Cholinergic enhancement of visual attention and neural oscillations in the human brain

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex.     

Functional dissociation of ongoing oscillatory brain states

The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8-12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer-interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states.     

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Stimulus-induced gamma oscillations in the 30–80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABA_A agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.     

Evidence for human fronto-central gamma activity during long-term memory encoding of word sequences

Although human gamma activity (30-80 Hz) associated with visual processing is often reported, it is not clear to what extend gamma activity can be reliably detected non-invasively from frontal areas during complex cognitive tasks such as long term memory (LTM) formation. We conducted a memory experiment composed of 35 blocks each having three parts: LTM encoding, working memory (WM) maintenance and LTM retrieval. In the LTM encoding and WM maintenance parts, participants had to respectively encode or maintain the order of three sequentially presented words. During LTM retrieval subjects had to reproduce these sequences. Using magnetoencephalography (MEG) we identified significant differences in the gamma and beta activity. Robust gamma activity (55-65 Hz) in left BA6 (supplementary motor area (SMA)/pre-SMA) was stronger during LTM rehearsal than during WM maintenance. The gamma activity was sustained throughout the 3.4 s rehearsal period during which a fixation cross was presented. Importantly, the difference in gamma band activity correlated with memory performance over subjects. Further we observed a weak gamma power difference in left BA6 during the first half of the LTM rehearsal interval larger for successfully than unsuccessfully reproduced word triplets. In the beta band, we found a power decrease in left anterior regions during LTM rehearsal compared to WM maintenance. Also this suppression of beta power correlated with memory performance over subjects. Our findings show that an extended network of brain areas, characterized by oscillatory activity in different frequency bands, supports the encoding of word sequences in LTM. Gamma band activity in BA6 possibly reflects memory processes associated with language and timing, and suppression of beta activity at left frontal sensors is likely to reflect the release of inhibition directly associated with the engagement of language functions.     

Visual gamma oscillations: waves,correlations, and other phenomena,including comparison with experimental data

Mean-field theory of brain dynamics is applied to explain the properties of gamma (?30 Hz) oscillations of cortical activity often seen during vision experiments. It is shown that mm-scale patchy connections in the primary visual cortex can support collective gamma oscillations with the correct frequencies and spatial structure, even when driven by uncorrelated inputs. This occurs via resonances associated with the the periodic modulation of the network connections, rather than being due to single-cell properties alone. Near-resonant gamma waves are shown to obey the Schrödinger equation, which enables techniques and insights from quantum theory to be used in exploring these classical oscillations. Resulting predictions for gamma responses to stimuli account in a unified way for a wide range of experimental results, including why oscillations and zero-lag synchrony are associated, and variations in correlation functions with time delay, intercellular distance, and stimulus features. They also imply that gamma oscillations may enable a form of frequency multiplexing of neural signals. Most importantly, it is shown that correlations reproduce experimental results that show maximal correlations between cells that respond to related features, but little correlation with other cells, an effect that has been argued to be associated with segmentation of a scene into separate objects. Consistency with infill of missing contours and increase in response with length of bar-shaped stimuli are discussed. Background correlations expected in the absence of stimulation are also calculated and shown to be consistent in form with experimental measurements and similar to stimulus-induced correlations in structure. Finally, possible links of gamma instabilities to certain classes of photically induced seizures and visual hallucinations are discussed.     

Learning-induced modulation of oscillatory activities in the mammalian olfactory system: The role of the centrifugal fibres

In the mammalian olfactory system, oscillations related to odour representation have been described in field potential activities. Previous results showed that in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour presentation produced a decrease of oscillations in gamma frequency range (60-90 Hz) associated with a power increase in beta frequency range (15-40 Hz). This response pattern was strongly amplified in trained animals. The aim of this work was twofold: whether learning also induces similar changes in OB target structures and whether such OB response depends on its centrifugal inputs. Local field potentials (LFPs) were recorded through chronically implanted electrodes in the OB, piriform and enthorhinal cortices of freely moving rats performing an olfactory discrimination. Oscillatory activities characteristics (amplitude, frequency and time-course) were extracted in beta and gamma range by a wavelet analysis. First, we found that odour induced beta oscillatory activity was present not only in the OB, but also in the other olfactory structures. In each recording site, characteristics of the beta oscillatory responses were dependent of odour, structure and learning level. Unilateral section of the olfactory peduncle was made before training, and LFPs were symmetrically recorded in the two bulbs all along the acquisition of the learning task. Data showed that deprivation of centrifugal feedback led to an increase of spontaneous gamma activity. Moreover, under this condition olfactory learning was no longer associated with the typical large beta band. As a whole, learning modulation of the beta oscillatory response in olfactory structures may reflect activity of a distributed functional network involved in odour representation.     

Bistable,Irregular Firing and Population Oscillations in a Modular Attractor Memory Network

Attractor neural networks are thought to underlie working memory functions in the cerebral cortex. Several such models have been proposed that successfully reproduce firing properties of neurons recorded from monkeys performing working memory tasks. However, the regular temporal structure of spike trains in these models is often incompatible with experimental data. Here, we show that the in vivo observations of bistable activity with irregular firing at the single cell level can be achieved in a large-scale network model with a modular structure in terms of several connected hypercolumns. Despite high irregularity of individual spike trains, the model shows population oscillations in the beta and gamma band in ground and active states, respectively. Irregular firing typically emerges in a high-conductance regime of balanced excitation and inhibition. Population oscillations can produce such a regime, but in previous models only a non-coding ground state was oscillatory. Due to the modular structure of our network, the oscillatory and irregular firing was maintained also in the active state without fine-tuning. Our model provides a novel mechanistic view of how irregular firing emerges in cortical populations as they go from beta to gamma oscillations during memory retrieval.     

Gamma Activity Coupled to Alpha Phase as a Mechanism for Top-Down Controlled Gating

Coupling between neural oscillations in different frequency bands has been proposed to coordinate neural processing. In particular, gamma power coupled to alpha phase is proposed to reflect gating of information in the visual system but the existence of such a mechanism remains untested. Here, we recorded ongoing brain activity using magnetoencephalography in subjects who performed a modified Sternberg working memory task in which distractors were presented in the retention interval. During the anticipatory pre-distractor period, we show that the phase of alpha oscillations was coupled with the power of high (80-120Hz) gamma band activity, i.e. gamma power consistently was lower at the trough than at the peak of the alpha cycle (9-12Hz). We further show that high alpha power was associated with weaker gamma power at the trough of the alpha cycle. This result is in line with alpha activity in sensory region implementing a mechanism of pulsed inhibition silencing neuronal firing every ~100 ms.     

Driving oscillatory activity in the human cortex enhances motor performance

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.     

Hippocampal theta oscillations are slower in humans than in rodents: implications for models of spatial navigation and memory

The theta oscillation is a neuroscience enigma. When a rat runs through an environment, large-amplitude theta oscillations (4–10 Hz) reliably appear in the hippocampus''s electrical activity. The consistency of this pattern led to theta playing a central role in theories on the neural basis of mammalian spatial navigation and memory. However, in fact, hippocampal oscillations at 4–10 Hz are rare in humans and in some other species. This presents a challenge for theories proposing theta as an essential component of the mammalian brain, including models of place and grid cells. Here, I examine this issue by reviewing recent research on human hippocampal oscillations using direct brain recordings from neurosurgical patients. This work indicates that the human hippocampus does indeed exhibit rhythms that are functionally similar to theta oscillations found in rodents, but that these signals have a slower frequency of approximately 1–4 Hz. I argue that oscillatory models of navigation and memory derived from rodent data are relevant for humans, but that they should be modified to account for the slower frequency of the human theta rhythm.     

Oscillations in the prefrontal cortex: a gateway to memory and attention

We consider the potential role of oscillations in the prefrontal cortex (PFC) in mediating attention, working memory and memory consolidation. Activity in the theta, beta, and gamma bands is related to communication between PFC and different brain areas. While gamma/beta oscillations mediate bottom-up and top-down interactions between PFC and visual cortices, related to attention, theta rhythms are engaged by hippocampal/PFC interplay. These interactions are dynamic, depending on the nature and relevance of the information currently being processed. The profound modifications of the PFC neuronal network associated with changes in oscillatory coherence are controlled by neuromodulators such as dopamine, which thereby allow or prevent the formation of cell assemblies for information encoding and storage.     

Noisy Galvanic Vestibular Stimulation Modulates the Amplitude of EEG Synchrony Patterns

Noisy galvanic vestibular stimulation has been associated with numerous cognitive and behavioural effects, such as enhancement of visual memory in healthy individuals, improvement of visual deficits in stroke patients, as well as possibly improvement of motor function in Parkinson’s disease; yet, the mechanism of action is unclear. Since Parkinson’s and other neuropsychiatric diseases are characterized by maladaptive dynamics of brain rhythms, we investigated whether noisy galvanic vestibular stimulation was associated with measurable changes in EEG oscillatory rhythms within theta (4–7.5 Hz), low alpha (8–10 Hz), high alpha (10.5–12 Hz), beta (13–30 Hz) and gamma (31–50 Hz) bands. We recorded the EEG while simultaneously delivering noisy bilateral, bipolar stimulation at varying intensities of imperceptible currents – at 10, 26, 42, 58, 74 and 90% of sensory threshold – to ten neurologically healthy subjects. Using standard spectral analysis, we investigated the transient aftereffects of noisy stimulation on rhythms. Subsequently, using robust artifact rejection techniques and the Least Absolute Shrinkage Selection Operator regression and cross-validation, we assessed the combinations of channels and power spectral features within each EEG frequency band that were linearly related with stimulus intensity. We show that noisy galvanic vestibular stimulation predominantly leads to a mild suppression of gamma power in lateral regions immediately after stimulation, followed by delayed increase in beta and gamma power in frontal regions approximately 20–25 s after stimulation ceased. Ongoing changes in the power of each oscillatory band throughout frontal, central/parietal, occipital and bilateral electrodes predicted the intensity of galvanic vestibular stimulation in a stimulus-dependent manner, demonstrating linear effects of stimulation on brain rhythms. We propose that modulation of neural oscillations is a potential mechanism for the previously-described cognitive and motor effects of vestibular stimulation, and noisy galvanic vestibular stimulation may provide an additional non-invasive means for neuromodulation of functional brain networks.     

High Gamma Oscillations in Medial Temporal Lobe during Overt Production of Speech and Gestures

The study of the production of co-speech gestures (CSGs), i.e., meaningful hand movements that often accompany speech during everyday discourse, provides an important opportunity to investigate the integration of language, action, and memory because of the semantic overlap between gesture movements and speech content. Behavioral studies of CSGs and speech suggest that they have a common base in memory and predict that overt production of both speech and CSGs would be preceded by neural activity related to memory processes. However, to date the neural correlates and timing of CSG production are still largely unknown. In the current study, we addressed these questions with magnetoencephalography and a semantic association paradigm in which participants overtly produced speech or gesture responses that were either meaningfully related to a stimulus or not. Using spectral and beamforming analyses to investigate the neural activity preceding the responses, we found a desynchronization in the beta band (15–25 Hz), which originated 900 ms prior to the onset of speech and was localized to motor and somatosensory regions in the cortex and cerebellum, as well as right inferior frontal gyrus. Beta desynchronization is often seen as an indicator of motor processing and thus reflects motor activity related to the hand movements that gestures add to speech. Furthermore, our results show oscillations in the high gamma band (50–90 Hz), which originated 400 ms prior to speech onset and were localized to the left medial temporal lobe. High gamma oscillations have previously been found to be involved in memory processes and we thus interpret them to be related to contextual association of semantic information in memory. The results of our study show that high gamma oscillations in medial temporal cortex play an important role in the binding of information in human memory during speech and CSG production.     

Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Intracranial recordings from human olfactory cortex reveal a characteristic spectrotemporal response to odors, including theta, beta and gamma oscillations, and show that high-frequency responses are critical for accurate perception of odors.     

Phase locking of single neuron activity to theta oscillations during working memory in monkey extrastriate visual cortex

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.     

Dynamic Changes in Single Unit Activity and Gamma Oscillations in a Thalamocortical Circuit during Rapid Instrumental Learning

The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6–10 Hz) in the MD, but not in the mPFC. By contrast, gamma band oscillations (40–55 Hz) increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.     

Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans

Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (～0.75 Hz) during non-rapid eye movement sleep (NonREM) sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS) oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS) is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8-12 Hz) and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25-45 Hz) activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies.     

Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model

Alzheimer's disease (AD) results in cognitive decline and altered network activity, but the mechanisms are?unknown. We studied human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Electroencephalographic recordings in hAPP mice revealed spontaneous epileptiform discharges, indicating network hypersynchrony, primarily during reduced gamma oscillatory activity. Because this oscillatory rhythm is generated by inhibitory parvalbumin (PV) cells, network dysfunction in hAPP mice might arise from impaired PV cells. Supporting this hypothesis, hAPP mice and AD patients had decreased levels of the interneuron-specific and PV cell-predominant voltage-gated sodium channel subunit Nav1.1. Restoring Nav1.1 levels in hAPP mice by Nav1.1-BAC expression increased inhibitory synaptic activity and gamma oscillations and reduced hypersynchrony, memory deficits, and premature mortality. We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD.     

Does neuronal synchrony underlie visual feature grouping?

Previous research suggests that synchronous neural activity underlies perceptual grouping of visual image features. The generality of this mechanism is unclear, however, as previous studies have focused on pairs of neurons with overlapping or collinear receptive fields. By sampling more broadly and employing stimuli that contain partially occluded objects, we have conducted a more incisive test of the binding by synchrony hypothesis in area MT. We find that synchrony in spiking activity shows little dependence on feature grouping, whereas gamma band synchrony in field potentials can be significantly stronger when features are grouped. However, these changes in gamma band synchrony are small relative to the variability of synchrony across recording sites and do not provide a robust population signal for feature grouping. Moreover, these effects are reduced when stimulus differences nearby the receptive fields are eliminated using partial occlusion. Our findings suggest that synchrony does not constitute a general mechanism of visual feature binding.     

Beta,but Not Gamma,Band Oscillations Index Visual Form-Motion Integration

Electrophysiological oscillations in different frequency bands co-occur with perceptual, motor and cognitive processes but their function and respective contributions to these processes need further investigations. Here, we recorded MEG signals and seek for percept related modulations of alpha, beta and gamma band activity during a perceptual form/motion integration task. Participants reported their bound or unbound perception of ambiguously moving displays that could either be seen as a whole square-like shape moving along a Lissajou''s figure (bound percept) or as pairs of bars oscillating independently along cardinal axes (unbound percept). We found that beta (15–25 Hz), but not gamma (55–85 Hz) oscillations, index perceptual states at the individual and group level. The gamma band activity found in the occipital lobe, although significantly higher during visual stimulation than during base line, is similar in all perceptual states. Similarly, decreased alpha activity during visual stimulation is not different for the different percepts. Trial-by-trial classification of perceptual reports based on beta band oscillations was significant in most observers, further supporting the view that modulation of beta power reliably index perceptual integration of form/motion stimuli, even at the individual level.