Biomedical subjects

Hans C Lou

Publications and source records attributed to Hans C Lou.

8 recordsLinked to original sources

PubMed2005

Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder.

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 specific ADHD symptoms. To test this hypothesis, we measured by PET the effect of acute challenge with MP on the availability of striatal binding sites for [11C]raclopride (pB), an index of altered interstitial DA concentration, in nine unmedicated adolescents (1 female, 8 males; age 13.7 +/- 1.8 years) with a current diagnosis of ADHD. We estimated the pB of [11C]raclopride for brain dopamine D2/3 receptors first in a baseline resting condition, and again after an acute challenge with MP (0.3 mg/kg, p.o.), and calculated the percentage change in (%DeltapB) in left and right striatum. On another day, measurements of impulsivity and inattention were performed using a computerized continuous performance test. There was a significant correlation between the magnitude of %DeltapB in the right striatum and the severity of inattention and impulsivity. MP-evoked %DeltapB correlated with standard scores for impulse control (r = 0.68; P = 0.02), attention (r = 0.81; P = 0.005), information processing (r = 0.66; P = 0.02), and consistency of attention, or variability (r = 0.60; P = 0.04). In conclusion, the results link inattention and impulsivity with sensitivity of brain DA receptor availability to an MP challenge, corroborating the hypothesis that MP serves to potentiate decreased DA neurotransmission in ADHD.

Adolescent↗

PubMed2005

The mental self.

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 accompanied by a relatively increased perfusion in the sensory imagery system: hippocampus and sensory and higher order association regions, with decreased perfusion in the executive system: dorsolateral prefrontal cortex, anterior cingulate gyrus, striatum, thalamus, pons, and cerebellum. To identify regions active in both systems we performed a principal component analysis of the results. This separated the blood flow data into two groups of regions, explaining 25 and 18% of their variance: One group corresponded to the executive system, and the other to the systems supporting sensory imagery. A small group of regions contributed considerably to both networks: medial parietal and medial prefrontal cortices, together with the striatum. The inclusion of the striatum and our subsequent finding of increased striatal dopamine binding to D2 receptors during meditation suggested dopaminergic regulation of this circuit. We then investigated the neural networks supporting episodic retrieval of judgments of individuals with different degrees of self-relevance, in the decreasing order: self, best friend, and the Danish queen. We found that all conditions activated a medial prefrontal - precuneus/posterior cingulate cortex, thalamus, and cerebellum. This activation occurred together with the activation of the left lateral prefrontal/temporal cortex. The latter was dependent on the requirement of retrieval of semantic information, being most pronounced in the "queen" condition. Transcranial magnetic stimulation, targeting precuneus, was then applied to the medial parietal region to transiently disrupt the normal function of the circuitry. We found a decreased efficiency of retrieval of self-judgment compared to the judgment of best friend. This shows that the integrity of the function of precuneus is essential for self-reference, but not for reference to others.

Brain↗

PubMed2005

Behavioural effects of phenylalanine-free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria.

AIM: 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). METHODS: Phe-free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospective double-blinded crossover study. The adaptive behaviour of the patients was tested prior to the study and at 6 and 12 mo after the start, using a simplified version of the Vineland Adaptive Behaviour Scale. For each sub-domain, the patients were rated either "0" (for poor performance) or "1" (for good performance). Neurological signs and symptoms and specific behavioural characteristics were recorded monthly by caretakers. Every 6 mo, neurological examination of the patients was performed, and the caretakers were interviewed. The statistical significance of the results was tested by means of the Fisher's exact and Wilcoxon tests. RESULTS: The most significant changes were an improved concentration and the development of a meaningful smile, which were observed in 44% and 43% of the patients on AA tablet treatment, respectively, but not patients on placebo. Other important but less significant changes included increased awareness of external stimuli (63%) and less self-injury (43%), and 40% were smiling and laughing occasionally. The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment (p=0.002), and to 7.0 in patients when on placebo (p=0.068). The difference between active AA treatment and placebo was statistically significant (p=0.027). CONCLUSIONS: This pilot study suggests that Phe-free AA tablets enriched in tyrosine and tryptophan may improve the quality of life in some intellectually disabled adults with untreated PKU.

Adult↗

PubMed2004

Parietal cortex and representation of the mental Self.

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 parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness.

Adult↗

PubMed2004

ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow.

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 to persistent deficient dopaminergic neurotransmission, which is thought to be the pathophysiological basis of the disorder. We examined dopamine D(2/3) receptor binding with positron emission tomography (PET) using [11C] raclopride as a tracer, and continuous reaction times (RT) with a computerized test of variables (TOVA) in six adolescents (12-14 years of age, one female) who had been examined with cerebral blood flow (CBF) measurements at preterm birth and had a subsequent history of attention deficit. We found that high dopamine receptor availability ('empty receptors') was linked with increased RT and RT variability, supporting the concept of a dopaminergic role in symptomatology. High dopamine receptor availability was predicted by low neonatal CBF, supporting the hypothesis of cerebral ischaemia as a contributing factor in infants susceptible to ADHD.

Adolescent↗

PubMed2002

Cortical deactivation induced by visual stimulation in human slow-wave sleep.

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 of developmental neurobiological origin particular to a given age or to a general effect of sleep or sedative drugs. To further elucidate this issue, we used fMRI and positron emission tomography (PET) to study the brain activation pattern during visual stimulation in spontaneously sleeping adult volunteers. In five sleeping volunteers fMRI studies confirmed a robust signal decrease during stimulation in the rostro-medial occipital cortex. A similar relative decrease at the same location was found during visual stimulation and polysomnographically verified slow-wave sleep in a separate group of six subjects using H(2)(15)O PET measures of the regional cerebral blood flow (rCBF). This decrease was more rostro-dorsal compared to the relative rCBF increase along the calcarine sulcus found during visual stimulation in the awake state. This study reconfirms the previously described paradoxical stimulation-correlated negative BOLD signal change in the rostro-medial occipital cortex, expanding this response mode to an age spectrum ranging from the newborn to the adult. Further, the use of complementary brain mapping techniques suggests that this decrease was secondary to a relative rCBF decrease. Possible mechanisms for the paradoxical response pattern during sleep include an active inhibition of the visual cortex or a disruption of an energy-consuming process.

Adult↗

PubMed2002

Increased dopamine tone during meditation-induced change of consciousness.

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 decreased blood flow in prefrontal, cerebellar and subcortical regions, structures thought to be organized in open loops subserving executive control. In the striatum, dopamine modulates excitatory glutamatergic synapses of the projections from the frontal cortex to striatal neurons, which in turn project back to the frontal cortex via the pallidum and ventral thalamus. The present study was designed to investigate whether endogenous dopamine release increases during loss of executive control in meditation. Participants underwent two 11C-raclopride PET scans: one while attending to speech with eyes closed, and one during active meditation. The tracer competes with endogenous dopamine for access to dopamine D2 receptors predominantly found in the basal ganglia. During meditation, 11C-raclopride binding in ventral striatum decreased by 7.9%. This corresponds to a 65% increase in endogenous dopamine release. The reduced raclopride binding correlated significantly with a concomitant increase in EEG theta activity, a characteristic feature of meditation. All participants reported a decreased desire for action during meditation, along with heightened sensory imagery. The level of gratification and the depth of relaxation did not differ between the attention and meditation conditions. Here we show increased striatal dopamine release during meditation associated with the experience of reduced readiness for action. It is suggested that being in the conscious state of meditation causes a suppression of cortico-striatal glutamatergic transmission. To our knowledge this is the first time in vivo evidence has been provided for regulation of conscious states at a synaptic level.

Adult↗

PubMed2002

Reflective self-awareness and conscious states: PET evidence for a common midline parietofrontal core.

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 asked to think intensely on how they would describe the personality traits and physical appearance of themselves and a neutral reference person known to all the subjects (the Danish Queen). During each of the four conditions cerebral blood flow distribution was measured by the intravenous H(2)(15)O PET scanning technique. During scanning, no sensory or motor activity was intended. After each scan, the subjects reported the contents of their thoughts during the scan to ascertain that the instructions had been followed. The results confirmed our hypothesis: Statistical parametric mapping showed differential activity in precuneus and angular gyri during reflection on own personality traits and in anterior cingulate gyri during reflection on own physical traits. Connectivity analysis of synchrony showed these regions to be functionally connected during reflective self-awareness. The commonality between the neural networks of the resting conscious state and self-awareness reflects the phenomenological concept of a fundamental contribution of reflective self-awareness to the contents and coherence of the conscious state.

Adult↗