RESUMEN
It has long been assumed that the surface electroencephalography (EEG) signal depends on both the amplitude and spatial synchronization of underlying neural activity, though isolating their respective contribution remains elusive. To address this, we made simultaneous surface EEG measurements along with intracortical recordings of local field potentials (LFPs) in the primary visual cortex of behaving nonhuman primates. We found that trial-by-trial fluctuations in EEG power could be explained by a linear combination of LFP power and interelectrode temporal synchrony. This effect was observed in both stimulus and stimulus-free conditions and was particularly strong in the gamma range (30-100 Hz). Subsequently, we used pharmacological manipulations to show that neural synchrony can produce a positively modulated EEG signal even when the LFP signal is negatively modulated. Taken together, our results demonstrate that neural synchrony can modulate EEG signals independently of amplitude changes in neural activity. This finding has strong implications for the interpretation of EEG in basic and clinical research, and helps reconcile EEG response discrepancies observed in different modalities (e.g., EEG vs. functional magnetic resonance imaging) and different spatial scales (e.g., EEG vs. intracranial EEG).
Asunto(s)
Mapeo Encefálico , Ondas Encefálicas/fisiología , Encéfalo/fisiología , Electroencefalografía , Neuronas/fisiología , Anestésicos Locales/farmacología , Animales , Encéfalo/citología , Encéfalo/efectos de los fármacos , Ondas Encefálicas/efectos de los fármacos , Lidocaína/farmacología , Macaca mulatta , Neuronas/efectos de los fármacos , Estimulación LuminosaRESUMEN
In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI.
Asunto(s)
Química Encefálica/fisiología , Ácido Láctico/sangre , Corteza Visual/anatomía & histología , Corteza Visual/crecimiento & desarrollo , Envejecimiento/fisiología , Animales , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Interpretación Estadística de Datos , Fenómenos Electrofisiológicos , Femenino , Procesamiento de Imagen Asistido por Computador , Ácido Láctico/farmacología , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Microdiálisis , Oxígeno/sangre , Ácido Pirúvico/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
In vivo measurement of multiple functionally related neurochemicals and metabolites (NMs) is highly interesting but remains challenging in the field of basic neuroscience and clinical research. We present here an analytical method for determining five functionally and metabolically related polar substances, including acetylcholine (quaternary ammonium), lactate and pyruvate (organic acids), as well as glutamine and glutamate (amino acids). These NMs are acquired from samples of the brain and the blood of non-human primates in parallel by dual microdialysis, and subsequently analyzed by a direct capillary hydrophilic interaction chromatography (HILIC)-mass spectrometry (MS) based method. To obtain high sensitivity in electrospray ionization (ESI)-MS, lactate and pyruvate were detected in negative ionization mode whereas the other NMs were detected in positive ionization mode during each HILIC-MS run. The method was validated for linearity, the limits of detection and quantification, precision, accuracy, stability and matrix effect. The detection limit of acetylcholine, lactate, pyruvate, glutamine, and glutamate was 150 pM, 3 µM, 2 µM, 5 nM, and 50 nM, respectively. This allowed us to quantitatively and simultaneously measure the concentrations of all the substances from the acquired dialysates. The concentration ratios of both lactate/pyruvate and glutamine/glutamate were found to be higher in the brain compared to blood (p < 0.05). The reliable and simultaneous quantification of these five NMs from brain and blood samples allows us to investigate their relative distribution in the brain and blood, and most importantly paves the way for future non-invasive studies of the functional and metabolic relation of these substances to each other.
Asunto(s)
Análisis Químico de la Sangre/métodos , Química Encefálica , Encéfalo/metabolismo , Glutamina/análisis , Macaca mulatta/sangre , Macaca mulatta/metabolismo , Microdiálisis , Acetilcolina/análisis , Acetilcolina/sangre , Acetilcolina/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Ácido Glutámico/análisis , Ácido Glutámico/sangre , Ácido Glutámico/metabolismo , Glutamina/sangre , Glutamina/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Ácido Láctico/análisis , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Espectrometría de Masas , Ácido Pirúvico/análisis , Ácido Pirúvico/sangre , Ácido Pirúvico/metabolismoRESUMEN
Recent studies suggest the presence of a human homologue of monkey V6 in the dorsal posterior bank of the parieto-occipital sulcus. Monkey V6 comprises a retinotopic representation with relative peripheral visual field emphasis and is sensitive to visual motion. We studied sensitivity to visual motion in human parieto-occipital sulcus. Our upper peripheral visual field stimulus enabled us to distinguish V6 from neighbouring areas, whose upper VF representation is located far from V6. We recorded neuromagnetic signals while the subjects (N=10) fixated and a grating first appeared and then started to drift. The most prominent sustained activation for motion was at the posterior bank of the dorsal parieto-occipital sulcus; that is at the known location of the human V6. This finding suggests that human V6 is a motion-sensitive area. The responses in V6 occurred early, with about the same latency as in V1, in line with known connections in the monkey brain. In addition, on the medial surface of the hemisphere we observed a fast sequence of activations following V6: first precuneus and later an area at the dorsal end of the cingulate sulcus. On the lateral side, both temporo-occipital area and intraparietal sulcus were active, but with delayed onset compared to V6. This rapid flow of visual information along the medial dorsal visual pathway supports the view that in humans, as in monkeys, the V6 and the connected areas could be involved in online control of visually guided actions.