Insights into the structure and function of the hippocampal formation: Relevance to Parkinson's disease.

The link between the hippocampus and declarative memory dysfunctions following the removal of the medial temporal lobe opened unexplored fields in neuroscience. In the first part of our review, we summarized current theoretical frameworks discussing the role of hippocampus in learning and memory. Several theories are highlighted suggesting that the hippocampus is responsible for assembling stimulus elements into a unitary representation that later can be utilized to simulate future events. The hippocampal formation has been implicated in a growing number of disorders, from neurodegenerative diseases to atypical cognitive ageing and depression. Recent neuroimaging studies provided new opportunities to study in detail the hippocampal formation's role in higher levels of the nervous system. We will present data regarding the regional specialization of the hippocampus in experimental models developed for healthy and neurological conditions with a special focus on Parkinson's disease. Combined evidence from neuroimaging studies suggested that hippocampal volume is reduced in non-demented, newly diagnosed patients with Parkinson's disease, which is associated with impaired memory performance. These findings proposed that, beyond the well-known striatal dopamine loss, impaired hippocampal synaptic plasticity may contribute to cognitive and affective impairments in early Parkinson's disease.

A single dose of L-DOPA changes perceptual experiences and decreases latent inhibition in Parkinson's disease.

Despite the well-known neuropsychiatric side effects of dopaminergic medications, the possible subjective psychotomimetic effects of a single dose of L-DOPA in newly diagnosed, drug-naïve patients with Parkinson's disease (PD) are not known. To investigate this question, we used a visual search task for latent inhibition (LI), the Community Assessment of Psychic Experiences (CAPE) scale, and visual analog scales for psychotomimetic effects (perception, relaxation, and dysphoria) in 28 de novo PD patients before (off) and after (on) the adminstration of L-DOPA and in 25 matched healthy control individuals. Results revealed increased LI in PD-off and decreased LI in PD-on relative to the control subjects. After the administration of L-DOPA, we observed a significant decline in LI in PD. L-DOPA also enhanced perceptual experiences (changes in subjective feelings in thinking, time perception, and mental "highness"). Greater reduction in LI was associated with enhanced perceptual experiences. These results suggest that a single dose of L-DOPA has a significant psychotomimetic effect, which is associated with decreased LI, a behavioral marker of psychosis-like experiences.

Case report of a woman with anti amphiphysin positive stiff person syndrome.

Stiff person syndrome is a rare neuroimmunological disease, characterized by severe, involuntary stiffness with superimposed painful muscle spasms, which are worsened by external stimuli. The classical form is associated with high levels of antibodies against glutamic acid decarboxylase. One of the variant forms is associated with antibodies against amphiphysin. This entity is a paraneoplastic syndrome, caused primarily by breast cancer, secondarily by lung cancer. Symptomatic therapy of anti amphiphysin positive stiff person syndrome includes treatment with benzodiazepines and baclofen (including intrathecal baclofen therapy). The effect of immunological therapies is controversial. Treatment of the underlying cancer may be very effective. In this report, we describe a 68 year old female presenting with an unusally rapidly developing anti amphiphysin positive stiff person syndrome, which was associated with breast cancer. Her painful spasms abolished after intrathecal baclofen treatment was initiated. Her condition improved spontaneously and significantly after cancer treatment, which enabled to start her complex rehabilitation and the simultaneous dose reduction of the intrathecal baclofen. The bedridden patient improved to using a rollator walker and the baclofen pump could be removed 18 monthes after breast surgery. This highlights the importance of cancer screening and treatment in anti amphiphysin positive stiff person syndrome cases.

Behavioural aspects of a modified crosstalk between basal ganglia and limbic system in Parkinson's disease.

Dysfunctions in dopaminergic neurotransmission lead to motor symptoms and cognitive impairments associated with behavioural disturbances. Parkinson's disease is a neurodegenerative disorder which is primarily characterized by an abnormal basal ganglia activity. Recently, increased attention has been directed towards the hippocampus in the development of non-motor symptoms. Given the temporal progression of the disease, dopaminergic depletion firstly affects the dorsal striatum leaving the ventral striatum relatively intact. However, it is possible that the structure and function of the hippocampus shows alterations even in early stages of Parkinson's disease. Subtle cognitive impairments occur in the earliest stages, and therefore Parkinson's disease could provide a unique model to investigate the effect of replacement therapies on a neural network with different baseline dopaminergic levels. Strong evidence suggests that dopaminergic medications improve the motor symptoms, but these medications might have disadvantageous effects on cognitive functions. In this review, we examine the role of dopaminergic changes across several cognitive and behavioural impairments observed in Parkinson's disease, with a special reference to hippocampal dysfunctions.

Accuracy of high-density EEG electrode position measurement using an optical scanner compared with the photogrammetry method.

Objective: To determine the feasibility and accuracy of a handheld optical scanner to measure the three-dimensional (3D) EEG electrode coordinates in a high-density array of 256 electrodes. Methods: We compared the optical scanning with a previously validated method, based on photogrammetry. Electrode coordinates were co-registered with the MRI of the patients, and mean distance error relative to the three-dimensional MRI reconstruction was determined for each patient. We included 60 patients: 30 were measured using the photogrammetry method, and 30 age and gender matched patients were measured with the optical scanner. Results: Using the optical scanner, the mean distance error was 1.78 mm (95% confidence interval: 1.59-1.98 mm) which was significantly lower (p < 0.001) compared with the photogrammetry method (mean distance error: 2.43 mm; 95% confidence interval: 2.28-2.57 mm). The real-time scanning took 5-10 min per patient. Conclusions: The handheld optical scanner is more accurate and feasible, compared to the photogrammetry method. Significance: Measuring EEG electrode positions in high-density array, using the optical scanner is suitable for clinical implementation in EEG source imaging for presurgical evaluation.

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.

Dopamine improves exploration after expectancy violations and induces psychotic-like experiences in patients with Parkinson's disease.

Dopamine neurons are sensitive to novel and rewarding events, and dopamine signals can modulate learning in higher-level brain networks. Additionally, dopamine abnormalities appear to be central to the pathophysiology of schizophrenia spectrum disorders. In this study, we investigate the dopaminergic modulation of schizotypal traits and exploration after expectancy violations in Parkinson's disease (PD) patients on dopamine replacement therapy. Exploration after expectancy violations was measured with a latent inhibition and an anomaly categorisation task. Patients with PD had significantly elevated levels of schizotypy and reduced latent inhibition, relative to the controls. Anomaly categorisation was enhanced at trend level among the patients. Dopaminergic antiparkinsonian drugs showed dose-dependent effects: they induced psychotic-like experiences, and at the same time, they disrupted latent inhibition and made categorisation of anomaly more efficient. Most of these findings were replicated in an independent sample of patients with PD. An up-regulated dopamine system in medicated PD patients might tune higher-level brain networks to engage in learning when faced with unexpected information, and therefore hasten the updating of internal models.

International Issues: Cross-border mobility of junior neurologists within and to the European Union.

OBJECTIVE: To assess the general interest in and motivation for cross-border mobility among residents and junior neurologists from member states of the European Union and neighboring countries. METHODS: Questionnaire-based paper survey among 118 participants of a neurology course. RESULTS: Ninety-seven (82%) participants returned the survey. Most of them had at one point considered relocating within or to the European Union for postgraduate education (87%) or employment (71%). Common motivations were superior prospects for clinical training (85%), resources at work and academic environment (both 80%), and remuneration (70%). Barely half of the surveyed intended to return to their home country. The attractiveness of Europe as a destination for migration was ranked over other continents. The most common reasons that reduce enthusiasm for relocation were the loss of family connection (55%) and uncertain future prospects (41%), whereas language barriers were less relevant (21%). CONCLUSION: There is keen interest of the upcoming generation of neurologists to relocate within and to the European Union. The motives include regional differences in training and career opportunities as well as economic welfare. Appropriate steps toward the harmonization of educational and career prospects are urgently required to ensure adequate provision of neurology service and patient care throughout Europe.