Helga Nagy

Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients

Parkinsons disease is characterized by the degeneration of dopaminergic pathways projecting to the striatum. These pathways are implicated in reward prediction. In this study, we investigated reward and punishment processing in young, never-medicated Parkinsons disease patients, recently medicated patients receiving the dopamine receptor agonists pramipexole and ropinirole and healthy controls. The never-medicated patients were also re-evaluated after 12 weeks of treatment with dopamine agonists. Reward and punishment processing was assessed by a feedback-based probabilistic classification task. Personality characteristics were measured by the temperament and character inventory. Results revealed that never-medicated patients with Parkinsons disease showed selective deficits on reward processing and novelty seeking, which were remediated by dopamine agonists. These medications disrupted punishment processing. In addition, dopamine agonists increased the correlation between reward processing and novelty seeking, whereas these drugs decreased the correlation between punishment processing and harm avoidance. Our finding that dopamine agonist administration in young patients with Parkinsons disease resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side-effects of dopamine agonist therapy in some Parkinsons disease patients.

Cognitive sequence learning in Parkinson's disease and amnestic mild cognitive impairment: Dissociation between sequential and non-sequential learning of associations

Evidence suggests that dopaminergic mechanisms in the basal ganglia (BG) are important in the learning of sequential associations. To test the specificity of this hypothesis, we assessed never-medicated patients with Parkinsons disease (PD) and amnestic mild cognitive impairment (aMCI) using a chaining task. In the training phase of the chaining task, each link in a sequence of stimuli leading to reward is trained step-by-step using feedback after each decision, until the complete sequence is learned. In the probe phase of the chaining task, the context of stimulus-response associations must be used (the position of the associations in the sequence). Results revealed that patients with PD showed impaired learning during the training phase of the chaining task, but their performance was spared in the probe phase. In contrast, patients with aMCI with prominent medial temporal lobe (MTL) dysfunctions showed intact learning during the training phase of the chaining task, but their performance was impaired in the probe phase of the chaining task. These results indicate that when dopaminergic mechanisms in the BG are dysfunctional, series of stimulus-response associations are less efficiently acquired, but their sequential manner is maintained. In contrast, MTL dysfunctions may result in a non-sequential learning of associations, which may indicate a loss of contextual information.

The effects of reward and punishment contingencies on decision-making in multiple sclerosis.

Many patients with multiple sclerosis (MS) show cognitive and emotional disorders. The purpose of this study is to evaluate the role of contingency learning in decision-making in young, non-depressed, highly functioning patients with MS (n=21) and in matched healthy controls (n=30). Executive functions, attention, short-term memory, speed of information processing, and selection and retrieval of linguistic material were also investigated. Contingency learning based on the cumulative effect of reward and punishment was assessed using the Iowa Gambling Test (IGT). In the classic ABCD version of the IGT, advantageous decks are characterized by immediate small reward but even smaller future punishment. In the modified EFGH version, advantageous decks are characterized by immediate large punishment but even larger future reward. Results revealed that patients with MS showed significant dysfunctions in both versions of the IGT. Performances on neuropsychological tests sensitive to dorsolateral prefrontal functions did not predict and did not correlate with the IGT scores. These results suggest that patients with MS show impaired performances on tasks designed to assess decision-making in a situation requiring the evaluation of long-term outcomes regardless of gain or loss, and that this deficit is not a pure consequence of executive dysfunctions.

The Effect of Dopamine Agonists on Adaptive and Aberrant Salience in Parkinson's Disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinsons disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus–reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus–reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus–reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward.

Risk and protective haplotypes of the alpha-synuclein gene associated with Parkinson's disease differentially affect cognitive sequence learning.

Alpha‐synuclein (SNCA) is a key factor in the regulation of dopaminergic transmission and is related to Parkinson’s disease. In this study, we investigated the effects of risk and protective SNCA haplotypes associated with Parkinson’s disease on cognitive sequence learning in 204 healthy volunteers. We found that the 3′‐block risk SNCA haplotypes are associated with less effective stimulus‐reward learning of sequences and with superior context representation of sequences. In contrast, participants with protective haplotypes exhibit better stimulus‐reward learning and worse context representation, which suggest that these functions are inversely affected by risk and protective haplotypes. The Rep1 promoter polymorphism does not influence cognitive sequence learning. Because stimulus‐reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems.

Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson's disease

Background/Aims: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson’s disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. Methods: Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (l-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. Results: In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. Conclusion: Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.

Somatosensory evoked potentials correlate with genetics in Huntington's disease

Abnormalities of somatosensory evoked potentials (SEPs) have been reported in Huntingtons disease, a neuropsychiatric disorder caused by the expansion of a CAG trinucleotide repeat. The aim of our study was to determine the relationship between these electrophysiological changes and the length of the nucleotide repeat. We found a striking correlation between the decrease in the early component amplitudes (N20 and N30) of the median nerve SEP and the repeat length, suggesting that these SEP alterations are indeed related to the genetically determined pathological process. The cortical components of the tibial nerve SEP exhibited a dram-atic alteration in the patient group and were the only SEP changes found in the group of asymptomatic carriers of the mutation, being more sensitive than the median nerve SEPs.

Cervical juxtafacet cyst combined with spinal dysraphism

Juxtafacet cysts of the cervical and thoracic spine are rare and often cause radiculopathy or myelopathy. We present a case of a patient with radicular pain and early onset myelopathy. A juxtafacet cyst at the cervico-thoracic junction combined with discal herniation and spina bifida occulta was diagnosed with computed tomography (CT) and magnetic resonance imaging (MRI). Laminectomy with removal of the cyst was the treatment and the patient recovered rapidly.

The effect of sleep deprivation on median nerve somatosensory evoked potentials

The purpose of the study was to determine the effect of one nights sleep deprivation on the early and middle-latency median nerve (MN) somatosensory evoked potentials (SEPs). In 20 healthy volunteers, SEPs in response to electrical stimulation of the MN at the wrist were recorded for the 100-ms post-stimulus period, before and after one night of sleep deprivation. The P14 latency was significantly prolonged after sleep deprivation. We found significant increases in the amplitudes of the early parietal (N20-P24) and the frontal middle-latency (P45-N60) components following sleep deprivation. Our results indicate that somatosensory processing is altered after sleep deprivation.

Reduced CA2–CA3 Hippocampal Subfield Volume Is Related to Depression and Normalized by l-DOPA in Newly Diagnosed Parkinson’s Disease

Hippocampal dysfunctions may play an important role in the non-motor aspects of Parkinson’s disease (PD), including depressive and cognitive symptoms. Fine structural alterations of the hippocampus and their relationship with symptoms and medication effects are unknown in newly diagnosed PD. We measured the volume of hippocampal subfields in 35 drug-naïve, newly diagnosed PD patients without cognitive impairment and 30 matched healthy control individuals. Assessments were performed when the patients did not receive medications and after a 24-week period of l-DOPA treatment. We obtained a T1-weighted 3D magnetization-prepared rapid acquisition gradient echo image at each assessment. FreeSurfer v6.0 was used for image analysis. Results revealed a selectively decreased CA2–CA3 volume in non-medicated PD patients, which was normalized after the 24-week treatment period. Higher depressive symptoms were associated with smaller CA2–CA3 volumes. These results indicate that the CA2–CA3 subfield is structurally affected in the earliest stage of PD in the absence of cognitive impairment. This structural anomaly, normalized by l-DOPA, is related to depressive non-motor symptoms.