Jarmo Hietala

YNICL Journal 2026 Journal Article

Striatal dopamine synthesis capacity in Parkinson’s disease: Effects of age, sex, and body mass index in a large [18F]fluorodopa PET cohort

• Tuulia Malén
• Jouni Tuisku
• Marco Bucci
• Severi Santavirta
• Valtteri Kaasinen
• Sakari Kaasalainen
• Janne Isojärvi
• Jarmo Hietala

BACKGROUND: F]fluorodopa detects reduced striatal dopamine synthesis capacity in Parkinson's disease (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. MATERIAL, AIMS, AND METHODS: C]raclopride PET scan, and (3) scanner effects and atlas- versus MRI-based quantification approaches. We provide the mean dopamine synthesis brain maps of healthy controls and PD patients in NeuroVault. RESULTS: estimates for most subjects. CONCLUSIONS: Dopamine synthesis capacity is independently affected by PD and demographic factors and correlated between the striatal and thalamic regions in both controls and PD patients. Adjusting for scanner effects in multi-scanner datasets is recommended. When subject-specific MRI is unavailable, atlas-based normalization may be used with caution to prevent major data loss.

YNICL Journal 2024 Journal Article

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

• Tuulia Malén
• Severi Santavirta
• Sven De Maeyer
• Jouni Tuisku
• Valtteri Kaasinen
• Tuomas Kankare
• Janne Isojärvi
• Juha Rinne

PURPOSE: Aberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls. METHODS: R availability within each group. RESULTS: R availability, while this pattern was weaker in violent offenders. Subjects with schizophrenia, pathological gambling, depression, or overweight did not show clear changes in either the regional receptor availability or the interregional correlation. CONCLUSION: We conclude that the dopaminergic changes in neuropsychiatric conditions might not only affect the overall receptor availability but also how coupled regions are across people. The region-specific receptor availability more profoundly links to the motor symptoms, while the between-region coupling might be disrupted in violence.

YNIMG Journal 2022 Journal Article

Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort

• Tuulia Malén
• Tomi Karjalainen
• Janne Isojärvi
• Aki Vehtari
• Paul-Christian Bürkner
• Vesa Putkinen
• Valtteri Kaasinen
• Jarmo Hietala

BACKGROUND: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS: R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS: R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS: R expression.

YNIMG Journal 2021 Journal Article

Cerebral grey matter density is associated with neuroreceptor and neurotransporter availability: A combined PET and MRI study

• Sandra Manninen
• Tomi Karjalainen
• Lauri J. Tuominen
• Jarmo Hietala
• Valtteri Kaasinen
• Juho Joutsa
• Juha Rinne
• Lauri Nummenmaa

Positron emission tomography (PET) can be used for in vivo measurement of specific neuroreceptors and transporters using radioligands, while voxel-based morphometric analysis of magnetic resonance images allows automated estimation of local grey matter densities. However, it is not known how regional neuroreceptor or transporter densities are reflected in grey matter densities. Here, we analyzed brain scans retrospectively from 328 subjects and compared grey matter density estimates with neuroreceptor and transporter availabilities. µ-opioid receptors (MORs) were measured with [11C]carfentanil (162 scans), dopamine D2 receptors with [11C]raclopride (92 scans) and serotonin transporters (SERT) with [11C]MADAM (74 scans). The PET data were modelled with simplified reference tissue model. Voxel-wise correlations between binding potential and grey matter density images were computed. Regional binding of all the used radiotracers was associated with grey matter density in region and ligand-specific manner independently of subjects’ age or sex. These data show that grey matter density and MOR and D2R neuroreceptor / SERT availability are correlated, with effect sizes (r2) ranging from 0. 04 to 0. 69. This suggests that future studies comparing PET outcome measure different groups (such as patients and controls) should also analyze interactive effects of grey matter density and PET outcome measures.

YNIMG Journal 2020 Journal Article

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

• Tatu Kantonen
• Tomi Karjalainen
• Janne Isojärvi
• Pirjo Nuutila
• Jouni Tuisku
• Juha Rinne
• Jarmo Hietala
• Valtteri Kaasinen

Alterations in the brain’s μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. We compiled [11C]carfentanil positron emission tomography scans from 204 individuals with no neurologic or psychiatric disorders, and estimated the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential using between-subject regression analysis. We also examined hemispheric differences in MOR availability. Older age was associated with increase in MOR availability 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. Lateralized MOR system may reflect hemispheric work specialization in central emotion and pain processes.

YNIMG Journal 2019 Journal Article

Sex difference in brain CB1 receptor availability in man

• Heikki Laurikainen
• Lauri Tuominen
• Maria Tikka
• Harri Merisaari
• Reetta-Liina Armio
• Elina Sormunen
• Faith Borgan
• Mattia Veronese

The endocannabinoid system (ECS) has a widespread neuromodulatory function in the central nervous system and is involved in important aspects of brain function including brain development, cortical rhythms, plasticity, reward, and stress sensitivity. Many of these effects are mediated via the cannabinoid CB1 receptor (CB1R) subtype. Animal studies convincingly show an interaction between the ECS and sex hormones, as well as a sex difference of higher brain CB1R in males. Human in vivo studies of sex difference have yielded discrepant findings. Gender differences in CB1R availability were investigated in vivo in 11 male and 11 female healthy volunteers using a specific CB1R tracer [18F]FMPEP-d2 and positron emission tomography (PET). Regional [18F]FMPEP-d2 distribution volume was used as a proxy for CB1R availability. In addition, we explored whether CB1R availability is linked to neuropsychological functioning. Relative to females, CB1R availability was on average 41% higher in males (p = 0. 002) with a regionally specific effect larger in the posterior cingulate and retrosplenial cortices (p = 0. 001). Inter-subject variability in CB1R availability was similar in both groups. Voxel-based analyses revealed an inverse association between CB1R availability and visuospatial working memory task performance in both groups (p < 0. 001). A CB1R sex difference with a large effect size was observed and should be considered in the design of CB1R-related studies on neuropsychiatric disorders. The behavioural correlates and clinical significance of this difference remain to be further elucidated, but our studies suggest an association between CB1R availability and working memory.

YNIMG Journal 2015 Journal Article

Aberrant mesolimbic dopamine–opiate interaction in obesity

• Lauri Tuominen
• Jetro Tuulari
• Henry Karlsson
• Jussi Hirvonen
• Semi Helin
• Paulina Salminen
• Riitta Parkkola
• Jarmo Hietala

Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. μ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [11C]carfentanil and [11C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0. 62, p=0. 003) and dorsal caudate nucleus (r=0. 62, p=0. 004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity.

YNIMG Journal 2012 Journal Article

Mesolimbic dopamine release is linked to symptom severity in pathological gambling

• Juho Joutsa
• Jarkko Johansson
• Solja Niemelä
• Antti Ollikainen
• Mika M. Hirvonen
• Petteri Piepponen
• Eveliina Arponen
• Hannu Alho

Background Brain dopamine neurons code rewarding environmental stimuli by releasing endogenous dopamine, a transmission signal that is important for reinforcement learning. Human reward-seeking gambling behavior, and especially pathological gambling, has been presumed to be modulated by brain dopamine. Methods Striatal dopamine release was studied with [11C]raclopride positron emission tomography (PET) during gambling with an ecologically valid slot machine gambling task. Twenty-four males with and without pathological gambling (DSM-IV) were scanned three times, and the effects of different gambling outcomes (high-reward and low-reward vs. control task) on dopamine release were evaluated. Results Striatal dopamine was released in both groups during high-reward but also low-reward tasks. The dopamine release during the low-reward task was located in the associative part of the caudate nucleus. During the high-reward task, the effect was also seen in the ventral striatum and the magnitude of dopamine release was associated with parallel gambling “high”. Furthermore, there was a positive correlation between dopamine release during the low-reward and the high-reward task. There was no general difference in the magnitude of dopamine release between pathological gamblers and controls. However, in pathological gamblers, dopamine release correlated positively with gambling symptom severity. Conclusions Striatal dopamine is released during gambling irrespective of gambling outcome suggesting that the mere expectation/prediction of reward is sufficient to induce dopaminergic changes. Although dopamine release during slot machine gambling is comparable between healthy controls and pathological gamblers, greater gambling symptom severity is associated with greater dopaminergic responses. Thus, as the dopamine reward deficiency theory predicts blunted mesolimbic dopamine responses to gambling in addicted individuals, our results question the validity of the reward deficiency hypothesis in pathological gambling.

YNIMG Journal 2012 Journal Article

Temperament trait Harm Avoidance associates with μ-opioid receptor availability in frontal cortex: A PET study using [11C]carfentanil

• Lauri Tuominen
• Johanna Salo
• Jussi Hirvonen
• Kjell Någren
• Pauliina Laine
• Tarja Melartin
• Erkki Isometsä
• Jorma Viikari

Harm Avoidance is a temperament trait that associates with sensitivity to aversive and non-rewarding stimuli, higher anticipated threat and negative emotions during stress as well as a higher risk for affective disorders. The neurobiological correlates of interindividual differences in Harm Avoidance are largely unknown. We hypothesized that variability in Harm Avoidance trait would be explained by differences in the activity of μ-opioid system as the opioid system is known to regulate affective states and stress sensitivity. Brain μ-opioid receptor availability was measured in 22 healthy subjects using positron emission tomography and [11C]carfentanil, a selective μ-opioid receptor agonist. The subjects were selected from a large Finish population-based cohort (N=2075) on the basis of their pre-existing Temperament and Character Scores. Subjects scoring consistently in the upper (10) and lower (12) quartiles for the Harm Avoidance trait were studied. High Harm Avoidance score associated with high μ-opioid receptor availability (i. e. lower endogenous μ-opioid drive) in anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices and anterior insular cortex. These associations were driven by two subscales of Harm Avoidance; Shyness with Strangers and Fatigability and Asthenia. In conclusion, higher Harm Avoidance score in healthy subjects is associated with higher μ-opioid availability in regions involved in the regulation of anxiety as well as in the control of emotions, affective component of pain and interoceptive awareness. The results have relevance in the research of vulnerability factors for affective disorders.

YNIMG Journal 2010 Journal Article

Cortical dopamine D2/D3 receptors and verbal memory in man

• Ville Lumme
• Mika M. Hirvonen
• Tuula Ilonen
• Jussi Hirvonen
• Kjell Någren
• Jarmo Hietala

Introduction It has been previously reported that hippocampal dopamine D2/D3 receptors are involved in the regulation of verbal memory and learning in healthy volunteers. We tested this hypothesis further and studied whether cortical dopamine D2/D3 receptor availability in vivo is associated with verbal memory as assessed with the revised Wechsler Memory Scale (WMS-R). Methods Forty healthy Finnish subjects were evaluated according to the WMS-R and scanned with positron emission tomography (PET) and dopamine D2/D3 receptor radioligand [11C]FLB457 for the measurement of cortical D2/D3 receptor binding. Results WMS-R verbal memory and learning parameters did not significantly correlate with D2/D3 receptor binding potential (BP ND) in the studied cortical regions. Conclusions Our findings do not support a major role for cortical D2/D3 receptors in the regulation of verbal memory in healthy individuals.

YNIMG Journal 2010 Journal Article

Serotonin and harm avoidance revisited

• Lauri Tuominen
• Johanna Salo
• Jussi Hirvonen
• Kjell Någren
• Pauliina Laine
• Tarja Melartin
• Erkki Isometsä
• Jorma Viikari

YNIMG Journal 2010 Journal Article

Striatal dopamine function during gambling in pathological gamblers: Interim analysis of ongoing [11C]raclopride PET study

• Juho Joutsa
• Solja Niemelä
• Riitta Parkkola
• Jarmo Hietala
• Juha Rinne
• Valtteri Kaasinen

YNIMG Journal 2007 Journal Article

Shape variability of the human striatum—Effects of age and gender

• Juha Koikkalainen
• Jussi Hirvonen
• Mikko Nyman
• Jyrki Lötjönen
• Jarmo Hietala
• Ulla Ruotsalainen

Human striatum is involved in the regulation of movement, reinforcement, learning, reward, cognitive functioning, and addiction. Previous classical volumetric MRI studies have implicated age-, disease- and medication-related changes in striatal structures. Yet, no studies to date have addressed the effects of these factors on the shape variability and local structural alterations in the striatum. The local alterations may provide meaningful additional information in the context of functional neuroanatomy and brain connectivity. We developed image analysis methodology for the measurement of the volume and local shape variability of the human striatum. The method was applied in a group of 43 healthy controls to study the effects of age and gender on striatal shape variability. In the volume analysis, the volume of the striatum was normalized using the volume of the whole brain. In the local shape analysis, the deviations from a mean surface were studied for each surface point using high-dimensional mapping. Also, discriminant functions were constructed from a statistical shape model. The accuracy and reproducibility of the methods used were evaluated. The results confirmed that the volume of the striatum decreases as a function of age. However, the volume decrease was not uniform and age-related shape differences were observed in several subregions of the human striatum whereas no local gender differences were seen. Examination of the variability of striatal shape in the healthy population will pave the way for applying this method in clinical settings. This method will be particularly useful for investigating neuropsychiatric disorders that are associated with subtle morphological alterations of the brain, such as schizophrenia.