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Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Citalopram/farmacología , Ritmo Gamma/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Adulto , Corteza Cerebral/diagnóstico por imagen , Citalopram/administración & dosificación , Femenino , Voluntarios Sanos , Humanos , Espectroscopía de Resonancia Magnética , Magnetoencefalografía , Masculino , Proyectos Piloto , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto JovenRESUMEN
Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8-14 Hz) and beta (15-30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro-cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging.
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Envejecimiento , Atención/fisiología , Corteza Cerebral/fisiología , Memoria a Corto Plazo/fisiología , Anciano , Anciano de 80 o más Años , Ritmo alfa , Ritmo beta , Señales (Psicología) , Femenino , Lateralidad Funcional , Humanos , Individualidad , Magnetoencefalografía , Masculino , Recuerdo Mental/fisiología , Persona de Mediana EdadRESUMEN
We used magnetoencephalography to characterize the spatiotemporal dynamics of cortical activity during top-down control of working memory (WM). fMRI studies have previously implicated both the frontoparietal and cingulo-opercular networks in control over WM, but their respective contributions are unclear. In our task, spatial cues indicating the relevant item in a WM array occurred either before the memory array or during the maintenance period, providing a direct comparison between prospective and retrospective control of WM. We found that in both cases a frontoparietal network activated following the cue, but following retrocues this activation was transient and was succeeded by a cingulo-opercular network activation. We also characterized the time course of top-down modulation of alpha activity in visual/parietal cortex. This modulation was transient following retrocues, occurring in parallel with the frontoparietal network activation. We suggest that the frontoparietal network is responsible for top-down modulation of activity in sensory cortex during both preparatory attention and orienting within memory. In contrast, the cingulo-opercular network plays a more downstream role in cognitive control, perhaps associated with output gating of memory.
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Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Función Ejecutiva/fisiología , Magnetoencefalografía/métodos , Memoria a Corto Plazo/fisiología , Red Nerviosa/fisiología , Adulto , Ritmo alfa/fisiología , Femenino , Lóbulo Frontal/fisiología , Giro del Cíngulo/fisiología , Humanos , Masculino , Lóbulo Parietal/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
Hippocampal theta-band oscillations are thought to facilitate the co-ordination of brain activity across distributed networks, including between the hippocampus and prefrontal cortex (PFC). Impairments in hippocampus-PFC functional connectivity are implicated in schizophrenia and are associated with a polymorphism within the ZNF804A gene that shows a genome-wide significant association with schizophrenia. However, the mechanisms by which ZNF804A affects hippocampus-PFC connectivity are unknown. We used a multimodal imaging approach to investigate the impact of the ZNF804A polymorphism on hippocampal theta and hippocampal network coactivity. Healthy volunteers homozygous for the ZNF804A rs1344706 (A[risk]/C[nonrisk]) polymorphism were imaged at rest using both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). A dual-regression approach was used to investigate coactivations between the hippocampal network and other brain regions for both modalities, focusing on the theta band in the case of MEG. We found a significant decrease in intrahippocampal theta (using MEG) and greater coactivation of the superior frontal gyrus with the hippocampal network (using fMRI) in risk versus nonrisk homozygotes. Furthermore, these measures showed a significant negative correlation. Our demonstration of an inverse relationship between hippocampal theta and hippocampus-PFC coactivation supports a role for hippocampal theta in coordinating hippocampal-prefrontal activity. The ZNF804A-related differences that we find in hippocampus-PFC coactivation are consistent with previously reported associations with functional connectivity and with these changes lying downstream of altered hippocampal theta. Changes in hippocampal-PFC co-ordination, driven by differences in oscillatory activity, may be one mechanism by which ZNF804A impacts on brain function and risk for psychosis.
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Predisposición Genética a la Enfermedad , Hipocampo/fisiología , Factores de Transcripción de Tipo Kruppel/genética , Corteza Prefrontal/fisiología , Esquizofrenia/genética , Ritmo Teta/fisiología , Adolescente , Adulto , Mapeo Encefálico , Genotipo , Homocigoto , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Vías Nerviosas/fisiología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Esquizofrenia/fisiopatología , Adulto JovenRESUMEN
Working memory (WM) is strongly influenced by attention. In visual WM tasks, recall performance can be improved by an attention-guiding cue presented before encoding (precue) or during maintenance (retrocue). Although precues and retrocues recruit a similar frontoparietal control network, the two are likely to exhibit some processing differences, because precues invite anticipation of upcoming information whereas retrocues may guide prioritization, protection, and selection of information already in mind. Here we explored the behavioral and electrophysiological differences between precueing and retrocueing in a new visual WM task designed to permit a direct comparison between cueing conditions. We found marked differences in ERP profiles between the precue and retrocue conditions. In line with precues primarily generating an anticipatory shift of attention toward the location of an upcoming item, we found a robust lateralization in late cue-evoked potentials associated with target anticipation. Retrocues elicited a different pattern of ERPs that was compatible with an early selection mechanism, but not with stimulus anticipation. In contrast to the distinct ERP patterns, alpha-band (8-14 Hz) lateralization was indistinguishable between cue types (reflecting, in both conditions, the location of the cued item). We speculate that, whereas alpha-band lateralization after a precue is likely to enable anticipatory attention, lateralization after a retrocue may instead enable the controlled spatiotopic access to recently encoded visual information.
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Ritmo alfa/fisiología , Atención/fisiología , Corteza Cerebral/fisiología , Señales (Psicología) , Potenciales Evocados/fisiología , Memoria a Corto Plazo/fisiología , Adulto , Anticipación Genética/fisiología , Femenino , Lateralidad Funcional/fisiología , Neuroimagen Funcional , Humanos , Masculino , Adulto JovenRESUMEN
Gamma band oscillations arise in neuronal networks of interconnected GABAergic interneurons and excitatory pyramidal cells. A previous study found a correlation between visual gamma peak frequency, as measured with magnetoencephalography, and resting GABA levels, as measured with magnetic resonance spectroscopy (MRS), in 12 healthy volunteers. If true, this would allow studies in clinical populations testing modulation of this relationship, but this finding has not been replicated. We addressed this important question by measuring gamma oscillations and GABA, as well as glutamate, in 50 healthy volunteers. Visual gamma activity was evoked using an established gratings paradigm, and we applied a beamformer spatial filtering technique to extract source-reconstructed gamma peak frequency and amplitude from the occipital lobe. We determined gamma peak frequency and amplitude from the location with maximal activation and from the location of the MRS voxel to assess the relationship of GABA with gamma. Gamma peak frequency was estimated from the highest value of the raw spectra and by a Gaussian fit to the spectra. MRS data were acquired from occipital cortex. We did not replicate the previously found correlation between gamma peak frequency and GABA concentration. Calculation of a Bayes factor provided strong evidence in favor of the null hypothesis. We also did not find a correlation between gamma activity and glutamate or between gamma and the ratio of GABA/glutamate. Our results suggest that cortical gamma oscillations do not have a consistent, demonstrable relationship to excitatory/inhibitory network activity as proxied by MRS measurements of GABA and glutamate.
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Relojes Biológicos/fisiología , Ácido Glutámico/metabolismo , Imagen por Resonancia Magnética , Potenciales de la Membrana/fisiología , Lóbulo Occipital/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adulto , Femenino , Humanos , Masculino , Lóbulo Occipital/diagnóstico por imagen , RadiografíaRESUMEN
Converging electrophysiological evidence suggests that the alpha rhythm plays an important and active role in cognitive processing. Here, we systematically studied variability in posterior alpha peak frequency both between and within subjects. We recorded brain activity using MEG in 51 healthy human subjects under three experimental conditions - rest, passive visual stimulation and an N-back working memory paradigm, using source reconstruction methods to separate alpha activity from parietal and occipital sources. We asked how alpha peak frequency differed within subjects across cognitive conditions and regions of interest, and looked at the distribution of alpha peak frequency between subjects. In both regions we observed an increase of alpha peak frequency from resting state and passive visual stimulation conditions to the N-back paradigm, with a significantly higher alpha peak frequency in the 2-back compared to the 0-back condition. There was a trend for a greater increase in alpha peak frequency during the N-back task in the occipital vs. parietal cortex. The average alpha peak frequency across all subjects, conditions, and regions of interest was 10.3 Hz with a within-subject SD of 0.9 Hz and a between-subject SD of 2.8 Hz. We also measured beta peak frequencies, and except in the parietal cortex during rest, found no indication of a strictly harmonic relationship with alpha peak frequencies. We conclude that alpha peak frequency in posterior regions increases with increasing cognitive demands, and that the alpha rhythm operates across a wider frequency range than the 8-12 Hz band many studies tend to include in their analysis. Thus, using a fixed and limited alpha frequency band might bias results against certain subjects and conditions.