Modulation Of Gamma Oscillations Research Articles

Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations

The hypocretin (Hcrt) (also known as orexin) neuropeptidic wakefulness-promoting system is implicated in the regulation of spatial memory, but its specific role and mechanisms remain poorly understood. In this study, we revealed the innervation of the medial entorhinal cortex (MEC) by Hcrt neurons in mice. Using the genetically encoded G-protein-coupled receptor activation-based Hcrt sensor, we observed a significant increase in Hcrt levels in the MEC during novel object-place exploration. We identified the function of Hcrt at presynaptic glutamatergic terminals, where it recruits fast-spiking parvalbumin-positive neurons and promotes gamma oscillations. Bidirectional manipulations of Hcrt neurons' projections from the lateral hypothalamus (LHHcrt) to MEC revealed the essential role of this pathway in regulating object-place memory encoding, but not recall, through the modulation of gamma oscillations. Our findings highlight the significance of the LHHcrt-MEC circuitry in supporting spatial memory and reveal a unique neural basis for the hypothalamic regulation of spatial memory.

Shared Intentionality Modulation at the Cell Level: Low-Frequency Oscillations for Temporal Coordination in Bioengineering Systems

The theoretical article aims to develop knowledge about the modulation of shared intentionality at the cellular level. A hypothesis about the neurobiological processes during shared intentionality argues that this pre-perceptual communication occurs through nonlocal neuronal coupling in an ecosystem that can be described as the mother-fetus communication model. The current theoretical study analyses literature to discuss recent findings on the effect of oscillations on neuronal temporal coordination to verify whether external low-frequency oscillations can only synchronize specific local neuronal networks from peripheral and central nervous subsystems for modulating shared intentionality. The review discusses 4 findings. First, gamma oscillations are associated with the temporal coordination of local ensembles of cells. Second, there is a relationship between low-frequency brain oscillations and the temporal coordination of peripheral and central nervous subsystems. Third, delta oscillations influence neuronal activity by modulating gamma activity. Fourth, external delta and gamma oscillations increase cortical excitability. The article concludes that delta oscillations can modulate gamma oscillations in the different subsystems of the nervous system, providing temporal network coordination. An external low-frequency oscillator can coordinate only relevant local neuronal networks in various subsystems already exhibiting gamma activity.

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35-45 Hz) power (n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power (t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

Cross-regional phase amplitude coupling supports the encoding of episodic memories.

Phase amplitude coupling (PAC) between theta and gamma oscillations represents a key neurophysiological mechanism that promotes the temporal organization of oscillatory activity. For this reason, PAC has been implicated in item/context integration for episodic processes, including coordinating activity across multiple cortical regions. While data in humans has focused principally on PAC within a single brain region, data in rodents has revealed evidence that the phase of the hippocampal theta oscillation modulates gamma oscillations in the cortex (and vice versa). This pattern, termed cross-regional PAC (xPAC), has not previously been observed in human subjects engaged in mnemonic processing. We use a unique dataset with intracranial electrodes inserted simultaneously into the hippocampus and seven cortical regions across 40 human subjects to (1) test for the presence of significant cross-regional PAC (xPAC), (2) to establish that the magnitude of xPAC predicts memory encoding success, (3) to describe specific frequencies within the broad 2-9 Hz theta range that govern hippocampal-cortical interactions in xPAC, and (4) compare anterior versus posterior hippocampal xPAC patterns. We find that strong functional xPAC occurs principally between the hippocampus and other mesial temporal structures, namely entorhinal and parahippocampal cortices, and that xPAC is overall stronger for posterior hippocampal connections. We also show that our results are not confounded by alternative factors such as inter-regional phase synchrony, local PAC occurring within cortical regions, or artifactual theta oscillatory waveforms.

Ramelteon modulates gamma oscillations in the rat primary motor cortex during non-REM sleep

Sleep disorders adversely affect daily activities and cause physiological and psychiatric problems. The shortcomings of benzodiazepine hypnotics have led to the development of ramelteon, a melatonin MT1 and MT2 agonist. Although the sleep-promoting effects of ramelteon have been documented, few studies have precisely investigated the structure of sleep and neural oscillatory activities. In this study, we recorded electrocorticograms in the primary motor cortex, the primary somatosensory cortex and the olfactory bulb as well as electromyograms in unrestrained rats treated with either ramelteon or vehicle. A neural-oscillation-based algorithm was used to classify the behavior of the rats into three vigilance states (e.g., awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep). Moreover, we investigated the region-, frequency- and state-specific modulation of extracellular oscillations in the ramelteon-treated rats. We demonstrated that in contrast to benzodiazepine treatment, ramelteon treatment promoted NREM sleep and enhanced fast gamma power in the primary motor cortex during NREM sleep, while REM sleep was unaffected. Gamma oscillations locally coordinate neuronal firing, and thus, ramelteon modulates neural oscillations in sleep states in a unique manner and may contribute to off-line information processing during sleep.

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

BackgroundTemporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear. ObjectiveWe developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain. MethodsThe electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head. ResultsAmplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABAb) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ∼5 V/m (corresponding to ∼13 mA at the scalp surface), whereas, 1 kHz carrier frequency ∼60 V/m (∼160 mA) and 2 kHz carrier frequency ∼80 V/m (∼220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants. ConclusionThe TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.

Targeting Gamma-Related Pathophysiology in Autism Spectrum Disorder Using Transcranial Electrical Stimulation: Opportunities and Challenges.

A range of scalp electroencephalogram (EEG) abnormalities correlates with the core symptoms of autism spectrum disorder (ASD). Among these are alterations of brain oscillations in the gamma-frequency EEG band in adults and children with ASD, whose origin has been linked to dysfunctions of inhibitory interneuron signaling. While therapeutic interventions aimed to modulate gamma oscillations are being tested for neuropsychiatric disorders such as schizophrenia, Alzheimer's disease, and frontotemporal dementia, the prospects for therapeutic gamma modulation in ASD have not been extensively studied. Accordingly, we discuss gamma-related alterations in the setting of ASD pathophysiology, as well as potential interventions that can enhance gamma oscillations in patients with ASD. Ultimately, we argue that transcranial electrical stimulation modalities capable of entraining gamma oscillations, and thereby potentially modulating inhibitory interneuron circuitry, are promising methods to study and mitigate gamma alterations in ASD. Autism Res 2020, 13: 1051-1071. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Brain functions are mediated by various oscillatory waves of neuronal activity, ranging in amplitude and frequency. In certain neuropsychiatric disorders, such as schizophrenia and Alzheimer's disease, reduced high-frequency oscillations in the "gamma" band have been observed, and therapeutic interventions to enhance such activity are being explored. Here, we review and comment on evidence of reduced gamma activity in ASD, arguing that modalities used in other disorders may benefit individuals with ASD as well.

Modulation of gamma oscillations as a possible therapeutic tool for neuropsychiatric diseases: A review and perspective

Gamma oscillations (30–80 Hz) are well-known for their role in cortical signal transmission and cognitive brain functions. Aberrant gamma activity has been observed in various neuropsychiatric disorders, but the clinical potential of restoring gamma oscillations via noninvasive brain stimulation has been widely neglected. Only recently, therapeutic effects of gamma entrainment were documented in mouse models of Alzheimer's dementia (AD) using rhythmic sensory stimulation. In the present review, we first summarize the current status of the research on gamma entrainment in mouse models of AD and human AD patients. Then, we suggest transcranial alternating current stimulation (tACS) as an alternative brain stimulation technique and review the recent literature on the effects of gamma tACS in healthy volunteers and neuropsychiatric diseases to document the efficacy of gamma tACS in improving cognitive functions. We discuss several advantages of tACS compared to rhythmic sensory stimulation for the entrainment of gamma oscillations in the human brain and emphasize the need for more clinical studies applying tACS to drive gamma oscillations and, in turn, to improve cognitive functioning not only in AD but also in patients suffering from other neuropsychiatric disorders.

The Modulation of Gamma Oscillations by Methamphetamine in Rat Hippocampal Slices.

Gamma frequency oscillations (γ, 30–100 Hz) have been suggested to underlie various cognitive and motor functions. The psychotomimetic drug methamphetamine (MA) enhances brain γ oscillations associated with changes in psychomotor state. Little is known about the cellular mechanisms of MA modulation on γ oscillations. We explored the effects of multiple intracellular kinases on MA modulation of γ induced by kainate in area CA3 of rat ventral hippocampal slices. We found that dopamine receptor type 1 and 2 (DR1 and DR2) antagonists, the serine/threonine kinase PKB/Akt inhibitor and N-methyl-D-aspartate receptor (NMDAR) antagonists prevented the enhancing effect of MA on γ oscillations, whereas none of them affected baseline γ strength. Protein kinase A, phosphoinositide 3-kinase and extracellular signal-related kinases inhibitors had no effect on MA. We propose that the DR1/DR2-Akt-NMDAR pathway plays a critical role for the MA enhancement of γ oscillations. Our study provides an new insight into the mechanisms of acute MA on MA-induced psychosis.

Effect of noninvasive focused ultrasound stimulation on gamma oscillations in rat hippocampus.

In recent years, noninvasive focused ultrasound stimulation (FUS), with the advantage of high spatial resolution and high penetration depth, has developed rapidly for modulating neuron activities in the brain. Gamma oscillations serve to synchronize neurons and play important roles in cortical information processing and cognitive function. However, how FUS modulates gamma oscillations in the rat hippocampus is not well understood. In this work, we characterized the interactions between the gamma amplitude and phases of the delta, theta, and alpha bands during FUS. Our results show that FUS can significantly modulate the extent of phase-locked gamma amplitude and phase-amplitude coupling of brain oscillations. In summary, FUS can modulate gamma oscillations in the rat hippocampus, indicating its potential as a powerful noninvasive method to interfere with brain rhythms for diagnostic and therapeutic purposes.

Dopamine D3 Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony.

Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D3 receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D3 receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D3 receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D3 receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D3 receptors. Investigating the underlying cellular mechanisms for these effects showed that D3 receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D3 receptors may impair cognition and how, in converse, D3 antagonists may exert pro-cognitive and antipsychotic effects.

Modulation of hippocampal gamma oscillations by acetylcholine: insights from mathematical and in vitro optogenetic models

A neuronal oscillation involves the rhythmic, synchronous firing of a population of cells. Oscillations found throughout the cortex can be separated into bands of differing frequencies which are associated with various behavioural states. Gamma oscillations (30 - 100 Hz) occur coincidently with attention, sensory processing and learning and memory. The hippocampus, known for its role in learning and memory, shows gamma activity in vivo [1] and gamma oscillations can be induced in in vitro slices [2]. The release of acetylcholine (ACh) correlates with increases in oscillatory power in vivo [3] and knockout of specific ACh receptor subtypes provides evidence for this scenario [4]. To further investigate the role of ACh in the modulation of gamma oscillations we have utilised both in vitro and computational techniques. We implemented a mathematical model of the CA3 region of the hippocampus based on [5]. Using Hodgkin-Huxley single compartmental neurons, we verify that a network of 80 excitatory pyramidal cells and 20 inhibitory interneurons is able to produce oscillatory activity within the gamma range. We developed an optogenetic system (see [6,7]) to induce gamma oscillations enabling us to test modulation by specific acetylcholine receptors. Male mice received stereotaxic injection into the CA3 region of the hippocampus of a viral vector (AAV5) containing channelrhodopsin (hChR2(H134R)) under the control of the CaMKIIα promoter. Stimulation of the ChR expressing CA3 pyramidal cell bodies with short light pulses (5-50 ms) evoked action potentials and stimulation of Schaffer collateral axons elicited robust synaptic responses in the CA3 and CA1 regions that were blocked by the application of NBQX (10 µM) or TTX (1 µM). Local field potential recordings showed that a 1s step optical stimulation induced low power and low frequency gamma oscillations which attenuated over time. In vivo, gamma oscillations are often found 'nested' within an overlying theta oscillation [8]. Correlating well with these in vivo recordings, theta frequency (5 Hz) sine wave optical stimulation induced higher power and higher frequency gamma oscillations with less attenuation over a 1s period. We introduced, a similar, 5 Hz sine depolarising input to the pyramidal cells in our mathematical model and found that it was able to induce oscillations at gamma frequency. By manipulating specific currents within the model, we predicted the effect of specific ACh receptor subtype activation on gamma oscillations. These predictions were supported by our in vitro experimental evidence showing that we found that activation of ACh receptors did indeed modulate gamma oscillations with M1 receptor having a major effect.

Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABAA receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABAA receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABAA receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABAA-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABAA receptors, has been related to psychiatric disorders including schizophrenia and depression.

Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression.

Deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG) is becoming an effective therapeutic option for treatment resistant depression (TRD). Identifying the neurophysiological mechanisms altered by DBS may lead to more tailored treatment parameters and enhanced efficacy. Twenty TRD patients with implanted DBS in the SCG were recruited. Patients participated in three EEG recording sessions, one with DBS ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each session, subjects performed N-back working memory tasks, namely the 0-back and 3-back. Fourteen subjects with valid EEG were included in the analysis. Changes in frontal gamma oscillations (30-50 Hz) and coupling between theta (4-7 Hz) and gamma oscillations as a result of DBS stimulation were quantified and correlated with depressive symptoms. DBS stimulation resulted in suppression of frontal oscillations in the ON state relative to the OFF state during the N-back tasks. Greatest suppression was demonstrated in beta and gamma oscillations and most pronounced during the 3-back. Suppression of gamma oscillations in the 3-back correlated with a reduction in depressive symptoms. DBS ON relative to OFF in the 3-back also resulted in an increase in theta-gamma coupling that correlated with a reduction in depressive symptoms. Suppression of gamma oscillations and increased theta-gamma coupling through DBS is likely mediated by both SCG activation of inhibitory circuits and an enhancement of plasticity in the frontal cortex. Activation of both pathways may explain the therapeutic properties of DBS in TRD.

Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder.

Reduced levels of gamma-band activity are present in schizophrenia and bipolar disorder patients. In the same disorders, increased neuronal calcium sensor protein-1 (NCS-1) expression was reported in a series of postmortem studies. These disorders are also characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). The discovery of gamma-band activity in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed that such activity was mediated by high-threshold calcium channels that are regulated by NCS-1. We hypothesized that NCS-1 normally regulates gamma-band oscillations through these calcium channels and that excessive levels of NCS-1, such as would be expected with overexpression, decrease gamma-band activity. We found that PPN neurons in rat brain slices manifested gamma-band oscillations that were increased by low levels of NCS-1 but suppressed by high levels of NCS-1. Our results suggest that NCS-1 overexpression may be responsible for the decrease in gamma-band activity present in at least some schizophrenia and bipolar disorder patients.

Corticosterone and corticotropin-releasing factor acutely facilitate gamma oscillations in the hippocampus in vitro.

Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave-ripple (SW-R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress-responsive modulators, such as corticosterone (CORT), corticotropin-releasing factor (CRF) and the neurosteroid 3α, 21-dihydroxy-5α-pregnan-20-one (THDOC) are able to modulate gamma oscillations and SW-Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm) combined with physostigmine (2 μm). CORT increased the gamma oscillations in a dose-dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose-dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre-applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress-related neuromodulators had rather mild effects on spontaneous SW-R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress-related agents is an acute process, permitting fast adaptation to new attention-requiring situations in vivo.

5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation.

Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease.In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin(5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations.Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3.Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

Optogenetically evoked gamma oscillations are disturbed by cocaine administration

Drugs of abuse have enormous societal impact by degrading the cognitive abilities, emotional state and social behavior of addicted individuals. Among other events involved in the addiction cycle, the study of a single exposure to cocaine, and the contribution of the effects of that event to the continuous and further use of drugs of abuse are fundamental. Gamma oscillations are thought to be important neural correlates of cognitive processing in the prefrontal cortex (PFC) which include decision making, set shifting and working memory. It follows that cocaine exposure might modulate gamma oscillations, which could result in reduced cognitive ability. Parvalbumin-positive fast-spiking interneurons play an orchestrating role in gamma oscillation induction and it has been shown recently that gamma oscillations can be induced in an anesthetized animal using optogenetic techniques. We use a knock-in mouse model together with optogenetics and in vivo electrophysiology to study the effects of acute cocaine on PFC gamma oscillation as a step toward understanding the cortical changes that may underlie continuous use of stimulants. Our results show that acute cocaine administration increases entrainment of the gamma oscillation to the optogentically induced driving frequency. Our results also suggest that this modulation of gamma oscillations is driven trough activation of D1 receptors. The acute cocaine-mediated changes in mPFC may underlie the enhancement of attention and awareness commonly reported by cocaine users and may contribute to the further use and abuse of psychostimulants.

Transcranial magnetic stimulation on the modulation of gamma oscillations in schizophrenia

Cognitive dysfunction is suggested to be the best predictor of functional outcome in schizophrenia. Therefore, new diagnostic and treatment strategies are needed to both ascertain the biological underpinning of cognitive deficits and to restore them. Modulation of gamma oscillations (30-50 Hz) has been associated with cognitive performance, particularly in the dorsolateral prefrontal cortex (DLPFC). In this manuscript, we review evidence for gamma modulation deficits during cognitive performance in schizophrenia. We demonstrate that transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a reliable method that permits systematic quantification of gamma modulation in the cortex. Using TMS-EEG, we show that patients with schizophrenia have selective gamma inhibition deficits in the DLPFC. Finally, we demonstrate that repetitive TMS therapy over the DLPFC can normalize excessive gamma oscillations and ultimately cognitive performance in patients. We suggest that restoring gamma impairments in the DLPFC may be a potential strategy for improving cognitive deficits in schizophrenia.

Gamma Oscillations Are Generated Locally in an Attention-Related Midbrain Network

Gamma-band (25-140 Hz) oscillations are a hallmark of sensory processing in the forebrain. The optic tectum (OT), a midbrain structure implicated in sensorimotor processing and attention, also exhibits gamma oscillations. However, the origin and mechanisms of these oscillations remain unknown. We discovered that in acute slices of the avian OT, persistent (>100 ms) epochs of large amplitude gamma oscillations can be evoked that closely resemble those recorded in vivo. We found that cholinergic, glutamatergic, and GABAergic mechanisms differentially regulate the structure of the oscillations at various timescales. These persistent oscillations originate in the multisensory layers of the OT and are broadcast to visual layers via the cholinergic nucleus Ipc, providing a potential mechanism for enhancing the processing of visual information within the OT. The finding that the midbrain contains an intrinsic gamma-generating circuit suggests that the OT could use its own oscillatory code to route signals to forebrain networks.