Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.Siirretty Doriast

Pre- and postnatal nutrition – target for allergy risk reduction

A rapid increase in allergic diseases in Western societies has led to the conclusion that our modern lifestyle is a risk factor for immune dysregulation. Potential culprits and benefactors are searched among early dietary and microbial exposures, which may act to program later allergic disease. The aim of this thesis was to investigate the role of early maternal and child nutrition in reducing the risk of child allergy. The study population comprised of 256 mother – child pairs from families with a history of allergy participating in a randomized controlled dietary counseling and probiotic intervention (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12) study from early pregnancy onwards. The dietary counseling aimed for a diet complying with dietary recommendations for pregnant and lactating women, with special attention to fat quality. Maternal dietary counseling was reflected in cord blood fatty acids suggesting better essential fatty acid status in infants in the counseling group. Dietary counseling with probiotics or placebo had no effect on child allergy risk, but associations between maternal diet during pregnancy and breastfeeding and child allergic outcomes were found in secondary analyses. During pregnancy, milk intake was related to decreased and cheese intake to increased risk of child atopic eczema. During breastfeeding, intake of vitamin C was related to increased risk of asthma and intake of egg was related to decreased risk of atopic eczema. The timing of introduction of complementary foods to infant’s diet was not associated with risk of atopic eczema, when adjusted with parental opinion of child allergic symptoms (i.e., potential reverse causality). In conclusion, the results demonstrate that infant fatty acid supply can be modified via maternal dietary changes. In addition, interesting associations of maternal diet with child allergy risk were discovered. However, no difference in the incidence of allergic diseases with dietary counseling was observed. This suggests that more potent dietary interventions might be necessitated to induce clinical risk reduction of allergy. Highrisk families can safely adhere to dietary recommendations for pregnant and lactating women, and the results support the current conception that no additional benefit is gained with delaying introduction of complementary feeding.Varhainen ravitsemus ja allergian ehkäisy Allergiset sairaudet ovat lisääntyneet länsimaisissa yhteiskunnissa nopeasti, mikä on johtanut päätelmään, että elämäntapamme on riskitekijä immuunijärjestelmän häiriöille. Varhainen ravitsemus ja mikrobialtistus ovat nousseet esille mahdollisina riski- ja suojatekijöinä, jotka voivat vaikuttaa myöhempään riskiin sairastua allergiaan. Tämän satunnaistetun, kontrolloidun tutkimuksen tarkoituksena oli selvittää äidin ja lapsen varhaisen ravitsemuksen merkitystä lapsen allergiariskin vähentämisessä. Tutkimukseen osallistui 256 äiti-lapsi-paria allergisista riskiperheistä. Kahdelle ryhmälle alettiin varhaisraskauden aikana antaa yksilöllistä ravitsemusohjausta sekä joko probioottivalmistetta (Lactobacillus rhamnosus GG ja Bifidobacterium lactis Bb12) tai lumevalmistetta. Kontrolliryhmä sai lumevalmistetta ja ohjeita neuvolasta tavalliseen tapaan. Ravitsemusohjauksella tavoiteltiin suositusten mukaista ruokavaliota, ja erityisesti rasvan laatuun kiinnitettiin huomiota. Äidille annettu ravitsemusohjaus näkyi napaveren rasvahappoprofiilissa, mikä viittaa ravitsemusohjausryhmän parempaan välttämättömien rasvahappojen saantiin. Ravitsemusohjaus, johon liittyi joko probiootti- tai lumevalmiste, ei vaikuttanut lapsen allergiariskiin, mutta toissijaisissa analyyseissä paljastui yhteyksiä äidin ruokavalion ja lapsen allergisten sairauksien välillä. Raskaudenaikainen maidon kulutus oli yhteydessä lapsen pienempään atooppisen ekseeman riskiin, kun taas juuston kulutus oli yhteydessä suurempaan riskiin. Imetyksenaikainen C-vitamiinin saanti oli yhteydessä suurempaan astman riskiin, ja kananmunan kulutus pienempään atooppisen ekseeman riskiin. Lisäruokien aloitusikä ei ollut yhteydessä atooppisen ekseeman riskiin, silloin kun otettiin huomioon vanhempien käsitys lapsen mahdollisista allergisista oireista. Yhteenvetona voidaan todeta, että äidin ruokavaliolla voidaan vaikuttaa lapsen rasvahappojen saantiin. Lisäksi äidin ruokavaliolla sekä allergisten sairauksien riskillä vaikuttaa olevan yhteys. Koska ravitsemusohjauksella ei ollut vaikutusta allergiariskiin, tämä voisi viitata siihen, että ravitsemusinterventioiden pitäisi olla voimakkaampia toimiakseen. Allergiset riskiperheet voivat turvallisesti noudattaa ravitsemussuosituksia, ja tutkimuksen tulokset vahvistavat käsitystä siitä, ettei lisäruokien viivyttäminen auta allergian ehkäisyssä.Siirretty Doriast

Parallel Appearance of Compulsive Behaviors and Artistic Creativity in Parkinson's Disease

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity

Predictors of normal and abnormal outcome in clinical brain dopamine transporter imaging

Brain dopamine transporter (DAT) imaging with [123I]FP-CIT SPECT can be used to evaluate the integrity of the mesostriatal dopaminergic system in patients with clinically uncertain parkinsonism. To evaluate whether scanning a patient is clinically necessary, it is vital to understand possible factors that affect the scanning result. Therefore, we investigated an unselected sample of 538 consecutively scanned patients from a 6-year period, and the demographic data and indications for DAT SPECT were recorded. After scanning, the patients were divided into groups according to the scanning outcome. Multivariate binary logistic regression analyses were performed to investigate whether the pre-imaging variables had independent associations with the outcome of the scan. Three hundred and three (56.3 %) patients had abnormal scans showing a dopaminergic deficit. The independent factors associated with abnormal scans were older age (p = 0.002), asymmetry of motor symptoms (p = 0.005) and shorter symptom duration (p p = 0.004), whereas the possibility of medication-induced parkinsonism was associated with a higher probability of a normal scan (35.4 %, p = 0.036). The probability of an abnormal outcome in clinical brain DAT imaging increases with known risk factors of neurodegenerative parkinsonism. However, a long duration of uncertain motor symptoms and suspicion of medication-induced parkinsonism are associated with a higher probability of a normal outcome. The findings reflect epidemiological factors in parkinsonism together with referral biases that may be used to improve the clinical use of DAT imaging.</p

Hypermetabolism of Olivary Nuclei in a Patient with Progressive Ataxia and Palatal Tremor

Background: The pathophysiology of the movement disorder progressive ataxia with palatal tremor (PAPT) is unclear. Case report: A 77-year-old male presented with dysarthria, ataxia, and 1–2 Hz palatal tremor. A diagnosis of probable sporadic PAPT was established. Brain magnetic resonance imaging was normal at the presymptomatic phase but later showed olivary hypertrophy. Brain [18F]-fludeoxyglucose (FDG) positron emission tomography (PET) showed bilateral hypermetabolism in the olivary nuclei. Discussion: This second reported patient with PAPT and FDG-PET shows that olivary hypertrophy is paralleled with hypermetabolism. The olivary nuclei pathology also appears to be temporally associated with symptom onset

Beyond volume : A surface-based approach to bilingualism-induced grey matter changes

Bilingualism is a sustained experience associated with structural changes in cortical grey matter (GM) morphology. Apart from a few studies, a dominant method used to assess bilingualism-induced GM changes has been the voxel-based morphometry (VBM) analysis. While VBM is sensitive to GM volume/density differences in general, it cannot be used to identify whether the observed difference is due to relative changes in, e.g., cortical thickness, area or folding, as it uses a single combined measure of them all. Here, we used surface-based analysis (SBA) approach to investigate whether early acquisition of a second language (L2) affects the cortical GM morphology relative to late L2 acquisition. More specifically, our aim was to test a hypothesis that early acquisition of two languages induces GM changes that are predominantly surface area-driven, while late acquisition is supposedly characterised with primarily thickness-driven changes. To this end, several surface-based measures were concurrently compared between the groups. In line with the hypothesis, the results revealed that early bilingual experience is associated with significantly extended cortical surface area over the left pars opercularis and the right superior temporal gyrus. Contrary to our expectations, however, we found no evidence supporting the postulated association between late L2 acquisition and increased cortical thickness. Nevertheless, our study highlights the importance of including cortical surface measures when investigating bilingualism related GM modulations.Peer reviewe

Parkinsonin taudin ei-motoristen oireiden hoito

Parkinsonin tauti mielletään usein puhtaasti motoriseksi liikehäiriösairaudeksi, jonka oireita ovat liikkeiden hitaus, lihasjäykkyys, lepovapina ja tasapainovaikeudet. Parkinsonin tauti on kuitenkin laajempi keskus- ja ääreishermoston sairaus, joka aiheuttaa merkittäviä ei-motorisia oireita. Näihin kuuluvat muun muassa hajuaistin heikkeneminen, autonomisen hermoston toimintahäiriöt, muistihäiriöt, psykiatriset oireet ja uniongelmat. Ei-motorisia oireita esiintyy usein jo ennen motoristen oireiden puhkeamista, ja ne lisääntyvät taudin edetessä. Osa oireista liittyy aivojen dopamiinivajeeseen, osa aiheutuu lääkityksen haittavaikutuksena ja osa liittyy muiden hermovälittäjäainejärjestelmien häiriöihin. Ei-motoristen oireiden vaikutus potilaan elämänlaatuun on jopa voimakkaampi kuin motoristen oireiden, mutta niitä voidaan lievittää merkittävästi lääkehoidoilla.</p