Search

The role of the human hippocampus for musical memory is still unclear. While imaging studies in healthy humans have repeatedly shown hippocampal activation in musical memory tasks, studies in musicians with chronic bilateral medial temporal lobe damage and in non-musicians suffering from neuro-degenerative diseases suggest that musical memory may at least partly be independent of hippocampal integrity. Here, we report on a musical layperson who acutely developed an amnesic syndrome in the context of autoimmune encephalitis. Structural and resting state functional MRI revealed exceptionally selective bilateral lesions of the hippocampi and altered functional connectivity with retrosplenial cortex and precuneus. Neuropsychological testing showed a severe global amnesic syndrome. Perception and processing of scales, melodic contours, intervals, rhythms and meter were unaffected. Most notably, the patient performed completely normally on tests of recognition memory for unfamiliar melodies and excerpts of complex musical material, while recognition memory for visual and verbal information was severely impaired. Likewise, emotional evaluation of musical excerpts did not differ from controls. We infer that integrity of musical processing and recognition memory in patients with hippocampal dysfunction does not result from training-induced or post-lesional brain plasticity, but rather reflects integrity of brain networks outside the hippocampi and presumably also outside retrosplenial cortex and precuneus. Our findings suggest major differences in the neural substrates of musical and non-musical recognition memory.

ObjectiveHippocampal 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.MethodsWe 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.ResultsOur 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.ConclusionsAnti-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.

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.

IMPORTANCE: Some patients with multiple sclerosis (MS) can either present with or develop severe cognitive impairment during the course of their disease. However, the mechanisms underlying severe cognitive dysfunction in MS are not well understood. OBSERVATIONS: We report on a woman who was diagnosed as having MS at age 33 years and who after giving birth at age 37 years developed cognitive impairment with severe memory dysfunction as the leading symptom. Treatment with different immunotherapies, including cyclophosphamide and natalizumab, did not improve her cognitive deficits, necessitating admission to a nursing home at age 39 years. During a thorough reevaluation at age 43 years, analysis of current and stored cerebrospinal fluid and serum samples demonstrated an intrathecal synthesis of IgG antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor, that is, the characteristic laboratory finding of anti–N-methyl-D-aspartate receptor encephalitis. Although the patient initially stabilized under therapy with corticosteroids, plasma exchange, and mitoxantrone, severe cognitive impairment persisted and she eventually died from the sequelae of her disease. CONCLUSIONS AND RELEVANCE: This report suggests that the occasional occurrence of severe cognitive impairment in patients with MS may, in some cases, be related to a superimposed antibody-mediated autoimmune encephalitis.

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.

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.

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.

Zusammenfassung:In der neueren gerontologischen Kognitionsforschung haben sich wiederholt Alterseffekte bezüglich der Leistung in verschiedenen Arbeitsgedächtnisspannentests bestätigt. Bislang ist jedoch unklar, welche Rolle nicht-exekutive und exekutive Prozesse in diesen Alterseffekten spielen. Zur ersten Annäherung an diese Fragestellung wurden in der vorliegenden Studie 20 jüngere (M= 26 Jahre, SD= 7.14) und 21 ältere Erwachsene (M= 71 Jahre, SD= 5.87) in ihrer Leistung in zwei typischen Arbeitsgedächtnisspannentests (“Zahlen nachsprechen rückwärts”, Operation Span Aufgabe) untersucht. Außerdem wurden als mögliche Prädiktoren für nicht-exekutive Prozesse die Kurzzeitgedächtnisspanne und die tonische Aufmerksamkeit sowie für exekutive Prozesse die inhibitorische Kontrollleistung erhoben. Die Ergebnisse zeigen signifikante Altersdifferenzen in beiden Arbeitsgedächtnisspannentests. Zusätzlich ergeben hierarchische Regressionsanalysen, dass im Test “Zahlen nachsprechen rückwärts” nicht-exekutive Prozesse alleine, in der Operation Span Aufgabe dagegen eine Kombination aus nicht-exekutiven und exekutiven Prozessen die gefundene altersbezogene Varianz erklären können. Insgesamt deuten die Ergebnisse darauf hin, dass die beiden verwendeten Arbeitsgedächtnisspannentests schwerpunktmäßig mit unterschiedlichen kognitiven Prozessen zusammenhängen und somit in Diagnostik wie Grundlagenforschung nicht beliebig austauschbar angewandt werden sollten.