Olaf B Paulson

• MD, DMSc
• Professor (Full) at Rigshospitalet

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 stimu...

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...

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...

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. T...

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 stimu...

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 valua...

Background and Purpose: Magnetic resonance spectroscopy (MRS) – a method to analyse metabolites in vivo – has been utilized in several studies of brain glioma biomarkers at lower fields strengths. At ultrahigh field strengths, MRS provides improved signal-to-noise-ratio and spectral resolution, but 7T studies on patients with gliomas are sparse. Th...

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. DLGG’s usually transforms to higher malignancy, are causing progressive disability and premature death. MRI scans are v...

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 ther...

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 a...

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...

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...

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...

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy (¹H-MRS) after an intervention is of interest for studying various brain disorders. However, ¹H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. ¹H-MRS of more cortical structures at the ultrahigh magnetic fie...

Proton MR spectroscopy (1H-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 1H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was...

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 r...

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,...

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...

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 prospective...

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 p...

Background: Postoperative cognitive dysfunction (POCD) occurs commonly after cardiac surgery. Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rScO2) in order to minimise the occurrence of POCD by applying dedicated interventions when rScO2 decreases. However, the association between rScO2 intraoperat...

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. Re...

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 a...

Abstract The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroti...

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 G...

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 i...

Background: Studies involving human pharmacological migraine models have predominantly focused on the vasoactive effects of headache-inducing drugs, including sildenafil and calcitonin gene-related peptide (CGRP). However, the role of possible glutamate level changes in the brainstem and thalamus is of emerging interest in the field of migraine re...

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression but its neurocognitive mechanisms are unclear. This randomized, sham-controlled functional magnetic resonance imaging (fMRI) study explored the effects of a single ECT on neural response to affective pictures. Twenty-seven patients with major depressive disorder w...

Background: Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Methods: Longitudinal neuroimaging and clinical data from 10 in...

Background -Cerebral injury is an important complication following cardiac surgery with the use of cardiopulmonary bypass (CPB). The rate of overt stroke after cardiac surgery is 1-2%, whereas silent strokes, detected by diffusion-weighed magnetic resonance imaging (DWI), are found in up to 50% of patients. It is unclear if a higher versus a lower...

Purpose: With the advent of new very selective techniques like thermal laser ablation to treat drug-resistant focal epilepsy, the controversy of resection size in relation to seizure outcome versus cognitive deficits has gained new relevance. The purpose of this study was to test the influence of the selective amygdalohippocampectomy (SAH) versus...

BACKGROUND: Perinatal exposure to glucocorticoids and elevated endogenous glucocorticoid-levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid-treatment during childhood on brain volumes. METHODS: Thirty children and adolescents with rheumatic or nephrotic disease previously tr...

Background Negative neurocognitive bias is a core feature of depression that is reversed by antidepressant drug treatment. However, it is unclear whether modulation of neurocognitive bias is a common mechanism of distinct biological treatments. This randomized controlled functional magnetic resonance imaging study explored the effects of a single e...

We evaluated the use of hyperpolarized ¹³C magnetic resonance imaging (MRI) in an open-chest rat model of myocardial infarction to image regional changes in myocardial metabolism. In total, 10 rats were examined before and after 30 minutes of occlusion of the left anterior descending coronary artery using hyperpolarized [1-¹³C]pyruvate. Cardiac met...

Heightened levels of glucocorticoids in children and adolescents have previously been linked to prolonged changes in the diurnal regulation of the stress-hormone cortisol, a glucocorticoid regulated by the hypothalamic-pituitary-adrenal-axis (HPA-axis). To address this question, we examined the salivary cortisol awakening response (CAR) and daily c...

Purpose Concurrent EEG and fMRI is increasingly used to characterize the spatial-temporal dynamics of brain activity. However, most studies to date have been limited to conventional echo-planar imaging (EPI). There is considerable interest in integrating recently developed high-speed fMRI methods with high-density EEG to increase temporal resolutio...

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EEG cap with the respective temperature probes. Electrode display in the 256-channel (left) and the 64-channel (right). The temperature probes were placed underneath the electrodes marked with the red circle, or underneath one of the neighboring electrodes. The ear temperature probe was placed on the left or the right side. (TIF)

From which Fig 2 was constructed. (CSV)

Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocognitive bias in major depressive disorder. Patients wi...

Objective: Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. Method:...

Background: Debilitating brain injury occurs in 1.6-5 % of patients undergoing cardiac surgery with cardiopulmonary bypass. Diffusion-weighted magnetic resonance imaging studies have reported stroke-like lesions in up to 51 % of patients after cardiac surgery. The majority of the lesions seem to be caused by emboli, but inadequate blood flow cause...

Background: Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the...

This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) e...

Objective: To examine how the motor system recover from a motor relapse in multiple sclerosis (MS). We addressed this question by prospectively assessing functional brain connectivity with resting-state functional magnetic resonance imaging (fMRI) in patients with MS who presented with an acute motor relapse. Methods: 12 MS patients underwent resti...

To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). We used magnetic resonance (MR) imaging including diffusion tensor imaging (DTI) and proton MR spectroscopy ((1) H-MRS) to investigate hippocampal volume, diffusivity, and metabolite changes in 19 patients receiving ECT for severe depr...

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 n...

AimPerinatal exposure to glucocorticoids has been associated with adverse cerebral effects, but little is known about their effect on cognitive development and exposure later in childhood. This study examined intellectual abilities, memory and behavioural problems in children previously treated with glucocorticoids.Methods We evaluated 38 children...

To use dynamic magnetic resonance spectroscopy (MRS) of hyperpolarized (13) C-pyruvate to follow the progress over time in vivo of breast cancer metabolism in the MMTV-PymT model, and to follow the response to the anti-estrogen drug tamoxifen. Tumor growth was monitored by anatomical MRI by measuring tumor volumes. Dynamic MRS of hyperpolarized (13...

Background: Persistent cognitive dysfunction in depression and bipolar disorder (BD) impedes patients' functional recovery. Erythropoietin (EPO) increases neuroplasticity and reduces cognitive difficulties in treatment-resistant depression (TRD) and remitted BD. This magnetic resonance imaging study assessed the neuroanatomical basis for these eff...

Diffusion Weighted Imaging (DWI) is used to study white-matter fibre organization, orientation and structural connectivity by means of fibre reconstruction algorithms and tractography. For clinical settings, limited scan time compromises the possibilities to achieve high image resolution for finer anatomical details and signal-to-noise-ratio for re...

Objective: To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Methods: Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including th...

The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague-Dawley rats with laser Doppler technique. The blood...

Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study changes in long-range functional brain connectivity in multiple sclerosis (MS). Yet little is known about how MS affects functional brain connectivity at the local level. Here we studied 42 patients with MS and 30 matched healthy controls with whole-brain rs-fMRI a...

Bo K Siesjo was an outstanding brain researcher and will be remembered as such. He was born in Sweden on 8 January 1930 and died in his home country on the 27 June 2013. He graduated from medical school at the Lund's University in 1958 and defended his PhD thesis at the same university in 1962. His postgraduate training took place in Sweden and Cam...

Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. Method In a two-step functional magnetic resonance imaging (fMRI) investigation, we first...

Background: The serotonin 2A (5-HT2A) receptor has been implicated in neural-processing of emotionally salient information. To elucidate its role in processing of fear and anger, healthy individuals were studied with functional magnetic resonance imaging (fMRI) after 5-HT2A receptor blockade, while judging the gender of neutral, fearful and angry...

Pharmacological studies point to a role of the neurotransmitter serotonin (5-HT) in regulating the preference for risky decisions, yet the functional contribution of specific 5-HT receptors remains to be clarified. We used pharmacological fMRI to investigate the role of the 5-HT2A receptors in processing negative outcomes and regulating risk-averse...

Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute administration of phencyclidine (PCP) induces schizo...

In this meta-analysis, four of five placebo-controlled studies showed that antihypertensive treatment prevented stroke recurrence, most markedly in a study with a combination of an angiotensin-converting enzyme inhibitor and a diuretic. Studies with beta-blockers were not included. Two head-to-head comparisons of a calcium antagonist and an angiote...

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 task...

To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing–remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imagin...

Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent...

Poor behavioral inhibition is a common feature of neurological and psychiatric disorders. Successful inhibition of a prepotent response in 'NoGo' paradigms requires the integrity of both the inferior frontal gyrus (IFG) and the serotonergic system. We investigated individual differences in serotonergic regulation of response inhibition. In twenty-f...

The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow and metabolism was originally performed using the Kety-Schmi...

Risk avoidance is an important determinant of human behavior. The neurotransmitter serotonin has been implicated in processing negative outcomes caused by risky decisions. However, it is unclear whether serotonin provides a neurobiological link between making a risk aversive decision and the response to a negative outcome. Using pharmacological fMR...

The main objective of this study was to determine the sensitivity of [¹¹C]CUMI-101 to citalopram challenge aiming at increasing extracellular 5-HT. CUMI-101 has agonistic properties in human embryonic kidney 293 cells transfected with human recombinant 5-HT(1A) receptors (Hendry et al. [2011] Nucl Med Biol 38:273-277; Kumar et al. [2006] J Med Chem...

Background Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contribu...

Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender of neutral, fearful and angry faces. In three separate and...

We used functional MRI (fMRI) to test the hypothesis that blind subjects recruit the ventral visual stream during nonhaptic tactile-form recognition. Congenitally blind and blindfolded sighted control subjects were scanned after they had been trained during four consecutive days to perform a tactile-form recognition task with the tongue display uni...

The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish M...

Whereas the links between eye movements and the shifts in visual attention are well established, less is known about how eye position affects the prioritization of visual space. It was recently observed that visual sensitivity varies with the direction of gaze and the level of excitability in the eye proprioceptive representation in human left soma...

Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS....

Prepulse inhibition (PPI) of the startle response, a measure for sensorimotor gating, exhibits a relatively high inter-individual variability in elderly subjects. The aim of this study was to investigate whether white matter hyperintensities (WMH), frequently identified on cranial magnetic resonance imaging (MRI) in elderly subjects with and withou...

Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the...

Purpose: The developing visual cortex has a strong potential to undergo plastic changes. Little is known about the potential of the ageing visual cortex to express plasticity. A pertinent question is whether therapeutic interventions can trigger plastic changes in the ageing visual cortex by restoring vision. Methods: Twelve patients aged 50-85...

Recent research on aging has established important links between the neurobiology of normal aging and age-related decline in episodic memory, yet the exact nature of this relationship is still unknown. Functional neuroimaging of regions such as the medial temporal lobe (MTL) have produced conflicting findings. Using functional magnetic resonance im...

Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part of the cognitive impairment seen in MS and constitute a supplement to trad...