The history of Danish neuroscience Paulson, Olaf B.; Schousboe, Arne; Hultborn, Hans
The European journal of neuroscience,
August 2023, 2023-Aug, 2023-08-00, 20230801, Volume:
58, Issue:
4
Journal Article
Peer reviewed
Open access
The history of Danish neuroscience starts with an account of impressive contributions made at the 17th century. Thomas Bartholin was the first Danish neuroscientist, and his disciple Nicolaus Steno ...became internationally one of the most prominent neuroscientists in this period. From the start, Danish neuroscience was linked to clinical disciplines. This continued in the 19th and first half of the 20th centuries with new initiatives linking basic neuroscience to clinical neurology and psychiatry in the same scientific environment. Subsequently, from the middle of the 20th century, basic neuroscience was developing rapidly within the preclinical university sector. Clinical neuroscience continued and was even reinforced during this period with important translational research and a close co‐operation between basic and clinical neuroscience. To distinguish ‘history’ from ‘present time’ is not easy, as many historical events continue in present time. Therefore, we decided to consider ‘History’ as new major scientific developments in Denmark, which were launched before the end of the 20th century. With this aim, scientists mentioned will have been born, with a few exceptions, no later than the early 1960s. However, we often refer to more recent publications in documenting the developments of initiatives launched before the end of the last century. In addition, several scientists have moved to Denmark after the beginning of the present century, and they certainly are contributing to the present status of Danish neuroscience—but, again, this is not the History of Danish neuroscience.
Danish neuroscience dates back to the 17th century. From the early phases and until the middle of the 20th century, Danish neuroscience was linked to clinical neuroscience. From the middle of the 20th century, several basic neuroscience initiatives were created at the Danish universities. The present articles describe the Danish neuroscience form its start to the end of the 20th century. The figure illustrates brain research, activation when reading allowed and a prominent neuroscientist.
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.
Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.
The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery–Åsberg Depression Rating Scale change –1.0 SE 0.35, per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope –0.69 SE 0.38, p = .069).
The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.
Cigarette smoking increases cerebral blood flow. Both nicotine and carbon monoxide contribute to the flow increase. Due to carbon monoxide’s high affinity to hemoglobin and slow clearance from the ...blood, the effect lasts for hours. Nicotine also stays in the organism for some hours. This immediate effect of smoking may explain a recently observed higher cerebral blood flow in current-smokers as compared to former-smokers.
Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected ...by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients.
In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min
·m
. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions.
Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (
=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm
(interquartile range, 0-118 mm
; range, 0-25 261 mm
) in the low-target group versus 29 mm
(interquartile range, 0-143 mm
; range, 0-22 116 mm
) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028;
=0.99), as was the secondary outcome of number of new lesions (1 interquartile range, 0-2; range, 0-24 versus 1 interquartile range, 0-2; range, 0-29 respectively; median difference estimate, 0; 95% confidence interval, 0-0;
=0.71). No significant difference was observed in frequency of severe adverse events.
Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885.
Diffusion weighted imaging (DWI) is used to study white-matter fibre organisation, 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 reliable fibre reconstruction. We assessed the potential benefits of interpolating DWI datasets to a higher image resolution before fibre reconstruction using a diffusion tensor model. Simulations of straight and curved crossing tracts smaller than or equal to the voxel size showed that conventional higher-order interpolation methods improved the geometrical representation of white-matter tracts with reduced partial-volume-effect (PVE), except at tract boundaries. Simulations and interpolation of ex-vivo monkey brain DWI datasets revealed that conventional interpolation methods fail to disentangle fine anatomical details if PVE is too pronounced in the original data. As for validation we used ex-vivo DWI datasets acquired at various image resolutions as well as Nissl-stained sections. Increasing the image resolution by a factor of eight yielded finer geometrical resolution and more anatomical details in complex regions such as tract boundaries and cortical layers, which are normally only visualized at higher image resolutions. Similar results were found with typical clinical human DWI dataset. However, a possible bias in quantitative values imposed by the interpolation method used should be considered. The results indicate that conventional interpolation methods can be successfully applied to DWI datasets for mining anatomical details that are normally seen only at higher resolutions, which will aid in tractography and microstructural mapping of tissue compartments.
•Image resolution of DWI is compromised due to limited scan time and SNR.•Interpolating DWI datasets by up-sampling can improve anatomical details in DTI.•Conventional interpolation methods can be used but the method impact the results.•Validation using multi-resolutional ex vivo monkey data, simulations and histology.
Cerebral blood flow response to functional activation Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill ...
Journal of Cerebral Blood Flow & Metabolism,
01/2010, Volume:
30, Issue:
1
Journal Article, Book Review
Peer reviewed
Open access
Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and ...glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation.
Abstract
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: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P < 10−6; isocapnic hypoxia: $0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, 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.
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 intraoperatively and POCD has not been clarified.
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 rScO2 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 rScO2 ≥10% below its preoperative value.
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 rScO2 >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 rScO2 time thresholds that were assessed were also not significantly different between those with and without POCD at discharge. This applied both to absolute rScO2 values and relative changes from preoperative values. Similar results were found in relation to POCD at 3 months.
No significant association was found between intraoperative rScO2 values and POCD. These findings bring into question the rationale for attempting to avoid decreases in rScO2 if the goal is to prevent POCD.
NCT 02185885.
•We investigated the diagnostic added value of ESI in presurgical evaluation.•ESI provided non-redundant, diagnostic information in 34% of 82 consecutive patients.•Most changes (85.7%) were related ...to the implantation of intracranial electrodes.
To investigate the diagnostic added value of electrical source imaging (ESI) in presurgical evaluation of patients with drug resistant focal epilepsy.
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.
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.
ESI provides non-redundant information in one third of the patients undergoing presurgical evaluation.
This study provides evidence for the diagnostic added value of ESI in presurgical evaluation.
Despite the importance of vision for spatial navigation, blind subjects retain the ability to represent spatial information and to move independently in space to localize and reach targets. However, ...the neural correlates of navigation in subjects lacking vision remain elusive. We therefore used functional MRI (fMRI) to explore the cortical network underlying successful navigation in blind subjects. We first trained congenitally blind and blindfolded sighted control subjects to perform a virtual navigation task with the tongue display unit (TDU), a tactile-to-vision sensory substitution device that translates a visual image into electrotactile stimulation applied to the tongue. After training, participants repeated the navigation task during fMRI. Although both groups successfully learned to use the TDU in the virtual navigation task, the brain activation patterns showed substantial differences. Blind but not blindfolded sighted control subjects activated the parahippocampus and visual cortex during navigation, areas that are recruited during topographical learning and spatial representation in sighted subjects. When the navigation task was performed under full vision in a second group of sighted participants, the activation pattern strongly resembled the one obtained in the blind when using the TDU. This suggests that in the absence of vision, cross-modal plasticity permits the recruitment of the same cortical network used for spatial navigation tasks in sighted subjects.
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