Correlation of high-frequency oscillations with the sleep-wake cycle and cognitive activity in humans

While several authors have suggested that high-frequency electroencephalogram activity (gamma, >30 Hz) correlates with conscious thought, others have suggested that electroencephalogram activity >30 Hz shows the same relationships to cognitive activity and sleep as activity in the conventional beta frequency band. The existence of coherence of gamma over large distances also remains controversial. We studied quantitatively the relationship of gamma activity to the sleep-wake cycle and cognitive tasks during wakefulness in humans using intracranial electroencephalogram. Gamma activity made up less than 1% of the total power spectrum. A significant relationship was observed between gamma activity and the sleep-wake cycle such that gamma was highest during wakefulness, intermediate during light and rapid eye movement sleep, and lowest during slow-wave sleep. As well, gamma was higher during rapid eye movement sleep with eye movements than during rapid eye movement sleep without eye movements. During a cognitive task experiment, while lower frequencies, including beta, showed a stepwise reduction with increasing task difficulty, gamma was observed to increase during cognitive tasks as compared to the resting state. The relationship between gamma and the sleep-wake cycle and cognitive tasks was independent of brain region and hemisphere. Coherence of gamma activity at distances of 5 mm and greater was not observed. Our data support previously reported findings that gamma activity has a significant relationship to the sleep-wake cycle. The findings of differences in gamma during REM sleep with and without eye movements suggest that the presence or absence of eye movements may reflect two different states of brain activity. Our findings of differences in the relationships of the beta and gamma bands to both the sleep-wake cycle and cognitive tasks demonstrate that various components of the high-frequency spectrum behave differently in some situations.     

Feature integration in visual working memory: parietal gamma activity is related to cognitive coordination

The mechanism by which distinct subprocesses in the brain are coordinated is a central conundrum of systems neuroscience. The parietal lobe is thought to play a key role in visual feature integration, and oscillatory activity in the gamma frequency range has been associated with perception of coherent objects and other tasks requiring neural coordination. Here, we examined the neural correlates of integrating mental representations in working memory and hypothesized that parietal gamma activity would be related to the success of cognitive coordination. Working memory is a classic example of a cognitive operation that requires the coordinated processing of different types of information and the contribution of multiple cognitive domains. Using magnetoencephalography (MEG), we report parietal activity in the high gamma (80-100 Hz) range during manipulation of visual and spatial information (colors and angles) in working memory. This parietal gamma activity was significantly higher during manipulation of visual-spatial conjunctions compared with single features. Furthermore, gamma activity correlated with successful performance during the conjunction task but not during the component tasks. Cortical gamma activity in parietal cortex may therefore play a role in cognitive coordination.     

脑膜瘤患者伽玛刀治疗后脑白质损伤与认知功能的关系

目的探讨脑膜瘤患者伽玛刀治疗后脑白质损伤与患者认知功能的关系。方法 89例接受伽玛刀治疗的脑膜瘤患者在伽玛刀治疗前及治疗后1月、6月,分别进行磁共振检查(FLAIR序列),采用脑白质高信号Schelten评分评估脑白质损伤严重程度;同时以蒙特利尔认知评估量表(MoCA)评定患者认知功能。结果①治疗后1月、6月患者Schelten评分均较治疗前显著增高,差异均有统计学意义(t=4.066,5.376;P=0.000);②治疗后1月、6月患者MoCA评分均较治疗前显著下降,差异均有统计学意义(t=2.370,2.265;P=0.019,0.024);③治疗后1月、6月时患者的Schelten评分与MoCA评分之间有负性相关(r=-0.308,-0.402;P=0.038,0.007)。结论伽玛刀治疗可致脑膜瘤患者脑白质损伤,并与其认知功能的降低有关。     

The impact of cognitive training on spontaneous gamma oscillations in schizophrenia

Schizophrenia patients exhibit less gamma‐frequency EEG/MEG activity (>30 Hz), a finding interpreted as evidence of poor temporal neural organization and functional network communication. Research has shown that neuroplasticity‐oriented training can improve task‐related oscillatory dynamics, indicating some reorganization capacity in schizophrenia. Demonstrating a generalization of such task training effects to spontaneous oscillations at rest would not only enrich understanding of this neuroplastic potential but inform the interpretation of spontaneous gamma oscillations in the service of normal cognitive function. In the present study, neuromagnetic resting‐state oscillatory brain activity and cognitive performance were assessed before and after training in 61 schizophrenia patients, who were randomly assigned to 4 weeks of neuroplasticity‐oriented targeted cognitive training or treatment as usual (TAU). Gamma power of 40–90 Hz increased after training, but not after TAU, in a frontoparietal network. Across two types of training, this increase was related to improved cognitive test performance. These results indicate that abnormal oscillatory dynamics in schizophrenia patients manifested in spontaneous gamma activity can be changed with neuroplasticity‐oriented training parallel to cognitive performance.     

Comparative study of the gamma rhythm in normal conditions,during examination stress,and in patients with first depressive episode

We report here a comparative analysis of measures of spectral power and synchronization of the gamma rhythm (30–40 Hz) in healthy subjects in normal conditions and before examinations (a stress situation) and in patients with major depression (first episode), both without cognitive loading and during performance of tests (arithmetic counting and spatial imagination). The results showed that the power of the gamma rhythm in the frontal and temporal areas of the cortex was significantly greater in patients with depression than in normal subjects. In the stress situation, healthy subjects showed a reduction in the number of differences in this measure as compared with depression patients, both at rest and during performance of the arithmetic counting test. the spatial imagination test resulted in a smaller number of significant differences between patients with depression and healthy subjects, regardless of whether the latter were in normal conditions or in the stress situation. The levels of gamma rhythm synchronization between cortical areas at rest and during cognitive loading were not different in healthy subjects, though synchronization increased in healthy subjects during stress and in patients with depression. Thus, the stress situation in healthy subjects leads to decreases in the differences in EEG measures from those in depression both at rest (power) and during cognitive loading (both measures). This may be evidence that stress is a “trigger mechanism” for depression. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 2, pp. 219–227, March–April, 2006.     

Working memory related gamma oscillations in schizophrenia patients.

Recent reports show that the capability of neural networks supporting high-frequency synchronization is reduced in the brain of schizophrenia patients. Specifically, deficits in gamma activity have been shown in schizophrenia patients during perception and simple cognitive tasks. However little is known about alterations in gamma responses during complex and higher cognitive processing. The main objective of this study was to investigate modulation of event-related gamma responses in tasks varying working memory (WM) load in schizophrenia patients (N=10) and healthy controls (N=10). Gamma amplitude values were obtained for a simple choice reaction task, a low WM demand task, and a high WM demand task. During all three tasks schizophrenia patients showed significantly slower reaction times and higher error rates than controls. A gradual increase of gamma amplitudes after stimulus onset was associated with increase of WM load in controls. In contrast, high amplitude gamma oscillations remained constant regardless of task difficulty in patients. These results suggest that healthy subjects used various cognitive strategies depending on task difficulty, while schizophrenia patients needed to initiate complex cognitive processes similar to those used during processing of novel contexts or stimuli even for the simple choice reaction task with low cognitive demand.     

Gamma-band activity in the human superior temporal sulcus during mentalizing from nonverbal social cues

The posterior superior temporal sulcus (pSTS) is a key structure for our ability to infer others' mental states based on social cues including facial expressions, body posture, and gestures ("mentalizing"), but the neural mechanisms of this ability remain largely unknown. We recorded electrocorticogram directly from the pSTS in humans to show that enhanced neural oscillations in the gamma frequency range (35–55 Hz) accompany mentalizing. One patient with a lesion in pSTS was tested behaviorally on this task; he was unable to infer a virtual character's preferences from nonverbal social cues. Enhanced coherent gamma oscillations in the patients with intact pSTS may reflect a process by which social signals are bound into a unified representation to support mentalizing. This may be relevant for other social cognitive processes, as well as to the study of autism spectrum disorders, for which both mentalizing deficits and abnormal gamma activity have been reported.     

Enhancement of gamma activity after selective activation of dopamine D4 receptors in freely moving rats and in a neurodevelopmental model of schizophrenia

Dopamine D4 receptor (D4R) mechanisms have been implicated in several psychiatric diseases, including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and autism, which are characterized by cognitive deficits. The cellular mechanisms are poorly understood but impaired neuronal synchronization within cortical networks in the gamma frequency band has been proposed to contribute to these deficits. A D4R polymorphism was recently linked to variations in gamma power in both normal and ADHD subjects, and D4R activation was shown to enhance kainate-induced gamma oscillations in brain slices in vitro. The goal of this study was to investigate the effect of D4R activation on gamma oscillations in freely moving rats during natural behavior. Field potentials were recorded in the frontal, prefrontal, parietal, and occipital cortex and hippocampus. Gamma power was assessed before and after subcutaneous injection of a D4R agonist, A-412997, in several doses between 0.3 and 10.0 mg/kg. The experiments were also repeated in a neurodevelopmental model of schizophrenia, in which rats are prenatally treated with methylazoxymethanol (MAM). We found that the D4R agonist increased gamma power in all regions at short latency and lasted for ~2 h, both in normal and MAM-treated rats. The effect was dose dependent indicated by the significant difference between the effects after 3 and 10 mg/kg in pair-wise comparison, whereas 0.3 and 1.0 mg/kg injections were ineffective. This study demonstrates the involvement of D4R in cortical gamma oscillations in vivo and identifies this receptor as potential target for pharmacological treatment of cognitive deficits.     

Gamma-band oscillations in fronto-central areas during performance of a sensorimotor integration task: A qEEG coherence study

This study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when 23 healthy right-handed subjects had to catch a free falling object by qEEG gamma-band (30–100 Hz). It is involved in cognitive processes, memory, spatial/temporal and proprioceptive factors. Our hypothesis is that an increase in gamma coherence in frontal areas will be observed during moment preceding ball drop, due to their involvement in attention, planning, selection of movements, preparation and voluntary control of action and in central areas during moment after ball drop, due to their involvement in motor preparation, perception and execution of movement. However, through a paired t-test, we found an increase in gamma coherence for F3–F4 electrode pair during moment preceding ball drop and confirmed our hypothesis for C3–C4 electrode pair. We conclude that gamma plays an important role in reflecting binding of several brain areas in a complex motor task as observed in our results. Moreover, for selection of movements, preparation and voluntary control of action, motor preparation, perception and execution of movement, the integration of somatosensory and visual information is mandatory.     

MCI patients’ EEGs show group differences between those who progress and those who do not progress to AD

The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer's disease (AD, N = 18), converters to non-AD dementia (N = 14) and non-converters (N = 44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD.Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome.     

Modeling GABA alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment

The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15–70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20- and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD₆₇ (1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general.     

A Comparative EEG Study in Normal and Autistic Children

We report here a comparative analysis of spectral power and mean coherence in the alpha, beta, and gamma rhythms in children aged 5–7 years, both normal and with early childhood autism, at rest and in conditions of a cognitive task (counting). In baseline conditions, both healthy children and those with autism showed a marked frontal-occipital alpha gradient. The cognitive task led to increases in the spectral power of the alpha1 range and its displacement into the left hemisphere without any alteration of alpha2; the task also produced a marked increase in spectral power in the alpha3 range. In healthy children, the cognitive task, as compared with baseline conditions, produced significant increases in the spectral power and coherence of the rapid rhythms in the central and frontal areas of the left hemisphere. In patients with early childhood autism, there was a right-sided predominance of spectral power in the alpha range both in baseline conditions and during the cognitive task. Baseline gamma-range spectral power in early childhood autism had greater values than in normal children and did not change during the cognitive task.     

Gamma, alpha, delta, and theta oscillations govern cognitive processes.

The increased interest in gamma oscillations, now widely regarded as functionally relevant signals of the brain, underlines the importance of the concept of event-related oscillations for bridging the gap between single neurons and neural assemblies. Taking this concept further, we review experiments showing that oscillatory phenomena such as alpha, theta, and delta responses to events are, just as the gamma band, strongly interwoven with sensory and cognitive functions. This review argues that selectively distributed delta, theta, alpha and gamma oscillatory systems act as resonant communication networks through large populations of neurons. Thus, oscillatory processes might play a major role in functional communication in the brain in relation to memory and integrative functions.     

Brain wave synchronization and entrainment to periodic acoustic stimuli

As known, different brainwave frequencies show synchronies related to different perceptual, motor or cognitive states. Brainwaves have also been shown to synchronize with external stimuli with repetition rates of ca. 10–40 Hz. However, not much is known about responses to periodic auditory stimuli with periodicities found in human rhythmic behavior (i.e. 0.5–5 Hz). In an EEG study we compared responses to periodic stimulations (drum sounds and clicks with repetition rates of 1–8 Hz), silence, and random noise. Here we report inter-trial coherence measures taken at the Cz-electrode that show a significant increase in brainwave synchronization following periodic stimulation. Specifically, we found (1) a tonic synchronization response in the delta range with a maximum response at 2 Hz, (2) a phasic response covering the theta range, and (3) an augmented phase synchronization throughout the beta/gamma range (13–44 Hz) produced through increased activity in the lower gamma range and modulated by the stimulus periodicity. Periodic auditory stimulation produces a mixture of evoked and induced, rate-specific and rate-independent increases in stimulus related brainwave synchronization that are likely to affect various cognitive functions. The synchronization responses in the delta range may form part of the neurophysiological processes underlying time coupling between rhythmic sensory input and motor output; the tonic 2 Hz maximum corresponds to the optimal tempo identified in listening, tapping synchronization, and event-interval discrimination experiments. In addition, synchronization effects in the beta and gamma range may contribute to the reported influences of rhythmic entrainment on cognitive functions involved in learning and memory tasks.     

Age-dependent reduction of gamma oscillations in the mouse hippocampus in vitro

Normal brain ageing is associated with a decline in hippocampal memory functions. Neuronal oscillations in the gamma frequency band have been implicated in various cognitive tasks. In this study we test the effect of normal brain ageing on gamma oscillations in the mouse hippocampus in vitro. gamma Oscillations were evoked by either 10 microM carbachol or 100 nM kainate in ventral hippocampus slices from young (>5 month) and aged (>22 month) C57Bl/J6 mice. In slices from young mice carbachol-induced gamma oscillations were more regular and more coherent than those induced by kainate. Compared with young, the power in the 20-80 Hz frequency range in area CA3 of slices from aged mice was reduced to 14% for kainate-induced oscillations and to 7% for carbachol-induced oscillations, whereas waveform, dominant frequency and coherence of the oscillation were unchanged. Local network properties were assessed by paired-pulse stimulation of Schaffer collateral/commissural fibers. The excitatory synaptic response in stratum radiatum of CA3 was reduced, in correlation with the antidromic population spike, but functional inhibition in CA3 and CA1 was unaffected. Changes in local network properties could not explain the reduced gamma oscillation strength. Since oscillations driven by two different pathways are similarly affected with age, an age-dependent effect on tonic depolarizing drive of principal cells is unlikely to explain the current results. Other mechanisms, including a change with age in the use-dependent modulation of synaptic strength, should account for the impaired gamma oscillations in the aged hippocampus that may contribute to age-dependent memory impairment.     

Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density

Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele.     

Neuroinflammation-Induced Downregulation of Hippocampacal Neuregulin 1-ErbB4 Signaling in the Parvalbumin Interneurons Might Contribute to Cognitive Impairment in a Mouse Model of Sepsis-Associated Encephalopathy

Sepsis-associated encephalopathy (SAE) is a common complication associated with poor prognosis in septic patients, but the underlying mechanism remains unclear. We hypothesized that disturbed neuregulin 1 (NRG1)-ErbB4 signaling in the parvalbumin interneurons was involved in sepsis-induced cognitive impairment in a mouse model of SAE. The SAE model was induced by cecal ligation/perforation (CLP). Animals were randomly divided into the following six groups: sham + vehicle group, sham + NRG1 group, CLP + vehicle group, CLP + NRG1 group, CLP + NRG1 + AG1478 (ErbB4 inhibitor) group, and CLP + minocycline group. Behavioral tests and in vivo electrophysiology were performed at the indicated time points. The brain tissues were harvested to determine the levels of hippocampcal cytokines, IBA1-positive cells, NRG1, ErbB4, and parvalbumin. In the present study, sepsis induced the anxiety-like behavior and hippocampal-dependent cognitive impairment, as reflected by significantly increased distance spent in the open field test and decreased freezing time to context in the fear conditioning test. The abnormal behavioral changes co-occurred with significant increases in hippocampal IBA1-positive cells, IL-1β and IL-6 levels, and decreased NRG1, ErbB4, parvalbumin expressions, and evoked gamma activity. NRG1 treatment attenuated the sepsis-induced cognitive impairment and the associated biochemical markers, which were abolished by AG1478 administration. Notably, minocycline treatment attenuated neuroinflammation and mimicked the beneficial effects of NRG1 treatment. In summary, we provided additional evidence that the disruption of NRG1-ErbB4 signaling in the parvalbumin interneurons mediated by neuroinflammation might lead to abnormal gamma oscillations and thus contribute to cognitive impairment in a mouse model of SAE.     

Saccade Related Gamma-Band Activity in Intracerebral EEG: Dissociating Neural from Ocular Muscle Activity

Recent evidence suggests that transient increases in scalp electroencephalography (EEG) gamma band power (above 30 Hz) can be due to miniature eye movements. Although, these findings do not raise doubts about the widely established role of gamma range neural synchrony, it does call for caution when it comes to interpreting high frequency scalp EEG data. By contrast, gamma-band activity detected with intracerebral EEG (iEEG) is assumed to be immune to such miniature saccade artefacts. Here, we show for the first time, that while this is indeed largely the case, intracerebral recordings in the temporal pole of implanted patients can be contaminated by saccadic eye muscle artefacts resulting in typical high gamma-band power increases. By analyzing data from multiple depth electrodes, we show that this artefact is confined to the pole of the temporal lobe because of its immediate vicinity to extraocular muscles (rectus lateralis). For other brain structures, our analysis shows that the use of stereotactic EEG with a bipolar montage provides a robust and convenient tool to explore the functional role of gamma synchronization in humans with high anatomical accuracy during a wide range of cognitive processes, including oculomotor behaviour. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is one of five on the “Special Topic: Discussing Gamma” in issue 22(1) of Brain Topography.     

缝隙连接参与认知功能的机制研究

缝隙连接(gap junction,GJ)是真核细胞之间特化的提供直接物质和信息交流的连接结构,介导相邻细胞之间的电偶联和小分子物质的细胞间转移,这种物质和能量的交流称为缝隙连接介导的细胞间通讯(gap iunctional intercellular communication,GJIC).以往的研究提示,缝隙连接在神经系统的胚胎发育、细胞分化和生长控制等生物过程中起重要作用.     

Synaptic transmission is impaired prior to plaque formation in amyloid precursor protein–overexpressing mice without altering behaviorally-correlated sharp wave–ripple complexes

One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques in brains of affected patients. Several recent studies provided evidence that soluble oligomer forms of amyloid-β (Aβ) rather than plaques determine cognitive decline. In vitro studies using artificial Aβ oligomer preparations suggest that such pathophysiology is caused by a specific impairment of synaptic function. We examined whether synaptic deficits occur before deposition of insoluble fibrillar Aβ by analyzing brain slices taken from young Tg2576 mice overexpressing mutant amyloid precursor protein. Excitatory synaptic transmission in the hippocampal CA1 region was strongly impaired before plaque development, suggesting a dissociation of an early synaptic impairment, probably caused by soluble oligomeric amyloid-β, from subsequent plaque formation. At higher age neurotransmission was also decreased in wild type mice, paralleling a cognitive decline of normal aged animals. Memory formation in rats is accompanied by distinct hippocampal network oscillations. It has recently been shown that hippocampal gamma oscillations, a network correlate of exploratory behavior, are impaired in amyloid precursor protein (APP)–overexpressing mice. We determined whether sharp wave–ripple complexes, which contribute to memory consolidation during slow wave-sleep, are modified in Tg2576 mice. Interestingly, neither sharp waves nor superimposed ripples were changed at pre-plaque or plaque stages. During aging, however, there was a strong reduction of sharp wave frequency and ripple energy in wild type and APP-overexpressing animals. This indicates that the reported changes in network oscillations following APP-overexpression are specific for gamma oscillations, whereas aging has a more general effect on network properties. Taken together our data suggest that non-fibrillar forms of Aβ—possibly Aβ oligomers—specifically interfere with synaptic function in Tg2576, but do not globally alter memory-related network properties. We propose that mechanisms leading to Aβ-related cognitive decline are different from those related to aging.