BACKGROUND: Supplementary motor area syndrome (SMAS) may occur after frontal tumor surgery, with variable presentation and outcomes. We reviewed the literature on postoperative SMAS after brain... Show moreBACKGROUND: Supplementary motor area syndrome (SMAS) may occur after frontal tumor surgery, with variable presentation and outcomes. We reviewed the literature on postoperative SMAS after brain tumor resection.METHODS: PubMed, Web of Science, Scopus, and Cochrane were searched following the PRISMA guidelines to include studies reporting SMAS after brain tumor resection.RESULTS: We included 31 studies encompassing 236 patients. Most tumors were gliomas (94.5%), frequently of low grade (61.4%). Most lesions were located on the left hemisphere (64.4%), involving the supplementary motor area (61.4%) and the cingulate gyrus (20.8%). Tractography and functional magnetic resonance imaging evaluation were completed in 45 (19.1%) and 26 (11%) patients. Gross total resection was achieved in 46.3% patients and complete SMA resection in 69.4%. A total of 215 procedures (91.1%) used intraoperative neuromonitoring mostly consisting of direct cortical/subcortical stimulation (56.4%), motor (33.9%), and somatosensory (25.4%) evoked potentials. Postoperative SMAS symptoms occurred within 24 hours after surgery, characterized by motor deficits (97%), including paresis (68.6%) and hemiplegia (16.1%), and speech disorders (53%), including hesitancy (24.2%) and mutism (22%). Average SMAS duration was 45 days (range, 1-365 days), with total resolution occurring in 188 patients (79.7%) and partial improvement in 46 (19.5%). Forty-eight patients (20.3%) had persisting symptoms, mostly speech hesitancy (60.4%) and fine motor disorders (45.8%).CONCLUSIONS: Postoperative SMAS may occur within the first 24 hours after mesial frontal tumor surgery. Preoperative mapping and intraoperative neuromonitoring may assist resection and predict outcomes. Neuroplasticity and interhemispheric connectivity play a major role in resolution. Show less
The overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental... Show moreThe overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental patterns across adolescence of two forms of social learning: (1) learning about other people, specifically, whether they are (un)cooperative and (un)trustworthy, and (2) learning for other people (prosocial learning) to know what actions may benefit or help others. I made use of multiple experimental paradigms based on well-known economic games and/or probabilistic reinforcement learning paradigms to assess these forms of social learning. Secondly, I aimed to examine underlying mechanisms and factors that account for age-related and individual differences in social learning. Applying computational modeling and functional neuroimaging as additional tools contributed to a better understanding of the underlying mechanisms and how these develop across adolescence. The findings in this thesis converge to early-to-mid adolescence as a key developmental period for developing well-adjusted social behaviors, and especially in the cooperative domain there are pronounced improvements. These studies make an important contribution to the literature on social development and learning, and may eventually contribute to interventions targeted at promoting well-adjusted behavior in typically developing adolescents, as well as youth with maladaptive social tendencies. Show less
Whitehouse, D.P.; Monteiro, M.; Czeiter, E.; Vande Vyvere, T.; Valerio, F.; Ye, Z.; ... ; CENTER-TBI Participants Investigat 2022
Background We aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI.Methods... Show moreBackground We aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI.Methods Concentrations of six serum biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1) were measured in samples obtained <24 hours post-injury from 2869 patients with all severities of TBI, enrolled in the CENTER-TBI prospective cohort study (NCT02210221). Imaging phenotypes were defined as intraparenchymal haemorrhage (IPH), oedema, subdural haematoma (SDH), extradural haematoma (EDH), traumatic subarachnoid haemorrhage (tSAH), diffuse axonal injury (DAI), and intraventricular haemorrhage (IVH). Multivariable polynomial regression was performed to examine the association between biomarker levels and both distinct lesion types and lesion volumes. Hierarchical clustering was used to explore imaging phenotypes; and principal component analysis and k-means clustering of acute biomarker concentrations to explore patterns of biomarker clustering.Findings 2869 patient were included, 68% (n=1946) male with a median age of 49 years (range 2-96). All severities of TBI (mild, moderate and severe) were included for analysis with majority (n=1946, 68%) having a mild injury (GCS 13-15). Patients with severe diffuse injury (Marshall III/IV) showed significantly higher levels of all measured biomarkers, with the exception of NFL, than patients with focal mass lesions (Marshall grades V/VI). Patients with either DAI+IVH or SDH+IPH+tSAH, had significantly higher biomarker concentrations than patients with EDH. Higher biomarker concentrations were associated with greater volume of IPH (GFAP, S100B, t-tau;adj r2 range:0.48-0.49; p<0.05), oedema (GFAP, NFL, NSE, t-tau, UCH-L1;adj r2 range:0. 44-0.44; p<0.01), IVH (S100B;adj r2 range:0.48-0.49; p<0.05), Unsupervised k-means biomarker clustering revealed two clusters explaining 83.9% of variance, with phenotyping characteristics related to clinical injury severity.Interpretation Interpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury. Copyright (C) 2021 The Author(s). Published by Elsevier B.V. Show less
The estimated accuracy of a classifier is a random quantity with variability. A common practice in supervised machine learning, is thus to test if the estimated accuracy is significantly better... Show moreThe estimated accuracy of a classifier is a random quantity with variability. A common practice in supervised machine learning, is thus to test if the estimated accuracy is significantly better than chance level. This method of signal detection is particularly popular in neuroimaging and genetics. We provide evidence that using a classifier's accuracy as a test statistic can be an underpowered strategy for finding differences between populations, compared to a bona fide statistical test. It is also computationally more demanding than a statistical test. Via simulation, we compare test statistics that are based on classification accuracy, to others based on multivariate test statistics. We find that the probability of detecting differences between two distributions is lower for accuracy-based statistics. We examine several candidate causes for the low power of accuracy-tests. These causes include: the discrete nature of the accuracy-test statistic, the type of signal accuracy-tests are designed to detect, their inefficient use of the data, and their suboptimal regularization. When the purpose of the analysis is the evaluation of a particular classifier, not signal detection, we suggest several improvements to increase power. In particular, to replace V-fold cross-validation with the Leave-One-Out Bootstrap. Show less
Verwer, E.E.; Golla, S.S.V.; Kaalep, A.; Lubberink, M.; Velden, F.H.P. van; Bettinardi, V.; ... ; Boellaard, R. 2021
Purpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were... Show morePurpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed.Methods Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based "digital" systems) were used to acquire 30-min PET scans of a Hoffman 3D Brain phantom filled with similar to 33 kBq.mL(-1) [F-18]FDG. Scan data were reconstructed using various reconstruction settings. The images were rigidly coregistered to a template (voxel size 1.17 x 1.17 x 2.00 mm(3)) onto which several volumes of interest (VOIs) were defined. Recovery coefficients (RC) and grey matter to white matter ratios (GMWMr) were derived for eroded (denoted in the text by subscript e) and non-eroded grey (GM) and white (WM) matter VOIs as well as a mid-phantom cold spot (VOIcold) and VOIs from the Hammers atlas. In addition, left-right hemisphere differences and voxel-by-voxel differences compared to a reference image were assessed.Results Systematic differences were observed for reconstructions with and without point-spread-function modelling (PSFON and PSFOFF, respectively). Normalising to image-derived activity, upper and lower limits ensuring image comparability were as follows: for PSFON, RCGMe = [0.97-1.01] and GMWMr(e) = [3.51-3.91] for eroded VOI and RCGM = [0.78-0.83] and GMWMr = [1.77-2.06] for non-eroded VOI, and for PSFOFF, RCGMe = [0.92-0.99] and GMWMr(e) = [3.14-3.68] for eroded VOI and RCGM = [0.75-0.81] and GMWMr = [1.72-1.95] for non-eroded VOI.Conclusions To achieve inter-scanner comparability, we propose selecting reconstruction settings based on RCGMe and GMWMr(e) as specified in "Results". These proposed standards should be tested prospectively to validate and/or refine the harmonisation criteria. Show less
Christensen, C.E.; Younis, S.; Lindberg, U.; Koning, P. de; Tolnai, D.; Paulson, O.B.; ... ; Ashina, M. 2021
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,... Show moreThe 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. Show less
Drenth, N.; Grond, J. van der; Rombouts, S.A.R.B.; Buchem, M.A. van; Terwindt, G.M.; Wermer, M.J.H.; ... ; Rooden, S. van 2021
Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain... Show moreCerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain functioning needs further investigation. Here we study functional brain connectivity in patients with Dutch type hereditary CAA using resting state functional MRI. Twenty-four DNA-proven Dutch CAA mutation carriers (11 presymptomatic, 13 symptomatic) and 29 age-matched control subjects were included. Using a set of standardized networks covering the entire cortex, we assessed both within- and between-network functional connectivity. We investigated group differences using general linear models corrected for age, sex and gray matter volume. First, all mutation carriers were contrasted against control subjects and subsequently presymptomatic- and symptomatic mutation carriers against control subjects separately, to assess in which stage of the disease differences could be found. All mutation carriers grouped together showed decreased connectivity in the medial and lateral visual networks, default mode network, executive control and bilateral frontoparietal networks. Symptomatic carriers showed diminished connectivity in all but one network, and between the left and right frontoparietal networks. Presymptomatic carriers also showed diminished connectivity, but only in the frontoparietal left network. In conclusion, global brain functioning is diminished in patients with CAA, predominantly in symptomatic CAA and can therefore be considered to be a late consequence of the disease. Show less
Purpose of ReviewClinical presentation of central hypersomnolence disorders, including narcolepsy type 1 and 2 and idiopathic hypersomnia, is often similar, and determining the correct diagnosis... Show morePurpose of ReviewClinical presentation of central hypersomnolence disorders, including narcolepsy type 1 and 2 and idiopathic hypersomnia, is often similar, and determining the correct diagnosis remains challenging. Neuroimaging techniques have provided valuable insights into the pathophysiology of narcolepsy and idiopathic hypersomnia. Here, we review current structural and functional brain imaging findings in central hypersomnolence disorders and discuss the future perspectives of neuroimaging in these sleep disorders.Recent FindingsMost studies have focused on narcolepsy type 1 (or narcolepsy with cataplexy), showing inconsistent but extensive structural differences in the hypothalamus and its normally widespread projections. Functional studies have mainly focused on resting-state or emotion regulation in narcolepsy type 1 and have revealed disturbed activity in limbic and mesolimbic structures in relation to cataplexy. Finally, recent studies suggest a disruption of the default-mode network in patients with idiopathic hypersomnia.SummaryMost neuroimaging studies to date have been conducted in small samples, while narcolepsy type 2 (or narcolepsy without cataplexy) and idiopathic hypersomnia remain relatively understudied. Larger studies with consistent clinical phenotyping should be the focus of future investigations. In addition, multi-modal imaging methods will be crucial to resolve previous inconsistencies and identify reliable objective biomarkers that could aid in understanding the pathophysiology and potentially support the diagnostic process. Show less
In this thesis a literature review was conducted to map the results of earlier neuroimaging studies in minors who experienced childhood psychological trauma. Next, three different structural... Show moreIn this thesis a literature review was conducted to map the results of earlier neuroimaging studies in minors who experienced childhood psychological trauma. Next, three different structural neuroimaging techniques were employed to study the effects of childhood sexual trauma in youth .Main findings:1. Neuroimaging studies in traumatised children and adolescents are scarce and heterogeneous in design, in particular with regard to the sample studied and type of trauma.2. The results of structural neuroimaging studies in traumatised minors differ from those in adult populations, in particular with regard to findings on hippocampus and corpus callosum (CC).3. Paralleling the inconsistent findings on hippocampal volume reduction in traumatised minors, our VBM-study did not show differences between groups for hippocampal volume.4. VBM showed smaller volumes of key regions of the limbic system (ACC, amygdala) in the CSA-related PTSD group compared to controls.5. Adolescents with sexual abuse-related PTSD show no abnormalities in cortical thickness, in line with findings in adults. 6. Adolescents with CSA-related PTSD show less integrity of parts of the CC compared to healthy non-traumatised controls.7. Our structural neuroimaging studies showed limited associations with trauma symptomatology, in line with findings in studies in minors. Show less
Duchenne muscular dystrophy is a multifactorial disease including a cognitive phenotype. It is caused by mutations in the X-chromosomal DMD gene from which dystrophin is synthesized. Multiple... Show moreDuchenne muscular dystrophy is a multifactorial disease including a cognitive phenotype. It is caused by mutations in the X-chromosomal DMD gene from which dystrophin is synthesized. Multiple isoforms of dystrophin have been identified. The full length dystrophin isoform Dp427 m is expressed predominantly in muscle. Other isoforms include: Dp427(c), Dp427(p), Dp260, Dp140, Dp116, Dp71 and Dp40. The majority of these isoforms are expressed in brain and several hypotheses exist on their role in subtypes of neurons and astrocytes. However, their function in relation to cognition remains unclear. Unlike progressive muscle wasting, cognitive involvement is not seen in all DMD patients and the severity varies greatly. To achieve a better understanding of brain involvement in DMD, a multidisciplinary approach is required. Here, we review the latest findings on dystrophin isoform expression in the brain; specific DMD-associated learning and behavioural difficulties; and imaging and spectroscopy findings relating to brain structure, networks, perfusion and metabolism. The main challenge lies in determining links between these different findings. If we can determine which factors play a role in the differentiation between severe and minor cognitive problems in DMD in the near future, we can both provide better advise for the patients and also develop targeted therapeutic interventions. (C) 2020 The Author(s). Published by Elsevier B.V. Show less
Christensen, C.E.; Amin, F.M.; Younis, S.; Lindberg, U.; Koning, P. de; Petersen, E.T.; ... ; Ashina, M. 2019
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... Show moreBackground 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 invivo. 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. Show less
Doef, T.F. van der; Domingo, S.Z.; Jacobs, G.E.; Drevets, W.C.; Marston, H.M.; Nathan, P.J.; ... ; Kas, M.J.H. 2018
*****This dissertation has been published as : "Love and Selfhood : Self-understanding Through Philosophy and Cognitive Neuroscience" and can be found at : https://link.springer.com/book/10.1007...Show more*****This dissertation has been published as : "Love and Selfhood : Self-understanding Through Philosophy and Cognitive Neuroscience" and can be found at : https://link.springer.com/book/10.1007/978-3-031-06801-0 *****‘Who am I really?’ When people ask themselves this question, they often find themselves in situations or dilemmas that may be labeled ‘existential’. They need to take an important decision, for example, and reflect on what is of fundamental importance to them. Also without explicit self-reflection, people’s behavior and experiences are influenced by what they care about most. Several philosophers have reflected on this existential aspect of selfhood. These days, cognitive neuroscientists too investigate e.g. love and self-reflection. What contributions to our understanding of the existential aspect of human lives can philosophy and cognitive neuroscience (CNS) make?I investigate existing CNS research into love and self-reflection and existing philosophies of existential selfhood, by Harry Frankfurt, Søren Kierkegaard and Charles Taylor, amongst others. I argue that CNS and philosophy are not in opposition with each other, as they address different types of questions. Moreover, CNS may benefit from cooperation with philosophy where reflection on moments of interpretation in its research process is concerned. I develop conceptual review as a tool to do so. I end with a philosophical view on existential selfhood and existential self-understanding that improves on existing philosophies and integrates insights from CNS where applicable. Show less
This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological... Show more This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological aging, with differences in network degeneration between different types of dementia. These disease-specific network differences suggest the potential of brain networks to improve diagnostic accuracy. However, at this moment, our findings are only applicable for groups of patients and not yet suitable as a diagnostic tool on an individual basis. Show less
Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur... Show moreDiffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur within neurons can be reflected as changes in the diffusivity of tNAA, whereas the changes in glial cells can cause pronounced changes in the diffusivities of tCr and tCho. This information combined with that obtained from diffusion tensor imaging (DTI) and other MRI tools can help elucidate various disease processes in the future. The main purposes of this thesis are (i) to investigate neuroanatomy in vivo with DW-MRS, (ii) to develop methodology to enable future clinical applications of the technique in human brain in vivo, and (iii) to characterize the microstructural deficit in neuropsychiatric systemic lupus erythematous (NPSLE) with DW-MRS and other microstructural tools such as DTI and magnetization transfer imaging. The studies presented in this thesis show the robustness and clinical relevance of microstructural information obtained via DW-MRS. The contributions of this thesis such as the optimized acquisition protocols for single volume DW-MRS, the robust DW-CSI and DW-MRS post-processing pipelines that comprise information from DTI, will all facilitate the applications of DW-MRS both for basic neuroscience research and clinical research studies. Show less
Klinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with... Show moreKlinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with 47,XXY, boys with idiopathic autism spectrum disorder, and non-clinical controls, using multiple imaging techniques. The goal was to assess the mechanisms underlying social dysfunction in 47,XXY, and to investigate to what degree these mechanisms differ from those in individuals with idiopathic autism. The results show that individuals with 47,XXY show characteristic deviations in brain structure and function associated with higher order cognitive functions, social emotional information processing, and language processing. Additionally, while boys with 47,XXY show considerable overlap with boys with idiopathic ASD in autism symptomatology, there are specific differences in the underlying neural mechanisms that revolve around the frontal lobes and insular cortices. These findings may have implications for intervention studies (e.g. focused on real time fMRI neurofeedback), as well as clinical practice. It may impact the selection of mental health care strategies that take into account this variability in mechanisms underlying social dysfunction in individuals with autism spectrum disorder. Show less
