern of cortical abnormalities shown in heroin use disorder.

Access to Healthcare and Harm Reduction Services During the COVID-19 Pandemic for People Who Use Drugs.

: Globally, there are concerns about access to healthcare and harm reduction services for people who use drugs (PWUD) during the coronavirus disease 2019 (COVID-19) pandemic. Members from the Network of Early Career Professionals working in Addiction Medicine shared their experiences of providing treatment to PWUD during the COVID-19 pandemic. Drawing on these qualitative reports, we highlight the similarities and discrepancies in access to services for PWUD in 16 countries under COVID-10 restrictions. In most countries reported here, efforts have been made to ensure continued access to services, such as mobilising opioid agonist maintenance treatment and other essential medicines to patients. However, due to travel restrictions and limited telemedicine services, several Network of Early Career Professionals working in Addiction Medicine members from lower-resourced countries experienced challenges with providing care to their patients during periods of COVID-19 lock-down. The insights provided in this commentary illustrate how the COVID-19 lock-down restrictions have impacted access to services for PWUD.

The Changing Landscape of Alcohol Use and Alcohol Use Disorder During the COVID-19 Pandemic - Perspectives of Early Career Professionals in 16 Countries.

: Alcohol use is a major risk factor for infectious disease and reduction of harms associated with alcohol consumption are essential during times of humanitarian crises, such as the COVID-19 pandemic. As a network of early career professionals working in the area of addiction medicine, we provide our views with regards to national actions related to reducing alcohol-related harm and providing care for people with alcohol use disorder during COVID-19. We believe that COVID-19 related measures have affected alcohol consumption in the majority of countries represented in this commentary. Examples of these changes include changes in alcohol consumption patterns, increases in cases of alcohol withdrawal syndrome, disruptions in access to medical care for alcohol use disorder and increases in illegal production of alcohol. Our members urge that treatment for acute and severe conditions due to substance use should be considered as essential services in times of humanitarian crises like COVID-19.

Human Self-Domestication and the Extended Evolutionary Synthesis of Addiction: How Humans Evolved a Unique Vulnerability.

Humans are more vulnerable to addiction in comparison to all other mammals, including nonhuman primates, yet there is a lack of research addressing this. This paper reviews the field of comparative addiction neuroscience, highlighting the significant inter-species variation in the mesocortical dopaminergic and other neuromodulatory systems involved in addiction. Artificial selection gives rise to significant changes in neuroanatomy, neurophysiology and behaviour as shown in certain rodent strains and other domesticated animals. These changes occur over a few generations, relatively short periods of time in evolutionary terms, and demonstrate how dynamic these neuromodulatory systems are in response to the environment. During the course of human evolution, traits crucial to our survival, expansion and domination (traits such as the ability to innovate, adapt to different environments and thrive in a civilization) have been positively selected for, yet also predispose humans to addiction. This is evident in our unique neurochemistry and receptor-drug activation potencies. Examples of these are provided as possible targets for precision medicine.

An introduction to psychedelic neuroscience.

This chapter is an introduction to the volume "Psychedelic Neuroscience" of Elsevier's Progress in Brain Research addressing the neurobiological mechanisms of psychedelic drugs, the resulting changes in brain activity and integration of traditional viewpoints. As the field is relatively new, there are discrepancies in the literature related to classification, composition and effects of the various psychedelics. Currently, psychedelics are grouped according to their neuro-receptor affinities into classic and atypical psychedelics, each with individual treatment potentials and abilities to elicit potent acute experiences and long-lasting changes in neurobiology through concurrent activation of several neuromodulatory systems. There is disparity in psychedelic brain imaging studies, delineating what is neural activity and hemodynamic needs further investigation for us to understand the brain "state" changes that are apparent. The psychedelic brain "state" is often compared to acute psychosis and we review the psychedelic animal models of psychosis and human brain imaging studies and contrast these to psychosis. The term "psychedelic" means mind-revealing and psychedelics have exceptional anti-amnesic effects and are able to "make conscious" that which was previously unconscious through changes in brain "state," but also there is growing evidence which demonstrates the role of epigenetic mechanisms. This supports traditional therapeutic use of psychedelics to heal ancestral trauma. Details of these mechanisms are provided along with suggestions for further research.

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder.

Ibogaine is a plant-derived alkaloid and dissociative psychedelic that demonstrates anti-addictive properties with several substances of abuse, including alcohol. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring psychedelic known to occasion potent mystical-type experiences and also demonstrates anti-addictive properties. The potential therapeutic effects of both compounds in treating alcohol use disorder require further investigation and there are no published human neuroimaging findings of either treatment to date. We present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in Mexico that utilized a sequential protocol with ibogaine hydrochloride (1550mg, 17.9mg/kg) on day 1, followed by vaporized 5-MeO-DMT (bufotoxin source 50mg, estimated 5-MeO-DMT content, 5-7mg) on day 3. The patient received SPECT neuroimaging that included a resting-state protocol before, and 3 days after completion of the program. During the patient's ibogaine treatment, he experienced dream-like visions that included content pertaining to his alcohol use and resolution of past developmental traumas. He described his treatment with 5-MeO-DMT as a peak transformational and spiritual breakthrough. On post-treatment SPECT neuroimaging, increases in brain perfusion were noted in bilateral caudate nuclei, left putamen, right insula, as well as temporal, occipital, and cerebellar regions compared to the patient's baseline scan. The patient reported improvement in mood, cessation of alcohol use, and reduced cravings at 5 days post-treatment, effects which were sustained at 1 month, with a partial return to mild alcohol use at 2 months. In this case, serial administration of ibogaine and 5-MeO-DMT resulted in increased perfusion in multiple brain regions broadly associated with alcohol use disorders and known pharmacology of both compounds, which coincided with a short-term therapeutic outcome. We present theoretical considerations regarding the potential of both psychedelic medicines in treating alcohol use disorders in the context of these isolated findings, and areas for future investigation.

The extended evolutionary synthesis and addiction: the price we pay for adaptability.

Humans are more likely to become addicted and to stay addicted than are other animals. This chapter is a neurobiological and molecular review of addiction and the cooccurring traits and psychiatric disorders from the perspective of the Extended Evolutionary Synthesis (EES). Addiction is an example of pleiotropy as many common haplotypes that are associated with individual differences in vulnerability to substance dependence express a variety of important brain-based phenotypes such as neuroadaptive processes. The neurochemical mechanisms of addiction are shared with behavioral flexibility and the ability to innovate, which are hallmark features of our species. The dopaminergic system provides a link between addiction and the cooccurring traits and psychiatric disorders evident in the shared genetic profile. A hypofunctioning dopaminergic system is also a common characteristic feature of addiction and the cooccurring traits and psychiatric disorders. Epigenetics allows for environmental factors to create lasting and heritable phenotypic changes enabling rapid adaptation to an environment. Addiction "high-jacks" this system as well as the neurochemical mechanisms that control flexibility and innovation and is, thus, the price we pay for adaptability.

Nuclear organisation of some immunohistochemically identifiable neural systems in five species of insectivore-Crocidura cyanea, Crocidura olivieri, Sylvisorex ollula, Paraechinus aethiopicus and Atelerix frontalis.

The organization of the cholinergic, catecholaminergic, and serotonergic neurons in the brains of five species of insectivores and the orexinergic (hypocretinergic) system in four insectivore species is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of other mammalian species. Brains of insectivores were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei were similar among the species investigated and to mammals in general, but certain differences in the nuclear complement highlighted potential phylogenetic interrelationships. In the cholinergic system, the three shrew species lacked parabigeminal and Edinger-Westphal nuclei. In addition, the appearance of the laterodorsal tegmental nucleus in all insectivores revealed a mediodorsal arch. All three of these features are the same as those present in microchiropterans. The catecholaminergic system of the three shrew species lacked the A4 and A15d nuclei, as well as having an incipient A9v nucleus, again features found in microchiropteran brains. The serotonergic and orexinergic systems of the insectivores are similar to those seen across most eutherian mammals. The analysis of similarities and differences across mammalian species indicates a potential phylogenetic relationship between the Soricidae (shrews) and the microchiropterans.

Nuclear organization of some immunohistochemically identifiable neural systems in two species of the Euarchontoglires: A Lagomorph, Lepus capensis, and a Scandentia, Tupaia belangeri.

The present study describes the organization of the nuclei of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of two members of Euarchontoglires, Lepus capensis and Tupaia belangeri. The aim of the present study was to investigate the nuclear complement of these neural systems in comparison to previous studies on Euarchontoglires and generally with other mammalian species. Brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei revealed in the current study were similar between the species investigated and to mammals generally, but certain differences in the nuclear complement highlight potential phylogenetic interrelationships within the Euarchontoglires and across mammals. In the northern tree shrew the nucleus of the trapezoid body contained neurons immunoreactive to the choline acetyltransferase antibody with some of these neurons extending into the lamellae within the superior olivary nuclear complex (SON). The cholinergic nature of the neurons of this nucleus, and the extension of cholinergic neurons into the SON, has not been noted in any mammal studied to date. In addition, cholinergic neurons forming the medullary tegmental field were also present in the northern tree shrew. Regarding the catecholaminergic system, the cape hare presented with the rodent specific rostral dorsal midline medullary nucleus (C3), and the northern tree shrew lacked both the ventral and dorsal divisions of the anterior hypothalamic group (A15v and A15d). Both species were lacking the primate/megachiropteran specific compact portion of the locus coeruleus complex (A6c). The nuclei of the serotonergic and orexinergic systems of both species were similar to those seen across most Eutherian mammals. Our results lend support to the monophyly of the Glires, and more broadly suggest that the megachiropterans are more closely related to the primates than are any other members of Euarchontoglires studied to date.

Organization of cholinergic, catecholaminergic, serotonergic and orexinergic nuclei in three strepsirrhine primates: Galago demidoff, Perodicticus potto and Lemur catta.

The nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of three species of strepsirrhine primates is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of simian primates, megachiropterans and other mammalian species. The brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The nuclei identified were identical among the strepsirrhine species investigated and identical to previous reports in simian primates. Moreover, a general similarity to other mammals was found, but specific differences in the nuclear complement highlighted potential phylogenetic interrelationships. The central feature of interest was the structure of the locus coeruleus complex in the primates, where a central compactly packed core (A6c) of tyrosine hydroxylase immunopositive neurons was surrounded by a shell of less densely packed (A6d) tyrosine hydroxylase immunopositive neurons. This combination of compact and diffuse divisions of the locus coeruleus complex is only found in primates and megachiropterans of all the mammalian species studied to date. This neural character, along with variances in a range of other neural characters, supports the phylogenetic grouping of primates with megachiropterans as a sister group.

Nuclear organisation of some immunohistochemically identifiable neural systems in three Afrotherian species--Potomogale velox, Amblysomus hottentotus and Petrodromus tetradactylus.

The present study describes the organisation of the cholinergic, catecholaminergic, and serotonergic neurons in the brains of the giant otter shrew, the Hottentot golden mole and the four-toed sengi, and the orexinergic (hypocretinergic) system in the giant otter shrew and four-toed sengi. The aim of the present study was to investigate the possible differences in the nuclear complement of these neural systems in comparison to previous studies on other Afrotherian species and mammalian species in general. Brains of the golden mole, sengi and giant otter shrew were coronally sectioned and immunohistochemically stained with antibodies against cholineacetyl-transferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei revealed in the current study were similar among the species investigated, to other Afrotherian species, and to mammals generally, but certain differences in the nuclear complement highlighted phylogenetic interrelationships. The golden mole was observed to have cholinergic interneurons in the cerebral cortex, hippocampus, olfactory bulb and amygdala. The four-toed sengi had cholinergic neurons in both colliculi and in the cochlear nucleus, but lacked the catecholaminergic A15d group in the hypothalamus. In both the golden mole and the four-toed sengi, the locus coeruleus (A6d group) was made up of few neurons. The golden mole also exhibited an unusual foreshortening of the brain, such that a major (mesencephalic?) flexure in the brainstem was evident.