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Neuropsychopharmacology : Official... Jun 2024A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences...
A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences and has therefore been used to model an altered state of self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms for ketamine's effects on the bodily sense of self in the context of affective touch. Thirty healthy participants (15 females/15 males, age 19-39) received intravenous ketamine or placebo while performing self-touch and receiving touch by someone else during functional MRI - a previously established neural measure of tactile self-other-differentiation. Afterwards, tactile detection thresholds during self- and other-touch were assessed, as well as dissociative states, interoceptive awareness, and social touch attitudes. Compared to placebo, ketamine administration elicited dissociation and reduced neural activity associated with self-other-differentiation in the right temporoparietal cortex, which was most pronounced during other-touch. This reduction correlated with ketamine-induced reductions in interoceptive awareness. The temporoparietal cortex showed higher connectivity to somatosensory cortex and insula during other- compared to self-touch. This difference was augmented by ketamine, and correlated with dissociation strength for somatosensory cortex. These results demonstrate that disrupting the self-experience through ketamine administration affects neural activity associated with self-other-differentiation in a region involved in touch perception and social cognition, especially with regard to social touch by someone else. This process may be driven by ketamine-induced effects on top-down signaling, rendering the processing of predictable self-generated and unpredictable other-generated touch more similar. These findings provide further evidence for the intricate relationship of the bodily self with the tactile sense.
PubMed: 38918578
DOI: 10.1038/s41386-024-01906-2 -
Advances in Experimental Medicine and... 2024The measurement of time in the subsecond scale is critical for many sophisticated behaviors, yet its neural underpinnings are largely unknown. Recent neurophysiological... (Review)
Review
The measurement of time in the subsecond scale is critical for many sophisticated behaviors, yet its neural underpinnings are largely unknown. Recent neurophysiological experiments from our laboratory have shown that the neural activity in the medial premotor areas (MPC) of macaques can represent different aspects of temporal processing. During single interval categorization, we found that preSMA encodes a subjective category limit by reaching a peak of activity at a time that divides the set of test intervals into short and long. We also observed neural signals associated with the category selected by the subjects and the reward outcomes of the perceptual decision. On the other hand, we have studied the behavioral and neurophysiological basis of rhythmic timing. First, we have shown in different tapping tasks that macaques are able to produce predictively and accurately intervals that are cued by auditory or visual metronomes or when intervals are produced internally without sensory guidance. In addition, we found that the rhythmic timing mechanism in MPC is governed by different layers of neural clocks. Next, the instantaneous activity of single cells shows ramping activity that encodes the elapsed or remaining time for a tapping movement. In addition, we found MPC neurons that build neural sequences, forming dynamic patterns of activation that flexibly cover all the produced interval depending on the tapping tempo. This rhythmic neural clock resets on every interval providing an internal representation of pulse. Furthermore, the MPC cells show mixed selectivity, encoding not only elapsed time, but also the tempo of the tapping and the serial order element in the rhythmic sequence. Hence, MPC can map different task parameters, including the passage of time, using different cell populations. Finally, the projection of the time varying activity of MPC hundreds of cells into a low dimensional state space showed circular neural trajectories whose geometry represented the internal pulse and the tapping tempo. Overall, these findings support the notion that MPC is part of the core timing mechanism for both single interval and rhythmic timing, using neural clocks with different encoding principles, probably to flexibly encode and mix the timing representation with other task parameters.
Topics: Animals; Time Perception; Motor Cortex; Neurons; Psychomotor Performance
PubMed: 38918349
DOI: 10.1007/978-3-031-60183-5_7 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Jun 2024To summarize the morphological characteristics of sagittal beak-like deformity of head-neck fragment in femoral intertrochanteric fractures and to investigate the...
OBJECTIVE
To summarize the morphological characteristics of sagittal beak-like deformity of head-neck fragment in femoral intertrochanteric fractures and to investigate the technical skills in fracture reduction.
METHODS
A clinical data of 31 patients with femoral intertrochanteric fractures between May 2021 and April 2023 was retrospectively analyzed. The fractures had sagittal beak-like deformity of head-neck fragment in all patients. There were 13 males and 18 females, with an average age of 76.2 years (range, 68-83 years). The time from injury to operation was 36-76 hours (mean, 51.2 hours). Fractures were classified as type A1.2 in 10 cases, type A1.3 in 11 cases, type A2.2 in 6 cases, and type A2.3 in 4 cases according to the AO/Orthopaedic Trauma Association (AO/OTA)-2018 classification; and as type A1.3 in 10 cases, type A2.1 in 11 cases, type A2.2 in 6 cases, type A2.3 in 2 cases, and type A2.4 in 2 cases according to a novel comprehensive classification for femoral intertrochanteric fractures proposed by the "Elderly Hip Fracture" Research Group of the Reparative and Reconstructive Surgery Committee of the Chinese Rehabilitation Medical Association. Based on preoperative X-ray films, CT scan and three-dimensional reconstruction, the fractures were classified into two types: type 1 (14 cases), with uncomplicated fracture morphology, severe bone interlocking and (or) soft tissue incarceration; type 2 (17 cases), with severe fracture crushing, obvious dissociation between bone blocks, and severe soft tissue hinge destruction. After the failure of the closed reduction, all patients underwent fracture reduction assisted with instrument via anterior minimal incision and proximal femoral nail antirotation nails internal fixation. The operation time, intraoperative fluoroscopy, intraoperative visible blood loss, length of hospital stay, and incidence of complications were recorded. The fracture reduction quality and stability score were assessed at immediate after operation under fluoroscopy. The fracture healing was evaluated and healing time was recorded by X-ray films. The pain visual analogue scale (VAS) score was performed at 48 hours after operation and Parker-Palmer activity score at 3 months after operation for function evaluation.
RESULTS
The operation time was 39-58 minutes (mean, 46.3 minutes); fluoroscopy was performed 13-38 times (mean, 23.5 times) during operation; the intraoperative visible blood loss was 45-90 mL (mean, 65.3 mL). The fracture reduction quality and stability score were rated as good in 29 cases and acceptable in 2 cases. The pain VAS score was 2-6 (mean, 3.1) at 48 hours after operation. Eleven patients developed deep vein thrombosis of the lower limbs after operation. Patients were hospitalized for 6-10 days (mean, 7.3 days). All patients were followed up 5-8 months (mean, 6.5 months). All fractures healed at 3.5-8.0 months after operation (mean, 4.5 months). Parker-Palmer activity score at 3 months after operation was 9 in 28 cases and 6 in 3 cases.
CONCLUSION
The femoral intertrochanteric fracture with sagittal beak-like deformity of head-neck fragment is difficult to manually reduce. The pin combined with cannulated screw insertion to the neck cortex can hold the fragment and assist fracture reduction, which is a simple and effective technique.
Topics: Humans; Male; Female; Aged; Retrospective Studies; Aged, 80 and over; Fracture Fixation, Internal; Hip Fractures; Bone Screws; Fracture Fixation, Intramedullary
PubMed: 38918192
DOI: 10.7507/1002-1892.202402004 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024It is crucial to understand how anesthetics disrupt information transmission within the whole-brain network and its hub structure to gain insight into the network-level...
It is crucial to understand how anesthetics disrupt information transmission within the whole-brain network and its hub structure to gain insight into the network-level mechanisms underlying propofol-induced sedation. However, the influence of propofol on functional integration, segregation, and community structure of whole-brain networks were still unclear. We recruited 12 healthy subjects and acquired resting-state functional magnetic resonance imaging data during 5 different propofol-induced effect-site concentrations (CEs): 0, 0.5, 1.0, 1.5, and 2.0 μg/ml. We constructed whole-brain functional networks for each subject under different conditions and identify community structures. Subsequently, we calculated the global and local topological properties of whole-brain network to investigate the alterations in functional integration and segregation with deepening propofol sedation. Additionally, we assessed the alteration of key nodes within the whole-brain community structure at each effect-site concentrations level. We found that global participation was significantly increased at high effect-site concentrations, which was mediated by bilateral postcentral gyrus. Meanwhile, connector hubs appeared and were located in posterior cingulate cortex and precentral gyrus at high effect-site concentrations. Finally, nodal participation coefficients of connector hubs were closely associated to the level of sedation. These findings provide valuable insights into the relationship between increasing propofol dosage and enhanced functional interaction within the whole-brain networks.
Topics: Humans; Propofol; Male; Magnetic Resonance Imaging; Brain; Adult; Female; Hypnotics and Sedatives; Young Adult; Nerve Net; Anesthetics, Intravenous; Brain Mapping
PubMed: 38918077
DOI: 10.1093/cercor/bhae263 -
Progress in Neuro-psychopharmacology &... Jun 2024The impulsive choice is characterized by the preference for a small immediate reward over a bigger delayed one. The mechanisms underlying impulsive choices are linked to...
BACKGROUND
The impulsive choice is characterized by the preference for a small immediate reward over a bigger delayed one. The mechanisms underlying impulsive choices are linked to the activity in the Nucleus Accumbens (NAc), the orbitofrontal cortex (OFC), and the dorsolateral striatum (DLS). While the study of functional connectivity between brain areas has been key to understanding a variety of cognitive processes, it remains unclear whether functional connectivity differentiates impulsive-control decisions.
METHODS
To study the functional connectivity both between and within NAc, OFC, and DLS during a delay discounting task, we concurrently recorded local field potential in NAc, OFC, and DLS in rats. We then quantified the degree of phase-amplitude coupling (PAC), coherence, and Granger Causality between oscillatory activities in animals exhibiting either a high (HI) or low (LI) tendency for impulsive choices.
RESULTS
Our results showed a differential pattern of PAC during decision-making in OFC and NAc, but not in DLS. While theta-gamma PAC in OFC was associated with self-control decisions, a higher delta-gamma PAC in both OFC and NAc biased decisions toward impulsive choices in both HI and LI groups. Furthermore, during the reward event, Granger Causality analysis indicated a stronger NAc➔OFC gamma contribution in the HI group, while the LI group showed a higher OFC➔NAc gamma contribution.
CONCLUSIONS
The overactivity in NAc during reward in the HI group suggests that exacerbated contribution of NAcCore can lead to an overvaluation of reward that biases the behavior toward the impulsive choice.
PubMed: 38917880
DOI: 10.1016/j.pnpbp.2024.111064 -
Neuroscience Letters Jun 2024Prenatal stress increases the risk of neurodevelopmental disorders. NMDA-type glutamate receptor (NMDAR) activity plays an important pathophysiological role in the...
Prenatal stress increases the risk of neurodevelopmental disorders. NMDA-type glutamate receptor (NMDAR) activity plays an important pathophysiological role in the cortico-hippocampal circuit in these disorders. We tested the hypothesis that transcription of NMDAR subunits is modified in the frontal cortex (FCx) and hippocampus after exposure to prenatal restraint stress (PRS) in mice. At 10 weeks of age, male PRS offspring (n = 20) and non-stressed controls (NS, n = 20) were treated with haloperidol (1 mg/kg), clozapine (5 mg/kg) or saline twice daily for 5 days, before measuring social approach (SOC). Saline-treated and haloperidol-treated PRS mice had reduced SOC relative to NS (P < 0.01), but clozapine-treated PRS mice had similar SOC to NS mice. These effects of PRS were associated with increased transcription of NMDAR subunits encoded by GRIN2A and GRIN2B genes in the hippocampus but not FCx. GRIN transcription in FCx correlated positively with SOC, but hippocampal GRIN transcription had negative correlation with SOC. The ratio of GRIN2A/GRIN2B transcription is known to increase during development but was lower in PRS mice. These results suggest that GRIN2A and GRIN2B transcript levels are modified in the hippocampus by PRS, leading to life-long deficits in social behavior. These data have some overlap with the molecular pathophysiology of schizophrenia. Similar to PRS in mice, schizophrenia, has been associated with social withdrawal, with increased GRIN2 expression in the hippocampus, and reduced GRIN2A/GRIN2B expression ratios in the hippocampus. These findings suggest that PRS in mice may have construct validity as a preclinical model for antipsychotic drug development.
PubMed: 38917870
DOI: 10.1016/j.neulet.2024.137886 -
Physics in Medicine and Biology Jun 2024Although tDCS constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is...
Although tDCS constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the Efield over this region. Methods: Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages. E-field parameters such as magnitude, focality and orientation were calculated over three regions of interest (ROI): M1S1, SMA and preSMA. The role of anatomical characteristics as a source of inter-subject variability on E-field parameters was addressed using linear mixed-effect models. Results: P3F3 showed a more confined E-field distribution over M1S1 than C3Fp2; the latter elicited higher E-fields over supplementary motor areas. Both montages showed high inter-subject variability, especially for the normal component over C3Fp2. Skin, bone and CSF ROI volumes showed a negative association with E-field magnitude irrespective of montage. Grey matter volume and montage were the main sources of variability for focality. The curvature of gyri was found to be significantly associated with the variability of normal E-fields. Conclusions: Computational modelling proves useful in the assessment of E-field variability. Our simulations predict significant differences in E-field magnitude and focality for C3Fp2 and P3F3. However, anatomical characteristics were also found to be significant sources of E-field variability irrespective of electrode montage. .
PubMed: 38917834
DOI: 10.1088/1361-6560/ad5bb9 -
Journal of Chromatography. B,... Jun 2024Cortex Morin Radicis (CMR) is the dried root bark of Morus alba. L. It has a variety of effects such as antibacterial, anti-tumour, treatment of cardiovascular diseases...
Screening for promising multi-target bioactive components from Cortex Mori Radicis for the treatment of chronic cor pulmonale based on immobilized beta-adrenergic receptor and beta-adrenergic receptor chromatography.
Cortex Morin Radicis (CMR) is the dried root bark of Morus alba. L. It has a variety of effects such as antibacterial, anti-tumour, treatment of cardiovascular diseases or upper respiratory tract disease and so on. The pursuit for drugs selected from Cortex Mori Radicis having improved therapeutic efficacy necessitates increasing research on new assays for screening bioactive compounds with multi-targets. In this work, we applied immobilized β-AR and β-AR as the stationary phase in chromatographic column to screen bioactive compounds from Cortex Morin Radicis. Specific ligands of the two receptors (e.g. esmolol, metoprolol, atenolol, salbutamol, methoxyphenamine, tulobuterol and clorprenaline) were utilized to characterize the specificity and bioactivity of the columns. We used high performance affinity chromatography coupled with ESI-MS to screen targeted compounds of Cortex Morin Radicis. By zonal elution, we identified morin as a bioactive compound simultaneously binding to β-AR and β-AR. The compound exhibited the association constants of 3.10 × 10 and 2.60 × 10 M on the β-AR and β-AR column. On these sites, the dissociation rate constants were calculated to be 0.131 and 0.097 s. Molecular docking indicated that the binding of morin to the two receptors occurred on Asp200, Asp121, and Val122 of β-AR, Asn312, Thr110, Asp113, Tyr316, Gly90, Phe193, Ile309, and Trp109 of β-AR. Likewise, mulberroside C was identified as the bioactive compound binding to β-AR. The association constants and dissociation rate constants were calculated to be 1.08 × 10 M and 0.900 s. Molecular docking also indicated that mulberroside C could bind to β-AR receptor on its agonist site. Taking together, we demonstrated that the chromatographic strategy to identify bioactive natural products based on the β-AR and β-AR immobilization, has potential for screening bioactive compounds with multi-targets from complex matrices including traditional Chinese medicines.
PubMed: 38917653
DOI: 10.1016/j.jchromb.2024.124175 -
Schizophrenia Research Jun 2024Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates...
Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions.
PubMed: 38917555
DOI: 10.1016/j.schres.2024.06.019 -
Neurology(R) Neuroimmunology &... Sep 2024To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).
BACKGROUND AND OBJECTIVES
To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).
METHODS
CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs.
RESULTS
The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN ( < 0.001), CXCL13 ( = 0.001), and sTNFR1 ( = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN ( = 0.002) and IL19 ( = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], = 0.004) at the multivariate logistic regression model.
DISCUSSION
These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.
Topics: Humans; Osteopontin; Female; Male; Adult; Multiple Sclerosis, Relapsing-Remitting; Atrophy; Middle Aged; Cerebral Cortex; Magnetic Resonance Imaging; Biomarkers; Follow-Up Studies; Young Adult; Disease Progression
PubMed: 38917380
DOI: 10.1212/NXI.0000000000200265