Biology subjects

Malen, T.

Publications and source records attributed to Malen, T..

8 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↗

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

Taxonomy for human social perception

Every day, humans encounter complex social situations that need to be encoded effectively to allow interaction with others. Yet, principles for organizing the perception of social features from the external world remain poorly characterised. In this large-scale study we investigated the principles of social perception in dynamic scenes. In the primary dataset, we presented 234 movie clips (41 minutes) containing various social situations to 1140 participants and asked them to evaluate the presence of 138 social features in each clip. Analyses of the social feature ratings revealed that some features are perceived categorically (present or absent) and others continuously (intensity) and simple social features requiring immediate response are perceived most consistently across participants. To establish the low-dimensional perceptual organization for social features based on movies, we used principal coordinate analysis and consensus clustering for the feature ratings. These dimension reduction analyses revealed that the social perceptual structure can be modelled with eight main dimensions and that behaviourally relevant perceptual categories emerge from these main dimensions. This social perceptual structure generalized from the perception of unrelated Hollywood movie clips to the perception of a full Finnish movie (70 min), and to the perception of static images (n = 468) and across three independent sets of participants (n = 2254). Based on the results, we propose eight basic dimensions of social perception as a model for rapid social perception where social situations are perceived along eight orthogonal perceptual dimensions (most importantly emotional valence, empathy versus dominance, and cognitive versus physical behaviour).

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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.

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bioRxiv2022

Decoding brain basis of laughter and crying in natural scenes.

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 minutes of a full-length feature film, and iii) listened to 15 minutes of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others bonding and distress signals. Significance statementLaughter and crying are universal signals of prosociality and distress, respectively. They occur in complex, dynamic social settings with variable and dynamically evolving time courses. Here we used functional magnetic resonance imaging experiments and statistical pattern recognition for disentangling the neural systems that encode laughter and crying signals from dynamic and highly naturalistic scenes. These results show that separable neural circuits are engaged in processing distinct types of social attachment cues, and that pattern recognition during dynamic scene perception allows reliable separation of laughter and crying evoked activation patterns. Coordinated activity of these networks allows managing appropriate behavioral responses to others bonding and distress signals.

neuroscience↗

bioRxiv2022

Brain glucose metabolism and ageing: A 5-year longitudinal study in a large PET cohort

BackgroundAgeing and clinical factors impact brain glucose metabolism. However, there is a substantial variation of the reported effects on brain glucose metabolism across studies due to the limited statistical power and cross-sectional study designs. MethodsWe retrospectively analyzed data from 441 healthy males (mean 42.8, range 38-50 years) who underwent health check-up program twice at baseline and 5-year follow-up. Health check-up program included 1) brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET), 2) anthropometric and body composition measurements, 3) blood samples, and 4) questionnaires for stress and depression. After spatial normalization of brain FDG PET scans, standardized uptake value ratio (SUVR) was measured from 12 region-of-interests. We used hierarchical clustering analysis to reduce their dimensionality before the Bayesian hierarchical modelling. Five clusters were established for predicting regional SUVR; 1) metabolic cluster (body mass index, waist-to-hip ratio, fat percentage, muscle percentage, homeostatic model assessment index-insulin resistance), 2) blood pressure (systolic, diastolic), 3) glucose (fasting plasma glucose level, HbA1c), 4): psychological cluster (stress, depression), and 5) heart rate. The effects of clinical variable clusters on regional SUVR were investigated using Bayesian hierarchical modelling with brms that applies the Markov-Chain Monte Carlo sampling tools. ResultsAll the clinical variables except depression changed during the 5-year follow-up. SUVR decreased in caudate, cingulate, frontal lobe and parietal lobe and increased in cerebellum, hippocampus, occipital lobe, pallidum, putamen, temporal lobe and thalamus. SUVRs of thalamus, pallidum, hippocampus, putamen and parietal lobe were negatively associated with metabolic cluster and the effects of glucose on SUVRs varied across regions. SUVRs of thalamus, hippocampus, cingulate, cerebellum increased and those with occipital lobe decreased with heart rate. The effects of blood pressure and psychological cluster markedly overlapped with zero across regions. ConclusionRegionally selective decline in brain glucose utilization begins already in the middle age, while individual differences in brain glucose metabolism remain stable. In addition to ageing, brain glucose utilization is also associated with metabolic cluster, blood glucose levels and heart rate. These effects are also consistent over the studied period of 5 years in the middle adulthood.

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bioRxiv2021

Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort

BACKGROUNDThe 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. METHODSIn this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) 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. RESULTSStriatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. 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). CONCLUSIONSD2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

neuroscience↗

bioRxiv2021

Endogenous μ-opioid receptor system modulates sex drive in human males

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. Here we measured healthy male subjects (n=52) brains MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

neuroscience↗