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Objective: Cognitive dysfunction is a core symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here, we performed a prospective longitudinal study to assess cognitive long-term outcome and identify clinical predictors., Methods: Standardized comprehensive neuropsychological assessments were performed in 43 patients with NMDAR encephalitis 2.3 years and 4.9 years (median) after disease onset. Cognitive assessments covered executive function, working memory, verbal/visual episodic memory, attention, subjective complaints, and depression and anxiety levels. Cognitive performance of patients was compared to that of 30 healthy participants matched for age, sex, and education., Results: All patients had persistent cognitive deficits 2.3 years after onset, with moderate or severe impairment in >80% of patients. Core deficits included memory and executive function. After 4.9 years, significant improvement of cognitive function was observed, but moderate to severe deficits persisted in two thirds of patients, despite favorable functional neurological outcomes (median modified Rankin Scale = 1). Delayed treatment, higher disease severity, and longer duration of the acute phase were predictors for impaired cognitive outcome. The recovery process was time dependent, with greater gains earlier after the acute phase, although improvements were possible for several years after disease onset., Interpretation: Cognitive deficits are the main contributor to long-term morbidity in NMDAR encephalitis and persist beyond functional neurological recovery. Nonetheless, cognitive improvement is possible for several years after the acute phase and should be supported by continued cognitive rehabilitation. Cognition should be included as an outcome measure in future clinical studies. ANN NEUROL 2021;90:949-961., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Atrial fibrillation (AF) is associated with cognitive decline and dementia irrespective of AF-related ischemic stroke. We investigated whether AF burden after ablation in patients with symptomatic paroxysmal AF has an impact on cognitive function. After enrolment to the prospective MACPAF study, study patients received an insertable loop recorder (ILR) and underwent serial neurological/cognitive assessment. To compare cognitive function, the delta of baseline and six months test results (Δ pre/post ) and a score to assess overall cognitive performance were computed. Thirty patients (median age 65 years (IQR 57-69), 40% female) were divided into groups according to median AF burden (<0.5% vs. ≥0.5%) after ablation. Overall cognitive performance did not differ in patients with an AF burden < 0.5% (median 120% [IQR 100-150]) vs. ≥0.5% (median 120% [IQR 100-160]) within six months after ablation (p = 0.74). Comparing Δ pre/post , patients with an AF burden ≥ 0.5% showed significantly better results in the digit-span backwards test (median + 1 [IQR 0 - +2 points]) compared to patients with an AF burden < 0.5% (median 0 [IQR -1-+1]) six months after ablation (p = 0.03). In patients with an AF burden < 0.5%, there was a statistical trend towards better results in the RAVLT test (median + 3 [IQR 0-+4]; p = 0.08) and the ROC test (median + 3 [IQR -1-+5; p = 0.07) compared to patients with an AF burden ≥ 0.5% (median -1 [IQR -3-+2] words and median -1 [IQR -5-+2] points, respectively). Therefore, AF burden had no significant impact on cognitive performance within six months after ablation. Clinical Trial Registration: clinicaltrials.gov NCT01061931., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Normal cognition is an established selection criteria for subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD), while concern has been raised as to aggravated cognitive decline in PD patients following STN-DBS. The present longterm study investigates cognitive status in all patients (n = 104) suffering from PD, who were treated via continuous bilateral STN-DBS between 1997 and 2006 in a single institution. Preoperative neuropsychological results were available in 79/104 of the patients. Thirty-seven of these patients were additionally assessed after 6.3 ± 2.2 years (range 3.6-10.5 years) postsurgery via neuropsychological and motor test batteries, classifying cognitive conditions according to established criteria. At DBS-surgery patients, available for longterm follow-up (n = 37; mean age 67.6 ± 6.9 years, mean disease duration 11.3 ± 4.1 years), showed no (24.3%; 9/37) or mild preoperative cognitive impairment (MCI, 75.7%; 28/37). Postoperatively (mean disease duration: 17.1 ± 5.1 years), 19% of the patients (7/37) had no cognitive impairment, while 41% of the patients presented with either MCI or dementia (15/37, respectively). Preoperative MCI correlated with conversion to dementia by trend. Overall, STN-DBS-treated patients deteriorated by 1.6/140 points/year in the Mattis dementia rating scale. Disease duration, but not age, at DBS-surgery negatively correlated with postoperative cognitive decline and positively correlated with conversion to dementia. This observational, "real-life" study provides longterm results of cognitive decline in STN-DBS-treated patients with presurgical MCI possibly predicting the conversion to dementia. Although, the present data is lacking a control group of medically treated PD patients, comparison with other studies on cognition and PD do not support a disease-modifying effect of STN-DBS on cognitive domains.

Objective: Hippocampal inflammation in anti-LGI1 encephalitis causes memory deficits, seizures and behavioural abnormalities. Recent findings suggest that extralimbic brain areas are additionally affected and that patients also suffer from non-limbic cognitive symptoms. Moreover, up to 60% of patients show no structural MRI abnormalities in the acute disease stage. We therefore investigated whether functional connectivity analyses can identify brain network changes underlying disease-related symptoms., Methods: We studied 27 patients and a matched healthy control group using structural and functional MRI. Intrinsic functional networks were analysed using Independent Component Analysis and Dual Regression. Cognitive testing covered working memory, episodic memory, attention and executive function., Results: Our analysis revealed functional connectivity alterations in several large-scale networks, including the default mode network (DMN) which showed an aberrant structure-function relationship with the damaged hippocampus. In addition, connectivity in the sensorimotor, salience and higher visual networks was impaired independent of hippocampal damage. Increased connectivity in ventral and dorsal DMN regions significantly correlated with better memory performance. In contrast, stronger connectivity of the insula with the salience network and DMN was linked to impaired memory function., Conclusions: Anti-LGI1 encephalitis is associated with a characteristic pattern of widespread functional network alterations. Increased DMN connectivity seems to represent a compensatory mechanism for memory impairment induced by hippocampal damage. Network analyses may provide a key to the understanding of clinical symptoms in autoimmune encephalitis and reveal changes of brain function beyond apparent structural damage., Competing Interests: Competing interests: FP and TB report personal fees outside the submitted work. None declared for all other authors., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Importance: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood., Objective: To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis., Design, Setting, and Participants: A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015., Main Outcomes and Measures: Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy)., Results: Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P < .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P = .047) and impaired left hippocampal microstructural integrity (RAVLT recognition, r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = -0.46; P = .03) memory deficits., Conclusions and Relevance: Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.

Background: The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention., Methods: Forty patients with anti-NMDAR encephalitis after the acute disease stage and 25 healthy control subjects underwent multimodal structural imaging that combined volumetry of hippocampal subfields with analysis of hippocampal microstructural integrity. Verbal and visuospatial memory performance was assessed in all patients and correlation and mediation analyses were performed to examine associations between hippocampal structural integrity, memory performance, and disease severity., Results: Hippocampal volumes were significantly reduced in patients and hippocampal subfield analysis revealed bilateral atrophy of the input and output regions of the hippocampal circuit. Microstructural integrity was impaired in both hippocampi in patients. Importantly, hippocampal volumetric and microstructural integrity measures correlated with memory performance and disease severity and duration. Mediation analysis revealed that hippocampal microstructure mediated the effect of disease severity on memory performance., Conclusions: Data from this largest cohort of anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic resonance imaging demonstrate that structural hippocampal damage and associated memory deficits are important long-term sequelae of the encephalitis. Correlation with disease duration and severity highlights the need for rapid diagnosis and adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced imaging protocols may allow a more detailed analysis of structural damage to assess disease progression in clinical routine examinations and for therapy evaluation in prospective trials., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Mixed dopaminergic medication, comprising dopamine agonists and levodopa, may affect habit-learning in patients with Parkinson’s disease (PD). However, the specific impact of levodopa on this effect is unknown. We assessed habit-learning in 20 non-demented PD-patients both with and without levodopa. We observed intact habit-learning in PD-patients OFF-medication. In contrast, the administration of 200 mg of levodopa impaired habit-learning. We conclude that potential deficits in habit-learning in PD may be attributed to the intake of levodopa.

Background: MRI-detected brain lesions are common after left atrial catheter ablation for symptomatic atrial fibrillation. The clinical relevance of these acute ischemic lesions is not fully understood, but ablation-related cerebral injury could contribute to cognitive dysfunction., Methods and Results: In the prospective Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) study, serial 3-T brain MRIs and neuropsychological assessment were performed to analyze the rate of ablation-related brain lesions and their effect on cognitive function. Thirty-seven patients with paroxysmal atrial fibrillation (median age, 63.0 [interquartile range, 57-68] years; 41% female; median CHA2DS2VASc score 2 [interquartile range, 1-3]) underwent 41 ablation procedures according to study criteria. None of these patients had overt neurological deficits after ablation. High-resolution diffusion-weighted imaging, performed within 48 hours after ablation, showed that new brain lesions (range, 1-17) were present in 16 (43.2%) patients after 18 (43.9%) left atrial catheter ablation procedures. Follow-up MRI at 6 months (median, 6.5; interquartile range, 6-7) revealed that 7 (12.5%) of the 56 total acute brain lesions after ablation formed a persistent glial scar in 5 (31.3%) patients. Large diffusion-weighted imaging lesions and a corresponding fluid-attenuated inversion recovery lesion 48 hours after ablation predicted lesion persistence on 6-month follow-up. Neither persistent brain lesions nor the ablation procedure itself had a significant effect on attention or executive functions, short-term memory, or verbal and nonverbal learning after 6 months., Conclusions: Ablation-related acute ischemic brain lesions persist to some extent but do not cause cognitive impairment 6 months after the ablation procedure., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061931.

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis., Methods: Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry., Results: Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls., Interpretation: Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis., (© 2013 American Neurological Association.)

Previous patient studies suggest that thalamic stroke may yield persistent deficits in several cognitive domains. At present, the subjective dimension and everyday relevance of these impairments is unclear, since many patients with thalamic stroke only show minor changes on physical examination. Here, we have studied subjective consequences of focal thalamic lesions. A sample of 68 patients with a history of ischemic thalamic stroke was examined by using established clinical self-report questionnaires assessing memory, attention, executive functions, emotional status and health-related quality of life. In order to control for general factors related to cerebrovascular disease, self-reports were compared to an age-matched group of 34 patients with a history of transient ischemic attack. Thalamic lesions were co-registered to an atlas of the human thalamus. Lesion overlap and subtraction analyses were used for lesion-to-symptom mapping. When both patient groups were compared, no significant differences were found for either questionnaire. However, when subgroups were compared, patients with infarctions involving the posterior thalamus showed significant emotional disturbances and elevated anxiety levels compared to patients with more anterior lesions. Our findings thus point to the existence of a persistent affective impairment associated with chronic lesions of the posterior thalamus. This syndrome may result from damage to connections between medial pulvinar and extra-thalamic regions involved in affective processing. Our findings suggest that the posterior thalamus may contribute significantly to the regulation of mood.

Background: Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF)., Objective: Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function., Methods: Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure., Results: There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation., Conclusions: According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure., (© 2012 Wiley Periodicals, Inc.)

Thalamic stroke is associated with neurological and cognitive sequelae. Resulting neuropsychological deficits vary with the vascular territory involved. Whereas sensory, motor and memory deficits following thalamic stroke are comparatively well characterized, the exact relationship between executive dysfunction and thalamic damage remains more ambiguous. To assess the pattern of executive-cognitive deficits following thalamic stroke and its possible association with distinct thalamic nuclei, 19 patients with focal thalamic lesions were examined with high-resolution structural imaging and neuropsychological testing. Twenty healthy individuals served as controls. Patient MRIs were co-registered to an atlas of the human thalamus. Lesion overlap and subtraction analyses were used for lesion-to-symptom mapping. In eight patients (42.1%), neuropsychological assessment demonstrated a disproportionate deficit in the Wisconsin Card Sorting Test (WCST), while other executive and memory functions were much less affected. Subtraction analysis revealed an area in the left medial thalamus, mainly consisting of the centromedian and parafascicular nuclei (CM-Pf complex) that was damaged in these patients and spared in patients with normal WCST performance. Thus, damage to the CM-Pf complex may yield a distinct dysexecutive syndrome in which deficient maintenance and shifting between cognitive sets predominates. We hypothesize that the CM-Pf complex may contribute to maintenance and shifting of cognitive sets by virtue of its dense connections with the striatum. The pattern of executive dysfunction following thalamic stroke may vary considerably with lesion location., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Anti-NMDA receptor (NMDAR) encephalitis is a recently characterised autoimmune disorder mainly affecting young women. Although the clinical features of the acute disease are well characterised, cognitive long-term outcome has not been examined in detail., Methods: The authors investigated cognitive performance in nine patients with proven anti-NMDAR encephalitis after recovery from the acute disease period (median 43 months after disease onset, range 23 to 69). Patients underwent a comprehensive neuropsychological assessment, including memory tasks that have previously been shown to be sensitive for hippocampal dysfunction., Results: Substantial persistent cognitive impairments were observed in eight out of nine patients that mainly consisted of deficits in executive functions and memory. The severity of these deficits varied inter-individually. Patients with early immunotherapy performed significantly better. The most severe deficits were observed with inefficient or delayed initial treatment., Conclusion: Our results suggest that cognitive deficits constitute a major long-term morbidity of anti-NMDAR encephalitis. These deficits relate to the distribution of NMDARs in the human brain and their functional role in normal cognition. Good cognitive long-term outcome may depend on early and aggressive treatment.

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus-dystonia (MD). We investigated short- and long-term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi- and VIM-DBS in MD. Ten MD-patients (nine epsilon-sarcoglycan-mutation-positive) were evaluated pre- and post-surgically following continuous bilateral GPi- and VIM-DBS at four time points: presurgical, 6, 12, and as a last follow-up at a mean of 62.3 months postsurgically, and in OFF-, GPi-, VIM-, and GPi-VIM-DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke-Fahn-Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL-scores. MD-symptoms significantly improved at 6 months post-surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long-term evaluation post-surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long-lasting stimulation-related adverse events (AEs) were observed. Both GPi- and VIM-DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation-induced events of GPi-DBS in comparison with VIM-DBS, GPi-DBS seems to be preferable. Combined GPi-VIM-DBS can be useful in cases of incapaciting myoclonus, refractory to GPi-DBS alone.

In healthy humans, memory for words with emotional valence is better than memory for neutral words. At the same time, the word preceding the emotional word in a word list learning task is remembered less often than other neutral words. Both effects, enhanced memory for emotional words and retrograde amnesia for preceding words, are dependent on intactness of the amygdala. In this study we asked whether patients with temporal lobe epilepsy (TLE), a disease that often involves the amygdala as well, show altered memory for emotional words and the words presented in close temporal proximity. Whereas we found enhanced memory performance for emotional and decreased recognition performance for the preceding and successive word in our 19 control subjects, both effects were strongly reduced in our 21 patients. No group differences occurred in memory for perceptually deviant words. The lack of emotion effects on memory in the patients cannot simply be attributed to altered perception of emotions as the patients rated the emotionality of the words no different than control subjects. Hence, we conclude that patients with TLE have a specific deficit in the emotion-driven encoding enhancement mediated by the amygdala-hippocampus loop.

The aim of this study was to assess the effect of dopaminergic treatment on emotional memory in patients with Parkinson's disease (PD). We tested memory for emotional and neutral visual stimuli in ten non-demented PD patients on and off dopaminergic medication. Patients recalled significantly more emotional items during the off- than on-medication testing session. In contrast, treatment condition did not affect memory for neutral items. These findings demonstrate that emotional memory deficits observed in PD may result from dopaminergic treatment and suggest an involvement of dopaminergic neurotransmission in emotional processing.

Vascular dementia (VD) and Alzheimer's dementia (AD) are the most common differential diagnoses in patients with cognitive impairment. Although of different etiology, small vessel disease is postulated to be present in both conditions. We investigated global cerebral blood flow (CBF), global cerebral circulation time (CCT) and global cerebral blood volume (CBV) in VD and AD patients using a multimodal ultrasound (US) approach. 20 VD and 20 AD patients were included and compared with 12 age-matched controls. Duplex US of both internal carotid and vertebral arteries was performed to measure CBF. CCT was defined as the time delay of an echo-contrast bolus arrival between the internal carotid artery and internal jugular vein using extracranial Doppler. CBV was calculated as the product of CBF and CCT. CBF was significantly lower (VD: 570 +/- 61; AD: 578 +/- 77; controls: 733 +/- 54 ml/min) and CCT significantly longer (8.8 +/- 2.6; 8.2 +/- 1.4; 6.4 +/- 0.8 s) in both patient groups compared with controls (p < 0.003). No difference in CBF and CCT was found between the two patient groups. CBV was similar in all three groups (82 +/- 20; 79 +/- 19; 78 +/- 9 ml). The equally reduced CBF and prolonged CCT in VD and AD support the hypothesis, that small vessel disease is a relevant factor in both types of dementia. The presented multimodal US approach helps to assess the extent of changes in the global cerebral hemodynamics in patients with dementia but does not allow a differentiation between VD and AD.

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems., (Copyright 2004 Lippincott Williams & Wilkins)