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7 Tesla magnetic resonance spectroscopy estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex.
GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by magnetic resonance spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high-field 7 Tesla MRS and transcranial magnetic stimulation coupled with high-density electroencephalography (TMS-hdEEG) from the motor cortex of 20 healthy participants (age 23.95 ± 6.4 years), while they were at rest. We first applied a neural mass model (NMM) to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of parametric empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS. Our work will help fulfil the promises of MRS-GABA, enhancing our understanding of human behaviour, brain physiology and pathophysiology. KEY POINTS: GABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke. Quantification of GABA in the human brain is typically obtained by magnetic resonance spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. By using a biophysical neural mass model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex.
Evaluating CBT for health anxiety and obsessive compulsive disorder adapted for online delivery in the context of COVID-19.
BACKGROUND: The COVID-19 pandemic has had a negative impact on the population's mental health, particularly for individuals with health anxiety (HA) and obsessive compulsive disorder (OCD). This is in conjunction with a significant change in accessibility of face-to-face psychological services which have had to rapidly adapt to the remote delivery of therapy. AIMS: Using a single-arm open trial design, the study aimed to evaluate the effectiveness of evidence-based CBT interventions for HA and OCD delivered via a blend of online therapist consultations interspersed with self-study reading materials. A secondary aim was to evaluate remote training workshops provided to therapists. METHOD: Therapists attended three half-day remote workshops after which consecutive participants with HA or OCD were assigned to therapists for treatment. Monthly expert supervision was provided. Patients completed routine outcome measures at each session and an idiosyncratic measure of pre-occupation with COVID-19 at pre- and post-treatment. RESULTS: Significant and comparable improvements were observed on measures of anxiety, depression and social adjustment from pre- to post-treatment in both the HA (n=14) and OCD (n=20) groups. Disorder-specific measures also showed significant improvements after treatment. The HA group showed greater levels of change on the COVID-19-specific questionnaire. The training workshops were well received by therapists, who valued the monthly supervision sessions. CONCLUSIONS: The study provides support for the effectiveness of the online delivery of CBT for HA and OCD supported by the inclusion of additional self-study booklets.
Radiofrequency thalamotomy for tremor outcomes correlate with dentorubrothalamic tract distance.
BACKGROUND: Thalamotomy was the main surgical treatment for medically refractory tremor before deep brain stimulation (DBS). While DBS is now preferred, it has drawbacks such as hardware failure, infection risk, frequent battery replacements, and multiple programming adjustments. Radiofrequency (RF) thalamotomy avoids these issues, can be performed under local anaesthesia, and suits patients in poor health. This study examines long-term outcomes of RF thalamotomy. METHODS: We reviewed 14 consecutive RF thalamotomies performed in Oxford from 2016 to 2021. Three patients died from unrelated causes, leaving eight for long-term assessment. We recorded Bain and Findlay (BF) tremor scores, Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Change (CGI-C), Patient's Global Impression of Change (PGI-C), and Efficacy Index (EI). The median follow-up was 39 months (range 12-126). Post-operative tractography was correlated with clinical outcomes. RESULTS: Six patients had essential tremor and eight had Parkinson's disease. Reasons for choosing thalamotomy over DBS included medical comorbidities, patient preference, age, and previous DBS failure. Ten patients (71%) reported significant tremor improvement, with relapse in two after six months. The mean BF tremor score decreased from 16.1 preoperatively to 8.5 postoperatively (p = 0.0043). Adverse events occurred in seven patients (50%), resolving completely in three, partially in three, and persisting in one. Sustained outcomes correlated with a wider distance of residual dentrorubrothalamic tract (DRTT) fibres from the lesion. CONCLUSIONS: RF thalamotomy is an effective long-term treatment for medication-refractory tremor and should be considered for select patients needing unilateral tremor control.
Global, regional, and national burden of epilepsy, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
BACKGROUND: Epilepsy is one of the most common serious neurological disorders and affects individuals of all ages across the globe. The aim of this study is to provide estimates of the epilepsy burden on the global, regional, and national levels for 1990-2021. METHODS: Using well established Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodology, we quantified the prevalence of active idiopathic (epilepsy of genetic or unknown origin) and secondary epilepsy (epilepsy due to an underlying abnormality of the brain structure or chemistry), as well as incidence, death, and disability-adjusted life-years (DALYs) by age, sex, and location (globally, 21 GBD regions and seven super-regions, World Bank country income levels, Socio-demographic Index [SDI], and 204 countries) and their trends from 1990 to 2021. Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy, largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). FINDINGS: In 2021, there were 51·7 million (95% UI 44·9-58·9) people with epilepsy (idiopathic and secondary combined) globally, with an age-standardised prevalence of 658 per 100 000 (569-748). Idiopathic epilepsy had an age-standardised prevalence of 307 per 100 000 (235-389) globally, with 24·2 million (18·5-30·7) prevalent cases, and secondary epilepsy had a global age-standardised prevalence of 350 per 100 000 (322-380). In 2021, 0·7% of the population had active epilepsy (0·3% attributed to idiopathic epilepsy and 0·4% to secondary epilepsy), and the age-standardised global prevalence of epilepsy from idiopathic and secondary epilepsy combined increased from 1990 to 2021 by 10·8% (1·1-21·3), mainly due to corresponding changes in secondary epilepsy. However, age-standardised death and DALY rates of idiopathic epilepsy reduced from 1990 to 2021 (decline of 15·8% [8·8-22·8] and 14·5% [4·2-24·2], respectively). There were three-fold to four-fold geographical differences in the burden of active idiopathic epilepsy, with the bulk of the burden residing in low-income to middle-income countries: 82·1% (81·1-83·4) of incident, 80·4% prevalent (79·7-82·7), 84·7% (83·7-85·1) fatal epilepsy, and 87·9% (86·2-89·2) epilepsy DALYs. INTERPRETATION: Although the global trends in idiopathic epilepsy deaths and DALY rates have improved in the preceding decades, in 2021 there were almost 52 million people with active epilepsy (24 million from idiopathic epilepsy and 28 million from secondary epilepsy), with the bulk of the burden (>80%) residing in low-income to middle-income countries. Better treatment and prevention of epilepsy are required, along with further research on risk factors of idiopathic epilepsy, good-quality long-term epilepsy surveillance studies, and exploration of the possible effect of stigma and cultural differences in seeking medical attention for epilepsy. FUNDING: Bill and Melinda Gates Foundation.
Non-canonical plant metabolism.
Metabolism is essential for plant growth and has become a major target for crop improvement by enhancing nutrient use efficiency. Metabolic engineering is also the basis for producing high-value plant products such as pharmaceuticals, biofuels and industrial biochemicals. An inherent problem for such engineering endeavours is the tendency to view metabolism as a series of distinct metabolic pathways-glycolysis, the tricarboxylic acid cycle, the Calvin-Benson cycle and so on. While these canonical pathways may represent a dominant or frequently occurring flux mode, systematic analyses of metabolism via computational modelling have emphasized the inherent flexibility of the metabolic network to carry flux distributions that are distinct from the canonical pathways. Recent experimental estimates of metabolic network fluxes using 13C-labelling approaches have revealed numerous instances in which non-canonical pathways occur under different conditions and in different tissues. In this Review, we bring these non-canonical pathways to the fore, summarizing the evidence for their occurrence and the context in which they operate. We also emphasize the importance of non-canonical pathways for metabolic engineering. We argue that the introduction of a high-flux pathway to a desired metabolic product will, by necessity, require non-canonical supporting fluxes in central metabolism to provide the necessary carbon skeletons, energy and reducing power. We illustrate this using the overproduction of isoprenoids and fatty acids as case studies.
Cortical evoked activity is modulated by the sleep state in a ferret model of tinnitus. A cross-case study.
Subjective tinnitus is a phantom auditory perception in the absence of an actual acoustic stimulus that affects 15% of the global population. In humans, tinnitus is often associated with disturbed sleep and, interestingly, there is an overlap between the brain areas involved in tinnitus and regulation of NREM sleep. We used eight adult ferrets exposed to mild noise trauma as an animal model of tinnitus. We assessed the phantom percept using two operant paradigms sensitive to tinnitus, silent gap detection and silence detection, before and, in a subset of animals, up to six months after the mild acoustic trauma. The integrity of the auditory brainstem was assessed over the same period using auditory brainstem response recordings. Following noise overexposure, ferrets developed lasting, frequency-specific impairments in operant behaviour and evoked brainstem activity. To explore the interaction between sleep and tinnitus, in addition to tracking the behavioural markers of noise-induced tinnitus and hearing impairment after noise overexposure, we evaluated sleep-wake architecture and spontaneous and auditory-evoked EEG activity across vigilance states. Behavioural performance and auditory-evoked activity measurements after noise overexposure suggested distinct degrees of tinnitus and hearing impairment between individuals. Animals that developed signs of tinnitus consistently developed sleep impairments, suggesting a link between the emergence of noise-induced hearing loss and/or tinnitus and sleep disruption. However, neural markers of tinnitus were reduced during sleep, suggesting that sleep may transiently mitigate tinnitus. These results reveal the importance of sleep-wake states in tinnitus and suggest that understanding the neurophysiological link between sleep and tinnitus may provide a new angle for research into the causes of phantom percepts and inform future treatments.
Sleep-wake-related changes in intracellular chloride regulate plasticity at glutamatergic cortical synapses.
Wakefulness and sleep affect the brain's ability to exhibit plastic changes.1,2 For instance, the potentiation of cortical excitatory synaptic connections is associated with the active period, when animals are mainly awake.3,4,5,6,7 It is unclear, however, how changes in neuronal physiology that are associated with sleep-wake history, affect the mechanisms responsible for synaptic plasticity. Recently, it has been shown that sleep-wake history alters transmembrane chloride (Cl-) gradients in cortical pyramidal neurons via Cl- cotransporter activity, which shifts the reversal potential for gamma-aminobutyric acid (GABA) type A receptors (EGABAA) when assessed in vivo and in vitro.8,9 Hyperpolarizing EGABAA values are associated with recent sleep, whereas depolarizing EGABAA values are associated with recent waking. Here, we demonstrate that sleep-wake-history-related changes in EGABAA affect membrane potential dynamics and glutamatergic long-term potentiation (LTP) elicited by spiking activity in pyramidal neurons of the mouse cortex. Reducing the depolarized shift in EGABAA during the active period reduces the potentiation of cortical excitatory synapses onto layer 5 (L5) pyramidal neurons. Depolarized EGABAA values facilitate LTP induction by promoting residual membrane depolarization during synaptically evoked spiking. Changes in LTP induction associated with sleep-wake history can be reversed by switching the EGABAA-dependent effects, either by using direct current injection to counteract the effects upon residual membrane potential depolarization or by modulating cotransporters that regulate EGABAA. We conclude that EGABAA dynamics provide a functional link between changes in a neuron's physiology that are associated with sleep-wake history and the mechanisms responsible for the induction of glutamatergic synaptic plasticity.
Stereoscopic Vision
The fundamental geometry underlying binocular stereoscopic depth perception was first appreciated in the mid-nineteenth century. Progress in understanding how brain mechanisms enable stereoscopic vision began about 50 years ago and has moved forward steadily since that time. The present view is that different areas of the extrastriate cortex have important and distinct roles in the elaboration of the stereoscopic visual percept.
sUPRa is a dual-color reporter for unbiased quantification of the unfolded protein response with cellular resolution.
The unfolded protein response (UPR) maintains proteostasis upon endoplasmic reticulum (ER) stress, and is initiated by a range of physiological and pathological processes. While there have been advances in developing fluorescent reporters for monitoring individual signaling pathways of the UPR, this approach may not capture a cell's overall UPR activity. Here we describe a novel sensor of UPR activity, sUPRa, which is designed to report the global UPR. sUPRa displays excellent response characteristics, outperforms reporters of individual UPR pathways in terms of sensitivity and kinetics, and responds to a range of different ER stress stimuli. Furthermore, sUPRa's dual promoter and fluorescent protein design ensures that both UPR-active and inactive cells are detected, and controls for reporter copy number. Using sUPRa, we reveal UPR activation in layer 2/3 pyramidal neurons of mouse cerebral cortex following a period of sleep deprivation. sUPRa affords new opportunities for quantifying physiological UPR activity with cellular resolution.
Local anaesthetic transperineal biopsy versus transrectal prostate biopsy in prostate cancer detection (TRANSLATE): a multicentre, randomised, controlled trial.
BACKGROUND: Prostate cancer diagnosis requires biopsy, traditionally performed under local anaesthetic with ultrasound guidance via a transrectal approach (TRUS). Local anaesthetic ultrasound-guided transperineal biopsy (LATP) is gaining popularity in this setting; however, there is uncertainty regarding prostate sampling, infection rates, tolerability, side-effects, and cost-effectiveness. TRANSLATE was a randomised clinical trial that aimed to compare detection of Gleason Grade Group (GGG) 2 or higher prostate cancer, side-effects, tolerability, and patient-reported outcomes, after LATP versus TRUS biopsy. METHODS: In this randomised clinical trial which was done at ten hospitals in the UK, patients aged 18 years or older were eligible if investigated for suspected prostate cancer based on elevated age-specific prostate-specific antigen or abnormal digital rectal examination, and if biopsy-naive having received pre-biopsy MRI on a 1·5 or higher Tesla scanner. Individuals were excluded if they had any previous prostate biopsy, extensive local disease easily detectable by any biopsy (prostate-specific antigen >50 ng/mL or entire gland replaced by tumour on MRI), symptoms of concurrent or recent urinary tract infection, history of immunocompromise, need for enhanced antibiotic prophylaxis, absent rectum, or inability to position in lithotomy. Participants were randomly assigned in a 1:1 ratio to receive LATP or TRUS biopsy, using web-based software with a randomisation sequence using a minimisation algorithm to ensure balanced allocation across biopsy groups for minimisation factors (recruitment site, and location of the MRI lesion). The primary outcome was detection of GGG 2 or higher prostate cancer, analysed in the modified intention-to-treat population (all randomly assigned to treatment who had a biopsy result available). Key secondary endpoints assessing post-biopsy adverse events were infection, bleeding, urinary and sexual function, tolerability, and patient-reported outcomes. This trial is registered with ClinicalTrials.gov (NCT05179694) and at ISRCTN (ISRCTN98159689), and is complete. FINDINGS: Between Dec 3, 2021, and Sept 26, 2023, 2078 (76%) of 2727 assessed individuals were eligible, and 1126 (41%) of 2727 agreed to participate. 1044 (93%) of the 1126 participants were White British. Participants were allocated to TRUS (n=564) or LATP (n=562) biopsy, and were followed up at time of biopsy, and at 7 days, 35 days, and 4 months post-biopsy. We found GGG 2 or higher prostate cancer in 329 (60%) of 547 participants with biopsy results randomly assigned to LATP compared with 294 (54%) of 540 participants with biopsy results randomly assigned to TRUS biopsy (odds ratio [OR] 1·32 [95% CI 1·03-1·70]; p=0·031). Infection requiring admission to hospital within 35 days post-biopsy occurred in 2 (<1%) of 562 participants in the LATP group compared with 9 (2%) of 564 in the TRUS group. No statistically significant difference was observed in the reporting of overall biopsy-related complications (LATP 454 [81%] of 562 vs TRUS 436 [77%] of 564, OR 1·23 [95% CI 0·93 to 1·65]), urinary retention requiring catheterisation (LATP 35 [6%] of 562 vs TRUS 27 [5%] of 564), urinary symptoms (median International Prostate Symptom Score: LATP 8 [IQR 4-14] vs TRUS 8 [4-13], OR 0·36 [95% CI -0·38 to 1·10]), nor sexual function (median International Index of Erectile Function score: LATP 5 [2-25] vs TRUS 8 [3-24], OR -0·60 [-1·79 to 0·58]) at 4 months after biopsy. Trial participants more commonly reported LATP biopsy to be immediately painful and embarrassing compared with TRUS (LATP 216 [38%] of 562 vs TRUS 153 [27%] of 564; OR 1·84 [95% CI 1·40 to 2·43]). Serious adverse events occurred in 14 (2%) of 562 participants in the LATP group and 25 (4%) of 564 in the TRUS group. INTERPRETATION: Among biopsy-naive individuals being investigated for possible prostate cancer, biopsy with LATP led to greater detection of GGG 2 or higher disease compared with TRUS. These findings will help to inform patients, clinicians, clinical guidelines, and policy makers regarding the important trade-offs between LATP and TRUS prostate biopsy. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment.
Non-equilibrium whole-brain dynamics arise from pairwise interactions
The human brain is a complex system of multiple neural elements that interact at different orders (pairwise, triplets, etc.), displaying non-equilibrium processes from the neuronal scale to the whole-brain scale. Here, we study how non-equilibrium dynamics of large-scale brain activity is driven by the interaction of its constituent elements at different orders. We hypothesize that the interactions generating non-equilibrium dynamics at the macroscopic brain scale are typically pairwise, with higher-order dependences playing a diminishing role. By expanding the entropy production into a sequence of orders of interactions, we find that pairwise interactions contribute dominantly. In light of this finding, we demonstrate that it is possible to characterize non-equilibrium brain dynamics using the interactions of pairs of macroscopic brain regions rather than complex interactions involving three or more regions. Furthermore, we propose that the entropy production of pairs of brain regions is a sensitive indicator for characterizing task-induced brain states.
LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement.
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.
Standardized pancreatic MRI-T1 measurement methods: comparison between manual measurement and a semi-automated pipeline with automatic quality control.
OBJECTIVES: Scanner-referenced T1 (srT1) is a method for measuring pancreas T1 relaxation time. The purpose of this multi-centre study is two-fold: (1) to evaluate the repeatability of manual ROI-based analysis of srT1, (2) to validate a semi-automated measurement method with an automatic quality control (QC) module to identify likely discrepancies between automated and manual measurements. METHODS: Pancreatic MRI scans from a scan-rescan cohort (46 subjects) were used to evaluate the repeatability of manual analysis. 708 scans from a longitudinal multi-centre study of 466 subjects were divided into training, internal validation (IV), and external validation (EV) cohorts. A semi-automated method for measuring srT1 using machine learning is proposed and compared against manual analysis on the validation cohorts with and without automated QC. RESULTS: Inter-operator agreement between manual ROI-based method and semi-automated method had low bias (3.8 ms or 0.5%) and limits of agreement [-36.6, 44.1] ms. There was good agreement between the two methods without automated QC (IV: 3.2 [-47.1, 53.5] ms, EV: -0.5 [-35.2, 34.2] ms). After QC, agreement on the IV set improved, was unchanged in the EV set, and the agreement in both was within inter-operator bounds (IV: -0.04 [-33.4, 33.3] ms, EV: -1.9 [-37.6, 33.7] ms). The semi-automated method improved scan-rescan agreement versus manual analysis (manual: 8.2 [-49.7, 66] ms, automated: 6.7 [-46.7, 60.1] ms). CONCLUSIONS: The semi-automated method for characterization of standardized pancreatic T1 using MRI has the potential to decrease analysis time while maintaining accuracy and improving scan-rescan agreement.
Traumatic Brain Injury and Alzheimer's Disease: A Shared Neurovascular Hypothesis.
Traumatic brain injury (TBI) is a modifiable risk factor for Alzheimer's disease (AD). TBI and AD share several histopathological hallmarks: namely, beta-amyloid aggregation, tau hyperphosphorylation, and plasma protein infiltration. The relative contributions of these proteinopathies and their interplay in the pathogenesis of both conditions remains unclear although important differences are emerging. This review synthesises emerging evidence for the critical role of the neurovascular unit in mediating protein accumulation and neurotoxicity in both TBI and AD. We propose a shared pathogenic cascade centred on a neurovascular unit, in which increased blood-brain barrier permeability induces a series of noxious mechanisms leading to neuronal loss, synaptic dysfunction and ultimately cognitive dysfunction in both conditions. We explore the application of this hypothesis to outstanding research questions and potential treatments for TBI and AD, as well as other neurodegenerative and neuroinflammatory conditions. Limitations of this hypothesis, including the challenges of establishing a causal relationship between neurovascular damage and proteinopathies, are also discussed.
The behavioural effects of the serotonin 1A receptor agonist buspirone on cognition and emotional processing in healthy volunteers.
RATIONALE: The 5-HT1A receptor is expressed widely across the brain and is implicated in the mechanism of action of several therapeutics for mood disorders. However, there is limited and contradictory evidence about the role of this receptor in emotional processing and cognition. OBJECTIVES: The current study tested the acute effects of a single dose of the 5-HT1A agonist buspirone (20 mg), on a range of emotional processing (Emotional Test Battery) and cognitive (Auditory Verbal Learning Task (AVLT) and N-back) tasks in healthy, male and female volunteers (N = 62). The study was a randomised, double-blind, placebo controlled, parallel group design. RESULTS: Buspirone reduced accuracy for detection of facial expressions of disgust and increased misclassification of negative facial emotions. It had no significant effects on categorisation or recall of emotionally-valanced words. Buspirone also reduced recall accuracy in the AVLT but had no significant effect in the N-back task. Participants receiving buspirone were more likely to experience nausea, light-headedness and sleepiness. CONCLUSIONS: Acute buspirone administration produced a mild impairment in verbal memory and a subtle negative bias in emotional processing in healthy volunteers. These effects are consistent with the mixed effects of buspirone on pre- and post-synaptic 5-HT1A receptors.
Comparison between EEG and MEG of static and dynamic resting-state networks.
The characterisation of resting-state networks (RSNs) using neuroimaging techniques has significantly contributed to our understanding of the organisation of brain activity. Prior work has demonstrated the electrophysiological basis of RSNs and their dynamic nature, revealing transient activations of brain networks with millisecond timescales. While previous research has confirmed the comparability of RSNs identified by electroencephalography (EEG) to those identified by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), most studies have utilised static analysis techniques, ignoring the dynamic nature of brain activity. Often, these studies use high-density EEG systems, which limit their applicability in clinical settings. Addressing these gaps, our research studies RSNs using medium-density EEG systems (61 sensors), comparing both static and dynamic brain network features to those obtained from a high-density MEG system (306 sensors). We assess the qualitative and quantitative comparability of EEG-derived RSNs to those from MEG, including their ability to capture age-related effects, and explore the reproducibility of dynamic RSNs within and across the modalities. Our findings suggest that both MEG and EEG offer comparable static and dynamic network descriptions, albeit with MEG offering some increased sensitivity and reproducibility. Such RSNs and their comparability across the two modalities remained consistent qualitatively but not quantitatively when the data were reconstructed without subject-specific structural MRI images.