RESUMO
The pathophysiological processes underlying the development and progression of Alzheimer's disease (AD) on the neuronal level are still unclear. Previous research has hinted at metabolic energy deficits and altered sodium homeostasis with impaired neuronal function as a potential metabolic marker relevant for neurotransmission in AD. Using sodium (23 Na) magnetic resonance (MR) imaging on an ultra-high-field 7 Tesla MR scanner, we found increased cerebral tissue sodium concentration (TSC) in 17 biomarker-defined AD patients compared to 22 age-matched control subjects in vivo. TSC was highly discriminative between controls and early AD stages and was predictive for cognitive state, and associated with regional tau load assessed with flortaucipir-positron emission tomography as a possible mediator of TSC-associated neurodegeneration. TSC could therefore serve as a non-invasive, stage-dependent, metabolic imaging marker. Setting a focus on cellular metabolism and potentially disturbed interneuronal communication due to energy-dependent altered cell homeostasis could hamper progressive cognitive decline by targeting these processes in future interventions.
Assuntos
Doença de Alzheimer , Tomografia por Emissão de Pósitrons , Sódio/metabolismo , Transmissão Sináptica , Idoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Carbolinas , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Sódio/efeitos da radiação , Proteínas tau/metabolismoRESUMO
Rationale: Face expertise is a pivotal social skill. Developmental prosopagnosia (DP), i.e., the inability to recognize faces without a history of brain damage, affects about 2% of the general population, and is a renowned model system of the face-processing network. Within this network, the right Fusiform Face Area (FFA), is particularly involved in face identity processing and may therefore be a key element in DP. Neural representations within the FFA have been examined with Representational Similarity Analysis (RSA), a data-analytical framework in which multi-unit measures of brain activity are assessed with correlation analysis. Objectives: Our study intended to scrutinize modifications of FFA-activation during face encoding and maintenance based on RSA. Methods: Thirteen participants with DP (23-70 years) and 12 healthy control subjects (19-62 years) participated in a functional MRI study, including morphological MRI, a functional FFA-localizer and a modified Sternberg paradigm probing face memory encoding and maintenance. Memory maintenance of one, two, or four faces represented low, medium, and high memory load. We examined conventional activation differences in response to working memory load and applied RSA to compute individual correlation-matrices on the voxel level. Group correlation-matrices were compared via Donsker's random walk analysis. Results: On the functional level, increased memory load entailed both a higher absolute FFA-activation level and a higher degree of correlation between activated voxels. Both aspects were deficient in DP. Interestingly, control participants showed a homogeneous degree of correlation for successful trials during the experiment. In DP-participants, correlation levels between FFA-voxels were significantly lower and were less sustained during the experiment. In behavioral terms, DP-participants performed poorer and had longer reaction times in relation to DP-severity. Furthermore, correlation levels were negatively correlated with reaction times for the most demanding high load condition. Conclusion: We suggest that participants with DP fail to generate robust and maintained neural representations in the FFA during face encoding and maintenance, in line with poorer task performance and prolonged reaction times. In DP, alterations of neural coding in the FFA might therefore explain curtailing in working memory and contribute to impaired long-term memory and mental imagery.