Hans C Lou's research while affiliated with Aarhus University and other places
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Publications (147)
![Distribution of [¹¹C] Ro15-4513. Main binding sites with placebo are...](publication/360906420/figure/fig2/AS:11431281115303419@1674828627854/Distribution-of-C-Ro15-4513-Main-binding-sites-with-placebo-are-prefrontal-and_Q320.jpg)
Biological evolution has led to more and more complex organisms, including humans with highly developed brains. This has facilitated adaptation to changing circumstances through conscious self-monitoring, allowing individuals to learn from experiences and to form cultural entities. More recently, a paralimbic brain network instrumental in self-awar...
![FIGURE 2 | Distribution of [11C] Ro15-4513 GABA receptor ligand. After...](publication/338863538/figure/fig2/AS:852310947295236@1580218173629/Distribution-of-11C-Ro15-4513-GABA-receptor-ligand-After-the-placebo-the-ligand-was_Q320.jpg)
The electrophysiology of the paralimbic network (“default mode”) for self-awareness has drawn much attention in the past couple of decades. In contrast, knowledge of the molecular organization of conscious experience has only lately come into focus. We here review newer data on dopaminergic control of awareness in humans, particularly in self-aware...
Introduction
We have previously shown that an interaction between medial prefrontal and parietal cortices is instrumental in promoting self‐awareness via synchronizing oscillations in the gamma range. The synchronization of these oscillations is modulated by dopamine release. Given that such oscillations result from intermittent GABA stimulation of...
Self-awareness is a pivotal component of conscious experience. It is correlated with a paralimbic network of medial prefrontal/anterior cingulate and medial parietal/posterior cingulate cortical "hubs" and associated regions. Electromagnetic and transmitter manipulation have demonstrated that the network is not an epiphenomenon but instrumental in...
![Figure 1. Distribution of [ 11 C]Ro15-4513. After placebo, the ligand...](publication/301943721/figure/fig1/AS:514958567931904@1499787098386/Distribution-of-11-CRo15-4513-After-placebo-the-ligand-was-bound-primarily-in-medial_Q320.jpg)
Background:
While it has recently been shown that dopamine release stimulates conscious self-monitoring through the generation of gamma oscillations in medial prefrontal/anterior cingulate cortex, and that the GABAergic system is effective in producing such oscillations, interaction of the two transmitter systems has not been demonstrated in human...
Supporting Information
When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self-awareness and dopaminergic activity. This network includes medial pre-frontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self-awareness. Conversely, we hypothes...
The incentive sensitization theory is a promising model for understanding the mechanisms underlying drug addiction, and has received support in animal and human studies. So far the theory has not been applied to the case of behavioral addictions like Gambling Disorder, despite sharing clinical symptoms and underlying neurobiology. We examine the re...
The introduction of magnetoencephalography has made it possible to study electromagnetic signaling in deeper, paralimbic cortical structures such as the medial prefrontal/anterior cingulate (ACC) and medial parietal/posterior cingulate (PCC) cortices. Self-awareness and self-control have been attributed to these regions. To test the hypothesis that...
Much research has been done on positive self-evaluation and its relationship to mental health. However, little is known about its neural underpinnings. Imaging studies have suggested that the brain’s default network is involved with self-related processing and that one portion of the default network, medial prefrontal cortex (MPFC), is particularly...
Both systemic inflammation and impaired cerebral autoregulation (CA) have been associated with brain injury in preterm infants. We hypothesized that impaired CA represents a hemodynamic link between inflammation and brain injury.
Neither fetal vasculitis nor interleukin-6 (IL-6) affected CA significantly. A high level of IL-6 was associated with hy...
Consciousness has been proposed to play a key role in shaping flexible learning and as such is thought to confer an evolutionary advantage. Attention and awareness are the perhaps most important underlying processes, yet their precise relationship is presently unclear. Both of these processes must, however, serve the evolutionary imperatives of sur...
Background and aims: Systemic inflammation as well as impaired cerebral autoregulation (CA) has been associated with brain injury in preterm infants. We hypothesized that impaired CA represents a hemodynamic link between inflammation and brain injury. Furthermore, we evaluated the relationship between hypotension and CA.
Self-awareness is a pivotal component of any conscious experience and conscious self-regulation of behaviour. A paralimbic network is active, specific and causal in self-awareness. Its regions interact by gamma synchrony. Gamma synchrony develops throughout infancy, childhood and adolescence into adulthood and is regulated by dopamine and other neu...
It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity in the visual system as a response to visual stimu...
We here review experimental findings relevant for the pharmacology of conscious experience, an issue largely neglected in pharmacological research. First, we focus on self-awareness, a pivotal component of conscious experience and its integration within the global neuronal network (GNW), a theoretical concept that unifies convergent approaches on t...
Emotion and reward have been proposed to be closely linked to conscious experience, but empirical data are lacking. The anterior cingulate cortex (ACC) plays a central role in the hedonic dimension of conscious experience; thus potentially a key region in interactions between emotion and consciousness. Here we tested the impact of emotion on consci...
Liberal acceptance, overconfidence, and increased activity of the neurotransmitter dopamine have been proposed to account for abnormal sensory experiences, for instance, hallucinations in schizophrenia. In normal subjects, increased sensory experience in Yoga Nidra meditation is linked to striatal dopamine release. We therefore hypothesize that the...
In examining neural processing specific to the self, primarily by contrasting self-related stimuli with non-self-related stimuli (i.e., self vs. other), neuroimaging studies have activated a consistent set of regions, including medial prefrontal cortex (MPFC), precuneus, and right and left inferior parietal cortex. However, criticism has arisen tha...
It is generally assumed that one reason why white matter injury is common in preterm infants is the relatively poor vascular supply.
To examine whether blood flow to the white matter is relatively more reduced at low blood pressure than is blood flow to the brain as a whole.
Thirteen normoxic preterm infants had blood flow imaging on 16 occasions...
A coherent and meaningful percept of the world is essential for human nature. Consequently, much speculation has focused on how this is achieved in the brain. It is thought that all conscious experiences have reference to the self. Self-reference may either be minimal or extended, i.e., autonoetic. In minimal self-reference subjective experiences a...
The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis.
Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were compared with 39 controls. NIRS examination was done within the first...
An hypothesis of increased endorphinergic activity has been proposed to account for the characteristic symptoms of Rett syndrome. Cerebrospinal fluid samples from eight girls with Rett syndrome were analysed for β‐endorphin (β‐EP) immunoactivity and compared with samples from a control group of 15 children with acute leukaemia in remission. Severit...
Perinatal anoxia/ischemia or premature birth increases the risk of developing attention deficit/hyperactivity disorder (ADHD). Brain imaging studies of idopathic ADHD reveal elevated dopamine transporter density in striatum of patients, predicting abnormal response to a challenge with methylphenidate in this population. We hypothesized that the sev...
To evaluate the effects of phenylalanine (Phe)-free essential amino acid (AA) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria (PKU).
Phe-free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospective...
This chapter introduces the study of meditation as a vehicle for discovering the neural correlates of the self. It begins with a thorough introduction to experiments designed to isolate the neural components of meditation. Studies on meditation are discussed, which show precuneal, medial frontal, and striatal activation during meditation. It is arg...
Abnormal central dopamine (DA) neurotransmission has been implicated in the impulsivity, inattention, and hyperactivity of attention deficit hyperactivity disorder (ADHD). We hypothesized that a pharmacological challenge with methylphenidate (MP) at a therapeutic dose increases extracellular DA concentrations in proportion to the severity of these...
In meditation both the quality and the contents of consciousness may be voluntarily changed, making it an obvious target in the quest for the neural correlate of consciousness. Here we present the results of a positron emission tomography study of yoga nidra relaxation meditation when compared with the normal resting conscious state. Meditation is...
![Table 1 . Regional [Brodmann area (BA)] activations by retrieval of...](profile/Troels-Kjaer/publication/8606914/figure/tbl1/AS:667874226102282@1536245032612/Regional-Brodmann-area-BA-activations-by-retrieval-of-judgment-of-mental-Self-and_Q320.jpg)
For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit "autonoetic consciousness" is thought to emerge by retrieval of memory of personally experienced events ("episodic memory"). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parie...
Attention-deficit-hyperactivity disorder (ADHD), while largely thought to be a genetic disorder, has environmental factors that appear to contribute significantly to the aetiopathogenesis of the disorder. One such factor is pretern birth with vulnerable cerebrovascular homeostasis. We hypothesised that cerebral ischaemia at birth could contribute t...
It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation. It is unresolved whether this negative BOLD response pattern is o...
A recent meta-analysis has shown precuneus, angular gyri, anterior cingulate gyri, and adjacent structures to be highly metabolically active in support of resting consciousness. We hypothesize that these regions constitute a functional network of reflective self-awareness thought to be a core function of consciousness. Seven normal volunteers were...
Perinatal anoxia/ischemia or premature birth increases the risk of developing attention deficit/hyperactivity disorder (ADHD). Brain imaging studies of idopathic ADHD reveal elevated dopamine transporter density in striatum of patients, predicting abnormal response to a challenge with methylphenidate in this population. We hypothesized that the sev...
This is the first in vivo demonstration of an association between endogenous neurotransmitter release and conscious experience. Using 11C-raclopride PET we demonstrated increased endogenous dopamine release in the ventral striatum during Yoga Nidra meditation. Yoga Nidra is characterized by a depressed level of desire for action, associated with de...
Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase o...
Awareness is a personal experience, which is only accessible to the rest of world through interpretation. We set out to identify a neural correlate of visual awareness, using brief subliminal and supraliminal verbal stimuli while measuring cerebral blood flow distribution with H(2)(15)O PET. Awareness of visual verbal stimuli differentially activat...
Emotional stress during organogenesis could, in theory, cause congenital malformations by increasing the level of cortisone, but documentation is lacking. We undertook a follow-up study to test the hypothesis that psychosocial stress increases the prevalence of malformations, in particular malformations of the cranial neural crest.
We defined serio...
Introduction: Emotional stress during organogenesis could, in theory, cause congenital malformations by increasing the level of cortisone, but documentation is lacking. We undertook a follow-up study to test the hypothesis that psychosocial stress increases the prevalence of malformations, in particular malformations of the cranial neural crest. Ma...
Functional magnetic resonance imaging (fMRI) in young children may provide information about the development of the visual cortex, and may have predictive value for later visual performance. The purpose of this study was to evaluate the usefulness of fMRI for examining cerebral processing of vision in very young infants and in infants with brain da...
Twenty-nine high-risk preterm born children, from a cohort with cerebral blood flow (CBF) measurements in the first 2 d of life, were examined prospectively at the age of 5.5-7 y neurologically, neuropsychologically and by magnetic resonance imaging (MRI). They were compared to 57 control children in terms of neurology and neuropsychology. Abnormal...
The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O-H20 PET technique in nine young adults, who were highly e...
The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O-H2O PET technique in nine young adults, who were highly e...
The purpose of this study was to determine whether visual stimulation in sleeping infants and young children can be examined by functional magnetic resonance imaging. We studied 17 children, aged 3 d to 48 mo, and three healthy adults. Visual stimulation was performed with 8-Hz flickering light through the sleeping childs' closed eyelids. Functiona...
110
Purpose: To evaluate the feasibility of performing measurements of cerebral blood flow (CBF) in human infants with MRI flow measurement of the neck vessels.
Material and Methods: Eighteen infants, GA 26-41 (mean 32.3) weeks, chronological age 2-72 (median 9) days. Eleven infants were healthy. Flow was measured in the carotid and vertebral arter...
The wide variation in phenylalanine hydroxylating capacity observed among patients with phenylketonuria (PKU) is primarily due to allelic heterogeneity at the phenylalanine hydroxylase (PAH) locus. In this study, we examined phenylalanine metabolism after an oral phenylalanine load in 148 carriers of known PAH gene mutations. As a group, heterozygo...
With the use of 99mTc-D, L,-hexamethylpropylenamine oxime and single photon emission computed tomography, regional cerebral blood flow was measured ictally in 12 mature infants with recurrent seizures and compared with a reference group of nine interictal studies. The study indicates that both clinical and electrical seizures in neonates are associ...
The aim of the present study was to evaluate the striatum's involvement in verbal awareness (semantic processing and supra-modal attention) in normals and children with attention deficit hyperactivity disorder (ADHD). Our previous finding of striatal hypoperfusion in ADHD at rest, supports our prediction that the striatum will also show reduced act...
The neurophysiological basis of consciousness is hotly debated in the neurobiological literature at present. The subject is often confused by imprecise terminology. One of the core issues is the definition of consciousness. According to one standard English dictionary (Webster, 1989), consciousness has three aspects, or meanings: awareness of one’s...
To determine the diagnostic potential of magnetic resonance imaging (MRI) in neonatal seizures; to elucidate the aetiology, timing, and prognosis of the cerebral lesions detected.
Thirty one term neonates with clinical seizures underwent ultrasonography between days 1-7 (mean 2.5 days) and a high field spin-echo MRI scan on days 1-30 (mean 8.1 days...
The purpose of the study is to investigate the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol and smoking on intrauterine growth retardation and premature delivery. At a Copenhagen university hospital 2432 consecutive Danish-speaking women in 20th week of pregnancy completed a questionnaire i...
To investigate the metabolic consequences of germinal matrix hemorrhage (GMH) we used volume-selective 1H magnetic resonance spectroscopy in the striatal region in 12 preterm infants with predominantly small GMH. Both sides of the brain were investigated twice. Metabolite indices were calculated as the metabolite signal, recorded with TR = 1.6 s an...
Intrauterine growth retardation and premature delivery: the effect of smoking and psychosocial factors. The purpose of the study is to investigate the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol and smoking on intrauterine growth retardation and premature delivery. At a Copenhagen universi...
The purpose was to obtain normal values of the apparent diffusion coefficient (ADC) in the infant brain and to compare ADC maps with T1- and T2-weighted images.
Diffusion was measured in nine infants with an ECG-gated SE sequence compensated for first-order motion. One axial slice at the basal ganglia level was investigated with the diffusion-encod...
Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MR...
Perinatal asphyxia is an important cause of neurological disability, but early prediction of outcome can be difficult. We performed proton magnetic resonance spectroscopy (MRS) and global cerebral blood flow measurements by xenon-133 clearance in 16 infants with evidence of perinatal asphyxia. Cerebral blood flow was determined daily in the first 3...
In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-III-R categories 3 to 5), in combination with an inadequate social network. Th...
This study investigated the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol, and smoking on intrauterine growth retardation and premature delivery.
At a Copenhagen university hospital, 2432 pregnant women completed a questionnaire on general health, psychosocial stressors, and sociodemographic...
Unlabelled:
Mutations in the gene encoding phenylalanine hydroxylase (PAH) cause persistent hyperphenylalaninaemia. To date, more than 200 point mutations and microdeletions have been characterized. Each mutation has a particular quantitative effect on enzyme activity and recessive expression of different mutant alleles results in a marked interin...
Twenty-eight infants with postmenstrual ages (PMA) in the range of 32-80 weeks were investigated. Twenty were newborn; among these the observed birth weight divided by the expected weight ranged from 0.31 to 1.1. Axial magnetic resonance images were recorded with a triple spin-echo sequence and the volumes were determined by encircling each structu...
Glucose is the predominant cerebral energy source under physiological conditions, although other substrates may support cerebral metabolism. The present study was undertaken to determine if lactate is present in the immature human brain, and if so, whether or not concentrations of lactate differ between small-for-gestational-age and appropriate-for...
Blood-brain barrier permeability to phenylalanine and leucine in four patients with phenylketonuria and in four volunteers was measured five times by the double-indicator method at increasing plasma concentrations of phenylalanine. Based on the permeability-surface area product (PS) from blood to brain (PS1) and on plasma phenylalanine levels, Vmax...
The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal of the brain slice investigated decreased by 1.2-2.6...
For more than a century two opposing views on the pathogenetic mechanisms and the timing of the origin of cerebral palsy (CP) have prevailed: the idea first formulated by Little attributing CP to "difficult deliveries" has been opposed by the view by Freud recognizing fetal influences, and the issue seems to be unsettled. The present review seeks t...
In a population‐based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid‐gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life‐events (DSM‐111‐R categories 3 to 5), in combination with an inadequate social network. Th...
The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM (stimulated-echo acquisition mode) sequences with dif...