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We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

Previous memory research has suggested that the effects of prior study observed in priming tasks are functionally, and neurobiologically, distinct phenomena from the kind of memory expressed in conventional (explicit) memory tests. Evidence for this position comes from observed dissociations between memory scores obtained with the two kinds of tasks. However, there is continuing controversy about the meaning of these dissociations. In recent studies, Ostergaard (1998a, Memory Cognit, 26:40-60; 1998b, J. Int. Neuropsychol. Soc., in press) showed that simply degrading visual word stimuli can dramatically alter the degree to which word priming shows a dissociation from word recognition; i.e., effects of a number of factors on priming paralleled their effects on recognition memory tests when the words were degraded at test. In the present study, cerebral blood flow changes were measured while subjects performed the word identification (reading) and recognition memory tasks used previously by Ostergaard. The results are the direct comparisons of the two tasks and the effects of stimulus degradation on blood flow patterns during the tasks. Clear differences between word identification and word recognition were observed: the latter task evoked considerably more prefrontal activity and stronger cerebellar activation. Stimulus degradation was associated with focal increases in bilateral fusiform regions within the occipital lobe. No task, degradation, or item repetition effects were demonstrated in mesial temporal regions, no repetition effects were observed in any region, and there was no evidence for different effects of stimulus degradation in the priming and recognition memory conditions. Power limitations may have contributed to the null effects.

1. The identification of a vascular wall renin angiotensin system and of angiotensin converting enzyme on the luminal surface of the endothelium in many tissues, including the brain, has stimulated research on the influence of the renin angiotensin system on regional blood flows. 2. In experimental studies inhibition of the angiotensin converting enzyme shifts the limits of cerebral blood flow autoregulation towards lower blood pressure values. 3. In patients with chronic arterial hypertension and in patients with chronic heart failure cerebral blood flow is not changed by acute or chronic angiotensin converting enzyme inhibition, despite in some cases pronounced reductions in the mean arterial blood pressure. Angiotensin converting enzyme inhibition does not change ischaemic regional cerebral blood flow in acute stroke. 4. It is concluded that following angiotensin converting inhibition cerebral blood flow is maintained at an unchanged level. The mechanism may include inhibition of locally produced angiotensin II leading to a selective dilation of larger cerebral arteries with a compensatory constriction of the smaller cerebral arteries. [ABSTRACT FROM AUTHOR]

A recent publication in JCBFM, "Static autoregulation in humans" gives rise to critical comments. Autoregulation of cerebral blood flow implies that flow is rather constant within a certain blood pressure (BP) range with a lower and an upper pressure limit. The physiology at the two limits is very different, making comparison of the brain's vulnerability at the limits questionable. The recent publication in JCBFM claims a narrow autoregulatory range based on pooling of data from several studies. However, we argue that such pooling blurs the autoregulatory limits. We summarize the classical literature, therefrom we argue for a broad autoregulatory range., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Supplementary materialSupplemental material for this article is available online.

Background: Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards., Objective: This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC)., Methods: 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T 0 ), within one-week post-ECT (T 1 ), and one to six months post-ECT (T 2 ). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics., Results: 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T 0 to T 1 inGMV, followed by significant decrease from T 1 to T 2 and no difference between T 0 and T 2 , except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T 2 remained higher compared to T 0 . No consistent relationship was found between GMV change pattern and clinical status., Conclusion: The GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. M. Laroy is an aspirant researcher for the Research Foundation Flanders (FWO, grant no. 1168821 N). M. Vandenbulcke, F. Bouckaert, L. Emsell received funding from KU Leuven Research Fund C24/18/095 and KU Leuven Sequoia Fund for Research on Aging and Mental Health. L. Oltedal received funding from Western Norway Regional Health Authority Grant (No. 912238). O. Paulson and M.B. Jorgensen received support from the Lundbeck Foundation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression., (© 2023. The Author(s).)

Objective: Single-photon emission computed tomography (SPECT) with the tracer 99m Tc-HMPAO is a method to visualize the cerebral hyperperfusion during an epileptic seizure and thus localize the epileptogenic zone and seizure propagation. Subtraction of interictal from Ictal SPECT Co-registered to MRI (SISCOM) visualizes areas with relative increases in cerebral blood flow. The purpose of this retrospective study is to explore the added value of visualizing areas of hypoperfusion as well as hyperperfusion, so-called reversed SISCOM., Methods: Fifty-six patients operated for epilepsy who had been investigated with SISCOM were included in the analysis. The patients were divided into two groups based on seizure duration after tracer injection, above or below 30 s. The preoperative SISCOM description was compared to the area of resection and given a concordance score. The 56 SISCOM were recalculated visualizing also areas of hypoperfusion and again compared to the site of resection using the same scale of concordance. The reversed SISCOM were categorized into three subgroups: "Altered Conclusion," "Confirmed Conclusion," and "Adds Nothing." If an area of hyperperfusion had an area of hypoperfusion in close proximity, it was re-interpreted as noise, thus possibly altering the conclusion. If the areas of hypoperfusion were in the opposite hemisphere it was interpreted as confirming factor. Further the concordance scores from conventional SISCOM and reversed SISCOM was compared to surgical outcome to explore the difference in sensitivity, positive predictive value (PPV), and odds ratio., Results: In approximately half of the cases reversed SISCOM added additional value, meaning either altered the conclusion or confirmed the conclusion. The sensitivity, PPV, and odds ratio was also better in the subgroup of long, >30 s seizure duration after injection, and got worse in the group with short, <30 s seizure duration after injection., Significance: Adding reversed SISCOM performed better than conventional SISCOM at predicting good surgical outcome., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: This retrospective study investigates the predictive value of ictal subtraction single-photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) for successful epilepsy surgery., Methods: 57 patients examined with SISCOM as a part of epilepsy surgery evaluation were divided into two groups based on seizure duration after tracer injection (group 1: Seizure duration above or equal to 30 s, group 2: Seizure duration under 30 s). SISCOM was compared to the surgical site and categorized as good or poor concordance. Subsequently, Odds ratios (ORs) and positive predictive values (PPVs) were calculated for each group for good surgical outcome, freedom from disabling seizures., Results: The PPVs and ORs for good surgical outcome was 74.1% and 5.71 for group 1 and 40% and 0.22 for group 2. SISCOM had a similar positive predictive value regardless of whether the focus was in the same or neighboring lobe, but same hemisphere as the resection., Conclusion: In conclusion, the implementation of a precise definition for a well-executed ictal SPECT scan with respect to seizure duration after injection enhances the positive predictive value (PPV) and odds ratio (OR) for successful surgical outcome, surpassing previous findings, whether the focus in resected lobe or the neighboring., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Purpose: Magnetic resonance spectroscopy (MRS)-a method of analysing metabolites in vivo-has been utilized in several studies of brain glioma biomarkers at lower field strengths. At ultra-high field strengths, MRS provides an improved signal-to-noise-ratio and spectral resolution, but 7T studies on patients with gliomas are sparse. The purpose of this exploratory study was to evaluate the potential clinical implication of the use of single-voxel MRS at 7T to assess metabolic information on lesions in a pilot cohort of patients with grade II and III gliomas., Methods: We scanned seven patients and seven healthy controls using the semi-localization by adiabatic-selective refocusing sequence on a Philips Achieva 7T system with a standard dual-transmit head coil. The metabolic ratios were calculated relative to water and total creatine. Additionally, 2-hydroxyglutarate (2-HG) MRS was carried out in four of the patients, and the 2-HG concentration was calculated relative to water., Results: When comparing the tumour data to control regions in both patients and healthy controls, we found that the choline/creatine and myo-inositol/creatine ratios were significantly increased and that the N-acetylaspartate/creatine and the neurotransmitter glutamate/creatine ratios were significantly decreased. The N-acetylaspartate/water and glutamate/water ratios were also significantly decreased. The lactate/water and lactate/creatine ratios showed increases, although not significant. The GABA/water ratio was significantly decreased, but the GABA/creatine ratio was not. MRS spectra showed the presence of 2-HG in three of the four patients studied. Three of the patients, including the MRS 2-HG-negative patient, were operated on, and all of them had the IDH mutation., Conclusion: Our findings were consistent with the existing literature on 3T and 7T MRS.

Purpose: Diffuse low-grade gliomas (DLGGs) are low-malignancy brain tumors originating from the glial cells of the brain growing continuously and infiltratively along the neural axons and infiltrating the surrounding brain tissue. DLGGs usually transform into higher malignancy, causing progressive disability and premature death. MRI scans are valuable when assessing soft tissue abnormalities, but, due to the infiltrative properties of DLGGs, delineating the tumor borders is a challenging task. Therefore, the aim of this study was to explore the difference in gross tumor volume (GTV) of DLGGs delineated from 7 Tesla and 3 Tesla MRI scans., Method: Patients were recruited at the department of neurosurgery and were scanned in both a 7T and a 3T MRI scanner prior to the operation. Two observers delineated the tumors using semi-automatic delineation software. The results from each observer were blinded to the other observer's delineation., Results: Comparing GTVs from 7T and 3T, the percentage difference varied up to 40.4% on the T2-weighted images. The percentage difference in GTV varied up to 15.3% on the fluid-attenuated inversion recovery (FLAIR) images. On the T2-weighted images, most cases varied by approximately 15%; on the FLAIR sequence, half of the cases varied by approximately 5% and the other half by approximately 15%. The overall inter-observer agreement was near perfect, with an intraclass correlation of 0.969. The intraclass correlation was better on the FLAIR sequence than on the T2 sequence., Conclusion: Overall, the GTVs delineated from 7T images were smaller. The increase in field strength improved the inter-observer agreement only on the FLAIR sequence.

Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P < 10-4), whereas the CMRO2 remained unaffected (P > 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}&#95;{\mathrm{a}}{\mathrm{O}}&#95;2}$, P < 10-6; isocapnic hypoxia: $0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}&#95;{\mathrm{a}}{\mathrm{O}}&#95;2}$, P = 0.003) but was unaffected by CO (P = 0.36). Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle., Methods: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls., Results: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally., Conclusions: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure., Impact: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy ( 1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1 H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing., (© 2021 International Society for Neurochemistry.)

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT., Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc., Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT., Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change., Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding., Competing Interests: A. Dale reports that he was a founder of and holds equity in CorTechs Labs, Inc., and serves on its scientific advisory board; he is a member of the scientific advisory boards of Human Longevity, Inc., the Mohn Medical Imaging and Visualization Centre; he receives funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by the University of California, San Diego in accordance with its conflict of interest policies. No other competing interests declared., (© 2021 CMA Joule Inc. or its licensors.)

Migraine is a complex disorder, involving peripheral and central brain structures, where mechanisms and site of attack initiation are an unresolved puzzle. While abnormal pontine neuronal activation during migraine attacks has been reported, exact implication of this finding is unknown. Evidence suggests an important role of glutamate in migraine, implying a possible association of pontine hyperactivity to increased glutamate levels. Migraine without aura patients were scanned during attacks after calcitonin gene-related peptide and sildenafil in a double-blind, randomized, double-dummy, cross-over design, on two separate study days, by proton magnetic resonance spectroscopy and pseudo-continuous arterial spin labeling at 3T. Headache characteristics were recorded until 24 h after drug administrations. Twenty-six patients were scanned during migraine, yielding a total of 41 attacks. Cerebral blood flow increased in dorsolateral pons, ipsilateral to pain side during attacks, compared to outside attacks (13.6%, p = 0.009). Glutamate levels in the same area remained unchanged during attacks (p = 0.873), while total creatine levels increased (3.5%, p = 0.041). In conclusion, dorsolateral pontine activation during migraine was not associated with higher glutamate levels. However, the concurrently increased total creatine levels may suggest an altered energy metabolism, which should be investigated in future studies to elucidate the role of pons in acute migraine.

The middle meningeal artery is a proposed surrogate marker for activation of trigeminal nociceptors during migraine. Previous studies focused on the extracranial part of the artery; hence, vasoreactivity in the intradural arteries during migraine is unknown. Thirty-four patients with migraine without aura were given sildenafil on one day and calcitonin gene-related peptide on another in double-blind crossover fashion. Patients were scanned with 3.0 T MR angiography before drug administration and again 6 hours later during induced attacks of migraine. We measured circumference of the intradural segment of the middle meningeal artery before and during induced migraine attacks. The middle cerebral and superficial temporal arteries were also examined. Fourteen patients had attacks during the second scan after both study drugs and 11 had a migraine after either one or the other, resulting in a total of 39 attacks included in the final analysis. Mean circumference of the intradural middle meningeal artery at baseline was 3.18 mm with an increase of 0.11 mm during attacks (P = 0.005), corresponding to a relative dilation of 3.6% [95% CI: 1.4%-5.7%]. Middle cerebral artery dilated by 9.4% [95% CI: 7.1%-11.7%] and superficial temporal artery by 2.3% [95% CI: 0.2%-4.4%]. Our study shows that the intradural middle meningeal artery and the middle cerebral artery are dilated during migraine induced by calcitonin gene-related peptide as well as sildenafil. We propose that intradural vasculature is affected by migraine-driven activation of trigeminal afferents during migraine attacks.

In the pons, glutamatergic mechanisms are involved in regulating inhibitory descending pain modulation, serotoninergic neurotransmission as well as modulating the sensory transmission of the trigeminovascular system. Migraine involves altered pontine activation and structural changes, while biochemical, genetic and clinical evidence suggests that altered interictal pontine glutamate levels may be an important pathophysiological feature of migraine abetting to attack initiation. Migraine without aura patients were scanned outside attacks using a proton magnetic resonance spectroscopy protocol optimized for the pons at 3 Tesla. The measurements were performed on two separate days to increase accuracy and compared to similar repeated measurements in healthy controls. We found that interictal glutamate (i.e. Glx) levels in the pons of migraine patients (n = 33) were not different from healthy controls (n = 16) (p = 0.098), while total creatine levels were markedly increased in patients (9%, p = 0.009). There was no correlation of glutamate or total creatine levels to migraine frequency, days since the last attack, usual pain intensity of attacks or disease duration. In conclusion, migraine is not associated with altered interictal pontine glutamate levels. However, the novel finding of increased total creatine levels suggests that disequilibrium in the pontine energy metabolism could be an important feature of migraine pathophysiology., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Treatment options for the subgroup of people who develop long-lasting symptoms following mild traumatic brain injury are limited. Transcranial pulsating low-frequency electromagnetic stimulation (T-PEMF) in other patient groups has shown promising results in several studies with proposed neuroprotective and anti-inflammatory effects., Objective: The present pilot study was conducted to access feasibility and tolerability of T-PEMF in treating post-concussion syndrome., Methods: Seven patients with post-concussion syndrome received 5 weeks of daily 30 minutes T-PEMF treatment with evaluation after 2 and 5 weeks and 3 months after ending treatment., Results: Compliance was high as all subject completed the full treatment. Two patients however experienced a worsening of their concussion symptoms during the course of treatment. The remaining patients had some discomfort in relation to treatment, mainly headache, but passing and less for each treatment. The majority (n = 5) had a reduction in symptoms overall, up to 61% (2%-61%) based on the Rivermead Post-Concussion Symptoms Questionnaire., Conclusion: Further studies on T-PEMF as a treatment option for post-concussion syndrome are warranted., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Objectives: Brain dysfunction is a serious complication after cardiac surgery. In the Perfusion Pressure Cerebral Infarcts trial, we allocated cardiac surgery patients to a mean arterial pressure of either 70-80 or 40-50 mmHg during cardiopulmonary bypass (CPB). In this secondary analysis, we compared selected cerebral metabolites using magnetic resonance spectroscopy hypothesizing that a postoperative decrease in occipital grey matter (GM) N-acetylaspartate-to-total-creatine ratio, indicative of ischaemic injury, would be found in the high-target group., Methods: Of the 197 patients randomized in the Perfusion Pressure Cerebral Infarcts trial, 55 and 42 patients had complete and useful data from GM and white matter (WM), respectively. Spectroscopies were done preoperatively and on postoperative days 3-6. Cognitive function was assessed prior to surgery, at discharge and at 3 months. We predefined the statistical significance level to be 0.01., Results: A postoperative decrease was found in GM N-acetylaspartate-to-total-creatine ratio in the high-target group [mean difference -0.09 (95% confidence interval -0.14 to -0.04), P = 0.014]. No significant differences were found in other metabolite ratios investigated in GM or WM. No significant association was found between changes in metabolite ratios and new cerebral infarcts, WM lesion score or cognitive dysfunction., Conclusions: A higher mean arterial pressure during CPB was associated with signs of impaired cerebral metabolism, though not at the predefined significance level of 0.01. No significant association was found between metabolite ratio changes and neuroradiological pathology or change in cognitive function., Clinical Trial Registration Number: Clinicaltrials.gov: NCT02185885., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy ( 1 H-MRS) after an intervention is of interest for studying various brain disorders. However, 1 H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1 H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1 H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1 H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) ( p < 0.001), lower linewidth ( p = 0.001) and lower Cramér-Rao lower bounds (CRLB) ( p < 0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T ( p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1 H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1 H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is advantageous for future investigations of excitatory-inhibitory mechanisms in brain disorders., (Copyright © 2020 Younis, Hougaard, Christensen, Vestergaard, Petersen, Boer, Paulson, Ashina, Marsman and Larsson.)

Proton MR spectroscopy ( 1 H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1 H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1 H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N -acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy ( 1 H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1 H-MRS at ultra-high field strength can potentially improve the consistency of findings. Using 7T 1 H-MRS, we assessed levels of mIns, tCr, and tCho (glia-related metabolites) and tNAA and Glu (neuron-related metabolites) in ACC, DLPFC, hippocampus, and thalamus. We found higher levels of glia-related metabolites in all brain regions in older individuals. Working memory performance correlated negatively with regional levels of glia-related metabolites. This study is the first to investigate normal ageing in these brain regions using 7T 1 H-MRS and findings indicate that glia-related metabolites could be valuable in cognitive ageing studies., (Copyright © 2020 the authors.)

Background: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response., Methods: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites., Results: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome., Conclusions: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the diagnostic added value of electrical source imaging (ESI) in presurgical evaluation of patients with drug resistant focal epilepsy., Methods: Eighty-two consecutive patients were included. We analyzed both low density (LD) and high density (HD) EEG recordings. LD ESI was done on interictal and ictal signals recorded during long-term video-EEG monitoring (LTM), with standard 25 electrodes and age-matched template head models. HD ESI was done on shorter recordings (90-120 min), with 256 electrodes, using individual head model. The multidisciplinary team made decisions first blinded to ESI (based on all other modalities) and then discussed the results of the ESI. We considered that ESI had diagnostic added value, when it provided non-redundant information that changed the patientś management plan., Results: ESI had diagnostic added value in 28 patients (34%). In most cases (85.7%), these changes were related to planning of the invasive recordings. In nine out of 13 patients, invasive recordings confirmed the localization. Out of eight patients in whom the ESI source was resected, six became seizure-free., Conclusions: ESI provides non-redundant information in one third of the patients undergoing presurgical evaluation., Significance: This study provides evidence for the diagnostic added value of ESI in presurgical evaluation., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of spatial sampling and of recording duration on the diagnostic yield of EEG for identification of interictal epileptiform discharges (IEDs). Previous studies demonstrated that high-density (HD) recordings increased accuracy of localization compared to low-density (LD) recordings., Methods: We have prospectively evaluated the effect of spatial sampling and of recording duration in patients who had short-term (ST) recordings with a HD array of 256 electrodes following long-term (LT) recordings with a LD array consisting of the standard IFCN array of 25 electrodes. IED clusters were identified in four datasets: LT-LD, ST-LD (spatially down-sampled to the standard IFCN array), ST-HD and a shortened (90 minutes) epoch of LT-LD., Results: Sixty consecutive patients were recruited. We identified 89 IED clusters totally. Two clusters were found by increasing spatial sampling from 25 to 256 electrodes. This modest increase was not statistically significant. Eight clusters were missed by reducing the recording duration to 90 minutes, as compared with the LT recordings (p = 0.003)., Conclusions: Recording duration is more important for the diagnostic yield of EEGs than increasing spatial sampling beyond the standard IFCN electrode array., Significance: The standard IFCN electrode array provides sufficient spatial sampling for identification of the IEDs., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Postoperative cognitive dysfunction (POCD) occurs commonly after cardiac surgery. Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rScO 2 ) in order to minimise the occurrence of POCD by applying dedicated interventions when rScO 2 decreases. However, the association between rScO 2 intraoperatively and POCD has not been clarified., Methods: This is a secondary analysis of a randomised trial with physician-blinded NIRS monitoring and cognitive testing at discharge from hospital and at 3 months after surgery. The association between intraoperative rScO 2 values and POCD at discharge from hospital and at 3 months after surgery was investigated. The prespecified candidate predictive variable of interest was cumulative time during surgery with rScO 2 ≥10% below its preoperative value., Results: One hundred and fifty-three patients had complete NIRS data and neurocognitive assessments at discharge, and 44 of these patients (29%) had POCD. At 3 months, 148 patients had complete data, and 12 (8%) of these patients had POCD. The median time with rScO 2 >10% below preoperative values did not differ for patients with and without POCD at discharge (difference=0.0 min; Hodges-Lehmann 95% confidence interval, -3.11-1.47, P=0.88). Other rScO 2 time thresholds that were assessed were also not significantly different between those with and without POCD at discharge. This applied both to absolute rScO 2 values and relative changes from preoperative values. Similar results were found in relation to POCD at 3 months., Conclusions: No significant association was found between intraoperative rScO 2 values and POCD. These findings bring into question the rationale for attempting to avoid decreases in rScO 2 if the goal is to prevent POCD., Clinical Trial Registration: NCT02185885., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Autoregulation of cerebral blood flow (CBF) denotes that CBF is constant despite fluctuation of blood pressure within wide limits. Inhibition of the renin-angiotensin system (RAS) is known to decrease the lower and upper limits of CBF autoregulation. We have previously shown that this includes inhibition by the angiotensin receptor blocker (ARB) candesartan. In the present study we investigated the influence of the ARB candesartan on the lower limit of CBF autoregulation in two groups of Sprague-Dawley rats, on high (4.0% Na + ) and low (0.004% Na + ) sodium diet, respectively. Control animals were given the same diet, but no ARB. CBF was studied with the laser Doppler method. Blood pressure was lowered by controlled bleeding. Results revealed that both high and low sodium diet with low and high renin levels respectively block the influence of candesartan on CBF autoregulation. This was expected in rats on a high salt diet with a low renin level, but unexpected in rats with a low salt intake with a high renin level.

Background: Brain injury and cognitive dysfunction are serious complications after cardiac surgery. In the perfusion pressure cerebral infarcts (PPCI) trial, we allocated cardiac surgery patients to a mean arterial pressure of either 70-80 mm Hg (high-target) or 40-50 mm Hg (low-target) during cardiopulmonary bypass. In this secondary analysis, we aimed to assess potential differences in domain-specific patterns of cognitive deterioration between allocation groups and to investigate any associations of postoperative cognitive dysfunction (POCD) with diffusion-weighted magnetic resonance imaging (DWI)-detected brain lesions., Methods: Of the 197 patients randomized in the PPCI trial, 89 in the low-target group and 80 in the high-target group had complete DWI datasets, and 92 and 80 patients had complete data for an evaluation of cognitive function at discharge respectively. Cognitive function was assessed prior to surgery, at discharge and at 3 months. DWI was obtained at baseline and on postoperative days 3 to 6., Results: We found no statistically significant differences between the two groups when comparing the proportion of patients with a domain-specific deterioration over the pre-defined critical level in seven individual test variables at discharge. Significant deterioration was most common in tests thought to assess cognitive flexibility and interference susceptibility and least common in the memory test. POCD at discharge was more frequent in patients with DWI-positive brain lesions (OR adjusted for age and group allocation: 2.24 [95% CI 1.48-3.00], P = 0.036)., Conclusions: Domain-specific patterns of POCD were comparable between groups. A significant association was seen between DWI-positive brain lesions and POCD., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery., Methods: Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design., Results: Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable between 3.0 T and 7.0 T., Conclusions: Our findings suggest no gain from the increase in voxel resolution but cemented dilatory findings from earlier. The implemented software update improved variance in circumference measurements in the intradural middle meningeal artery, which should be exploited in future studies., Trial Registration: The study is part of a parent study, which is registered at ClinicalTrials.gov ( NCT03143465 ).

Background: Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery., Methods: In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days., Results: Twelve healthy volunteers completed the study. The area under the curve Baseline-120min was significantly larger on both the sildenafil and the calcitonin gene-related peptide day in the intradural middle meningeal artery (calcitonin gene-related peptide, p = 0.013; sildenafil, p = 0.027) and the extracranial middle meningeal artery (calcitonin gene-related peptide, p = 0.0003; sildenafil, p = 0.021), compared to placebo. Peak intradural middle meningeal artery dilation was 9.9% (95% CI [2.9-16.9]) after sildenafil (T 30min ) and 12.5% (95% CI [8.1-16.8]) after calcitonin gene-related peptide (T 30min ). Peak dilation of the extracranial middle meningeal artery after calcitonin gene-related peptide (T 30min ) was 15.7% (95% CI [11.2-20.1]) and 18.9% (95% CI [12.8-24.9]) after sildenafil (T 120min )., Conclusion: An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels. We suggest that intradural artery dilation is associated with headache induced by calcitonin gene-related peptide and sildenafil.

Purpose: For rapid spatial mapping of gamma-aminobutyric acid (GABA) at the increased sensitivity and spectral separation for ultra-high magnetic field strength (7 tesla [T]), an accelerated edited magnetic resonance spectroscopic imaging technique was developed and optimized for the human brain at 7 T., Methods: A MEGA-sLASER sequence was used for GABA editing and volume selection to maximize editing efficiency and minimize chemical shift displacement errors. To accommodate the high bandwidth requirements at 7 T, a single-shot echo planar readout was used for rapid simultaneous encoding of the temporal dimension and 1 spatial. B 0 and B 1 field aspects specific for 7 T were studied together with correction procedures, and feasibility of the EPSI MEGA-sLASER technique was tested in vivo in 5 healthy subjects., Results: Localized edited spectra could be measured in all subjects giving spatial GABA signal distributions over a central brain region, having 45- to 50-Hz spatial intervoxel B 0 field variations and up to 30% B 1 field deviations. MEGA editing was found unaffected by the B 0 inhomogeneities for the optimized sequence. The correction procedures reduced effects of intervoxel B 0 inhomogeneities, corrected for spatial editing efficiency variations, and compensated for GABA resonance phase and frequency shifts from subtle motion and acquisition instabilities. The optimized oscillating echo-planar gradient scheme permitted full spectral acquisition at 7 T and exhibited minimal spectral-spatial ghosting effects for the selected brain region., Conclusion: The EPSI MEGA-sLASER technique was shown to provide time-efficient mapping of regional variations in cerebral GABA in a central volume of interest with spatial B 1 and B 0 field variations typical for 7 T., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: Glucocorticoids are widely used in the treatment of several pediatric diseases with undisputed disease-related benefits. Perinatal exposure to high levels of glucocorticoids can have long-term adverse cerebral effects. In adults, glucocorticoid treatment has been associated with smaller volumes of subcortical grey matter structures. Recently, we observed smaller total brain volumes in children and adolescents treated with glucocorticoid during childhood compared to healthy controls. The possible long-term effects of glucocorticoid treatment during childhood on subcortical brain volume and microstructure remain unknown., Method: We examined 30 children and adolescents, who had previously been treated with glucocorticoids for nephrotic syndrome or rheumatic disease, and 30 healthy volunteers. Patients and healthy control groups were matched by age, gender, and level of parent education. Participants underwent 3 T magnetic resonance (MR) brain imaging. T1-weighted and diffusion-weighted images were acquired. Volume and mean diffusivity (MD) measures were extracted for hippocampus, amygdala, nucleus accumbens, caudate nucleus and putamen. Multiple linear regression analyses were used to assess differences between patients and controls, and to evaluate possible dose-response relationships. A priori, we expected patients to display lower hippocampal and amygdala volumes., Results: While children previously treated with glucocorticoids displayed smaller right hippocampal volumes than controls, this difference did not survive correction for multiple comparisons. Furthermore, patients as compared to controls showed lower right hippocampal MD, which remained when correcting for global changes in MD. The longer the time between the glucocorticoid treatment termination and MR-scan, the more right hippocampal MD values resembled that of healthy controls. Patient and controls did not differ in amygdala volume or MD. Analyses of the nucleus accumbens, caudate nucleus and putamen only revealed smaller putamen volumes in patients compared to controls, which remained significant when controlling for total brain volume., Conclusion: The results suggest that extra-cerebral diseases during childhood treated with glucocorticoids may be associated with reduced subcortical grey matter volumes and lower right hippocampal mean diffusivity later in life. Our findings warrant replication and elaboration in larger, preferably prospective and longitudinal studies. Such studies may also allow disentangling disease-specific effects from possible glucocorticoid treatment effects., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)