Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study.

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

Risks associated with colonoscopy in a population-based colon screening program: an observational cohort study.

BACKGROUND: The risks associated with colonoscopy performed through the British Columbia Colon Screening Program (BCCSP) are not known. We aimed to determine the rate of colonoscopy-related serious adverse events within this program. METHODS: For this prospective observational study, we used the BCCSP database to identify participants 50 to 74 years of age who had a positive result on fecal immunochemical testing (FIT) between Nov. 15, 2013, and Dec. 31, 2017, followed by colonoscopy. Unplanned medical events were recorded at the time of colonoscopy and 14 days later. We reviewed the unplanned events and defined them as serious adverse events if they resulted in death, hospital admission or intervention; we also classified them as probably, possibly or unlikely related to the colonoscopy. The primary outcome was the overall rate of serious adverse events; the secondary outcomes were 14-day post-colonoscopy rates of perforation, bleeding and death. RESULTS: During the study period, a total of 96 192 colonoscopies were performed by 308 physicians at 50 sites. The median age of patients was 62 (10th-90th percentile 52-71) years, and 56% were male. Of these, 78 831 patients were contacted after the colonoscopy. Serious adverse events were deemed to have occurred in 350 colonoscopies (44 per 10 000, 95% confidence interval [CI] 39-50 per 10 000), with a number needed to harm of 225. Of the 332 (94.9%) serious adverse events that were probably or possibly related to colonoscopy, perforation occurred in 6 (95% CI 5-8) per 10 000 colonoscopies, bleeding in 26 (95% CI 22-30) per 10 000 colonoscopies and death in 3 (95% CI 1-10) per 100 000 colonoscopies. INTERPRETATION: The rate of serious adverse events associated with colonoscopy in the BCCSP was in keeping with previous publications and met accepted benchmarks. The findings of this study inform stakeholders of the risks associated with colonoscopy in an FIT-based colon screening program.

Bilateral regional extracranial blood flow regulation to hypoxia and unilateral duplex ultrasound measurement error.

NEW FINDINGS: What is the central question of this study? Is blood flow regulation to hypoxia different between the internal carotid arteries (ICAs) and vertebral arteries (VAs), and what is the measurement error in unilateral extracranial artery assessments compared to bilateral? What is the main finding and its importance? ICA and VA blood flow regulation to hypoxia is comparable when factoring for vessel type and vessel side. Compared to bilateral assessment, vessels assessed unilaterally had individual measurement errors of up to 37%. Assessing the vessel with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error. ABSTRACT: Whether blood flow regulation to hypoxia is similar between left and right internal carotid arteries (ICAs) and vertebral arteries (VAs) is unclear. Extracranial blood flow is regularly calculated by doubling a unilateral assessment; however, lateral artery differences may lead to measurement error. This study aimed to determine extracranial blood flow regulation to hypoxia when factoring for vessel type (ICAs or VAs) and vessel side (left or right) effects, and to investigate unilateral assessment measurement error compared to bilateral assessment. In a repeated-measures crossover design, extracranial arteries of 44 participants were assessed bilaterally by duplex ultrasound during 90 min of normoxic and poikilocapnic hypoxic (12.0% fraction of inspired oxygen) conditions. Linear mixed model analyses revealed no Condition × Vessel Type × Vessel Side interaction for blood flow, vessel diameter and flow velocity (all P > 0.05) indicating left and right ICA and VA blood flow regulation to hypoxia was similar. Bilateral hypoxic reactivity was comparable (ICAs, 1.4 (1.0) vs. VAs, 1.7 (1.1) Δ%·Δ SpO2-1 ; P = 0.12). Compared to bilateral assessment, unilateral mean measurement error of the relative blood flow response to hypoxia was up to 5%, but individual errors reached 37% and were greatest in ICAs and VAs with the smaller resting blood flow due to a ratio-scaling problem. In conclusion, left and right ICA and VA regulation to hypoxia is comparable when factoring for vessel type and vessel side. Assessing the ICA and VA vessels with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error.

Neurochemistry of response inhibition and interference in gambling disorder: a preliminary study of γ-aminobutyric acid (GABA+) and glutamate-glutamine (Glx).

BACKGROUND: Neurobehavioral research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is multifaceted with different experimental tasks measuring different subprocesses, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD. METHODS: We investigated inhibition with the stop signal task (SST) and interference with the Eriksen Flanker task, and related performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate-glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel. RESULTS: We found slower processing of complex stimuli in the Flanker task in GD (P < .001, η2p = 0.78), and no group differences in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = 0.92, P = .001). Larger positive correlations were found for those with GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, P = .004), as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, P = .03), indicating general Glx-related error processing deficits. Both groups expressed equivalent positive correlations between posterror slowing and Glx/Cr in the right dlPFC (GD: r = 0.74, P = .02; non-GD: r = .71, P = .01). CONCLUSION: Inhibition and interference impairments are reflected in dACC baseline metabolite levels and error processing deficits in GD.

Minimum Reporting Standards for in vivo Magnetic Resonance Spectroscopy (MRSinMRS): Experts' consensus recommendations.

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post-processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta-analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full.

Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia.

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.

Impulsive decision-making and gambling severity: The influence of γ-amino-butyric acid (GABA) and glutamate-glutamine (Glx).

Discounting larger, delayed rewards for smaller, immediate rewards is a stable psychological trait known to be impaired in gambling disorder (GD). Neuroimaging with non-GD populations indicates involvement of anterior cingulate (ACC) and dorsolateral prefrontal cortex (dlPFC) in delay discounting. However, little is known about the role of intrinsic properties of brain functioning, such as neurotransmitter action, in impaired discounting in GD. Here, we used magnetic resonance spectroscopy to assess glutamate-glutamine (Glx) and γ-amino-butyric acid (GABA+) concentrations in the dorsal ACC (dACC), dlPFC and occipital cortex of human males with and without GD. Gambling symptom severity correlated negatively with Glx levels in the dACC and occipital voxels. Discounting of small and medium delayed rewards was negatively associated with GABA+ in the dACC, while the discounting of large delayed rewards was negatively associated with GABA+/Glx ratios in the dlPFC. Additionally, in GD, discounting of large delayed rewards was negatively correlated with occipital GABA+ levels. Overall, these findings show that high gambling symptom severity is associated with low levels of Glx and that dACC (GABA+), right dlPFC (GABA+/Glx), and occipital areas (GABA+) track the magnitude of delayed rewards during discounting.

Circadian circuits in humans: White matter microstructure predicts daytime sleepiness.

The suprachiasmatic nucleus of the hypothalamus is the chief circadian pacemaker in the brain, and is entrained to day-night cycles by visual afferents from melanopsin containing retinal ganglion cells via the inferior accessory optic tract. Tracer studies have demonstrated efferents from the suprachiasmatic nucleus projecting to the paraventricular nucleus of the hypothalamus, which in turn project to first-order sympathetic neurons in the intermedio-lateral grey of the spinal cord. Sympathetic projections to the pineal gland trigger the secretion of the sleep inducing hormone melatonin. The current study reports the first demonstration of potential sympathopetal hypothalamic projections involved in circadian regulation in humans with in vivo virtual white matter dissections using probabilistic diffusion tensor imaging (DTI) tractography. Additionally, our data shows a correlation between individual differences in white matter microstructure (measured with fractional anisotropy) and increased daytime sleepiness [measured with the Epworth Sleepiness Scale (ESS, Johns, 1991)]. Sympathopetal connections with the hypothalamus were virtually dissected using designated masks on the optic chiasm, which served as an anatomical landmark for retinal fibres projecting to the suprachiasmatic nucleus, and a waypoint mask on the lateral medulla, where hypothalamic projections to the sympathetic nervous system traverse in humans. Sympathopetal projections were demonstrated in each hemisphere in twenty-six subjects. The tract passed through the suprachiasmatic nucleus of the hypothalamus and its trajectory corresponds to the dorsal longitudinal fasciculus traversing the periaqueductal region and the lateral medulla. White matter microstructure (FA) in the left hemisphere correlated with high scores on the ESS, suggesting an association between circadian pathway white matter microstructure, and increased daytime sleepiness.

Patients' Perspectives on Early Liver Transplantation in Alcohol-Related Liver Disease.

Liver transplant programs in Canada require a period of 6 months of abstinence from alcohol before considering a patient with liver disease secondary to alcohol for transplantation. Although some studies have demonstrated good outcomes following a transplant in carefully selected patients before the 6-month abstinence period has been met, there have been arguments against this, including the claim that the public has a general negative perception of those with alcohol dependence. We performed a multicenter cross-sectional survey to determine the perception of people in British Columbia, Canada, toward liver transplantation in patients with liver disease due to alcohol who have not demonstrated the capacity to remain abstinent from alcohol for 6 months. A total of 304 patient questionnaires were completed, and 83.1% agreed with a period of abstinence of 6 months. In those patients who were unlikely to survive 6 months without a transplant, 34.1% of respondents agreed with, 44.1% did not agree with, and 21.4% were neutral about, early transplantation; 42.8% would have less trust in the process of transplantation if a period of abstinence was not maintained, but relaxing the requirement for an abstinence period would not have an impact on the majority's decision to donate organs. Only 30.5% would support abandoning the abstinence criteria. Conclusion: Among patients followed at general gastroenterology, medicine, or transplant clinics, there is a willingness to relax the criteria in selected patients unlikely to survive without a transplant, although a general consensus remains in support of the existing 6-month alcohol abstinence rule. A larger scale survey of all provinces in Canada would be required to assess support for such a change in policy.

Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility.

Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age = 25.2 years, range = 18-32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained interindividual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioral flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry.SIGNIFICANCE STATEMENT Behavioral flexibility is a crucial component of adaptation and survival. Evidence from the animal literature shows that the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioral flexibility, but this system remains understudied in humans. Using proton magnetic resonance spectroscopy, we showed that choline levels at rest in the dorsal striatum are associated with performance specifically during reversal learning. These novel findings help to bridge the gap between animal and human studies by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioral flexibility. Importantly, the methods described here cannot only be applied to furthering our understanding of healthy human neurochemistry, but also to extending our understanding of cholinergic disorders.

Methodological consensus on clinical proton MRS of the brain: Review and recommendations.

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

Errors in 1 H-MRS estimates of brain metabolite concentrations caused by failing to take into account tissue-specific signal relaxation.

Accurate measurement of brain metabolite concentrations with proton magnetic resonance spectroscopy (1 H-MRS) can be problematic because of large voxels with mixed tissue composition, requiring adjustment for differing relaxation rates in each tissue if absolute concentration estimates are desired. Adjusting for tissue-specific metabolite signal relaxation, however, also requires a knowledge of the relative concentrations of the metabolite in gray (GM) and white (WM) matter, which are not known a priori. Expressions for the estimation of the molality and molarity of brain metabolites with 1 H-MRS are extended to account for tissue-specific relaxation of the metabolite signals and examined under different assumptions with simulated and real data. Although the modified equations have two unknowns, and hence are unsolvable explicitly, they are nonetheless useful for the estimation of the effect of tissue-specific metabolite relaxation rates on concentration estimates under a range of assumptions and experimental parameters using simulated and real data. In simulated data using reported GM and WM T1 and T2 times for N-acetylaspartate (NAA) at 3 T and a hypothetical GM/WM NAA ratio, errors of 6.5-7.8% in concentrations resulted when TR = 1.5 s and TE = 0.144 s, but were reduced to less than 0.5% when TR = 6 s and TE = 0.006 s. In real data obtained at TR/TE = 1.5 s/0.04 s, the difference in the results (4%) was similar to that obtained with simulated data when assuming tissue-specific relaxation times rather than GM-WM-averaged times. Using the expressions introduced in this article, these results can be extrapolated to any metabolite or set of assumptions regarding tissue-specific relaxation. Furthermore, although serving to bound the problem, this work underscores the challenge of correcting for relaxation effects, given that relaxation times are generally not known and impractical to measure in most studies. To minimize such effects, the data should be acquired with pulse sequence parameters that minimize the effect of signal relaxation.

Beyond static measures: A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia.

Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.

Towards a theory of functional magnetic resonance spectroscopy (fMRS): A meta-analysis and discussion of using MRS to measure changes in neurotransmitters in real time.

Proton magnetic resonance spectroscopy is a powerful tool to investigate neurochemistry and physiology in vivo. Recently researchers have started to use MRS to measure neurotransmitter changes related to neural activity, so called functional MRS (fMRS). Particular interest has been placed on measuring glutamate changes associated with neural function, but differences are reported in the size of changes seen. This review discusses fMRS, and includes meta-analyses of the relative size of glutamate changes seen in fMRS, and the impact experimental design and stimulus paradigm may have. On average glutamate was found to increase by 6.97% (±1.739%) in response to neural activation. However, factors of experimental design may have a large impact on the size of these changes. For example an increase of 4.749% (±1.45%) is seen in block studies compared to an increase of 13.429% (±3.59) in studies using event related paradigms. The stimulus being investigated also seems to play a role with prolonged visual stimuli showing a small mean increase in glutamate of 2.318% (±1.227%) while at the other extreme, pain stimuli show a mean stimulation effect of 14.458% (±3.736%). These differences are discussed with regards to possible physiologic interpretations, as well experimental design implications.

Functional neurochemical imaging of the human striatal cholinergic system during reversal learning.

Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in reversal learning. However, this has not been studied in humans due to a lack of appropriate non-invasive techniques. Proton magnetic resonance spectroscopy (1 H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly, 1 H-MRS can be used to study choline, an ACh precursor, which is linked to activity-dependent ACh release. The aim of this study was to use functional-1 H-MRS (fMRS) to measure changes in choline levels in the human dorsal striatum during performance of a probabilistic reversal learning task. We demonstrate a task-dependent decrease in choline, specifically during reversal, but not initial, learning. We interpret this to reflect a sustained increase in ACh levels, which is in line with findings from the animal literature. This task-dependent change was specific to choline and was not observed in control metabolites. These findings provide support for the use of fMRS in the in vivo study of the human cholinergic system.

Aging-Related Microstructural Alterations Along the Length of the Cingulum Bundle.

The aim of this study was to investigate the aging-related structural changes of the cingulum, one of the major components of the limbic network, which has a critical role in emotion, attention, and memory. Thirty-five healthy young adults (22.3 ± 2.7 years) and 33 healthy older adults (69.5 ± 3.5 years) were recruited. Diffusion weighted imaging data were acquired with a b-value = 2000 sec/mm2 and 61 diffusion directions and 4 non-weighted images. The fiber directions in each voxel were based on the constrained spherical deconvolution model. The cingulum was segmented into three branches using deterministic tractography (subgenual, retrosplenial, and parahippocampal), using a region-of-interest-based approach. Atlas-based tractography was the method used to obtain the output tracts of each branch of the cingulum. Along-tract analysis was performed on each branch. We found a statistically significant change with aging in the left subgenual branch of the cingulum with a decrease in fractional anisotropy and axial diffusivity, as well as an increase in radial diffusivity. No statistically significant differences were found between young and older groups in the other two branches. This study adds to knowledge about how the cingulum changes structurally along its entire length during aging in a more detailed way, thanks to an advanced methodological approach.

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention.

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans.

What do people with dementia and their carers want to know about neuroimaging for dementia?

Neuroimaging forms an important part of dementia diagnosis. Provision of information on neuroimaging to people with dementia and their carers may aid understanding of the pathological, physiological and psychosocial changes of the disease, and increase understanding of symptoms. This qualitative study aimed to investigate participants' knowledge of the dementia diagnosis pathway, their understanding of neuroimaging and its use in diagnosis, and to determine content requirements for a website providing neuroimaging information. Structured interviews and a focus group were conducted with carers and people with dementia. The findings demonstrate an unmet need for information on neuroimaging both before and after the examination. Carers were keen to know about neuroimaging at a practical and technical level to help avoid diagnosis denial. People with dementia requested greater information, but with a caveat to avoid overwhelming detail, and were less likely to favour an Internet resource.

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia.

KEY POINTS: Cognitive performance is impaired by hypoxia despite global cerebral oxygen delivery and metabolism being maintained. Using arterial spin labelled (ASL) magnetic resonance imaging, this is the first study to show regional reductions in cerebral blood flow (CBF) in response to decreased oxygen supply (hypoxia) at 2 h that increased in area and became more pronounced at 10 h. Reductions in CBF were seen in brain regions typically associated with the 'default mode' or 'task negative' network. Regional reductions in CBF, and associated vasoconstriction, within the default mode network in hypoxia is supported by increased vasodilatation in these regions to a subsequent hypercapnic (5% CO2 ) challenge. These results suggest an anatomical mechanism through which hypoxia may cause previously reported deficits in cognitive performance. ABSTRACT: Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2 h) and prolonged (10 h) poikilocapnic normobaric hypoxia. We found that 2 h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the 'default mode' or 'task negative' network. After 10 h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO2 ) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady-state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory.

Current Practice in the Referral of Individuals with Suspected Dementia for Neuroimaging by General Practitioners in Ireland and Wales.

OBJECTIVES: While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales. METHODS: A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued. RESULTS: 48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively). CONCLUSIONS: The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia.