Kinematic adaptations from self-selected to fast speed walking in patients with adult spinal deformity.

PURPOSE: To investigate kinematic adaptations from self-selected to fast speed walking in ASD patients. METHODS: 115 primary ASD and 66 controls underwent biplanar radiographic X-rays and 3D gait analysis to calculate trunk, segmental spine and lower limb kinematics during self-selected and fast speed walking. Kinematic adaptation was calculated as the difference (Δ) between fast and self-selected speed walking. ASD with 7 or more limited kinematic adaptation parameters were classified as ASD-limited-KA, while those with less than 7 limited kinematic adaptation parameters were classified as ASD-mild-KA. RESULTS: 25 patients were classified as ASD-limited-KA and 90 as ASD-mild-KA. ASD-limited-KA patients walked with a lesser increase of pelvic rotation (Δ = 1.7 vs 5.5°), sagittal hip movement (Δ = 3.1 vs 7.4°) and shoulder-pelvis axial rotation (Δ = 3.4 vs 6.4°) compared to controls (all p < 0.05). ASD-limited-KA had an increased SVA (60.6 vs - 5.7 mm), PT (23.7 vs 11.9°), PI-LL (9.7 vs - 11.7°), knee flexion (9.2 vs - 0.4°) and a decreased LL (44.0 vs 61.4°) compared to controls (all p < 0.05). Kinematic and radiographic alterations were less pronounced in ASD-mild-KA. The limited increase of walking speed was correlated to the deteriorated physical component summary score of SF-36 (r = 0.37). DISCUSSION: Kinematic limitations during adaptation from self-selected to fast speed walking highlight an alteration of a daily life activity in ASD patients. ASD with limited kinematic adaptations showed more severe sagittal malalignment with an increased SVA, PT, PI-LL, and knee flexion, a decreased LL and the most deteriorated quality of life. This highlights the importance of 3D movement analysis in the evaluation of ASD.

Neurobiology of Behavior-Influences of Neuropsychiatric Disorders on Neurobiology and Behavior.

The field of neuroscience continues to unravel the mysteries of the human brain and its association with neuropsychiatric disorders [...].

Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders.

The ketogenic diet, known as a low-carbohydrate, high-protein, and high-fat diet, drastically restrains the major source of energy for the body, forcing it to burn all excess fat through a process called ketosis-the breaking down of fat into ketone bodies. First suggested as a medical treatment for children suffering from epilepsy, this diet has gained increased popularity as a rapid weight loss strategy. Over the past few years, there have been numerous studies suggesting that the ketogenic diet may provide therapeutic effects for several psychiatric conditions such as mood- and anxiety-related disorders. However, despite significant progress in research, the mechanisms underlying its therapeutic effects remain largely unexplored and are yet to be fully elucidated. This chapter provides an in-depth overview of preclinical and clinical evidence supporting the use of a ketogenic diet in the management of mood and anxiety disorders and discusses its relationship with inflammatory processes and potential mechanisms of actions for its therapeutic effects.

Neurobiology of Aggression-Review of Recent Findings and Relationship with Alcohol and Trauma.

Aggression can be conceptualized as any behavior, physical or verbal, that involves attacking another person or animal with the intent of causing harm, pain or injury. Because of its high prevalence worldwide, aggression has remained a central clinical and public safety issue. Aggression can be caused by several risk factors, including biological and psychological, such as genetics and mental health disorders, and socioeconomic such as education, employment, financial status, and neighborhood. Research over the past few decades has also proposed a link between alcohol consumption and aggressive behaviors. Alcohol consumption can escalate aggressive behavior in humans, often leading to domestic violence or serious crimes. Converging lines of evidence have also shown that trauma and posttraumatic stress disorder (PTSD) could have a tremendous impact on behavior associated with both alcohol use problems and violence. However, although the link between trauma, alcohol, and aggression is well documented, the underlying neurobiological mechanisms and their impact on behavior have not been properly discussed. This article provides an overview of recent advances in understanding the translational neurobiological basis of aggression and its intricate links to alcoholism and trauma, focusing on behavior. It does so by shedding light from several perspectives, including in vivo imaging, genes, receptors, and neurotransmitters and their influence on human and animal behavior.

Exercise and Dietary Factors Mediate Neural Plasticity Through Modulation of BDNF Signaling.

The term "neural plasticity" was first used to describe non-pathological changes in neuronal structure. Today, it is generally accepted that the brain is a dynamic system whose morphology and function is influenced by a variety of factors including stress, diet, and exercise. Neural plasticity involves learning and memory, the synthesis of new neurons, the repair of damaged connections, and several other compensatory mechanisms. It is altered in neurodegenerative disorders and following damage to the central or peripheral nervous system. Understanding the mechanisms that regulate neural plasticity in both healthy and diseased states is of significant importance to promote cognition and develop rehabilitation techniques for functional recovery after injury. In this minireview, we will discuss the mechanisms by which environmental factors promote neural plasticity with a focus on exercise- and diet-induced factors. We will highlight the known circulatory factors that are released in response to exercise and discuss how all factors activate pathways that converge in part on the activation of BDNF signaling. We propose to harness the therapeutic potential of exercise by using BDNF as a biomarker to identify novel endogenous factors that promote neural plasticity. We also discuss the importance of combining exercise factors with dietary factors to develop a lifestyle pill for patients afflicted by CNS disorders.

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity.

PURPOSE: To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations. METHODS: One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°). Kinematics were compared between groups. RESULTS: ASD-Sag had a decreased pelvic mobility compared to controls with a decreased ROM of hips (38 vs. 45°) and knees (51 vs. 61°). Furthermore, ASD-Sag exhibited a decreased walking speed (0.8 vs. 1.2 m/s) and GDI (80 vs. 95, all p < 0.05) making them more prone to falls. ASD-HyperTK showed similar patterns but in a less pronounced way. ASD-Front had normal walking patterns. GDI, knee flex/extension and walking speed were significantly associated with SVA and PT (r = 0.30-0.65). CONCLUSION: Sagittal spinal malalignment seems to be the driver of gait alterations in ASD. Patients with higher GT, SVA, PT or PI-LL tended to walk slower, with shorter steps in order to maintain stability with a limited flexibility in the pelvis, hips and knees. These changes were found to a lesser extent in ASD with only hyperkyphosis but not in those with only frontal deformity. 3D gait analysis is an objective tool to evaluate functionality in ASD patients depending on their type of spinal deformity. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Depression following traumatic brain injury: a comprehensive overview.

Traumatic brain injury (TBI) represents a major health concern affecting the neuropsychological health; TBI is accompanied by drastic long-term adverse complications that can influence many aspects of the life of affected individuals. A substantial number of studies have shown that mood disorders, particularly depression, are the most frequent complications encountered in individuals with TBI. Post-traumatic depression (P-TD) is present in approximately 30% of individuals with TBI, with the majority of individuals experiencing symptoms of depression during the first year following head injury. To date, the mechanisms of P-TD are far from being fully understood, and effective treatments that completely halt this condition are still lacking. The aim of this review is to outline the current state of knowledge on the prevalence and risk factors of P-TD, to discuss the accompanying brain changes at the anatomical, molecular and functional levels, and to discuss current approaches used for the treatment of P-TD.

Optogenetics: A revolutionary approach for the study of depression.

Depression is a severe and chronic mental disorder that affects millions of individuals worldwide. Symptoms include depressed mood, loss of interest, reduced motivation and suicidal thoughts. Even though findings from genetic, molecular and imaging studies have helped provide some clues regarding the mechanisms underlying depression-like behaviors, there are still many unanswered questions that need to be addressed. Optogenetics, a technique developed in the early 2000s, has proved effective in the study and treatment of depression and depression-like behaviors and has revolutionized already known experimental techniques. This technique employs light and genetic tools to either inhibit or excite specific neurons or pathways within the brain. In this review paper, an up-to-date understanding of the use of optogenetics in the study of depression-like behaviors is provided, along with suggestions for future research directions.

Alteration of the Sitting and Standing Movement in Adult Spinal Deformity.

Adults with spinal deformity (ASD) are known to have spinal malalignment affecting their quality of life and daily life activities. While walking kinematics were shown to be altered in ASD, other functional activities are yet to be evaluated such as sitting and standing, which are essential for patients' autonomy and quality of life perception. In this cross-sectional study, 93 ASD subjects (50 ± 20 years; 71 F) age and sex matched to 31 controls (45 ± 15 years; 18 F) underwent biplanar radiographic imaging with subsequent calculation of standing radiographic spinopelvic parameters. All subjects filled HRQOL questionnaires such as SF36 and ODI. ASD were further divided into 34 ASD-sag (with PT > 25° and/or SVA >5 cm and/or PI-LL >10°), 32 ASD-hyperTK (with only TK >60°), and 27 ASD-front (with only frontal malalignment: Cobb >20°). All subjects underwent 3D motion analysis during the sit-to-stand and stand-to-sit movements. The range of motion (ROM) and mean values of pelvis, lower limbs, thorax, head, and spinal segments were calculated on the kinematic waveforms. Kinematics were compared between groups and correlations to radiographic and HRQOL scores were computed. During sit-to-stand and stand-to-sit movements, ASD-sag had decreased pelvic anteversion (12.2 vs 15.2°), hip flexion (53.0 vs 62.2°), sagittal mobility in knees (87.1 vs 93.9°), and lumbar mobility (L1L3-L3L5: -9.1 vs -6.8°, all p < 0.05) compared with controls. ASD-hyperTK showed increased dynamic lordosis (L1L3-L3L5: -9.1 vs -6.8°), segmental thoracic kyphosis (T2T10-T10L1: 32.0 vs 17.2°, C7T2-T2T10: 30.4 vs 17.7°), and thoracolumbar extension (T10L1-L1L3: -12.4 vs -5.5°, all p < 0.05) compared with controls. They also had increased mobility at the thoracolumbar and upper-thoracic spine. Both ASD-sag and ASD-hyperTK maintained a flexed trunk, an extended head along with an increased trunk and head sagittal ROM. Kinematic alterations were correlated to radiographic parameters and HRQOL scores. Even after controlling for demographic factors, dynamic trunk flexion was determined by TK and PI-LL mismatch (adj. R 2 = 0.44). Lumbar sagittal ROM was determined by PI-LL mismatch (adj. R 2 = 0.13). In conclusion, the type of spinal deformity in ASD seems to determine the strategy used for sitting and standing. Future studies should evaluate whether surgical correction of the deformity could restore sitting and standing kinematics and ultimately improve quality of life.

Peripheral Anti-nociceptive and Anti-inflammatory Effect of Oleanolic Acid in a Rat Model of Osteoarthritis.

BACKGROUND: Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. The anti-inflammatory effect it exerts when taken orally is the most important; however, the underpinning mechanisms of such effects have not yet been fully explored. METHODS: In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that can lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment group, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation. RESULTS: Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behavior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fibers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord. CONCLUSION: Overall, our findings suggest that OA can be used as a preventive and therapeutic approach for the management of osteoarthritis.

Electromagnetic Field in Alzheimer's Disease: A Literature Review of Recent Preclinical and Clinical Studies.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloid-beta (Aß) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aß expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis.

Background Despite the wide use of gadolinium-based contrast agents (GBCAs) for enhanced MRI, their neurochemical and behavioral consequences, if any, remain poorly understood. Purpose To investigate the effect of repeated exposure to a linear or macrocyclic GBCA on gadolinium retention in the central and peripheral nervous system of rats and to assess the functional implications of such retention on hippocampal neurogenesis and sensory and cognitive processing. Materials and Methods Seventy male Sprague-Dawley rats (4 weeks old) received intraperitoneal injections of gadoterate meglumine (0.6 or 2.5 mmol per kilogram of body weight), gadodiamide (0.6 or 2.5 mmol/kg), or saline daily for 20 days (February 2018-March 2019). The 5-bromo-2'-deoxyuridine injections were administered every 3 days to determine the number of proliferating cells and the number of newly maturing neurons in the hippocampus. Sensory and cognitive behavioral tests were performed to assess the effect of GBCAs on pain sensitivity and spatial working memory function, respectively. Finally, inductively coupled plasma mass spectrometry analysis was used to quantify gadolinium retention in the brain, spinal cord, and peripheral nerves 24 hours after the last GBCA administration. One-way and mixed-design analyses of variance were used for statistical analysis. Results All GBCAs resulted in significant gadolinium retention in central and peripheral nervous tissues (1.8-333.2 nmol Gd/g tissue). Pain hypersensitivity to thermal and mechanical stimuli (P < .001) was observed after gadodiamide exposure in rats but not after gadoterate meglumine exposure. Rats injected with both GBCAs showed no changes in spatial working memory or in hippocampal cell proliferation and maturation. Conclusion Gadolinium was retained in the spinal cord and peripheral nerves in rats exposed to multiple administrations of linear and macrocyclic contrast agents. Gadodiamide (linear contrast agent) but not gadoterate meglumine (macrocyclic contrast agent) led to pain hypersensitivity, but neither affected spatial working memory performance, hippocampal cellular proliferation, or hippocampal neurogenesis. © RSNA, 2020 See also the editorial by Radbruch in this issue.

Modulation of brain stimulation reward and locomotor activity by ionotropic glutamate receptors of the tail of the ventral tegmental area.

The rostromedial tegmental nucleus also referred to as the tail of the ventral tegmental area (tVTA) contains a cluster of gamma-aminobutyric acid (GABA)ergic neurons that receive dense glutamatergic afferents from the lateral habenula (LHb), and project to dopamine (DA) neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). In light of previous evidence implicating glutamate transmission in the regulation of midbrain DA neuronal activity, we first assessed the impact of intra-tVTA microinjection of NBQX (0.8 nmol/side) and PPPA (0.825 nmol/side), respectively AMPA and NMDA receptor antagonists, on reward induced by intracranial self-stimulation (ICSS) and on locomotor activity. Since the tVTA contains a large concentration of mu opioid receptors, additional measures were obtained following microinjection of endomorphin-1 (EM-1, 1 nmol/side) to confirm tVTA placements. Then, using small interfering RNAs (siRNAs), we tested the effect of tVTA downregulation of the GluN1 subunit of the NMDA receptor on reward and locomotor activity. Results show that NBQX, PPPA and EM-1 all enhance reward and locomotor activity, effects that were of different magnitude in rostral and intermediate parts of the tVTA. On the other hand, a reduction in GluN1 subunits used a marked decrease in operant responding for ICSS, but failed to alter ICSS reward and the reward-enhancing effect of PPPA. Our results support a role for the tVTA as a main inhibitory component of DA-dependent behavioral measures, and suggest that tVTA NMDA receptors that modulate reward are most likely expressed on tVTA afferent terminals.

The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation.

The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.

Artificial Intelligence in Psychiatry.

Scientific findings over the past few decades have shaped our understanding of the underlying neurobiology associated with psychiatric illnesses. However, despite significant advances in research, there is widespread disappointment with the overall pace of progress in detecting and treating psychiatric disorders. Current approaches for the diagnosis of psychiatric disorders largely rely on physician-patient questionnaires that are most of the time inaccurate and ineffective in providing a reliable assessment of symptoms. These limitations can, however, be overcome by applying artificial intelligence (AI) to electronic medical database and health records. AI in psychiatry is a general term that implies the use of computerized techniques and algorithms for the diagnosis, prevention, and treatment of mental illnesses. Although the past few years have witnessed an increase in the use of AI in the medical practice, its role in psychiatry remains a complex and unanswered question. This chapter provides the current state of knowledge of AI's use in the diagnosis, prediction, and treatment of psychiatric disorders, and examines the challenges and limitations of this approach in the medical practise.

The dorsal diencephalic conduction system in reward processing: Spotlight on the anatomy and functions of the habenular complex.

The dorsal diencephalic conduction system (DDC) is a highly conserved pathway in vertebrates that provides a route for the neural information to flow from forebrain to midbrain structures. It contains the bilaterally paired habenular nuclei along with two fiber tracts, the stria medullaris and the fasciculus retroflexus. The habenula is the principal player in mediating the dialogue between forebrain and midbrain regions, and functional abnormalities in this structure have often been attributed to pathologies like mood disorders and substance use disorder. Following Matsumoto and Hikosaka seminal work on the lateral habenula as a source of negative reward signals, the last decade has witnessed a great surge of interest in the role of the DDC in reward-related processes. However, despite significant progress in research, much work remains to unfold the behavioral functions of this intriguing, yet complex, pathway. This review describes the current state of knowledge on the DDC with respect to its anatomy, connectivity, and functions in reward and aversion processes.

The tail of the ventral tegmental area in behavioral processes and in the effect of psychostimulants and drugs of abuse.

The tail of the ventral tegmental area (tVTA) is a recently identified structure that exerts a major inhibitory drive onto midbrain dopamine (DA) neurons. Also referred to as the rostromedial tegmental nucleus (RMTg), the tVTA is a cluster of gamma-aminobutyric acid (GABA)ergic neurons that starts within the posterior end of the VTA, where it is restricted dorsolateral to the caudal part of the interpeduncular nucleus, and extends into the pons. First identified in the rat, the tVTA has been described in many species, including mice and monkeys, as a region exhibiting similar anatomical and behavioral properties; it receives strong excitatory inputs from the lateral habenula (LHb), conveys negative reward-related information, and inhibits midbrain DA neuron activity. As an important inhibitory afferent to midbrain DA neurons, the tVTA is also implicated in drug abuse and in the complex interplay between reward and aversion processes. The overarching goal of this review is to provide the current state of knowledge on the anatomy and connectivity of the tVTA and to discuss recent evidence implicating this structure in reward-related processes and in the effect of psychostimulants and drugs of abuse.

Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy.

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid ß peptides and the formation of neurofibrillary tangles (NFTs) in the brain. Mounting evidence also implicates sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD. METHODS: This paper provides an overview of findings from both human and animal studies investigating the role of microglia and astrocytes in AD, and discusses potential avenues for therapeutic intervention. RESULTS: Glial-mediated inflammation is a 'double-edged sword', performing both detrimental and beneficial functions in AD. Despite tremendous effort in elucidating the molecular and cellular mechanisms underlying AD pathology, to date, there is no treatment that could prevent or cure this disease. Current treatments are only useful in slowing down the progression of AD and helping patients manage some of their behavioral and cognitive symptoms. CONCLUSION: A better understanding of the role of microglia and astrocytes in the regulation of AD pathology is needed as this could pave the way for new therapeutic strategies.