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

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

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

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

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

No relevant midbrain atrophy in Parkinson's disease

Aims of the study - To investigate whether significant midbrain atrophy is present in Parkinson's disease (PD), and if so, whether it can be used as a marker of striatal dopaminergic degeneration. Methods - In total, 150 PD patients and 155 controls were scanned with both brain dopamine transporter (DAT) [I-123]FP-CIT SPECT and 1.5T MRI. Midbrain atrophy was measured from sagittal MRIs using the midbrain-to-pons ratios. Both striatal region-of-interest-based (Brass) and striatal and extrastriatal voxel-by-voxel-based DAT binding (SPM8) were investigated in relation to midbrain atrophy. Results - The midbrain-to-pons ratios in PD patients were slightly lower than those in the controls (mean 0.59 vs 0.61, P </p

Mapping holmes tremor circuit using the human brain connectome

ObjectiveHolmes tremor is a debilitating movement disorder with limited treatment options. Lesions causing Holmes tremor can occur in multiple different brain locations, leaving the neuroanatomical substrate unclear. Here, we test whether lesion locations that cause Holmes tremor map to a connected brain circuit and whether this circuit might serve as a useful therapeutic target.MethodsCase reports of Holmes tremor caused by focal brain lesions were identified through a systematic literature search. Connectivity between each lesion location and the rest of the brain was computed using resting state functional connectivity magnetic resonance imaging data from 1,000 healthy volunteers. Commonalities across lesion locations were identified. This Holmes tremor circuit was then compared to neurosurgical treatment targets and clinical efficacy.ResultsWe identified 36 lesions causing Holmes tremor, which were scattered across multiple different brain regions. However, all lesion locations were connected to a common brain circuit with nodes in the red nucleus, thalamus, globus pallidus, and cerebellum. In cases with effective neurosurgical treatment, the treatment target was connected with the lesion location, indicating that a second hit to the same circuit might be beneficial. Commonly used deep brain stimulation targets such as the ventral intermediate nucleus and subthalamic nucleus fell outside our Holmes tremor circuit, whereas the globus pallidus target was close, consistent with published clinical response rates for these targets.InterpretationLesions causing Holmes tremor are part of a single connected brain circuit that may serve as an improved therapeutic target.</p