Biology subjects

Tuisku, J.

Publications and source records attributed to Tuisku, J..

14 recordsLinked to original sources

bioRxiv2025

Striatal dopamine synthesis capacity in Parkinson's disease: Effects of age, sex, and body mass index in a large fluorodopa PET cohort

BACKGROUNDIn Parkinsons disease (PD), the degeneration of nigrostriatal dopaminergic neurons leads to motor symptoms. Positron emission tomography (PET) using radioligand [18F]fluorodopa detects reduced striatal dopamine synthesis capacity in PD patients. Demographic factors such as sex and BMI are also associated with dopamine synthesis capacity. The combined contribution of demographic and clinical effects however remains elusive. It also remains unresolved how the dopamine synthesis capacity is correlated between striatal subregions and how the dopamine synthesis capacity and dopamine receptor function across striatal regions are associated with each other in PD patients and healthy controls. MATERIAL, AIMS, AND METHODSFor this retrospective register-based study, we used baseline [18F]fluorodopa PET data acquired at the Turku PET Centre between the years 1988-2016 with three different scanners (Ecat 931, GE Advance, HRRT). The data included scans of 350 adult human subjects, including 132 healthy controls (65 males and 67 females), and 218 PD patients (134 males and 84 females). The primary aim was to simultaneously investigate the effects of PD, age, sex and BMI on regional dopamine synthesis capacity (influx rate constant Kiref quantified with Patlak) using Bayesian linear regression. Secondary aims were to assess interregional correlations of dopamine synthesis capacity, and the association between regional presynaptic dopamine synthesis and postsynaptic dopamine type 2 receptor (D2R) availability in subjects who also had a proximal [11C]raclopride PET scan. RESULTSWe found modest support for age-dependent decline in dopamine synthesis capacity, increased capacity for higher BMIs, and for higher capacity in females versus males. These effects were smaller than the effect of PD status. Dopamine synthesis capacity across regions was correlated in both patients and controls. Support for positive correlation between the synthesis capacity and the D2R was observed in caudate nucleus. CONCLUSIONSPD and demographic effects are independently associated with the striatal dopamine synthesis capacity. The capacity is reduced by PD, decreased through age (particularly after the age of around 50), higher in females versus males, and weakly increased in higher BMIs. Synthesis capacity is correlated between the striatal and thalamic regions in both PD patients and controls. The dopamine synthesis capacity was positively correlated with the D2R availability in caudate. Scanner affects the estimates of dopamine synthesis capacity measured with [18F]fluorodopa PET, and it is preferrable to adjust for such variation in the data.

neuroscience↗

bioRxiv2025

Inter-individual variability of neurotransmitter receptor and transporter density in the human brain

Neurotransmitter receptors guide the propagation of signals between brain regions. Mapping receptor distributions in the brain is therefore necessary for understanding how neurotransmitter systems mediate the link between brain structure and function. Normative receptor density can be estimated using group averages from Positron Emission Tomography (PET) imaging. However, the generalizability and reliability of group-average receptor maps depends on the inter-individual variability of receptor density, which is currently unknown. Here we collect group standard deviation brain maps of PET-estimated protein abundance for 12 different neurotransmitter receptors and transporters across 7 neurotransmitter systems, including dopamine, serotonin, acetylcholine, glutamate, GABA, cannabinoid, and opioid. We illustrate how cortical and subcortical inter-individual variability of receptor and transporter density varies across brain regions and across neurotransmitter systems. We complement inter-individual variability with inter-regional variability, and show that receptors that vary more across brain regions than across individuals also demonstrate greater out-of-sample spatial consistency. Altogether, this work quantifies how receptor systems vary in healthy individuals, and provides a means of assessing the generalizability of PET-derived receptor density quantification.

neuroscience↗

bioRxiv2025

CEREBRAL GLUCOSE UTILISATION DURING MUSICAL EMOTIONS: A MULTIMODAL FUNCTIONAL PET/MRI STUDY.

Functional magnetic resonance imaging (fMRI) studies have demonstrated music-induced activation of the blood-oxygen-level-dependent (BOLD) signal across brain networks associated with auditory perception, motor control, and emotion. However, BOLD-fMRI reflects vascular responses that may not fully capture underlying neural activity. Here, we used simultaneous [18F]fluorodeoxyglucose (FDG) functional positron emission tomography (fPET) and fMRI to examine glucose metabolism closely linked to neural activity, alongside hemodynamic responses during pleasurable music listening. Thirty-five female participants listened to self-selected pleasurable music and control stimuli while undergoing 90-minute PET-MRI scans. fPET revealed music-evoked increase in glucose consumption in auditory and motor cortices, as well as reward-related regions, including the nucleus accumbens (NAcc), caudate, insula, and orbitofrontal cortex. The fPET and fMRI results showed substantial overlap though some discrepancies were also observed. Notably, the NAcc exhibited increased glucose consumption in fPET but showed no activation in fMRI. Conversely, deactivation of the default mode network during music processing was only observed with fMRI. These results highlight the complementary nature of neurometabolic and neurovascular processes and offer novel insights into their dynamics during the processing of aesthetic rewards.

neuroscience↗

bioRxiv2025

TURBO: Automated Total-body PET Image Processing and Kinetic Modeling Toolbox

Long axial field of view (LAFOV) PET imaging requires a high level of automation and standardization, as the large number of target tissues increases the manual workload significantly. We introduce an automated analysis pipeline (TurBO, Turku total-BOdy) for preprocessing and kinetic modelling of LAFOV [15O]H2O and [18F]FDG PET data, enabling efficient and reproducible analysis of tissue perfusion and metabolism at regional and voxel-levels. The approach employs automated processing including co-registration, motion correction, automated CT segmentation for region of interest (ROI) delineation, image-derived input determination, and region-specific kinetic modelling of PET data. MethodsWe validated the analysis pipeline using Biograph Vision Quadra (Siemens Healthineers) LAFOV PET/CT scans from 21 subjects scanned with [15O]H2O and 16 subjects scanned with [18F]FDG using six segmented CT-based ROIs (cortical brain gray matter, left iliopsoas muscle, right kidney cortex and medulla, pancreas, spleen and liver) representing different levels of blood flow and glucose metabolism. ResultsModel fits showed good quality with consistent parameter estimates at both regional and voxel-levels (R{superscript 2} > 0.83 for [15O]H2O, R{superscript 2} > 0.99 for [18F]FDG). Estimates from manual and automated input functions were in concordance (R{superscript 2} > 0.74 for [15O]H2O, and R{superscript 2} > 0.78 for [18F]FDG) with minimal bias (<4% for [15O]H2O and <10% for [18F]FDG). Manually and automatically (CT-based) extracted ROI level data showed strong agreement (R{superscript 2} > 0.82 for [15O]H2O and R{superscript 2} > 0.83 for [18F]FDG), while motion correction had little impact on parameter estimates (R{superscript 2} > 0.71 for [15O]H2O and R{superscript 2} > 0.78 for [18F]FDG) compared with uncorrected data. ConclusionOur automated analysis pipeline provides reliable and reproducible parameter estimates across different regions, with an approximate processing time of 1-1.5 h per subject. This pipeline completely automates LAFOV PET analysis, reducing manual effort and enabling reproducible studies of inter-organ blood flow and metabolism, including brain-body interactions.

neuroscience↗

bioRxiv2025

Shared brain basis of aggression in clinical, forensic, and healthy samples: A meta-analysis

BackgroundAggression, violence, and antisocial behaviour constitute a large-scale societal problem. Aggression is common in incarcerated offenders and psychiatric conditions, but also healthy and noninstitutionalized populations vary in violent and aggressive behaviour. The brain basis of aggression has been studied extensively in the past, but the similarities between criminal, pathological and everyday aggression in the brain remain elusive. MethodsWe conducted an activation likelihood estimation (ALE) meta-analysis of 406 neuroimaging studies with 28 968 subjects using structural magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single photon emission tomography (SPECT). The included studies had either i) measured haemodynamic responses during aggression-related functional tasks, ii) compared the brain structure, molecular organization, or function between aggressive forensic and psychiatric populations and control groups, or iii) addressed the effects of trait aggression on brain structure or function. ResultsAggression was consistently associated with altered function and structure in the amygdala, hippocampus, basal ganglia, anterior cingulate cortex, and the dorsolateral and orbitofrontal cortices. Functional coactivation analysis suggested that these regions are most consistently associated with emotional and reward function as well as their regulation. The results were comparable in healthy subjects as well as forensic and psychiatric populations. ConclusionsAggression is linked with alterations in multiple neurocognitive systems forming a common network for aggressiveness. Particularly the neural systems implicated in reward, emotions and regulation were commonly associated with aggression. The established network is involved in the whole continuum of aggression from benign variations in healthy volunteers to forensic subjects and violent clinical populations, suggesting a common aggression network whose severe perturbations may be linked with criminal behaviour or pathological aggression.

neuroscience↗

bioRxiv2024

Dopamine D2R and opioid MOR availability in autism spectrum disorder

Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive. Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11C]raclopride (D2R) and [11C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 19 age and sex matched controls. Regional group differences in D2R and MOR receptor availabilities were tested with linear mixed models and associations between regional receptor availabilities were examined with correlations. There were no group differences in whole-brain voxel-wise analysis of DR2 but ROI analysis presented a lower overall mean D2R availability in striatum of the ASD versus control group. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens of the ASD group. The whole-brain voxel-wise analysis of MOR revealed precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens. These alterations may translate to disrupted modulation of social motivation and reward in ASD.

neuroscience↗

bioRxiv2023

Seasonal variation in D2/3 dopamine receptor availability in the human brain

Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmic in vivo dopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. Here, based on historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. We found that daylength at the time of scanning was negatively correlated with availability of this type of receptors in the striatum. Likely, seasonally varying D2/3 receptor signaling also underlies the seasonality of mood, feeding, and motivational processes. Significance of the studyBrain in vivo neurotransmitter signaling demonstrates seasonal patterns. The dopamine D2/3 receptor, with both pre- and postsynaptic expressions, has been targeted by major antipsychotic and antiparkinsonian pharmaceuticals. The current study, based on a large dataset of healthy brain PET images quantifying these receptors, shows that dark seasons are associated with increased receptor availability in the striatum. Considering the previous findings of increased dopamine synthesis and lowered number of transporters, findings may suggest elevated presynaptic control of dopamine release and increased dopamine receptor sensitivity during dark seasons. The rhythmic D2/3 receptor availability may be a mechanism underlying seasonality in mood, feeding, and motivational processes.

neuroscience↗

bioRxiv2023

Aberrant type 2 dopamine receptor availability in criminal psychopathy

BackgroundPsychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. MethodsHere we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n=11) and healthy matched controls (n=19) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. ResultsPsychopathic subjects had lowered D2R availability in caudate and putamen, and D2R striatal availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability amygdala and nucleus accumbens. ConclusionsWe conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for the aberrant MOR system is more limited.

neuroscience↗

bioRxiv2023

Alterations in type 2 dopamine receptors across neuropsychiatric conditions: A large-scale PET cohort

Aberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls. Here, we investigated the variation in striatal (caudate nucleus, nucleus accumbens, and putamen) and thalamic type 2 dopamine receptor (D2R) availability using [11C]raclopride positron emission tomography (PET) data from a large sample of 437 humans including healthy controls and subjects with Parkinsons disease (PD), antipsychotic-naive schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We analyzed regional group differences in D2R availability using Bayesian mixed effects modeling. Subjects with PD showed clearest decline in D2R availability. Healthy controls and patients with PD showed high interregional correlation of D2R availability, while this pattern was weaker in schizophrenia, severe violent behavior, and depression. Subjects with pathological gambling or overweight did not show clear changes in either the regional receptor availability or the interregional correlation. We conclude that the dopaminergic changes in neuropsychiatric conditions might not only affect the overall receptor availability but also the connectivity between the regions. The region-specific receptor availability more profoundly links to the motor symptoms, while the between-region connectivity might be disrupted in affective symptoms. HighlightsWe compared human striatal and thalamic type 2 dopamine receptor (D2R) availability between healthy controls, and subjects with Parkinsons disease (PD), antipsychotic-naive schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We present the mean brain maps of group specific D2R availabilities in NeuroVault (https://neurovault.org; https://identifiers.org/neurovault.collection:12799). Dopamine type 2 receptor availability is lowered in PD in caudate nucleus, nucleus accumbens and thalamus. Antipsychotic-naive schizophrenia, severe violent behavior, and depression were associated with decreased connectivity between the striatal and thalamic D2R availability. Altered regional D2R availability in the striatum and thalamus is linked with motor disorders, while lowered regional connectivity in D2R might relate to affective disturbance.

neuroscience↗

bioRxiv2022

Endogenous opioid release following orgasm in man: A combined PET-fMRI study

Sex is one of the most rewarding and motivating behaviours for humans. Endogenous mu-opioid receptor system (MORs) plays a key role in the mammalian reward circuit. Both human and animal experiments suggest the involvements of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. We used positron emission tomography (PET) with the radioligand [11C]carfentanil, which has high affinity for MORs to quantify endogenous opioid release following orgasm in man. Subjects were scanned twice: Once immediately after reaching an orgasm and once in a baseline state. Haemodynamic activity was measured with functional magnetic resonance imaging during penile stimulation from partner. The PET data revealed significant opioid release in hippocampus. Haemodynamic activity in somatosensory and motor cortices as well as hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Altogether these data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal.

neuroscience↗

bioRxiv2022

APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology

Increased reactivity of microglia and astrocytes is known to be present at various stages of the Alzheimers continuum but their relationship with core Alzheimers disease pathology in the preclinical stages is less clear. We investigated glial reactivity and {beta}-amyloid pathology in cognitively unimpaired APOE {varepsilon}4 homozygotes, heterozygotes and non-carriers using 11C-PK11195 PET (targeting 18-kDa translocator protein), 11C-PiB PET (targeting {beta}-amyloid), brain MRI, and a preclinical cognitive composite (APCC). Plasma glial fibrillary acidic protein (GFAP) by and plasma A{beta}1-42/1-40 were measured using single molecule array and immunoprecipitation combined with mass spectrometry, respectively. We observed that (i) 11C-PiB-binding was significantly higher in APOE {varepsilon}4 homozygotes compared with non-carriers in all evaluated regions, (ii) regional 11C-PK11195-binding did not differ between the APOE {varepsilon}4 gene doses or between A{beta}-positive and -negative individuals, and (iii) higher 11C-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, and elevated 11C-PiB-binding and plasma GFAP concentration with lower APCC scores. Increased glial reactivity might emerge in later stages of preclinical Alzheimers disease in parallel with early neurodegenerative changes.

neuroscience↗

bioRxiv2019

Interindividual variability and lateralization of μ-opioid receptors in the human brain

The brains {micro}-opioid receptors (MORs) are involved in analgesia, reward and mood regulation. Several neuropsychiatric diseases have been associated with dysfunctional MOR system, and there is also considerable variation in receptor density among healthy individuals. Sex, age, body mass and smoking have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. Here we quantified in vivo MOR availability in the brains of 204 individuals with no neurologic or psychiatric disorders using positron emission tomography (PET) with tracer [11C]carfentanil. We then used Bayesian hierarchical modeling to estimate the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential. We also examined hemispheric lateralization of MOR availability. Age had regionally specific effects on MOR availability, with age-dependent increase in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders.

neuroscience↗

bioRxiv2019

Magia: Robust automated modeling and image processing toolbox for PET neuroinformatics

IntroductionModelling of the radioactivity images produced by PET scanners into biologically meaningful quantities, such as binding potential, is a complex multi-stage process involving data retrieval, preprocessing, drawing reference regions, kinetic modelling, and post-processing of parametric images. The process is challenging to automatize mainly because of manual work related to input generation, thus prohibiting large-scale standardized analysis of brain PET data. To resolve this problem, we introduce the Magia pipeline that enables processing of brain PET data with minimal user intervention. We investigated the accuracy of Magia in the automatic brain-PET data processing with four tracers binding to different binding sites: [11C]raclopride, [11C]carfentanil, [11C]MADAM, and [11C]PiB.\n\nMaterials and methodsFor each tracer, we processed 30 historical control subjects data with manual and automated methods. Five persons manually delineated the reference regions (cerebellar or occipital cortex depending on tracer) for each subject according to written and visual instructions. The automatic reference-region extraction was based on FreeSurfer parcellations. We first assessed inter-operator variance resulting from manual delineation of reference regions. Then we compared the differences between the manually and automatically produced reference regions and the subsequently obtained metrics.\n\nResultsThe manually delineated reference regions were remarkably different from each other. The differences translated into differences in outcome measures (binding potential or SUV-ratio), and the intra-class correlation coefficients were between 47 % and 96 % for the tracers. While the Magia-derived reference regions were topographically very different from the manually defined reference regions, Magia produced outcome measures highly consistent with average of the manually obtained estimates. For [11C]carfentanil and [11C]PiB there was no bias, while for [11C]raclopride and [11C]MADAM Magia produced 3-5 % higher binding potentials as a result of slightly lower time-integrals of reference region time-activity curves.\n\nConclusionEven if Magia produces reference regions that are anatomically different from manually drawn reference regions, the resulting outcome measures are highly similar. Based on these results and considering the high inter-operator variance of the manual method, the high level of standardization and strong scalability of Magia, we conclude that Magia can be reliably used to process brain PET data.

neuroscience↗

bioRxiv2019

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre PBR28 HRRT PET study

PurposeTo investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [11C]PBR28. Methods[11C]PBR28 data from 140 healthy volunteers (72 males and 68 females; n=78 with HAB and n=62 MAB genotype; age range 19-80 years; BMI range 17.6 - 36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (n=53), Turku PET centre (n=62) and Yale University PET Center (n=25). The total volume of distribution (VT) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. ResultsThere were significant positive correlations between age and VT in the frontal and temporal cortex. BMI showed a significant negative correlation with VT in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher VT. A subgroup analysis revealed a positive correlation between VT and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. ConclusionThese findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.

immunology↗