Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

Transient gamma-band (40–80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

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Localizing spontaneous memory reprocessing during human sleep

10.1101/2021.11.29.470230 ◽

2021 ◽

Author(s):

Lea Himmer ◽

Zoé Bürger ◽

Leonie Fresz ◽

Janina Maschke ◽

Lore Wagner ◽

...

Keyword(s):

Machine Learning ◽

Memory Consolidation ◽

High Frequency ◽

Gamma Oscillations ◽

Gamma Activity ◽

Related Activity ◽

Memory Processing ◽

Slow Oscillations ◽

Parallel Memory ◽

Human Sleep

Reactivation of newly acquired memories during sleep across hippocampal and neocortical systems is proposed to underlie systems memory consolidation. Here, we investigate spontaneous memory reprocessing during sleep by applying machine learning to source space-transformed magnetoencephalographic data in a two-step exploratory and confirmatory study design. We decode memory-related activity from slow oscillations in hippocampus, frontal cortex and precuneus, indicating parallel memory processing during sleep. Moreover, we show complementary roles of hippocampus and neocortex: while gamma activity indicated memory reprocessing in hippocampus, delta and theta frequencies allowed decoding of memory in neocortex. Neocortex and hippocampus were linked through coherent activity and modulation of high-frequency gamma oscillations by theta, a dynamic similar to memory processing during wakefulness. Overall, we noninvasively demonstrate localized, coordinated memory reprocessing in human sleep.

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A Novel Tool for the Removal of Muscle Artefacts from EEG: Improving Data Quality in the Gamma Frequency Range

10.1101/2020.11.23.393702 ◽

2020 ◽

Author(s):

Alina Pauline Liebisch ◽

Thomas Eggert ◽

Alina Shindy ◽

Elia Valentini ◽

Stephanie Irving ◽

...

Keyword(s):

Data Quality ◽

Time Course ◽

Muscular Activity ◽

Gamma Oscillations ◽

Gamma Band ◽

Gamma Activity ◽

Single Muscle ◽

Frequency Range ◽

Continuous Eeg ◽

Artefact Removal

AbstractBackgroundThe past two decades have seen a particular focus towards high-frequency neural activity in the gamma band (>30Hz). However, gamma band activity shares frequency range with unwanted artefacts from muscular activity.New MethodWe developed a novel approach to remove muscle artefacts from neurophysiological data. We re-analysed existing EEG data that were decomposed by a blind source separation method (independent component analysis, ICA), which helped to better spatially and temporally separate single muscle spikes. We then applied an adapting algorithm that detects these singled-out muscle spikes.ResultsWe obtained data almost free from muscle artefacts; we needed to remove significantly fewer artefact components from the ICA and we included more trials for the statistical analysis compared to standard ICA artefact removal. All pain-related cortical effects in the gamma band have been preserved, which underlines the high efficacy and precision of this algorithm.ConclusionsOur results show a significant improvement of data quality by preserving task-relevant gamma oscillations of cortical origin. We were able to precisely detect, gauge, and carve out single muscle spikes from the time course of neurophysiological measures. We advocate the application of the tool for studies investigating gamma activity that contain a rather low number of trials, as well as for data that are highly contaminated with muscle artefacts. This validation of our tool allows for the application on event-free continuous EEG, for which the artefact removal is more challenging.

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Reward-Associated Gamma Oscillations in Ventral Striatum Are Regionally Differentiated and Modulate Local Firing Activity

Journal of Neurophysiology ◽

10.1152/jn.00432.2009 ◽

2010 ◽

Vol 103 (3) ◽

pp. 1658-1672 ◽

Cited By ~ 50

Author(s):

Tobias Kalenscher ◽

Carien S. Lansink ◽

Jan V. Lankelma ◽

Cyriel M. A. Pennartz

Keyword(s):

Ventral Striatum ◽

Phase Locking ◽

Gamma Oscillations ◽

Brain Regions ◽

Reward Processing ◽

Temporal Organization ◽

Gamma Activity ◽

Neural Ensembles ◽

Gamma Range ◽

Gamma Power

Oscillations of local field potentials (LFPs) in the gamma range are found in many brain regions and are supposed to support the temporal organization of cognitive, perceptual, and motor functions. Even though gamma oscillations have also been observed in ventral striatum, one of the brain's most important structures for motivated behavior and reward processing, their specific function during ongoing behavior is unknown. Using a movable tetrode array, we recorded LFPs and activity of neural ensembles in the ventral striatum of rats performing a reward-collection task. Rats were running along a triangle track and in each round collected one of three different types of rewards. The gamma power of LFPs on subsets of tetrodes was modulated by reward-site visits, discriminated between reward types, between baitedness of reward locations and was different before versus after arrival at a reward site. Many single units in ventral striatum phase-locked their discharge pattern to the gamma oscillations of the LFPs. Phase-locking occurred more often in reward-related than in reward-unrelated neurons and LFPs. A substantial number of simultaneously recorded LFPs correlated poorly with each other in terms of gamma rhythmicity, indicating that the expression of gamma activity was heterogeneous and regionally differentiated. The orchestration of LFPs and single-unit activity by way of gamma rhythmicity sheds light on the functional architecture of the ventral striatum and the temporal coordination of ventral striatal activity for modulating downstream areas and regulating synaptic plasticity.

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Abstract TP441: Neurovascular Coupling is Impaired in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.44.suppl_1.atp441 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Stefano Peca ◽

Cheryl R McCreary ◽

Emily Donaldson ◽

Karla Sanchez ◽

Anna Charlton ◽

...

Keyword(s):

White Matter ◽

Motor Cortex ◽

Primary Motor Cortex ◽

White Matter Lesion ◽

Motor Task ◽

Neurovascular Coupling ◽

Occipital Lobe ◽

Amyloid Angiopathy ◽

Bold Response ◽

Cerebral Amyloid

Introduction: Cerebral amyloid angiopathy (CAA) is marked by accumulation of vascular beta-amyloid which is toxic to smooth muscle cells. An animal study and a pilot study in humans suggest decreased vasodilation in CAA. We studied patients with CAA and matched controls to determine whether neurovascular coupling is impaired in CAA. Methods: Patients with CAA and controls underwent task-related fMRI with a visual task (viewing a flashing alternating checkerboard pattern) or a motor task (tapping the fingers of the dominant hand) using a block design, and visual evoked potentials (VEPs). CAA patients were diagnosed by Boston criteria and had normal corrected visual acuity, no visual field deficits and no paresis of the dominant arm. Controls were recruited by community advertising and were matched by gender and age (±5 years) to CAA cases. Results: Eighteen CAA patients (12 M, 6F; 72±7 yrs) and eighteen controls (12 M, 6F; 70±7 yrs) were studied. For the visual task, CAA patients had reduced activity in the occipital lobe (Figure) and lower amplitude of the BOLD response vs. controls (28% reduced, p=0.005). By contrast, for the motor task CAA patients had a similar response of the primary motor cortex vs. controls (9.6% reduced BOLD response, p=0.53). VEP P100 latencies and amplitudes did not differ between CAA and controls (p=0.49 and p=0.74). Lower visual cortex BOLD amplitudes were correlated with greater white matter lesion volumes in CAA (r=-0.66, p=0.003). Conclusions: Neurovascular coupling is impaired in the occipital lobe in CAA. BOLD signal amplitudes are reduced despite normal evoked potentials, suggesting impaired vasodilation. The association with white matter lesion volume raises the possibility that impaired vasodilation may be involved in the pathogenesis of these lesions. BOLD responses in the primary motor cortex in CAA were not reduced, likely reflecting the known posterior predominance of CAA with lesser involvement of the frontal lobe.

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Carbachol Induces Fast Oscillations in the Medial but not in the Lateral Entorhinal Cortex of the Isolated Guinea Pig Brain

Journal of Neurophysiology ◽

10.1152/jn.1999.82.5.2441 ◽

1999 ◽

Vol 82 (5) ◽

pp. 2441-2450 ◽

Cited By ~ 26

Author(s):

Solange van der Linden ◽

Ferruccio Panzica ◽

Marco de Curtis

Keyword(s):

Guinea Pig ◽

Entorhinal Cortex ◽

Gamma Oscillations ◽

Gamma Activity ◽

Oscillatory Activity ◽

Medial Entorhinal Cortex ◽

Arterial Perfusion ◽

Fast Oscillations ◽

Guinea Pig Brain

Fast oscillations at 25–80 Hz (gamma activity) have been proposed to play a role in attention-related mechanisms and synaptic plasticity in cortical structures. Recently, it has been demonstrated that the preservation of the entorhinal cortex is necessary to maintain gamma oscillations in the hippocampus. Because gamma activity can be reproduced in vitro by cholinergic activation, this study examined the characteristics of gamma oscillations induced by arterial perfusion or local intracortical injections of carbachol in the entorhinal cortex of the in vitro isolated guinea pig brain preparation. Shortly after carbachol administration, fast oscillatory activity at 25.2–28.2 Hz was observed in the medial but not in the lateral entorhinal cortex. Such activity was transiently associated with oscillations in the theta range that showed a variable pattern of distribution in the entorhinal cortex. No oscillatory activity was observed when carbachol was injected in the lateral entorhinal cortex. Gamma activity in the medial entorhinal cortex showed a phase reversal at 200–400 μm, had maximal amplitude at 400–500 μm depth, and was abolished by arterial perfusion of atropine (5 μM). Local carbachol application in the medial entorhinal cortex induced gamma oscillations in the hippocampus, whereas no oscillations were observed in the amygdala and in the piriform, periamygdaloid, and perirhinal cortices ipsilateral and contralateral to the carbachol injection. Hippocampal oscillations had higher frequency than the gamma activity recorded in the entorhinal cortex, suggesting the presence of independent generators in the two structures. The selective ability of the medial but not the lateral entorhinal cortex to generate gamma activity in response to cholinergic activation suggests a differential mode of signal processing in entorhinal cortex subregions.

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Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽

10.1093/neuros/nyz310_173 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Arjun Vivek Pendharkar ◽

Daniel L Smerin ◽

Lorenzo Gonzales ◽

Eric Wang ◽

Sabrina L Levy ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Motor Cortex ◽

Functional Recovery ◽

Neuronal Nitric Oxide Synthase ◽

Optogenetic Stimulation ◽

Oxide Synthase ◽

Nnos Expression ◽

Stimulation Of ◽

Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

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Interaction Between Finger Opposition Movements and Aftereffects of 1Hz-rTMS on Ipsilateral Motor Cortex

Journal of Neurophysiology ◽

10.1152/jn.90428.2008 ◽

2009 ◽

Vol 101 (3) ◽

pp. 1690-1694 ◽

Cited By ~ 8

Author(s):

Laura Avanzino ◽

Marco Bove ◽

Andrea Tacchino ◽

Carlo Trompetto ◽

Carla Ogliastro ◽

...

Keyword(s):

Motor Cortex ◽

Motor Performance ◽

Magnetic Stimulation ◽

Voluntary Movement ◽

Motor Behavior ◽

Repetitive Transcranial Magnetic Stimulation ◽

Motor Task ◽

The Other ◽

Experimental Conditions ◽

Opposition Movements

One-hertz repetitive transcranial magnetic stimulation (1Hz-rTMS) over ipsilateral motor cortex is able to modify up to 30 min the motor performance of repetitive finger opposition movements paced with a metronome at 2 Hz. We investigated whether the long-lasting rTMS effect on motor behavior can be modulated by subsequent engagement of the contralateral sensorimotor system. Motor task was performed in different experimental conditions: immediately after rTMS, 30 min after rTMS, or when real rTMS was substituted with sham rTMS. Subjects performing the motor task immediately after rTMS showed modifications in motor behavior ≤30 min after rTMS. On the other hand, when real rTMS was substituted with sham stimulation or when subjects performed the motor task 30 min after the rTMS session, the effect was no longer present. These findings suggest that the combination of ipsilateral 1Hz-rTMS and voluntary movement is crucial to endure the effect of rTMS on the movement itself, probably acting on synaptic plasticity-like mechanism. This finding might provide some useful hints for neurorehabilitation protocols.

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Pallidal thermolesion unleashes gamma oscillations in the motor cortex in Parkinson's disease

Movement Disorders ◽

10.1002/mds.27658 ◽

2019 ◽

Vol 34 (6) ◽

pp. 903-911 ◽

Cited By ~ 2

Author(s):

Coralie Hemptinne ◽

Doris D. Wang ◽

Svjetlana Miocinovic ◽

Witney Chen ◽

Jill L. Ostrem ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Cortex ◽

Gamma Oscillations

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Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model

Nature Communications ◽

10.1038/s41467-019-13260-9 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 17

Author(s):

Guillaume Etter ◽

Suzanne van der Veldt ◽

Frédéric Manseau ◽

Iman Zarrinkoub ◽

Emilie Trillaud-Doppia ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Mouse Model ◽

Spatial Memory ◽

Gamma Oscillations ◽

Optogenetic Stimulation ◽

Phase Amplitude ◽

Ad Mouse Model ◽

Parvalbumin Neurons ◽

Stimulation Of ◽

40 Hz

AbstractSlow gamma oscillations (30–60 Hz) correlate with retrieval of spatial memory. Altered slow gamma oscillations have been observed in Alzheimer’s disease. Here, we use the J20-APP AD mouse model that displays spatial memory loss as well as reduced slow gamma amplitude and phase-amplitude coupling to theta oscillations phase. To restore gamma oscillations in the hippocampus, we used optogenetics to activate medial septal parvalbumin neurons at different frequencies. We show that optogenetic stimulation of parvalbumin neurons at 40 Hz (but not 80 Hz) restores hippocampal slow gamma oscillations amplitude, and phase-amplitude coupling of the J20 AD mouse model. Restoration of slow gamma oscillations during retrieval rescued spatial memory in mice despite significant plaque deposition. These results support the role of slow gamma oscillations in memory and suggest that optogenetic stimulation of medial septal parvalbumin neurons at 40 Hz could provide a novel strategy for treating memory deficits in AD.

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