Dietary trends and the decline in male reproductive health.

Over the twentieth century, male reproductive health has suffered a substantial decline, as evidenced by decreases in sperm counts and testosterone levels and increases in reproductive pathologies. At the same time, the prevalence of chronic diseases such as obesity, diabetes, and metabolic syndrome has risen dramatically. Metabolic and reproductive health are highly interconnected, suggesting that their respective trends are intertwined and, given the timeframe of such trends, environmental and not genetic factors are most likely to be the primary causes. Industrialization, which began in Europe in the mid-eighteenth century, has resulted in profound changes to our diet, lifestyle, and environment, many of which are causal factors in the rise in chronic diseases. Industrialization results in a nutrition transition from an agricultural unprocessed to a modern processed diet, incorporating increases in sugar, vegetable oils, ultra-processed foods, linoleic acid, trans-fats, and total energy. This dietary shift has incurred numerous adverse effects on metabolic and reproductive health, characterized by chronic inflammation, oxidative stress, and insulin resistance. Moreover, these effects appear to multiply across subsequent generations via epigenetic inheritance. Men's fertility is markedly affected by obesity and diabetes, with an increase in total energy via processed food intake arguably being the key factor driving the diabesity pandemic. In contrast, wholefoods rich in micronutrients and phytonutrients support male fertility and a healthy body weight. Therefore, men wanting to maximize their fertility should consider making positive dietary changes, such as replacing processed foods with unprocessed foods that support metabolic and reproductive health.

High-protein diets and testosterone.

A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L) [Whittaker and Harris (2022) Low-carbohydrate diets and men's cortisol and testosterone: systematic review and meta-analysis. Nutrition and Health. DOI: 10.1177/02601060221083079]. This finding has generated substantial discussion, however, it has often lacked clarity and context, with the term 'high-protein' being used unqualified. Firstly, diets < 3.4 g/kg/day are not associated with a consistent decrease in testosterone. Secondly, the average protein intake is ∼1.3 g/kg/day, conventional 'high-protein' diets are ∼1.8-3 g/kg/day and the vast majority of athletes are < 3.4 g/kg/day; meaning very few individuals will ever surpass 3.4 g/kg/day. To avoid such confusion in the future, the following definitions are proposed: very high (> 3.4 g/kg/day), high (1.9-3.4 g/kg/day), moderate (1.25-1.9 g/kg/day) and low (<1.25 g/kg/day). Using these, very high-protein diets (> 3.4 g/kg/day) appear to decrease testosterone, however high- and moderate-protein diets (1.25-3.4 g/kg/day) do not.

The Spatiotemporal Dynamics of Cerebral Autoregulation in Functional Magnetic Resonance Imaging.

The thigh-cuff release (TCR) maneuver is a physiological challenge that is widely used to assess dynamic cerebral autoregulation (dCA). It is often applied in conjunction with Transcranial Doppler ultrasound (TCD), which provides temporal information of the global flow response in the brain. This established method can only yield very limited insights into the regional variability of dCA, whereas functional MRI (fMRI) has the ability to reveal the spatial distribution of flow responses in the brain with high spatial resolution. The aim of this study was to use whole-brain blood-oxygenation-level-dependent (BOLD) fMRI to characterize the spatiotemporal dynamics of the flow response to the TCR challenge, and thus pave the way toward mapping dCA in the brain. We used a data driven approach to derive a novel basis set that was then used to provide a voxel-wise estimate of the TCR associated haemodynamic response function (HRF TCR ). We found that the HRF TCR evolves with a specific spatiotemporal pattern, with gray and white matter showing an asynchronous response, which likely reflects the anatomical structure of cerebral blood supply. Thus, we propose that TCR challenge fMRI is a promising method for mapping spatial variability in dCA, which will likely prove to be clinically advantageous.

Advancing a cultural change agenda in higher education: issues and values related to reimagining academic leadership.

Traditional models of academic leadership are based largely on managerial and transactional approaches. Such efforts frequently support status quo individual success rather than values-based leadership based on collective institutional or sustainability-centered pursuits. Evolved reward systems and leaderships modes that support collective and institution-level effort and innovations prioritizing community and sustainability require new leadership models. Innovative leadership models that transcend traditional gatekeeping are needed and four leadership modes to support innovation and collective efforts are discussed, including shared leadership that draws on distributed contributions of multiple individuals; creative or innovative leadership that requires risk-taking, experimentation, and experiential learning; qualitative leadership that is data-driven and includes evidence-based innovation; and, dynamic leadership based on demonstrated agility and ability to traverse different spaces using diverse modes of doing and thinking. Progressive leaders can move in and out of these modes in response to ecosystem needs, demands, and changes through the use of design thinking and initiatives to support innovation and sustainability in higher education. Success in evolved leadership approaches, including centering sustainability goals that impact institutions themselves and communities in which they exist, require aligning reformed leadership goals and practices with funding models and reward systems, as well as policies and institutional change strategies.

Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.

Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).

Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates.

INTRODUCTION: Alcohol dependence is one of the most common substance use disorders, and novel treatment options are urgently needed. Neurofeedback training (NFT) based on real-time functional magnetic resonance imaging (rtf-MRI) has emerged as an attractive candidate for add-on treatments in psychiatry, but its use in alcohol dependence has not been formally investigated in a clinical trial. We investigated the use of rtfMRI-based NFT to prevent relapse in alcohol dependence. METHODS: Fifty-two alcohol-dependent patients from the UK who had completed a detoxification program were randomly assigned to a treatment group (receiving rtfMRI NFT in addition to standard care) or the control group (receiving standard care only). At baseline, alcohol consumption was assessed as the primary outcome measure and a variety of psychological, behavioral, and neural parameters as secondary outcome measures to determine feasibility and secondary training effects. Participants in the treatment group underwent 6 NFT sessions over 4 months and were trained to downregulate their brain activation in the salience network in the presence of alcohol stimuli and to upregulate frontal activation in response to pictures related to positive goals. Four, 8, and 12 months after baseline assessment, both groups were followed up with a battery of clinical and psychometric tests. RESULTS: Primary outcome measures showed very low relapse rates for both groups. Analysis of neural secondary outcome measures indicated that the majority of patients modulated the salience system in the desired directions, by decreasing activity in response to alcohol stimuli and increasing activation in response to positive goals. The intervention had a good safety and acceptability profile. CONCLUSION: We demonstrated that rtfMRI-neurofeedback targeting hyperactivity of the salience network in response to alcohol cues is feasible in currently abstinent patients with alcohol dependence.

Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies.

BACKGROUND: Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in dietary patterns, and men's testosterone levels have declined in western countries. Cross-sectional studies show inconsistent associations between fat intake and testosterone in men. METHODS: Studies eligible for inclusion were intervention studies, with minimal confounding variables, comparing the effect of low-fat vs high-fat diets on men's sex hormones. 9 databases were searched from their inception to October 2020, yielding 6 eligible studies, with a total of 206 participants. Random effects meta-analyses were performed using Cochrane's Review Manager software. Cochrane's risk of bias tool was used for quality assessment. RESULTS: There were significant decreases in sex hormones on low-fat vs high-fat diets. Standardised mean differences with 95 % confidence intervals (CI) for outcomes were: total testosterone [-0.38 (95 % CI -0.75 to -0.01) P = 0.04]; free testosterone [-0.37 (95 % CI -0.63 to -0.11) P = 0.005]; urinary testosterone [-0.38 (CI 95 % -0.66 to -0.09) P = 0.009]; and dihydrotestosterone [-0.3 (CI 95 % -0.56 to -0.03) P = 0.03]. There were no significant differences for luteinising hormone or sex hormone binding globulin. Subgroup analysis for total testosterone, European and North American men, showed a stronger effect [-0.52 (95 % CI -0.75 to -0.3) P < 0.001]. CONCLUSIONS: Low-fat diets appear to decrease testosterone levels in men, but further randomised controlled trials are needed to confirm this effect. Men with European ancestry may experience a greater decrease in testosterone, in response to a low-fat diet.

Measuring Arterial Pulsatility With Dynamic Inflow Magnitude Contrast.

The pulsatility of blood flow through cerebral arteries is clinically important, as it is intrinsically associated with cerebrovascular health. In this study we outline a new MRI approach to measuring the real-time pulsatile flow in cerebral arteries, which is based on the inflow phenomenon associated with fast gradient-recalled-echo acquisitions. Unlike traditional phase-contrast techniques, this new method, which we dub dynamic inflow magnitude contrast (DIMAC), does not require velocity-encoding gradients as sensitivity to flow velocity is derived purely from the inflow effect. We achieved this using a highly accelerated single slice EPI acquisition with a very short TR (15 ms) and a 90° flip angle, thus maximizing inflow contrast. We simulate the spoiled GRE signal in the presence of large arteries and perform a sensitivity analysis. The sensitivity analysis demonstrates that in the regime of high inflow contrast, DIMAC shows much greater sensitivity to flow velocity over blood volume changes. We support this theoretical prediction with in-vivo data collected in two separate experiments designed to demonstrate the utility of the DIMAC signal contrast. We perform a hypercapnia challenge experiment in order to experimentally modulate arterial tone within subjects, and thus modulate the arterial pulsatile flow waveform. We also perform a thigh-cuff release challenge, designed to induce a transient drop in blood pressure, and demonstrate that the continuous DIMAC signal captures the complex transient change in the pulsatile and non-pulsatile components of flow. In summary, this study proposes a new role for a well-established source of MR image contrast and demonstrates its potential for measuring both steady-state and dynamic changes in arterial tone.

Graded fMRI Neurofeedback Training of Motor Imagery in Middle Cerebral Artery Stroke Patients: A Preregistered Proof-of-Concept Study.

Ischemic stroke of the middle cerebral artery (MCA), a major brain vessel that supplies the primary motor and premotor cortex, is one of the most common causes for severe upper limb impairment. Currently available motor rehabilitation training largely lacks satisfying efficacy with over 70% of stroke survivors showing residual upper limb dysfunction. Motor imagery-based functional magnetic resonance imaging neurofeedback (fMRI-NF) has been suggested as a potential therapeutic technique to improve motor impairment in stroke survivors. In this preregistered proof-of-concept study (https://osf.io/y69jc/), we translated graded fMRI-NF training, a new paradigm that we have previously studied in healthy participants, to first-time MCA stroke survivors with residual mild to severe impairment of upper limb motor function. Neurofeedback was provided from the supplementary motor area (SMA) targeting two different neurofeedback target levels (low and high). We hypothesized that MCA stroke survivors will show (1) sustained SMA-region of interest (ROI) activation and (2) a difference in SMA-ROI activation between low and high neurofeedback conditions during graded fMRI-NF training. At the group level, we found only anecdotal evidence for these preregistered hypotheses. At the individual level, we found anecdotal to moderate evidence for the absence of the hypothesized graded effect for most subjects. These null findings are relevant for future attempts to employ fMRI-NF training in stroke survivors. The study introduces a Bayesian sequential sampling plan, which incorporates prior knowledge, yielding higher sensitivity. The sampling plan was preregistered together with a priori hypotheses and all planned analysis before data collection to address potential publication/researcher biases. Unforeseen difficulties in the translation of our paradigm to a clinical setting required some deviations from the preregistered protocol. We explicitly detail these changes, discuss the accompanied additional challenges that can arise in clinical neurofeedback studies, and formulate recommendations for how these can be addressed. Taken together, this work provides new insights about the feasibility of motor imagery-based graded fMRI-NF training in MCA stroke survivors and serves as a first example for comprehensive study preregistration of an (fMRI) neurofeedback experiment.

Corrigendum: Cerebral Autoregulation Evidenced by Synchronized Low Frequency Oscillations in Blood Pressure and Resting-State fMRI.

[This corrects the article DOI: 10.3389/fnins.2019.00433.].

Resting-State Network Patterns Underlying Cognitive Function in Bipolar Disorder: A Graph Theoretical Analysis.

Background: Synchronous and antisynchronous activity between neural elements at rest reflects the physiological processes underlying complex cognitive ability. Regional and pairwise connectivity investigations suggest that perturbations in these activity patterns may relate to widespread cognitive impairments seen in bipolar disorder (BD). Here we take a network-based perspective to more meaningfully capture interactions among distributed brain regions compared to focal measurements and examine network-cognition relationships across a range of commonly affected cognitive domains in BD in relation to healthy controls. Methods: Resting-state networks were constructed as matrices of correlation coefficients between regionally averaged resting-state time series from 86 cortical/subcortical brain regions (FreeSurferv5.3.0). Cognitive performance measured using the Wechsler Adult Intelligence Scale, Cambridge Automated Neuropsychological Test Battery (CANTAB), and Reading the Mind in the Eyes tests was examined in relation to whole-brain connectivity measures and patterns of connectivity using a permutation-based statistical approach. Results: Faster response times in controls (n = 49) related to synchronous activity between frontal, parietal, cingulate, temporal, and occipital regions, while a similar response times in BD (n = 35) related to antisynchronous activity between regions of this subnetwork. Across all subjects, antisynchronous activity between the frontal, parietal, temporal, occipital, cingulate, insula, and amygdala regions related to improved memory performance. No resting-state subnetworks related to intelligence, executive function, short-term memory, or social cognition performance in the overall sample or in a manner that would explain deficits in these facets in BD. Conclusions: Our results demonstrate alterations in the intrinsic connectivity patterns underlying response timing in BD that are not specific to performance or errors on the same tasks. Across all individuals, no strong effects of resting-state global topology on cognition are found, while distinct functional networks supporting episodic and spatial memory highlight intrinsic inhibitory influences present in the resting state that facilitate memory processing. Impact Statement Regional and pairwise-connectivity investigations suggest altered interactions between brain areas may contribute to impairments in cognition that are observed in bipolar disorder. However, the distributed nature of these interactions across the brain remains poorly understood. Using recent advances in network neuroscience, we examine functional connectivity patterns associated with multiple cognitive domains in individuals with and without bipolar disorder. We discover distinct patterns of connectivity underlying response-timing performance uniquely in bipolar disorder and, independent of diagnosis, inhibitory interactions that relate to memory performance.

Vascular physiology drives functional brain networks.

We present the first evidence for vascular regulation driving fMRI signals in specific functional brain networks. Using concurrent neuronal and vascular stimuli, we collected 30 BOLD fMRI datasets in 10 healthy individuals: a working memory task, flashing checkerboard stimulus, and CO2 inhalation challenge were delivered in concurrent but orthogonal paradigms. The resulting imaging data were averaged together and decomposed using independent component analysis, and three "neuronal networks" were identified as demonstrating maximum temporal correlation with the neuronal stimulus paradigms: Default Mode Network, Task Positive Network, and Visual Network. For each of these, we observed a second network component with high spatial overlap. Using dual regression in the original 30 datasets, we extracted the time-series associated with these network pairs and calculated the percent of variance explained by the neuronal or vascular stimuli using a normalized R2 parameter. In each pairing, one network was dominated by the appropriate neuronal stimulus, and the other was dominated by the vascular stimulus as represented by the end-tidal CO2 time-series recorded in each scan. We acquired a second dataset in 8 of the original participants, where no CO2 challenge was delivered and CO2 levels fluctuated naturally with breathing variations. Although splitting of functional networks was not robust in these data, performing dual regression with the network maps from the original analysis in this new dataset successfully replicated our observations. Thus, in addition to responding to localized metabolic changes, the brain's vasculature may be regulated in a coordinated manner that mimics (and potentially supports) specific functional brain networks. Multi-modal imaging and advances in fMRI acquisition and analysis could facilitate further study of the dual nature of functional brain networks. It will be critical to understand network-specific vascular function, and the behavior of a coupled vascular-neural network, in future studies of brain pathology.

Frontolimbic, Frontoparietal, and Default Mode Involvement in Functional Dysconnectivity in Psychotic Bipolar Disorder.

BACKGROUND: Functional abnormalities, mostly involving functionally specialized subsystems, have been associated with disorders of emotion regulation such as bipolar disorder (BD). Understanding how independent functional subsystems integrate globally and how they relate with anatomical cortical and subcortical networks is key to understanding how the human brain's architecture constrains functional interactions and underpins abnormalities of mood and emotion, particularly in BD. METHODS: Resting-state functional magnetic resonance time series were averaged to obtain individual functional connectivity matrices (using AFNI software); individual structural connectivity matrices were derived using deterministic non-tensor-based tractography (using ExploreDTI, version 4.8.6), weighted by streamline count and fractional anisotropy. Structural and functional nodes were defined using a subject-specific cortico-subcortical mapping (using Desikan-Killiany Atlas, FreeSurfer, version 5.3). Whole-brain connectivity alongside a permutation-based statistical approach and structure-function coupling were employed to investigate topological variance in individuals with predominantly euthymic BD relative to psychiatrically healthy control subjects. RESULTS: Patients with BD (n = 41) exhibited decreased (synchronous) connectivity in a subnetwork encompassing frontolimbic and posterior-occipital functional connections (T > 3, p = .048), alongside increased (antisynchronous) connectivity within a frontotemporal subnetwork (T > 3, p = .014); all relative to control subjects (n = 56). Preserved whole-brain functional connectivity and comparable structure-function coupling among whole-brain and edge-class connections were observed in patients with BD relative to control subjects. CONCLUSIONS: This study presents a functional map of BD dysconnectivity that differentially involves communication within nodes belonging to functionally specialized subsystems-default mode, frontoparietal, and frontolimbic systems; these changes do not extend to be detected globally and may be necessary to maintain a remitted clinical state of BD. Preserved structure-function coupling in BD despite evidence of regional anatomical and functional deficits suggests a dynamic interplay between structural and functional subnetworks.

Cerebral Autoregulation Evidenced by Synchronized Low Frequency Oscillations in Blood Pressure and Resting-State fMRI.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a widely used technique for mapping the brain's functional architecture, so delineating the main sources of variance comprising the signal is crucial. Low frequency oscillations (LFO) that are not of neural origin, but which are driven by mechanisms related to cerebral autoregulation (CA), are present in the blood-oxygenation-level-dependent (BOLD) signal within the rs-fMRI frequency band. In this study we use a MR compatible device (Caretaker, Biopac) to obtain a non-invasive estimate of beat-to-beat mean arterial pressure (MAP) fluctuations concurrently with rs-fMRI at 3T. Healthy adult subjects (n = 9; 5 male) completed two 20-min rs-fMRI scans. MAP fluctuations were decomposed into different frequency scales using a discrete wavelet transform, and oscillations at approximately 0.1 Hz show a high degree of spatially structured correlations with matched frequency fMRI fluctuations. On average across subjects, MAP fluctuations at this scale of the wavelet decomposition explain ∼2.2% of matched frequency fMRI signal variance. Additionally, a simultaneous multi-slice multi-echo acquisition was used to collect 10-min rs-fMRI at three echo times at 7T in a separate group of healthy adults (n = 5; 5 male). Multiple echo times were used to estimate the R2 ∗ decay at every time point, and MAP was shown to strongly correlate with this signal, which suggests a purely BOLD (i.e., blood flow related) origin. This study demonstrates that there is a significant component of the BOLD signal that has a systemic physiological origin, and highlights the fact that not all localized BOLD signal changes necessarily reflect blood flow supporting local neural activity. Instead, these data show that a proportion of BOLD signal fluctuations in rs-fMRI are due to localized control of blood flow that is independent of local neural activity, most likely reflecting more general systemic autoregulatory processes. Thus, fMRI is a promising tool for studying flow changes associated with cerebral autoregulation with high spatial resolution.

Changes in arterial cerebral blood volume during lower body negative pressure measured with MRI.

Cerebral Autoregulation (CA), defined as the ability of the cerebral vasculature to maintain stable levels of blood flow despite changes in systemic blood pressure, is a critical factor in neurophysiological health. Magnetic resonance imaging (MRI) is a powerful technique for investigating cerebrovascular function, offering high spatial resolution and wide fields of view (FOV), yet it is relatively underutilized as a tool for assessment of CA. The aim of this study was to demonstrate the potential of using MRI to measure changes in cerebrovascular resistance in response to lower body negative pressure (LBNP). A Pulsed Arterial Spin Labeling (PASL) approach with short inversion times (TI) was used to estimate cerebral arterial blood volume (CBVa) in eight healthy subjects at baseline and -40mmHg LBNP. We estimated group mean CBVa values of 3.13 ± 1.00 and 2.70 ± 0.38 for baseline and lbnp respectively, which were the result of a differential change in CBVa during -40mmHg LBNP that was dependent on baseline CBVa. These data suggest that the PASL CBVa estimates are sensitive to the complex cerebrovascular response that occurs during the moderate orthostatic challenge delivered by LBNP, which we speculatively propose may involve differential changes in vascular tone within different segments of the arterial vasculature. These novel data provide invaluable insight into the mechanisms that regulate perfusion of the brain, and establishes the use of MRI as a tool for studying CA in more detail.

The BOLD response in primary motor cortex and supplementary motor area during kinesthetic motor imagery based graded fMRI neurofeedback.

There is increasing interest in exploring the use of functional MRI neurofeedback (fMRI-NF) as a therapeutic technique for a range of neurological conditions such as stroke and Parkinson's disease (PD). One main therapeutic potential of fMRI-NF is to enhance volitional control of damaged or dysfunctional neural nodes and networks via a closed-loop feedback model using mental imagery as the catalyst of self-regulation. The choice of target node/network and direction of regulation (increase or decrease activity) are central design considerations in fMRI-NF studies. Whilst it remains unclear whether the primary motor cortex (M1) can be activated during motor imagery, the supplementary motor area (SMA) has been robustly activated during motor imagery. Such differences in the regulation potential between primary and supplementary motor cortex are important because these areas can be differentially affected by a stroke or PD, and the choice of fMRI-NF target and grade of self-regulation of activity likely have substantial influence on the clinical effects and cost effectiveness of NF-based interventions. In this study we therefore investigated firstly whether healthy subjects would be able to achieve self-regulation of the hand-representation areas of M1 and the SMA using fMRI-NF training. There was a significant decrease in M1 neural activity during fMRI-NF, whereas SMA neural activity was increased, albeit not with the predicated graded effect. This study has important implications for fMRI-NF protocols that employ motor imagery to modulate activity in specific target regions of the brain and to determine how they may be tailored for neurorehabilitation.

Cerebrovascular Function in the Large Arteries Is Maintained Following Moderate Intensity Exercise.

Exercise has been shown to induce cerebrovascular adaptations. However, the underlying temporal dynamics are poorly understood, and regional variation in the vascular response to exercise has been observed in the large cerebral arteries. Here, we sought to measure the cerebrovascular effects of a single 20-min session of moderate-intensity exercise in the one hour period immediately following exercise cessation. We employed transcranial Doppler (TCD) ultrasonography to measure cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) before, during, and following exercise. Additionally, we simultaneously measured cerebral blood flow (CBF) in the internal carotid artery (ICA) and vertebral artery (VA) before and up to one hour following exercise cessation using Duplex ultrasound. A hypercapnia challenge was used before and after exercise to examine exercise-induced changes in cerebrovascular reactivity (CVR). We found that MCAv and PCAv were significantly elevated during exercise (p = 4.81 × 10-5 and 2.40 × 10-4, respectively). A general linear model revealed that these changes were largely explained by the partial pressure of end-tidal CO2 and not a direct vascular effect of exercise. After exercise cessation, there was no effect of exercise on CBFV or CVR in the intracranial or extracranial arteries (all p > 0.05). Taken together, these data confirm that CBF is rapidly and uniformly regulated following exercise cessation in healthy young males.

The Functional Connectivity Between the Nucleus Accumbens and the Ventromedial Prefrontal Cortex as an Endophenotype for Bipolar Disorder.

BACKGROUND: Alterations in functional connectivity between the nucleus accumbens (NAcc) and frontal cortices have been previously associated with the presence of psychiatric syndromes, including bipolar disorder (BD). Whether these alterations are a consequence or a risk factor for mental disorders remains unresolved. METHODS: This study included 35 patients with BD, 30 nonaffected siblings of patients with BD, and 23 healthy control subjects to probe functional connectivity at rest between NAcc and the rest of the brain in a cross-sectional design. Blood oxygen level-dependent time series at rest from NAcc were used as seed region in a voxelwise correlational analysis. The strength of the correlations found was compared across groups after Fisher's Z transformation. RESULTS: We found increased functional connectivity between the NAcc and the ventromedial prefrontal cortex-comprising mainly the subgenual anterior cingulate-in patients compared with healthy control subjects. Participants at increased genetic risk but yet resilient-nonaffected siblings-showed functional connectivity values midway between the former two groups. CONCLUSIONS: Our results are indicative of the potential for the connectivity between NAcc and the ventromedial prefrontal cortex to represent an endophenotype for BD.

Neurofeedback training for alcohol dependence versus treatment as usual: study protocol for a randomized controlled trial.

BACKGROUND: Real-time functional magnetic resonance imaging (rtfMRI) is used for neurofeedback training (NFT). Preliminary results suggest that it can help patients to control their symptoms. This study uses rtfMRI NFT for relapse prevention in alcohol dependence. METHODS/DESIGN: Participants are alcohol-dependent patients who have completed a detoxification programme within the past 6 months and have remained abstinent. Potential participants are screened for eligibility, and those who are eligible are randomly assigned to the treatment group (receiving rtfMRI NFT in addition to treatment as usual) or the control group (receiving only treatment as usual). Participants in both groups are administered baseline assessments to measure their alcohol consumption and severity of dependence and a variety of psychological and behavioural characteristics that are hypothesised to predict success with rtfMRI NFT. During the following 4 months, experimental participants are given six NFT sessions, and before and after each session various alcohol-related measures are taken. Participants in the control group are given the same measures to coincide with their timing in the experimental group. Eight and 12 months after the baseline assessment, both groups are followed up with a battery of measures. The primary research questions are whether NFT can be used to teach participants to down-regulate their brain activation in the presence of alcohol stimuli or to up-regulate their brain activation in response to pictures related to healthy goal pursuits, and, if so, whether this translates into reductions in alcohol consumption. The primary outcome measures will be those derived from the functional brain imaging data. We are interested in improvements (i.e., reductions) in participants' alcohol consumption from pretreatment levels, as indicated by three continuous variables, not simply whether or not the person has remained abstinent. The indices of interest are percentage of days abstinent, drinks per drinking day, and percentage of days of heavy drinking. General linear models will be used to compare the NFT group and the control group on these measures. DISCUSSION: Relapse in alcohol dependence is a recurring problem, and the present evaluation of the role of rtfMRI in its treatment holds promise for identifying a way to prevent relapse. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02486900 , registered on 26 June 2015.