Neurobiological Findings Research Articles

Cannabis use disorder: from neurobiology to treatment.

Cannabis has been legalized for medical and recreational purposes in multiple countries. A large number of people are using cannabis and some will develop cannabis use disorder (CUD). There is a growing recognition that CUD requires specific interventions. This Review will cover this topic from a variety of perspectives, with a particular emphasis on neurobiological findings and innovative treatment approaches that are being pursued. We will first describe the epidemiology and burden of disease of CUD, including risk factors associated with CUD (both in terms of general risk and genetic risk variants). Neurobiological alterations identified in brain imaging studies will be presented. Several psychosocial interventions that are useful for the management of CUD, including motivational enhancement therapy, behavioral and cognitive therapy, and contingency management, will be covered. Although no pharmacological interventions are yet approved for CUD, we present the most promising pharmacological interventions being tested.

Theories on the Etiology of Deviant Sexual Interests: A Systematic Review.

Not much is known about the etiology, or development, of deviant sexual interests. The aim of this systematic review was to provide a broad overview of current theories on the etiology of sexual deviance. We conducted a systematic search of the databases PubMed and APA PsycInfo (EBSCO). Studies were included when they discussed a theory regarding the etiology or development of sexual deviance. Included studies were assessed on quality criteria for good theories. Common etiological themes were extracted using thematic analysis. We included 47 theories explaining sexual deviance in general as well as various specific deviant sexual interests, such as pedophilia and sadism/masochism. Few theories (k = 7) were of acceptable quality as suggested by our systematic assessment of quality criteria for good theories (QUACGOT). These theories indicated that deviant sexual interests may develop as the result of an interplay of various factors: excitation transfer between emotions and sexual arousal, conditioning, problems with "normative" sexuality, and social learning. Neurobiological findings could not be included as no acceptable quality neurobiological theories could be retrieved. The important roles of excitation transfer and conditioning designate that dynamic, changeable processes take part in the etiology of sexual deviance. These same processes could potentially be deployed to diminish unwanted deviant sexual interests.

Neuroimaging and Brain-Based Markers Identifying Neurobiological Markers Associated With Criminal Behaviour, Personality Disorders, and Mental Health: A Narrative Review.

We begin the review by pointing to the common stigma associated with mental health issues, which often derives from a lack of understanding or incomplete knowledge.Neurobiological research provides us with a new lens to help challenge and dispel common assumptions and misunderstandings and gives an understanding of sexual behaviours that influence society.As such, it generates substantial evidence for the structural and functional asymmetry of the brains of individuals with mental disorders.However, this type of representation poses many challenges to traditional thinking and constantly provokes change in perspective and empathy towards those individuals. In the review, we go deeper into the effects of neurobiological findings on understanding criminal behaviours and personality disorders, looking further beyond behavioural health.These problems, which were once mainly discussed as moral ones or viewed from the perspective of character flaws, are analysed today through neurological considerations pointing to their complexity.When the root of bipolar disorder is revealed to be neurological, society will react with more information and understanding, hence reducing the stigmatisation and discrimination meted out to people with these problems. At a macro level, findings from neurobiology affect society in ways that go beyond individuals; social attitudes, laws, and policies about the services rendered are influenced.Operating as a catalyst within the community, neurobiological research helps to initiate social change through the creation of an informed, understanding public forum.Thus, it creates broader value for those dealing with behavioural and mental health challenges. The first and most important question of this narrative review is focused on identifying identifiable neurobiological markers that are closely related to criminal conduct, personality disorders, and mental health disorders.Through this review, we aim to present detailed insights into the neurological foundations that anchor these phenomena via a narrative analysis of contemporary literature.The potential implications are finding problems early to apply specific treatment and learning an advanced strategy for social attitudes.This will promote a more humanistic approach based on adequate information on the behavioural and mental health issues involved.

Neurobiology and systems biology of stress resilience.

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.

Neuronal correlates of intensification and acceptance of symptoms during exposure therapy in patients with obsessive-compulsive disorder.

Cognitive behaviour therapy with exposure and response prevention is efficient in treating patients with obsessive-compulsive disorder (OCD). Nevertheless, it would be helpful for many patients to complement the therapeutic treatment with acceptance strategies to further increase the therapeutic benefit. The aim of the present study was to examine neurobiological responses to acceptance and intensification strategies during symptom provocation alongside the psychotherapeutic process. A total of 23 patients diagnosed with OCD (subtype: washing/contamination fear) was instructed to utilise either an acceptance strategy (ACS) or an intensification strategy (INS) to cope with their emotional and cognitive reactions to personalised symptom-triggering and neutral pictures. Fourteen patients participated twice: at the beginning [T1] and at the end [T2] of an inpatient multimodal treatment including cognitive behaviour therapy with response prevention to assess functional variations. For the contrast of T1 and T2, ACS showed increased brain activity in the left inferior frontal gyrus (IFG), left caudate body, and posterior cingulate gyrus (PCC). They also showed decreased activity in the left anterior insula. INS showed decreased activation in right lingual gyrus and right caudate body. At T2, ACS showed increased activation compared to INS in the left cerebrum: IFG, caudate nucleus, middle and superior temporal gyrus, and PCC/cuneus. For the comparison of T1 and T2, the ACS revealed increased brain activity in the left IFG, left caudate body, and right inferior parietal lobe. It showed decreased activity in the left anterior insula. The INS revealed decreased activity in right lingual gyrus and right caudate body.The psychometric questionnaires suggested that patients were able to reduce obsession, compulsion, and depression symptoms. Furthermore, patients rated the ACS as more useful for themselves compared with the INS. The increased left IFG activity using ACS (T1 vs. T2) could be interpreted as a better inhibitory top-down process, while the increased PCC response might be due to a better reappraisal strategy after therapy. ACS seems to mobilise neuronal activations under therapy, especially in the left hemisphere. Both strategies showed reductions in emotional networks as a neuronal correlate of therapy success. Overall, ACS may be more efficient than INS, as rated by the patients and as in accordance with neurobiological findings.

Is anti-NMDA receptor encephalitis real? I. Diagnostic challenges

After conducting a thorough analysis of clinical, neurophysiological, neuroimmunological, neurobiological, and neuropathological research findings, the authors of the review question on the validity of the anti-NMDA receptor encephalitis concept. The review highlights the significance of studying sanogenetic mechanisms in medicine and warns against hasty interpretations of neurobiological data without clinical knowledge.

An open chat with… Koji Yamanaka.

Koji Yamanaka is a Professor at the Research Institute of Environmental Medicine at Nagoya University of Japan. His research interests lie in understanding the mechanism of onset and progression of motor neuron disease as well as the role of glial cells in Alzheimer's disease neuroinflammation. Koji has been serving on the FEBS Open Bio Editorial Board since 2013. In this interview, he explains the implications of recent findings in neurobiology for amyotrophic lateral sclerosis, provides updates on the research environment in Japan and discusses how editors might use their position to positively influence academic culture.

Neuropsychiatry revisited: epilepsy as the borderland between neurology and psychiatry.

Since epilepsy is often complicated by psychiatric symptoms, the contributions of psychiatry are indispensable for the care and improvement of the quality of life of individuals with epilepsy. Moreover, the existence of a bidirectional relationship between epilepsy and psychiatric symptoms was recently proposed, based on the evidence that not only are some psychiatric symptoms more likely than others to follow epilepsy, but also that psychiatric symptoms may precede the onset of epilepsy and the presence of psychiatric symptoms may influence the outcome of treatment for seizures. There has also been a gradual accumulation of neurobiological findings related to psychosis, depressive, and anxiety symptoms that are associated with epilepsy with respect to abnormalities in brain networks and neurotransmission. This mini-review focuses on the neuropsychiatric aspects of epilepsy and proposes that a reconsideration of neuropsychiatry in light of epilepsy findings could serve as a bridge between psychiatry and neurology.

Thalamic functional connectivity and sensorimotor processing in neurodevelopmental disorders.

One of the earliest neurobiological findings in autism has been the differences in the thalamocortical pathway connectivity, suggesting the vital role thalamus plays in human experience. The present functional MRI study investigated resting-state functional connectivity of the thalamus in 49 (autistic, ADHD, and neurotypical) young adults. All participants underwent structural MRI and eyes-open resting state functional MRI scans. After preprocessing the imaging data using Conn's connectivity toolbox, a seed-based functional connectivity analysis was conducted using bilateral thalamus as primary seeds. Autistic participants showed stronger thalamic connectivity, relative to ADHD and neurotypical participants, between the right thalamus and right precentral gyrus, right pars opercularis-BA44, right postcentral gyrus, and the right superior parietal lobule (RSPL). Autistic participants also showed significantly increased connectivity between the left thalamus and the right precentral gyrus. Furthermore, regression analyses revealed a significant relationship between autistic traits and left thalamic-precentral connectivity (R2 = 0.1113), as well as between autistic traits and right postcentral gyrus and RSPL connectivity (R2 = 0.1204) in autistic participants compared to ADHD. These findings provide significant insights into the role of thalamus in coordinating neural information processing and its alterations in neurodevelopmental disorders.

Pragmatic grammar in genus homo

The question of how humans got language is crucial for understanding the uniqueness of the human mind and the cognitive resources and processes shared with nonhuman species. We discuss the origin of symbolic elements in hominins and how a pragmatic grammar emerged from action-based event-structures. In the context of comparative neurobiological findings, we report support for the global workspace hypothesis and social brain hypothesis. In addition, reverse linguistic analysis informs us about the particular role of a pragmatic grammar stage. We assume that this stage was associated with changes to the hominin genotype. Homo erectus may have used a pragmatic grammar which consisted of two or three symbolic elements. Extended syntax and morphology, including hierarchical branching, are not based on genotype changes but may reflect cultural accumulations related to socioecological adaptations. We conclude that the biological capacity for language may have emerged already 1.8 million years ago with the appearance of genus Homo.

Neurobehavioral Profiles of Six Genetically-based Rat Models of Schizophrenia- related Symptoms.

Schizophrenia is a chronic and severe mental disorder with high heterogeneity in its symptoms clusters. The effectiveness of drug treatments for the disorder is far from satisfactory. It is widely accepted that research with valid animal models is essential if we aim at understanding its genetic/ neurobiological mechanisms and finding more effective treatments. The present article presents an overview of six genetically-based (selectively-bred) rat models/strains, which exhibit neurobehavioral schizophrenia-relevant features, i.e., the Apomorphine-susceptible (APO-SUS) rats, the Low-prepulse inhibition rats, the Brattleboro (BRAT) rats, the Spontaneously Hypertensive rats (SHR), the Wisket rats and the Roman High-Avoidance (RHA) rats. Strikingly, all the strains display impairments in prepulse inhibition of the startle response (PPI), which remarkably, in most cases are associated with novelty-induced hyperlocomotion, deficits of social behavior, impairment of latent inhibition and cognitive flexibility, or signs of impaired prefrontal cortex (PFC) function. However, only three of the strains share PPI deficits and dopaminergic (DAergic) psychostimulant-induced hyperlocomotion (together with prefrontal cortex dysfunction in two models, the APO-SUS and RHA), which points out that alterations of the mesolimbic DAergic circuit are a schizophrenia-linked trait that not all models reproduce, but it characterizes some strains that can be valid models of schizophrenia-relevant features and drug-addiction vulnerability (and thus, dual diagnosis). We conclude by putting the research based on these genetically-selected rat models in the context of the Research Domain Criteria (RDoC) framework, suggesting that RDoC-oriented research programs using selectively-bred strains might help to accelerate progress in the various aspects of the schizophrenia-related research agenda.

Catatonia: A narrative review of its historical development, diagnosis, pathophysiology, and therapeutics.

Catatonia was initially a clinical presentation of certain types of schizophrenia, but basic and epidemiological evidence has demonstrated its association with multiple somatic and psychiatric conditions. We describe and discuss current clinical, etiological, pathophysiological, and therapeutic concepts regarding catatonia. We conducted a broad narrative review of articles published in MEDLINE/PubMed. The diagnosis is clinical and can be supported by additional tests, but there are psychometric instruments with different clinical focus. The most validated subtypes are inhibited and excited catatonia. It is mostly associated with somatic, neurological, affective, psychotic, and autistic spectrum disorders. Genetic factors related to oligodendrocytes have been studied in its pathophysiology. Some findings point to an imbalance in neurotransmission and density of GABA and dopamine receptors, consistent with their function in motor pathways and therapeutic response with benzodiazepines. Likewise, glutamatergic activity has been analyzed from the pathophysiological model of autoimmune encephalitis. The cortico-cortical and cortico-subcortical pathways would have a central role, including structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, involved in decision-making, emotion regulation, storage, planning, and motor processing. The main therapeutic lines are benzodiazepines and electroconvulsive therapy. Other interventions studied are zolpidem, antipsychotics, mood stabilizers, glutamatergic modulators, and transcranial magnetic stimulation. New neurobiological findings challenge nosological and therapeutic precepts, renewing the cycle in the conceptualization of catatonia. We highlight the affective component of the psychomotor syndrome and the role of interventions aimed at its modulation.

The separation distress hypothesis of depression – an update and systematic review

ABSTRACT The separation distress hypothesis of depression, formulated in 2009, offered an affective neuroscience perspective on our most common and costly mental health condition, as an alternative to molecular reductionism in psychiatry. Our hypothesis constituted a neurobiological extension of classic work on depression as intrinsically related to attachment and loss, integrating psychological and neurobiological findings from clinical and preclinical models. We posited three ideas: 1) depression is an evolutionarily conserved vulnerability within the social-affective endowment of mammalian brains, involving interactions between separation distress and other conserved CNS systems; 2) this mechanism adaptively shuts down protracted separation distress, potentially lethal to infant mammals, and thus protective in a circumscribed form, explaining its conservation; 3) this process has no single biological ‘lever’ and is instantiated through complex recursion. Like other conserved processes, it overlaps with kindred processes also serving behavioral shutdown, particularly hibernation and sickness behavior. Epicenters for depression include a large array of systems regulating the CNS and its behavioral/affective states: the stress axis, immune systems, monoamine and cholinergic systems, GABA and glutamate systems, and large molecule pro-social neuropeptide systems, all dynamically linked. This review tracks multiple developments in the last 10 years including growing public health and healthcare awareness about the biological and not just psychological impact of our primary relationships, and its corollary, the neurobiologically destructive effects of trauma, abuse, neglect, and social isolation. Secure attachment is both a psychological and biological necessity, and its loss or traumatic disruption may constitute a fertile ground for depression in all its forms.

Phylogenic evolution of beat perception and synchronization: a comparative neuroscience perspective.

The study of music has long been of interest to researchers from various disciplines. Scholars have put forth numerous hypotheses regarding the evolution of music. With the rise of cross-species research on music cognition, researchers hope to gain a deeper understanding of the phylogenic evolution, behavioral manifestation, and physiological limitations of the biological ability behind music, known as musicality. This paper presents the progress of beat perception and synchronization (BPS) research in cross-species settings and offers varying views on the relevant hypothesis of BPS. The BPS ability observed in rats and other mammals as well as recent neurobiological findings presents a significant challenge to the vocal learning and rhythm synchronization hypothesis if taken literally. An integrative neural-circuit model of BPS is proposed to accommodate the findings. In future research, it is recommended that greater consideration be given to the social attributes of musicality and to the behavioral and physiological changes that occur across different species in response to music characteristics.

The Matter With Things: Our Brains, Our Delusions, and the Unmaking of the World

The Matter With Things: Our Brains, Our Delusions, and the Unmaking of the World

Chemogenetics identifies separate area 25 brain circuits involved in anhedonia and anxiety in marmosets.

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies.

Downregulation of cyclic adenosine monophosphate levels in leukocytes of hibernating captive black bears is similar to reported cyclic adenosine monophosphate findings in major depressive disorder.

Cyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation. To compare cAMP levels between human MDD and mammalian hibernation and to investigate whether cAMP downregulation is another state-dependent neurobiological finding, we measured cAMP concentrations in lysed leukocytes, plasma, and serum in serial blood specimens from nine female captive black bears (Ursus americanus; CBBs), and cortisol levels in serum from 10 CBBs. Cortisol levels were significantly higher during hibernation in CBBs, confirming previous findings in hibernating black bears and similar to findings in humans with MDD. cAMP levels were significantly lower during hibernation versus active states (pre-hibernation and exit from hibernation) and were similar to the cAMP downregulation reported in MDD patients versus euthymic patients or controls. cAMP level changes during the different states (hibernation, pre-hibernation, active) confirm their state-dependent status. These findings are similar to the neurobiological findings associated with the hypometabolism (metabolic depression) observed during mammalian hibernation and reported during MDD. A sudden increase in cAMP levels was observed before entrance into pre-hibernation and during exit from hibernation. Further investigation is suggested into the possible role of elevated cAMP levels in initiation of the chain reaction of changes in gene expression, proteins, and enzymes leading to the suppression of mitochondrial metabolism and to low ATP turnover. This process leads to hypometabolism, the old adaptive mechanism that is used by organisms for energy preservation and is associated with both mammalian hibernation and human MDD.

ADHD classification combining biomarker detection with attention auto-encoding neural network

Attention Deficit Hyperactivity Disorder (ADHD) is one of most prevalent neurodevelopmental disorders in children. In decades, various neurobiological diagnosis methods have been well developed, yielding ADHD classification accuracy significantly improved. To our knowledge, deep-learning-based approaches attract more interest nowadays, since they effectively learn the potential features indicating ADHD disease. However, these learned features cannot directly project to certain biomarkers that have neurobiological meanings, which greatly hinders the neurobiological findings on ADHD. To ameliorate this problem, we proposed an attention auto-encoding network (Att-AENet) under an existing binary hypothesis testing (BHT) framework. By using brain functional connectivities (FCs) as input materials, an attention mechanism was employed to calculate the weights of FCs and measure the FC significance on ADHD. Therefore, the FC biomarkers of ADHD were conveniently identified from these weights. In detail, we built two attention subnetworks with dense and two-dimension convolution structures, respectively, and then evaluated the effect of these subnetworks from the viewpoint of ADHD classification. Sequentially, we took the biomarker detection analysis on the proposed dense-based attention subnetwork for its higher classification accuracy. On the test of ADHD-200 database, it shows the Att-AENet achieves a remarkable classification result with the average accuracy of 98.9%, especially 99.9% on some large-size datasets. More importantly, the FC biomarkers, corresponding to the discriminative weights learned by our attention subnetwork, are in accord with existing reported results. It demonstrates the reliability of these biomarkers. As a result, the proposed Att-AENet well fulfills the task of ADHD biomarker detection.

Late-life depression and frailty-Epidemiological, clinical and neurobiological associations

Depression is the most common mental disorder in older adults and is influenced by age-related processes. Frailty is awell-established clinical expression of ageing that implies astate of increased vulnerability to stressor events as well as increased risks of disability, hospitalization and death. Neurobiological findings will disentangle the comorbidity of frailty and depression and may inform future management of depression in old age. This narrative review provides an overview of the comorbidity of late-life depression and frailty, with afocus on neuroscientific findings that are organized within the research domain criteria (RDoC) framework. More than one third of old people with depression are affected by frailty, which results in more chronic depression and in poorer efficacy and tolerability of antidepressant medication. Depression and frailty share motivational and psychomotor characteristics, particularly apathy, decreased physical activity and fatigue. In patients with frailty, altered activity of the supplementary motor cortex is associated with motor performance deficits. Patients with late-life depression and apathy are characterized by abnormal structure and altered functional connectivity of the reward network and the salience network, along with altered functional connectivity of these networks with premotor brain areas. Identifying frailty in older adults with depression is relevant for prognostic assessment and treatment. Abetter understanding of the neuronal mechanisms of comorbidity will provide potential targets for future personalized therapeutic interventions.

The relationship between the clinical characteristics of patients with alcohol use disorder and drinking motives

Changes in the motivational structure are considered one of the central characteristics of Alcohol Use Disorder (AUD). The latest motivational models of AUD were developed based on recent neurobiological research findings. According to these models, three main drinking motives can be identified — drinking as a reward, as a relief, and as a habit. The goal of the study was to explore the main differences in the psychological and clinical characteristics of patients with AUD depending on the predominant drinking motive. For this study, 76 individuals (50 men (65.79 %), average age 42.25 ± 9.36 y. o. (М ± SD)) undergoing in-patient treatment for the symptoms of AUD were recruited. The following methods were used: clinical interview, UCLA Reward, Relief, Habit Drinking Scale, Penn Alcohol Craving Scale, Obsessive Compulsive Drinking Scale, Hospital Anxiety and Depression Scale, Snaith-Hamilton Pleasure Scale, Behavioral Activation Scale/Behavioral Inhibition Scale, and Cognitive Emotion Regulation Questionnaire. The participants were divided into three groups depending on their predominant drinking motive. The participants with the predominant “drinking as a habit” motivation reported using strategies of “refocusing on planning” and “positive reappraisal” significantly less often. At the same time, the intensity of “drinking as a habit” motive positively correlated with the severity of anxiety and depressive symptoms, and negatively — with the strength of the behavioral inhibition system. The participants with the “drinking as a reward” motivation reported having greater reward responsiveness as compared to the combined group of participants with the relief and habit drinking motives. The intensity of “drinking as a relief” motivation positively correlated with the severity of depressive symptoms. It was also noted that the participants, who did not identify the predominant drinking motive, reported having decreased levels of emotional and physical functioning and less frequent use of the certain adaptive emotional regulation strategies. In contrast with the previous studies, the relationship between the prevailing drinking motives and characteristics of drinking or the severity of AUD was not identified.