Biomedical subjects

Valtteri Kaasinen

Publications and source records attributed to Valtteri Kaasinen.

12 recordsLinked to original sources

PubMed2026

Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies.

The dopaminergic system has long been a central focus of functional neuroimaging. Positron emission tomography (PET) with the D2/D3 receptor radioligand [11C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [11C]raclopride PET studies (n = 1640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p < 0.001), and approximately twice that of alcohol (4.8%, p < 0.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p > 0.14) or overall striatum (p > 0.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [¹¹C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.

Journal Article↗

PubMed2007

Brain function during multi-trial learning in mild cognitive impairment: a PET activation study.

We explored functional brain changes with positron emission tomography (PET) in mild cognitive impairment (MCI) patients and elderly normal controls by employing an episodic memory task that included two successive encoding trials of semantically related word-pairs and final retrieval. Both groups demonstrated significant learning across the two trials. The control group showed predominantly left frontal activity during encoding, and right frontal plus left temporal activity during retrieval. However, the MCI patients recruited partly different brain regions. They failed to activate right frontal and left temporal areas during retrieval, and failed to show any different activation for encoding on the first and second trials, whereas the controls activated a region of posterior cingulate. There was indication of compensatory increases in rCBF of the occipital cortex during incremental learning and the left frontal lobe during retrieval in the patients. These results suggest different episodic memory processing in the MCI group, and a possible over-reliance on semantic processing. Subtle functional changes occur in the pre-Alzheimer brain before there are marked structural or behavioural abnormalities.

Aged↗

PubMed2004

Dopaminergic effects of caffeine in the human striatum and thalamus.

Epidemiological studies have provided evidence that caffeine, an adenosine receptor antagonist, reduces the risk for Parkinson's disease. There are indications of specific interactions between striatal adenosine A(2A) and dopamine D(2) receptors, but the in vivo effects of caffeine on human dopamine system have not been investigated. In the present study, the dopaminergic effects of caffeine were examined with [(11)C]raclopride positron emission tomography (PET) in eight healthy habitual coffee drinkers after 24 h caffeine abstinence. Compared to oral placebo, 200 mg oral caffeine induced a 12% decrease in midline thalamic binding potential (p < 0.001). A trend-level increase in ventral striatal [(11)C]raclopride binding potential was seen with a correlation between caffeine-related arousal and putaminal dopamine D(2) receptor binding (r = -0.81, p = 0.03). The findings indicate that caffeine has effects on dopaminergic neurotransmission in the human brain, which may be differential in the striatum and the thalamus.

Adult↗

PubMed2004

Insular dopamine D2 receptors and novelty seeking personality in Parkinson's disease.

Novelty seeking is a temperament trait characterized by impulsiveness and exploratory behavior. Dopamine has been suggested to be the primary neurotransmitter modulator of novelty seeking, and in young healthy subjects, a correlation between increased novelty seeking and decreased insular cortical dopamine D2 receptor availability has been reported. The proposed link between dopamine deficiency and reduction in novelty seeking in Parkinson's disease is controversial. The present study examined whether a link between insular D2 receptor availability and novelty seeking can be replicated in Parkinson's disease patients. [11C]FLB 457 positron emission tomography imaging was carried out in 28 patients with Parkinson's disease, and the data were analyzed using voxel-based statistical analysis. The results demonstrated a negative correlation between the novelty seeking score and the dopamine D2 availability bilaterally in the insular cortex (corrected P=0.001; r=-0.74 [right hemisphere]; r=-0.66 [left hemisphere]). The results provide further support for a relationship between novelty seeking and insular D2 receptors. They indicate that the association is cross-cultural, independent of age, and unaffected by dopaminergic degeneration.

Aged↗

PubMed2004

Expectation of caffeine induces dopaminergic responses in humans.

Recent neuroimaging studies indicate that placebo treatments can induce clinically relevant neurobiological responses in patients with Parkinson's disease, depression and pain. The present study aimed to investigate neurotransmitter function in psychostimulant expectation, with the focus on dopaminergic effects of placebo caffeine in healthy human subjects. Eight habitual coffee drinkers were examined twice with [11C]raclopride positron emission tomography after no treatment and after oral placebo tablets in a counter-balanced setting. During the placebo condition the subjects were instructed that they had a 50% chance of receiving caffeine, but all received placebo. As compared with no treatment, placebo induced a significant bilateral dopamine release in the thalamus, as reflected by a 15% reduction in thalamic [11C]raclopride binding (P < 0.001). The level of arousal after placebo correlated positively with the tracer binding in the putamen (r = -0.91, P = 0.004). The results indicate that caffeine expectation induces dopaminergic placebo effects, and that these effects are similar to previous findings with oral caffeine. The results therefore suggest that caffeine and placebo caffeine may share some dopaminergic mechanisms of action.

Adult↗

PubMed2003

Naming multiple objects: neural correlates as measured by positron emission tomography.

The aim of this study was to examine the neural substrates of multi-object naming by positron emission tomography in normals. Multi-object naming is used in a technique called contextual priming (CP) to elicit contextual effects on picture naming through systematic manipulation of the relatedness of to-be-named pictures in an array. Inhibitory and facilitatory effects of CP on naming have been used both to highlight the inner dynamics of the normal word retrieval system and to treat naming difficulties caused by acquired anomia. Because of the complexity of the CP technique, it is unclear whether it merely reflects lexical retrieval or whether it also recruits general cognitive resources such as attentional control and response selection to a significant degree. When compared with a baseline situation in which colored circles were named, multi-object naming elicited increased blood flow in the occipital lobe and in the left inferior temporal and fusiform gyri. These areas have been related to visual pattern recognition and semantic access, and the pattern of activation is in line with previous functional imaging studies on single picture naming. In conclusion, multi-object naming does not appear to activate brain regions beyond those needed for single object naming. These findings thus provide independent evidence for the claim that CP is a valid paradigm for the study of word production proper.

Adult↗

PubMed2002

Personality traits and striatal 6-[18F]fluoro-L-dopa uptake in healthy elderly subjects.

Positron emission tomography (PET) studies have been carried out to examine dopaminergic correlates of human personality traits. In patients with Parkinson's disease, right caudate 6-[(18)F]fluoro-L-dopa ((18)F-dopa) uptake has recently been reported to correlate with a depression/anxiety related-personality trait of harm avoidance. The present study aimed to further study personality and striatal dopaminergic function, now with (18)F-dopa in healthy individuals, and to determine specifically whether the link between harm avoidance and (18)F-dopa uptake is a general phenomenon, seen also in healthy subjects. Twenty-five Caucasian neurologically healthy elderly subjects (mean age=60 years; 13 men, 12 women) were scanned with 3D (18)F-dopa PET, coregistered with magnetic resonance imaging, and each subject filled out the Temperament and Character Inventory (TCI) and the Karolinska Scales of Personality (KSP). The TCI harm avoidance did not correlate with right caudate (18)F-dopa uptake (r=-0.08, P=0.71, uncorrected, effects of age and sex partialled out), or with the (18)F-dopa uptake in any other striatal region (r=-0.07-0.16, P>0.47). Correlations with other personality scales, including the TCI novelty-seeking and the KSP detachment, were also non-significant. The results indicate that the previous positive findings concerning harm avoidance and (18)F-dopa uptake in Parkinson's disease are disease-related, and that they can not be generalized to healthy individuals.

Aged↗

PubMed2002

Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease.

Modern functional imaging methods, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provide non-invasive, quantitative tools for the direct measurement of neurotransmitter function in the living human brain. The dopamine system has been of key interest; first, because it has a prominant role in several cognitive and motor processes, and secondly because the tracers currently available for the dopamine system enable an effective investigation of various pre, post- and intra-synaptic processes. Recent functional imaging findings indicate that certain cognitive deficits associated with both normal aging and Parkinson's disease are modulated by changes in the brain dopamine system. This review covers the literature related to age-associated phenomena in the dopamine system studied with in vivo imaging. In particular, the focus is on describing and discussing the relationships between aging, cognition and the dopaminergic system in healthy subjects and in patients with Parkinson's disease.

Aging↗

PubMed2002

Different brain activation patterns during production of animals versus artefacts: a PET activation study on category-specific processing.

To study neural correlates of category-specific processing, we measured relative cerebral blood flow changes by PET (oxygen-15) in young healthy subjects while they produced exemplars of animals or artefacts to written subcategory prompts. In comparison to a baseline (word reading), production of animal names elicited increased rCBF in the right inferior temporal region. This fits to recent lesion data on semantic impairment with animals, as well as imaging data on object recognition and semantic retrieval. In our study, it may represent an involvement of visual imagery in generation of animal names. In contrast, production of artefact names elicited increased rCBF in frontoparietal regions previously related to attention and mental effort.

Adult↗

PubMed2002

Age-related loss of extrastriatal dopamine D(2) -like receptors in women.

Positron emission tomography (PET) studies have indicated that the in vivo availability of dopamine D(2) -like receptors declines with age in the human brain. Most of the studies have been carried out with healthy male subjects, or with subject groups containing both sexes. The authors have recently demonstrated that the availability of D(2) -like receptors in the frontal cortex is higher in women than in men. The present study was aimed to further examine this phenomenon. Thirty-seven healthy women (age range 22-78 years) were examined with PET and [(11) C]FLB 457, a high-affinity tracer for the extrastriatal D(2) -like receptors. A negative relationship between age and dopamine D(2) -like receptor availability was seen in the frontal cortex (decrease of 12% per decade of life), the temporal cortex (9%) and the thalamus (6%). A non-linear s-shape association explained the relationship only in the frontal cortex, while in other regions the association was linear. Neither oestradiol nor progesterone levels had a significant relationship with the [(11) C]FLB 457 uptake in any of the brain regions studied after the effect of age was partialled out. The results indicate that: (i) the extrastriatal D(2) -like receptor availability decreases with age in healthy women with the fastest rate in the frontal cortex and with the overall rate close to the rate reported in healthy men; (ii) around midlife (age 40-60 years) in women, the frontal receptor decline plateaus while the decline continues to be linear in other extrastriatal brain regions; and (iii) serum oestradiol or progesterone levels are not associated with cortical or thalamic D(2) -like receptor availability in women. The results may prove to be important in studies where the biochemical basis of clinical sex differences is examined in patients with dopamine-related neuropsychiatric disorders.

Adult↗

PubMed2002

Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease.

Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.

Acetylcholinesterase↗

PubMed2001

Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study.

Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6-[(18)F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition.

Adult↗