Deep brain stimulation of the subthalamic nucleus restores spatial reversal learning in patients with Parkinson's disease.

Spatial learning and navigation are supported by distinct memory systems in the human brain such as the hippocampus-based navigational system and the striatum-cortex-based system involved in motor sequence, habit and reversal learning. Here, we studied the role of subthalamic circuits in hippocampus-associated spatial memory and striatal-associated spatial reversal learning formation in patients with Parkinson's disease, who underwent a deep brain stimulation of the subthalamic nucleus. Deep brain stimulation patients (Parkinson's disease-subthalamic nucleus: n = 26) and healthy subjects (n = 15) were tested in a novel experimental spatial memory task based on the Morris water maze that assesses both hippocampal place memory as well as spatial reversal learning. All subjects were trained to navigate to a distinct spatial location hidden within the virtual environment during 16 learning trials in a subthalamic nucleus Stim-On condition. Patients were then randomized into two groups with either a deep brain stimulation On or Off condition. Four hours later, subjects were retested in a delayed recall and reversal learning condition. The reversal learning was realized with a new hidden location that should be memorized during six consecutive trials. The performance was measured by means of an index indicating the improvement during the reversal learning. In the delayed recall condition, neither patients, healthy subjects nor the deep brain stimulation On- versus Off groups showed a difference in place memory performance of the former trained location. In the reversal learning condition, healthy subjects (reversal index 2.0) and patients in the deep brain stimulation On condition (reversal index 1.6) showed a significant improvement. However, patients in the deep brain stimulation Off condition (reversal index 1.1) performed significantly worse and did not improve. There were no differences between all groups in a final visual guided navigation task with a visible target. These results suggest that deep brain stimulation of subthalamic nucleus restores spatial reversal learning in a virtual navigation task in patients with Parkinson's disease and gives insight into the neuromodulation effects on cognition of subthalamic circuits in Parkinson's disease.

Perceived Health Benefits in Vestibular Schwannoma Patients with Long-Term Postoperative Headache: Insights from Personality Traits and Pain Coping-A Cross-Sectional Study.

Postoperative headaches (POHs) following retrosigmoid microsurgery for vestibular schwannoma (VS) can significantly impact patients' perceived health benefits (PHBs). In this cross-sectional observational study, 101 VS patients were investigated. For the assessment of pain, the Rostock Headache Compendium (RoKoKo) and the German pain processing questionnaire (FESV) were used. The perceived health benefits (PHBs) were assessed by the Glasgow Benefit Inventory (GBI) and Big Five personality traits were measured using the Ten-Item Personality Inventory (TIPI-G). We showed that 55% of the participants experienced POHs, leading to a marked reduction in overall PHBs compared to those without POHs. The correlation analysis revealed an association between decreased PHBs and elevated levels of pain-related helplessness, depression, anxiety, and anger. Positive correlations were identified between PHBs and action-planning competence, cognitive restructuring, and the experience of competence. Low emotional stability and openness yielded associations with pain-related psychological impairment. Hearing loss and facial paresis did not exert a significant impact on PHBs. The study highlights the influence of pain-related coping strategies on PHBs in long-term POH patients. Thus, coping mechanisms and personality traits should be assessed even before surgery for post-surgery pain prevention. The limitations of this study include a relatively small sample size, potential biases introduced by the overrepresentation of female patients, and the use of an online survey methodology. In conclusion, this research highlights that the interplay between headaches, PHBs, and psychological factors is also relevant in VS patients undergoing microsurgery. Short-term psychological interventions should therefore be taken into account to improve post-surgery adaptive coping strategies.

Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease.

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

Premorbid Psychological Factors Associated with Long-Term Postoperative Headache after Microsurgery in Vestibular Schwannoma-A Retrospective Pilot Study.

Associations between premorbid psychological factors and postoperative headache (POH) after microsurgical treatment via the retrosigmoid approach for vestibular schwannoma (VS) were investigated in this retrospective single-center study. A total of 101 VS patients completed the Rostock headache questionnaire (RoKoKo), the hospital and anxiety scale (HADS-D), and the screening for somatoform disorders (SOMS-2), all of which were used as short self-assessed questionnaires. Fifty-four patients with POH were compared with 47 non-POH patients in terms of premorbid psychological factors, somatization tendencies, and psychological burden using the chi2-test and Mann-Whitney U-test. Regression analyses were conducted to assess the weighted contribution of psychological and procedural factors to POH. In individuals with POH, mental ailments, preexisting headaches, premorbid chronic pain syndromes, and higher somatization tendencies were found to be significantly more common. POH was predicted by the number of premorbid psychosomatic symptoms, preexisting mental ailments, and premorbid chronic pain syndromes. Depression and anxiety were predicted by low emotional stability. Additionally, the number of premorbid psychosomatic symptoms predicted depression, anxiety, and overall psychological burden. It was observed that the reported symptoms of headache might fit into the classification of chronic postsurgical pain (CPSP) rather than being classified as secondary headaches after craniotomy. Premorbid psychological factors were found to play an important role in the emergence of POH in VS, particularly after microsurgery via the retrosigmoid approach. Therefore, it is suggested that psychological screening be incorporated into the treatment process.

Impaired learning of punishments in Parkinson's disease with and without impulse control disorder.

To document specific learning mechanisms in patients with Parkinson's disease (PD) with and without impulse control disorder (ICD). Thirty-two PD patients receiving dopamine replacement therapy (DRT) were investigated. Sixteen were diagnosed with ICD (ICD + ) and 16 PD patients matched for levodopa equivalence dosage, and DRT duration and severity of disease did not show impulsive behavior (non-ICD). Short-term learning of inhibitory control was assessed by an experimental procedure which was intended to mimic everyday life. Correct inhibition especially, had to be learned without reward (passive avoidance), and the failure to inhibit a response was punished (punishment learning). Results were compared to 16 healthy controls (HC) matched for age and sex. In ICD+ patients within-session learning of non-rewarded inhibition was at chance levels. Whereas healthy controls rapidly developed behavioral inhibition, non-ICD patients were also significantly impaired compared to HC, but gradually developed some degree of control. Both patient groups showed significantly decreased learning if the failure to withhold a response was punished. PD patients receiving DRT show impaired ability to acquire both punishment learning and passive avoidance learning, irrespective of whether or not ICD was developed. In ICD + PD patients, behavioral inhibition is nearly absent. Results demonstrate that by means of subtle learning paradigms it is possible to identify PD-DRT patients who show subtle alterations of punishment learning. This may be a behavioral measure for the identification of PD patients who are prone to develop ICD if DRT is continued.

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology.

Spatial learning deficits in Parkinson's disease with and without mild cognitive impairment.

BACKGROUND: Several MRI studies have demonstrated hippocampal atrophy in Parkinson's disease (PD), a structure considered a key element in spatial learning. Despite this, no study has been undertaken to investigate spatial navigation in PD using a virtual version of the Morris water maze, which is the gold standard for testing hippocampal function in rodents. METHODS: We studied 17 cognitively unimpaired PD patients, 12 PD patients with mild cognitive impairment (MCI) and 15 controls in a virtual water maze procedure. RESULTS: Measured by the main outcome parameters latency to locate the target and heading error (average difference between direction of movement toward anticipated target and real direction toward the target), controls performed significantly better on the virtual water maze task than cognitively unimpaired PD patients or PD patients with MCI, while there was no significant difference between latter two groups. CONCLUSIONS: The virtual water maze test differentiates PD patients from controls, but does not distinguish between cognitively normal and cognitively impaired PD patients, indicating a possible dopamine dependent component in spatial learning. Spatial performance deficits might thus constitute very early signs of dopamine depletion independent of the presence of MCI in Parkinson's disease.

Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.

BACKGROUND: Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. METHODS: To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. RESULTS: CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in (1)H-MRS. CONCLUSION: Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that (1)H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.

Effect of a single dialysis session on cognitive function in CKD5D patients: a prospective clinical study.

BACKGROUND: Cognitive function declines in parallel to the decrease in glomerular filtration rate, best epitomized by the markedly reduced cerebral performance in patients undergoing maintenance haemodialysis [chronic kidney disease stage 5 dialysis (CKD5D)]. Aside from structural permanent damage, there seems to be a reversible part of low cognitive performance. The potential effect of a single dialysis session on cognitive function remains still elusive. The aim of the study was to assess cognitive function using a widespread test battery and avoiding excluding effects of circadian variations. METHODS: Twenty-eight medically stable CKD5D patients (age: 54.9 ± 13.2 years, dialysis vintage: 46.2 ± 51.0 month) at two tertiary care centres with outpatient dialysis units were enrolled. Cognitive testing was always performed twice within 24 h, 1 h prior to haemodialysis (T1pre-dialysis) as well as 19 h after the end of dialysis (T2post-dialysis) including assessment of memory, attention and concentration, executive functioning, word fluency and psychomotor speed by using a well-validated neuropsychological test battery. Patients were randomized into two groups. One group was examined before (T1pre-dialysis) and after (T2post-dialysis) Dialysis Session 1. The other group was first examined the day after Dialysis Session 1 (T2post-dialysis) and then before Dialysis Session 2 (T1pre-dialysis) in order to exclude potential learning effects. Twenty age-matched subjects with normal excretory renal function were used for comparison. RESULTS: Neuropsychological testing found that the CKD5D performed significantly worse on measures of alertness, attention, working memory, logical and visual memory, word fluency and executive functions compared with non-CKD subjects. No differences in short-term memory, selective attention, as well as problem-solving and planning were found between CKD5D patients and non-CKD subjects. A single haemodialysis session led to a significant improvement in logical (Rivermead Behaviour Memory Test story: P < 0.001) and visual memories [Rey-Osterrieth Complex Figure Test (RCFT) memory quotient: P < 0.001], psychomotor speed [Trail Making Test (TMT) B: P = 0.020], activity planning (executive functions) (RCFT copy/points deduction: P < 0.001) and concentration (TMT A: P < 0.001). CONCLUSION: Our data demonstrate improvements in memory functions, executive functions and psychomotor abilities after a single dialysis session, pointing to a reversible component of low cognitive performance in CKD5D.

Cognitive function at 2443 µmol/l creatinine.

BACKGROUND: One hallmark of uremia is the impairment of neuro-cognitive function. Anecdotal clinical description from the early days of chronic dialysis therapy impressively illustrates the improvement of those functions by chronic hemodialysis treatment. Fortunately, today, uremia is only rarely observed in industrialized countries as many patients seek medical/nephrological attention prior to the occurrence of deadly complications of uremia. CASE PRESENTATION: We report a rare case of severe uremia and describe the day to day improvement in neuro-cognitive function by dialysis using state of the arte test battery--starting at a serum creatinine of 2443 µmol/l. CONCLUSIONS: Especially executive functions, which are assumed to be localized in the frontal cerebral regions, are impaired in severe uremia and improve remarkably with the correction of severe uremia, i.e., initiation of dialysis.