Attentional changes in pre-stimulus oscillatory activity within early visual cortex are predictive of human visual performance

Physiological and neuroimaging studies provide evidence to suggest that attentional mechanisms operating within the fronto-parietal network may exert top–down control on early visual areas, priming them for forthcoming sensory events. The believed consequence of such priming is enhanced task performance. Using the technique of magnetoencephalography (MEG), we investigated this possibility by examining whether attention-driven changes in cortical activity are correlated with performance on a line-orientation judgment task. We observed that, approximately 200 ms after a covert attentional shift towards the impending visual stimulus, the level of phase-resetting (transient neural coherence) within the calcarine significantly increased for 2–10 Hz activity. This was followed by a suppression of alpha activity (near 10 Hz) which persisted until the onset of the stimulus. The levels of phase-resetting, alpha suppression and subsequent behavioral performance varied between subjects in a systematic fashion. The magnitudes of phase-resetting and alpha-band power were negatively correlated, with high levels of coherence associated with high levels of performance. We propose that top–down attentional control mechanisms exert their initial effects within the calcarine through a phase-resetting within the 2–10 Hz band, which in turn triggers a suppression of alpha activity, priming early visual areas for incoming information and enhancing behavioral performance.

Cortical oscillatory activity associated with the perception of illusory and real visual contours

We used magnetoencephalography (MEG) to examine the nature of oscillatory brain rhythms when passively viewing both illusory and real visual contours. Three stimuli were employed: a Kanizsa triangle; a Kanizsa triangle with a real triangular contour superimposed; and a control figure in which the corner elements used to form the Kanizsa triangle were rotated to negate the formation of illusory contours. The MEG data were analysed using synthetic aperture magnetometry (SAM) to enable the spatial localisation of task-related oscillatory power changes within specific frequency bands, and the time-course of activity within given locations-of-interest was determined by calculating time-frequency plots using a Morlet wavelet transform. In contrast to earlier studies, we did not find increases in gamma activity (> 30 Hz) to illusory shapes, but instead a decrease in 10–30 Hz activity approximately 200 ms after stimulus presentation. The reduction in oscillatory activity was primarily evident within extrastriate areas, including the lateral occipital complex (LOC). Importantly, this same pattern of results was evident for each stimulus type. Our results further highlight the importance of the LOC and a network of posterior brain regions in processing visual contours, be they illusory or real in nature. The similarity of the results for both real and illusory contours, however, leads us to conclude that the broadband (< 30 Hz) decrease in power we observed is more likely to reflect general changes in visual attention than neural computations specific to processing visual contours.

Attentional shifts towards an expected visual target alter the level of alpha-band oscillatory activity in the human calcarine cortex

Neuronal operations associated with the top-down control process of shifting attention from one locus to another involve a network of cortical regions, and their influence is deemed fundamental to visual perception. However, the extent and nature of these operations within primary visual areas are unknown. In this paper, we used magnetoencephalography (MEG) in combination with magnetic resonance imaging (MRI) to determine whether, prior to the onset of a visual stimulus, neuronal activity within early visual cortex is affected by covert attentional shifts. Time/frequency analyses were used to identify the nature of this activity. Our results show that shifting attention towards an expected visual target results in a late-onset (600 ms postcue onset) depression of alpha activity which persists until the appearance of the target. Independent component analysis (ICA) and dipolar source modeling confirmed that the neuronal changes we observed originated from within the calcarine cortex. Our results further show that the amplitude changes in alpha activity were induced not evoked (i.e., not phase-locked to the cued attentional task). We argue that the decrease in alpha prior to the onset of the target may serve to prime the early visual cortex for incoming sensory information. We conclude that attentional shifts affect activity within the human calcarine cortex by altering the amplitude of spontaneous alpha rhythms and that subsequent modulation of visual input with attentional engagement follows as a consequence of these localized changes in oscillatory activity. © 2005 Elsevier B.V. All rights reserved.

Attentional modulation of oscillatory activity in human visual cortex

The effects of attentional modulation on activity within the human visual cortex were investigated using magnetoencephalography. Chromatic sinusoidal stimuli were used to evoke activity from the occipital cortex, with attention directed either toward or away from the stimulus using a bar-orientation judgment task. For five observers, global magnetic field power was plotted as a function of time from stimulus onset. The major peak of each function occurred at about 120 ms latency and was well modeled by a current dipole near the calcarine sulcus. Independent component analysis (ICA) on the non-averaged data for each observer also revealed one component of calcarine origin, the location of which matched that of the dipolar source determined from the averaged data. For two observers, ICA revealed a second component near the parieto-occipital sulcus. Although no effects of attention were evident using standard averaging procedures, time-varying spectral analyses of single trials revealed that the main effect of attention was to alter the level of oscillatory activity. Most notably, a sustained increase in alpha-band (7-12 Hz) activity of both calcarine and parieto-occipital origin was evident. In addition, calcarine activity in the range of 13-21 Hz was enhanced, while calcarine activity in the range of 5-6 Hz was reduced. Our results are consistent with the hypothesis that attentional modulation affects neural processing within the calcarine and parieto-occipital cortex by altering the amplitude of alpha-band activity and other natural brain rhythms. © 2003 Elsevier Inc. All rights reserved.

Pharmacologically induced and stimulus evoked rhythmic neuronal oscillatory activity in the primary motor cortex in vitro

Parkinson's disease (PD) is associated with enhanced synchronization of neuronal network activity in the beta (15-30 Hz) frequency band across several nuclei of the basal ganglia (BG). Deep brain stimulation of the subthalamic nucleus (STN) appears to reduce this pathological oscillation, thereby alleviating PD symptoms. However, direct stimulation of primary motor cortex (M1) has recently been shown to be effective in reducing symptoms in PD, suggesting a role for cortex in patterning pathological rhythms. Here, we examine the properties of M1 network oscillations in coronal slices taken from rat brain. Oscillations in the high beta frequency range (layer 5, 27.8 +/- 1.1 Hz, n=6) were elicited by co-application of the glutamate receptor agonist kainic acid (400 nM) and muscarinic receptor agonist carbachol (50 mu M). Dual extracellular recordings, local application of tetrodotoxin and recordings in M1 micro-sections indicate that the activity originates within deep layers V/VI. Beta oscillations were unaffected by specific AMPA receptor blockade, abolished by the GABA type A receptor (GABAAR) antagonist picrotoxin and the gap-junction blocker carbenoxolone, and modulated by pentobarbital and zolpidem indicating dependence on networks of GABAergic interneurons and electrical coupling. High frequency stimulation (HFS) at 125 Hz in superficial layers, designed to mimic transdural/transcranial stimulation, generated gamma oscillations in layers 11 and V (incidence 95%, 69.2 +/- 7.3 Hz, n=17) with very fast oscillatory components (VFO; 100-250 Hz). Stimulation at 4 Hz, however, preferentially promoted theta activity (incidence 62.5%, 5.1 +/- 0.6 Hz, n=15) that effected strong amplitude modulation of ongoing beta activity. Stimulation at 20 Hz evoked mixed theta and gamma responses. These data suggest that within M1, evoked theta, gamma and fast oscillations may coexist with and in some cases modulate pharmacologically induced beta oscillations.

Modulation of network oscillatory activity and GABAergic synaptic transmission by CB1 cannabinoid receptors in the rat medial entorhinal cortex

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500?nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

The role of oscillatory brain activity in object processing and figure-ground segmentation in human vision

The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks

INTRODUCTION: We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. METHODS: Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. RESULTS: Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. CONCLUSIONS: This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

Modulation of neuronal network activity in the primary motor cortex

In the present study I investigated the mechanisms of modulation of neuronal network activity in rat primary motor cortex using pharmacological manipulations employing the in vitro brain slice technique. Preparation of the brain slice in sucrose-based aCSF produced slices with low viability. Introducing the neuroprotectants N-acetyl-cysteine, taurine and aminoguanidine to the preparatory method saw viability of slices increase significantly. Co-application of low dose kainic acid and carbachol consistently generated beta oscillatory activity in M1. Analyses indicated that network activity in M1 relied on the involvement of GABAA receptors. Dose-response experiments performed in M1 showed that beta activity can be modulated by benzodiazepine site ligands. Low doses of positive allosteric modulators consistently desynchronised beta oscillatory activity, a mechanism that may be driven by a1-subunit containing GABAA receptors. Higher doses increased the power of beta oscillatory activity. Whole-cell recordings in M1 uncovered three interneuronal subtypes regularly encountered in M1; Fast-spiking, regular-spiking non-Pyramidal and low threshold spiking. With the paradoxical effects of positive allosteric modulators in mind, subsequent voltage-clamp recordings in FS cells revealed a constitutively active tonic inhibitory current that could be modulated by zolpidem in two different ways. Low dose zolpidem increased the tonic inhibitory current in FS cells, consistent with the desynchronisation of network oscillatory activity seen at this concentration. High dose zolpidem decreased the inhibitory tonic current seen in FS cells, coinciding with an increase in oscillatory power. These studies indicate a fundamental role for a tonic inhibitory current in the modulation of network activity. Furthermore, desynchronisation of beta activity in M1 decreased as viability of the in vitro brain slice increased, suggesting that the extent of desynchronisation is dependent upon the pathophysiological state of the network. This indicates that low dose zolpidem could be used as a therapeutic agent specifically for the desynchronisation of pathological oscillations in oscillopathies such as Parkinson’s disease.

Early gamma-band activity as a function of threat processing in the extrastriate visual cortex

Various neuroimaging investigations have revealed that perception of emotional pictures is associated with greater visual cortex activity than their neutral counterparts. It has further been proposed that threat-related information is rapidly processed, suggesting that the modulation of visual cortex activity should occur at an early stage. Additional studies have demonstrated that oscillatory activity in the gamma band range (40-100 Hz) is associated with threat processing. Magnetoencephalography (MEG) was used to investigate such activity during perception of task-irrelevant, threat-related versus neutral facial expressions. Our results demonstrated a bilateral reduction in gamma band activity for expressions of threat, specifically anger, compared with neutral faces in extrastriate visual cortex (BA 18) within 50-250 ms of stimulus onset. These results suggest that gamma activity in visual cortex may play a role in affective modulation of visual processing, in particular with the perception of threat cues.

Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity

The loss of dopamine in idiopathic or animal models of Parkinson's disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic-globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABAA receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic-globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity. © 2006 IBRO.

Beta frequency neuronal network activity in the primary motor cortex

In this study I investigated the mechanisms of neuronal network oscillatory activity in rat M1 using pharmacological manipulations and electrical stimulation protocols, employing the in vitro brain slice technique in rat and magnetoencephalography (MEG) in man. Co-application of kainic acid and carbachol generated in vitro beta oscillatory activity in all layers in M1. Analyses indicated that oscillations originated from deep layers and indicated significant involvement of GABAA receptors and gap junctions. A modulatory role of GABAB, NMDA, and dopamine receptors was also evident. Intracellular recordings from fast-spiking (FS) GABAergic inhibitory cells revealed phase-locked action potentials (APs) on every beta cycle. Glutamatergic excitatory regular-spiking (RS) and intrinsically-bursting (IB) cells both received phase locked inhibitory postsynaptic potentials, but did not fire APs on every cycle, suggesting the dynamic involvement of different pools of neurones in the overall population oscillations. Stimulation evoked activity at high frequency (HFS; 125Hz) evoked gamma oscillations and reduced ongoing beta activity. 20Hz stimulation promoted theta or gamma oscillations whilst 4Hz stimulation enhanced beta power at theta frequency. I also investigated the modulation of pathological slow wave (theta and beta) oscillatory activity using magnetoencephalography. Abnormal activity was suppressed by sub-sedative doses of GABAA receptor modulator zolpidem and the observed desynchronising effect correlated well with improved sensorimotor function. These studies indicate a fundamental role for inhibitory neuronal networks in the patterning beta activity and suggest that cortical HFS in PD re-patterns abnormally enhanced M1 network activity by modulating the activity of FS cells. Furthermore, pathological oscillation may be common to many neuropathologies and may be an important future therapeutic target.

Cortical oscillatory dynamics and benzodiazepine-site modulation of tonic inhibition in fast spiking interneurons

Tonic conductance mediated by extrasynaptic GABAA receptors has been implicated in the modulation of network oscillatory activity. Using an in vitro brain slice to produce oscillatory activity and a kinetic model of GABAA receptor dynamics, we show that changes in tonic inhibitory input to fast spiking interneurons underlie benzodiazepine-site mediated modulation of neuronal network synchrony in rat primary motor cortex. We found that low concentrations (10 nM) of the benzodiazepine site agonist, zolpidem, reduced the power of pharmacologically-induced beta-frequency (15–30 Hz) oscillatory activity. By contrast, higher doses augmented beta power. Application of the antagonist, flumazenil, also increased beta power suggesting endogenous modulation of the benzodiazepine binding site. Voltage-clamp experiments revealed that pharmacologically-induced rhythmic inhibitory postsynaptic currents were reduced by 10 nM zolpidem, suggesting an action on inhibitory interneurons. Further voltage -clamp studies of fast spiking cells showed that 10 nM zolpidem augmented a tonic inhibitory GABAA receptor mediated current in fast spiking cells whilst higher concentrations of zolpidem reduced the tonic current. A kinetic model of zolpidem-sensitive GABAA receptors suggested that incubation with 10 nM zolpidem resulted in a high proportion of GABAA receptors locked in a kinetically slow desensitized state whilst 30 nM zolpidem favoured rapid transition into and out of desensitized states. This was confirmed experimentally using a challenge with saturating concentrations of GABA. Selective modulation of an interneuron-specific tonic current may underlie the reversal of cognitive and motor deficits afforded by low-dose zolpidem in neuropathological states.

A general linear model for MEG beamformer imaging

A new general linear model (GLM) beamformer method is described for processing magnetoencephalography (MEG) data. A standard nonlinear beamformer is used to determine the time course of neuronal activation for each point in a predefined source space. A Hilbert transform gives the envelope of oscillatory activity at each location in any chosen frequency band (not necessary in the case of sustained (DC) fields), enabling the general linear model to be applied and a volumetric T statistic image to be determined. The new method is illustrated by a two-source simulation (sustained field and 20 Hz) and is shown to provide accurate localization. The method is also shown to locate accurately the increasing and decreasing gamma activities to the temporal and frontal lobes, respectively, in the case of a scintillating scotoma. The new method brings the advantages of the general linear model to the analysis of MEG data and should prove useful for the localization of changing patterns of activity across all frequency ranges including DC (sustained fields). © 2004 Elsevier Inc. All rights reserved.