Neurophysiological Changes Research Articles

Mechanisms Involved in the Link between Depression, Antidepressant Treatment, and Associated Weight Change.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

Neuroanatomical and Neurophysiological Changes and Complications of COVID-19: A Review of Literature (P11-13.006)

Neuroanatomical and Neurophysiological Changes and Complications of COVID-19: A Review of Literature (P11-13.006)

Ethnic–Racial Discrimination Exposure and Anxiety in Latina Girls: Amygdala Volume as an Indirect Neurobiological Pathway

Ethnic–racial discrimination, the differential treatment of individuals based on ethnic or racial group membership, predicts poor mental health outcomes such as anxiety. This is supported by long-standing theories on the social determinants of health and minority stress. However, these theories are rarely expanded to neurobiological sciences, limiting our understanding of mechanisms underlying observed associations. One potential neurobiological pathway between ethnic–racial discrimination exposure and anxiety is that ongoing exposure to racially charged encounters presents imminent threats that may modify stress-sensitive neurocircuitry, like the amygdala.The current study evaluated whether amygdala volume mediated associations between ethnic–racial discrimination exposure and anxiety symptoms in Latina girls, a group exhibiting heightened levels of untreated anxiety and disproportionately subjected to ethnic–racial discrimination.Thirty predominantly Mexican-identifying Latina girls residing in Southern California (MAge = 9.76, SD = 1.11 years) completed a T1-weighted structural MRI scan. Using the Perceptions of Racism in Children and Youth, participants self-reported the prevalence and severity of various discriminatory experiences. Participants also self-reported their anxiety symptoms via the Screen for Child Anxiety and Related Emotional Disorders. Controlling for total intracranial volume and annual household income, an indirect effect of ethnic–racial discrimination on anxiety symptoms via left amygdala volume was observed, β = −0.28, SE = 0.17, BC 95% CI [−0.690, −0.017]. The current findings suggest that the left amygdala is sensitive to racialized threats in childhood and that stress-related alterations may, in part, contribute to elevated anxiety in Latina girls. Our data elucidate a potential mechanism by which this form of sociocultural stress can adversely impact mental health, particularly in the transition from middle childhood to early adolescence, a period marked by a host of interlinked neurophysiological and social changes.

Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45min and 24h post-exercise. There were no differences in CSE or SICI between conditions (all P>0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P<0.005). PPTs were 12%-16% greater at 5min post-exercise in BFR40, BFR80 and HL compared to LL (P≤0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P>0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

Neuroimaging Markers for Differential Diagnosis Between Multifocal Motor Neuropathy and Multifocal Acquired Demyelinating Sensory and Motor Neuropathy

Introduction. Similar asymmetric patterns of motor disorders and neurophysiological changes complicate the differential diagnosis between multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) as two chronic dysimmune neuropathies with significantly different treatment approaches. The lack of specific paraclinical markers often result in misdiagnosis and selection of ineffective specific therapy. Identification of specific neuroimaging biomarkers to differentiate these conditions may improve diagnostic approaches.&#x0D; Objective: To identify neuroimaging markers for the differential diagnosis between MMN and MADSAM.&#x0D; Materials and methods. The study included 65 participants, particularly 30 individuals with MMN and 35 individuals with MADSAM followed up in the Center of Peripheral Nervous System Diseases, Research Center of Neurology, Moscow, Russia. We retrospectively analyzed their clinical and epidemiological characteristics as well as ultrasonography and magnetic resonance imaging (MRI) findings.&#x0D; Results. Ultrasonography was performed on the peripheral nerves of the upper extremities, the spinal nerves, and the brachial plexus. The results showed that participants with MADSAM had significantly greater cross-sectional areas (CSAs) and a higher incidence of intraneural ultrasonographic abnormalities compared to participants with MMN. CSA thresholds of the median nerves were identified using ROC analysis to differentiate between MMN and MADSAM. MRI scans of the brachial plexus revealed no abnormalities in 41.4% of the individuals with MMN and 27.3% of the individuals with MADSAM. Meanwhile, STIR hyperintense signal from the brachial plexus was most typical ( 70%) for the MADSAM group.&#x0D; Conclusions. This was the first detailed comparative analysis of neuroimaging findings in a large sample of patients with either MMN or MADSAM in Russia. Ultrasonographic markers for differential diagnosis have been determined. The advantages and limitations of ultrasonography and MRI of the brachial plexus and the spinal and peripheral nerves in diagnosing multifocal chronic dysimmune neuropathies have been demonstrated.

The Acute Effects of Ball Pressure on Anticipation Timing Following a Series of Purposeful Headers in Adult Football (Soccer) Players.

The purpose of this study is to investigate the acute effects of ball pressure on anticipation timing following a series of purposeful headers in adult football (soccer) players. There is evidence to suggest acute neurophysiological changes to the brain following purposeful heading; this may lead to altered anticipation timing as a result, potentially having future safety implications for players. A repeated measures crossover design was used. Seventeen participants aged between 20 and 30 years performed (i) 20 rotational headers with a lower-pressure match ball (58.6 kPa; 8.5 psi), (ii) 20 rotational headers with a higher-pressure match ball (103.4 kPa; 15 psi), or (iii) 20 non-headers (kicks) as a control each on separate days. The effect of ball pressure on anticipation timing accuracy, measured as absolute, constant, and variable errors, was assessed before and immediately after each intervention session using an anticipation timing task. Differences between group means were compared using repeated measures ANOVA and linear mixed effects models, with p-values of <0.05 considered statistically significant. No significant differences in anticipation timing accuracy across interventions were detected between control, occluded, and non-occluded trials. This finding differs from the previous literature regarding the measurable, acute effects of purposeful heading. The anticipation timing task may lack sensitivity for detecting the effects of repeated heading on brain function.

Efficacy of transcranial direct current stimulation for controlling of food craving in subjects with overweight or obesity

IntroductionThis study investigates the effects of transcranial direct current stimulation (tDCS) on food craving improvement and changes in brain function associated with craving in overweight and obese subjects.ObjectivesFood craving disregards the homeostatic mechanisms related to appetite and nullifies the rewarding effects of food, directly contributing to body weight and eventually leading to obesity. In this study, we aim to explore the effects of transcranial direct current stimulation (tDCS) on food craving improvement and changes in brain function associated with craving by conducting a total of 10 sessions of tDCS over a period of 2 weeks on overweight and obese subjects.MethodsA total of 86 patients who were overweight or obese (BMI ≥ 23 kg/m2) during the study period were included. The tDCS montage involved placing the anode over the left and the cathode over the right DLPFC. Weight, BMI, neuropsychological variables, and food craving-related variables were assessed. We measured absolute and relative EEG power in 19 channels and analyzed QEEG according to the following frequency ranges: delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–25 Hz), high beta (25–30 Hz), and gamma (30–80 Hz).ResultsAfter the application of tDCS, there was no significant reduction observed in weight and BMI. However, all measures related to food and eating showed a decrease in the intensity of cravings, and there was also a significant reduction in depression, anxiety, and perceived stress. In quantitative EEG analysis, an increase in theta waves was observed in the left frontal area (F7 and F3), an increase in alpha waves in the right parietal area (P4), and a decrease in beta waves in the frontal area (FP2) and occipital area (O1).ConclusionsThis study investigated the effects of tDCS on food craving in overweight and obese individuals, and it was found that there were improvements in psychological factors such as depression and anxiety. Additionally, using quantitative EEG, neurophysiological changes were observed, including an increase in theta waves and a decrease in beta waves.Disclosure of InterestNone Declared

Music and movement therapy improves quality of life and attention and associated electroencephalogram changes in patients with attention-deficit/hyperactivity disorder

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Treatments for ADHD include pharmacological and nonpharmacological therapy. However, pharmacological treatments have side effects such as poor appetite, sleep disturbance, and headache. Moreover, nonpharmacological treatments are not effective in ameliorating core symptoms and are time-consuming. Hence, developing an alternative and effective treatment without (or with fewer) side effects is crucial. Music therapy has long been used to treat numerous neurological diseases. Although listening to music is beneficial for mood and cognitive functions in patients with ADHD, research on the effects of music and movement therapy in children with ADHD is lacking. MethodsThe present study investigated the effects of an 8-week music and movement intervention in 13 children with ADHD. The Pediatric Quality of Life Inventory (PedsQL) was used to evaluate changes in participants' quality of life. Conners’ Kiddie Continuous Performance Test (K-CPT 2) and the Swanson, Nolan, and Pelham rating scale (SNAP-IV) were used to assess core symptoms. Electroencephalogram (EEG) recordings were analyzed to determine neurophysiological changes. ResultsThe results revealed that the participants' quality of life increased significantly after the 8-week intervention. Furthermore, the participants' hit reaction times in the block 1 and block 2 tests of K-CPT 2 decreased significantly after the intervention. EEG analysis demonstrated an increase in alpha power and Higuchi's fractal dimension and a decrease in delta power in certain EEG channels. ConclusionOur music and movement intervention is a potential alternative and effective tool for ADHD treatment and it can significantly improve patients’ quality of life and attention.

Effect of emotions on learning, memory, and disorders associated with the changes in expression levels: A narrative review.

Emotions, in general, have no scientific definition. Emotions can be denoted as the mental state because of the neurophysiological changes. Emotions are related to mood, personality, temperament, and consciousness. People exhibit different emotions in different situations causing changes in cognitive functions. One of the major cognitive functions is the ability to learn, to store the acquired information in the parts of the brain such as the hippocampus, amygdala, cortex, and cerebellum. Learning and memory are affected by different types of emotions. Emotional responses such as fear, depression, and stress have impaired effects on cognitive functions such as learning and memory, whereas optimistic and happy emotions have positive effects on long-term memory. Certain disorders have greater effects on the regions of the brain which are also associated with synaptic plasticity and Learning and Memory(LM). Neuroimaging techniques are involved in studying the changing regions of the brain due to varied emotions and treatment strategies based on the changes observed. There are many drugs, and in advancements, nanotechnology is also utilized in the treatment of such psychiatric disorders. To improve mental health and physical health, emotional balance is most important, and effective care should be provided for people with less emotional quotient and different types of disorders to inhibit cognitive dysfunctions. In this review, emotions and their varied effects on a cognitive function named learning and memory, disorders associated with the defects of learning due to emotional instability, the areas of the brain that are in control of emotions, diagnosis, and treatment strategies for psychiatric disorders dependent on emotions are discussed.

178 Brains on the Pitch: Investigating the Neurophysiological and Neurocognitive Effects of Repetitive Head Impacts in Adolescent Female Soccer Players During a Single Season

INTRODUCTION: Repetitive exposure to head impact in contact sports has raised concerns for potential long-term structural and functional neurologic effects. This relationship has been minimally explored in female athletes, with conflicting results arising from the limited reports on this topic. METHODS: Prospective cohort design with pre- and post-season assessments of neurocognitive function, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). Neurocognitive battery evaluated processing speed, memory, and executive function domains via computerized (ImPACT) and paper-and-pencil testing. TMS assessments included motor evoked potential onset; interhemispheric conduction times; intercortical and intracortical inhibition. DTI measures included fractional anisotropy (FA) for white matter tracts of interest, including: posterior limb of internal capsule; cortical spinal tract; corpus callosum - selected for common involvement in traumatic brain injury within other studies. RESULTS: One player was officially diagnosed with concussion and was included in analysis. Neurocognitive performance was intact relative to same aged peers, and there were no significant differences over the season based on mean reliable change indices (-0.79-0.93). Paired t-test analysis indicated that the TMS measures were not significantly different between the two timepoints. Furthermore, DTI FA values and TMS measures were not notably different pre- versus postseason. CONCLUSIONS: In this cohort of high school female athletes, we did not observe significant anatomic, physiologic, or functional effects from repetitive head impacts. Our findings contradict previous studies that showed significant neurophysiologic and neurocognitive changes, even in the absence of clinically-observed concussion. Further research is needed to fully understand the long-term consequences of repetitive head impacts in female athletes and to develop effective strategies for mitigating potential risks.

Clinical and diagnostic features of repeated mild traumatic brain injuries

Repeated mild traumatic brain injury (TBI) leads to new changes and exacerbates the existing ones caused by the primary trauma. The pathogenetic mechanisms of repeated TBI are the result of traumatic effects and their cumulation. They cause various morphological and functional changes in the brain. Objective — to improve the diagnosis of pathological changes in patients with repeated mild traumatic brain injury. Materials and methods. The study involved 199 patients with a history of repeated mild TBI. Men predominated among them — 158 (79.40 %). There were 80 (40.20 %) patients of youthful age (17—24 years), 78 (39.20 %) of young age (25—44 years), and 41 (20.60 %) of middle-aged (45—60 years). The number of repeated TBIs per patient ranged from two to five. All patients were examined in the remote period of TBI. The control group consisted of 30 people aged 18 to 50 years (mean age — (33.11 ± 3.09) years) who had no history of TBI. Cognitive impairment (CI) was assessed by neuropsychological examination using the Mini-Mental State Examination (MMSE), the Frontal Area Battery (FAB), and the clock drawing test. Methods of neuropsychological analysis, neuroimaging and neurophysiological methods were used. The data of clinical and neurological examinations and studies of cognitive functions were analyzed, structural changes of the brain and cerebrospinal tract were established on the basis of neuroimaging studies of the brain, and the peculiarities of cerebral hemodynamics in patients with mild repeated TBI were determined. The characteristics of neurophysiological changes in patients are given based on the study of the features of electroencephalographic changes and the study of cognitive evoked potentials of the brain. The immune status was evaluated in patients who had repeated mild TBI. Results. Repeated TBI in our study was observed in the form of mild concussions and brain contusions. Their number in one patient ranged from 1 to 5. Clinical manifestations of repeated mild TBI had peculiarities: cephalalgic, cerebral and cerebrospinal hypertensive syndrome, cognitive impairment, diffuse neurological symptoms, and pyramidal insufficiency prevailed in the clinical picture. Only in the main group were cases of a combination of three to eight neurological syndromes detected. A decrease in cognitive function was found in patients with repeated mild TBI compared to the control group according to neuropsychological testing. The analysis of cognitive evoked potentials revealed an increase in the latent period of the cognitive complex P300 in patients with repeated TBI compared with the control group, indicating a decrease in cognitive function. More frequent CP was detected in the main group. The use of modern neuroimaging methods revealed that patients with repeated TBI had increased width of the lateral ventricles on both sides, ventricle III, and the cavity of the septum compared with the control group, as well as a higher frequency of expansion of the septum and convexity of the subarachnoid spaces. Patients with repeated mild TBI are characterised by an increase in blood flow velocity in the extracranial parts of the carotid basin and a decrease in velocity in the vessels of the vertebrobasilar basin with a change in vascular resistance, in the segments of the intracranial part of the carotid basin — a decrease in blood flow velocity without a change in vascular resistance. Disorders of venous cerebral circulation (increased velocity in the internal jugular vein and Rosenthal veins) were recorded in the majority of the main group. According to the data of the CEG, in patients with repeated TBI against the background of diffuse changes in brain bioelectrical activity, focal changes in the left hemisphere of the brain are more common. Dominant arrhythmia was recorded in 97.78 % of patients in the main group. The amplitude of arrhythmia in patients with repeated TBI is lower compared to the control group, and the frequency of arrhythmic oscillations is higher. Conclusions. The use of clinical and diagnostic control allows to prevent the development of damage and obtain objective information about the state of the brain and its structures.

Serial electrodiagnostic testing: Utility and indications in adult neurological disorders.

Although existing guidelines address electrodiagnostic (EDX) testing in identifying neuromuscular conditions, guidance regarding the uses and limitations of serial (or repeat) EDX testing is limited. By assessing neurophysiological change longitudinally across time, serial electrodiagnosis can clarify a diagnosis and potentially provide valuable prognostic information. This monograph presents four broad indications for serial electrodiagnosis in adult peripheral neurological disorders. First, where clinical change has raised suspicion for a new or ongoing lesion, EDX reassessment for spatial spread of abnormality, involvement of previously normal muscle or nerve, and/or evolving pathophysiology can clarify a diagnosis. Second, where diagnosis of a progressive neuromuscular condition is uncertain, electrophysiological data from a second time point can confirm or refute suspicion. Third, to establish prognosis after a static nerve injury, a repeat study can assess the presence and extent of reinnervation. Finally, faced with a limited initial study (as when complicated by patient or environmental factors), a repeat EDX study can supplement missing or limited data to provide needed clarity. Repeat EDX studies carry certain limitations, however, such as with prognostication in the setting of remote or chronic lesions, sensory predominant fascicular injury, or mild axonal injury. Nevertheless, serial electrodiagnosis remains a valuable and underused tool in the diagnostic and prognostic evaluation of neuromuscular conditions.

Medical training to effectively support patients who use substances across practice settings: a scoping review of recommended competencies.

The responsibility for addressing the healthcare needs of PWUS is the responsibility of all physicians. Within the healthcare system, research consistently reveals inequitable experiences in healthcare with people who use substances (PWUS) reporting stigmatization, marginalization, and a lack of compassion. The aim of this scoping review was to find and describe competencies being taught, developed, and fostered within medical education and then to provide recommendations to improve care for this population of patients. Nineteen articles were included. Recommended knowledge competencies tend to promote understanding neurophysiological changes caused by substances, alongside knowing how to evaluate of 'risky' behaviours. Commonly recommended skills relate to the screening and management of substance use disorders. Recommended attitude competencies include identifying personal bias and establishing a patient-centered culture among practice teams. The disease model of addiction informed all papers, with no acknowledgement of potential beneficial or non-problematic experiences of substance use. To enhance knowledge-type competencies, medical education programs are advised to include addiction specialists as educators and prevent stigmatization through the hidden curriculum. To reduce experiences of stigmatization and marginalization among patients who use illicit substances and to improve quality of care, knowledge, skills, and attitudes competencies can be more effectively taught in medical education programs.Résumé.

Auditory aversive generalization learning prompts threat-specific changes in alpha-band activity.

Pairing a neutral stimulus with aversive outcomes prompts neurophysiological and autonomic changes in response to the conditioned stimulus (CS+), compared to cues that signal safety (CS-). One of these changes-selective amplitude reduction of parietal alpha-band oscillations-has been reliably linked to processing of visual CS+. It is, however, unclear to what extent auditory conditioned cues prompt similar changes, how these changes evolve as learning progresses, and how alpha reduction in the auditory domain generalizes to similar stimuli. To address these questions, 55 participants listened to three sine wave tones, with either the highest or lowest pitch (CS+) being associated with a noxious white noise burst. A threat-specific (CS+) reduction in occipital-parietal alpha-band power was observed similar to changes expected for visual stimuli. No evidence for aversive generalization to the tone most similar to the CS+ was observed in terms of alpha-band power changes, aversiveness ratings, or pupil dilation. By-trial analyses found that selective alpha-band changes continued to increase as aversive conditioning continued, beyond when participants reported awareness of the contingencies. The results support a theoretical model in which selective alpha power represents a cross-modal index of continuous aversive learning, accompanied by sustained sensory discrimination of conditioned threat from safety cues.

Reduced pre-attentive threat versus nonthreat signal discrimination in clinically healthy military personnel with recurrent combat exposure history: A preliminary event-related potential (ERP) study

Evidence now suggests that traumatic-stress impacts brain functions even in the absence of acute-onset post-traumatic stress disorder (PTSD) symptoms. These neurophysiological changes have also been suggested to account for increased risks of PTSD symptoms later developing in the aftermath of subsequent trauma. However, surprisingly few studies have explicitly examined brain function dynamics in high-risk populations, such as combat exposed military personnel without diagnosable PTSD. To extend available research, facial expression sensitive N170 event-related potential (ERP) amplitudes were examined in a clinically healthy sample of active service military personnel with recurrent combat exposure history. Consistent with several established theories of delayed-onset PTSD vulnerability, higher N170 amplitudes to backward-masked fearful and neutral facial expressions correlated with higher levels of past combat exposure. Significantly elevated amplitudes to nonthreatening neutral facial expressions also resulted in an absence of normal threat-versus-nonthreat signal processing specificity. While a modest sample size and cross-sectional design are key limitations here, ongoing prospective-longitudinal follow-ups may shed further light on the precise aetiology and prognostic utility of these preliminary findings in the near future.

Cognitive function and quantitative electroencephalogram analysis in subjects recovered from COVID-19 infection

Background & ObjectivesObjective assessment of post-COVID-19 cognitive dysfunction is highly warranted. This study aimed to evaluate the cognitive dysfunction of COVID-19 survivors with cognitive complaints, both clinically and neurophysiologically, using Quantitative Electroencephalogram (QEEG).MethodsThis case–control study was conducted on 50 recovered subjects from COVID-19 infection with cognitive complaints and 50 age, sex, and educational-matched healthy controls. Both groups were subjected to the following neurocognitive tests: Paired associate learning Test (PALT) and Paced Auditory Serial Addition Test (PASAT). The neurophysiological assessment was also done for both groups using QEEG.ResultsCOVID-19 survivors had significantly lower PALT scores than controls (P < 0.001). QEEG analysis found significantly higher levels of Theta / Beta ratio in both central and parietal areas in patients than in the controls (P < 0.001 for each). The interhemispheric coherence for the frontal, central, and parietal regions was also significantly lower in patients than in the control group regarding alpha and beta bands. There were statistically significant lower scores of PALT and PASAT among cases with severe COVID-19 infection (P = 0.011, 0.005, respectively) and those who needed oxygen support (P = 0.04, 0.01, respectively). On the other hand, a statistically significantly lower mean of frontal alpha inter-hemispheric coherence among patients with severe COVID-19 infection (P = 0.01) and those needing mechanical ventilation support (P = 0.04).ConclusionEpisodic memory deficit is evident in COVID-19 survivors with subjective cognitive complaints accompanied by lower inter-hemispheric coherence in frontal regions. These clinical and neurophysiological changes are associated with hypoxia and COVID-19 severity.

Circulating myeloid-derived MMP8 in stress susceptibility and depression

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.

Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations.

Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (HT2ARs), psychedelics induce enduring neurophysiological changes that parallel their therapeutic psychological and behavioral effects. Recent preclinical evidence suggests that the ability of psychedelics to exert their action is determined by their ability to permeate the neuronal membrane to target a pool of intracellular 5-HT2ARs. In this computational study, we employ classical molecular dynamics simulations and umbrella sampling techniques to investigate the permeation behavior of 12 selected tryptamines and to characterize the interactions that drive the process. We aim at elucidating the impact of N-alkylation, indole ring substitution and positional modifications, and protonation on their membrane permeability. Dimethylation of the primary amine group and the introduction of a methoxy group at position 5 exhibited an increase in permeability. Moreover, there is a significant influence of positional substitutions on the indole groups, and the protonation of the molecules substantially increases the energy barrier at the center of the bilayer, making the compounds highly impermeable. All the information extracted from the trends predicted by the simulations can be applied in future drug design projects to develop psychedelics with enhanced activity.

Physical activity level and physical fitness in subjects with chronic musculoskeletal pain: a cross-sectional study.

Low physical activity (PA) levels and low physical fitness (PF) have been reported in subjects with temporality-based chronic pain; however, it is unknown whether there are differences in subjects with nociplastic pain (NP) compared with subjects with non-nociplastic pain (NNP). The aim was to compare the levels of PA and PF in patients with chronic, nociplastic, and non-nociplastic musculoskeletal pain. This is an analytical, cross-sectional study. The sample comprised 30 patients receiving ambulatory physiotherapy treatment. Pain was classified as NP or NNP according to the International Association for the Study of Pain categorization system. The PA level was measured with the International Physical Activity Questionnaire-Short Form, and the PF level was measured with the hand grip strength test (HGS) to assess upper limb strength, the five Repetition Sit-to-Stand Test (5R-SRTS) to assess lower limb strength and power, and the YMCA 3 Min Step Test (YMCA-3MST) to estimate peak VO2. The results were compared with independent samples t-tests (with p < 0.05 considered significant). Cohen's d was calculated to determine the effect size. The NP group reported a significantly lower PA level than the NNP group, specifically the vigorous PA (p = 0.0009), moderate PA (p = 0.0002), and total PA (p = 0.005) dimensions. The NP group also showed significantly lower 5R-STS (p = 0.000) and HGS (p = 0.002) results compared with the NNP group. There were no significant differences in the YMCA-3MST between the NP and NNP groups (p = 0.635). It is possible that the neurophysiological and neuromuscular changes related to NP are associated with a reduced ability to perform vigorous PA. Clinicians should identify the presence of NP comorbidities in conjunction with the diagnosis when establishing the therapeutic goals.

Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats

Subanesthetic ketamine is increasingly used for the treatment of varied psychiatric conditions, both on- and off-label. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine’s mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of subanesthetic ketamine may be opioid dependent. Using pharmacological functional ultrasound imaging in rats, we found that blocking opioid receptors suppressed neurophysiologic changes evoked by ketamine, but not by a more selective NMDAR antagonist, in limbic regions implicated in the pathophysiology of depression and in reward processing. Importantly, this opioid-dependent response was strongly sex-dependent, as it was not evident in female subjects and was fully reversed by surgical removal of the male gonads. We observed similar sex-dependent effects of opioid blockade affecting ketamine-evoked postsynaptic density and behavioral sensitization, as well as in opioid blockade-induced changes in opioid receptor density. Together, these results underscore the potential for ketamine to induce its affective responses via opioid signaling, and indicate that this opioid dependence may be strongly influenced by subject sex. These factors should be more directly assessed in future clinical trials.