Gamma oscillations and their role in orchestrating balance and communication following stroke

Didn't your competent? doctor start creating protocols on this years ago? NO? So you DON'T have a competent doctor? Why are you there? Now if we just had someone in stroke with two functioning neurons to rub together we could easily get a protocol written on this and get survivors recovered! BUT WE HAVE NO ONE WITH BRAINS WORKING IN STROKE! You'll probably have to read the conclusion yourself and come up with your own protocols since everyone in stroke is a complete fucking failure!

• gamma oscillations (13 posts to May 2012)

  • gamma oscillations (5 posts to May 2021)

   

 Gamma oscillations and their role in orchestrating balance and communication following stroke

Montana Samantzis#, Cong Wang#, Matilde Balbi

Induced brain oscillations in the gamma range have recently garnered attention due to their reported neuroprotective effects in the treatment of Alzheimer’s disease. This method differs from pharmacological approaches by tapping into the neuronal population dynamics that underlie the homeostatic processes in the brain that are crucial for the recovery of function. Recently,induced gamma-range oscillations have been used to improve cerebral blood flow, motor function, and synaptic plasticity in a mouse model of focal stroke, highlighting the broad potential of recruiting intrinsic recovery processes for the treatment of neurological conditions. Addressing open questions, such as the frequency specificity of the benefits, will shed light on the intrinsic processes involved and allow clinicians to optimize recovery after stroke. Interneurons play a crucial role in orchestrating the coordinated activity of adjacent neurons through inhibitory mechanisms and are instrumental in the generation of oscillatory activity within the brain.In particular, the generation of gamma oscillations,rhythmic patterns of activity that occur within the frequency range of 25–100 Hz, is tied to the firing activity of parvalbumin interneurons (Cardin et al.,2009). In the cortex, parvalbumin neurons inhibit excitatory pyramidal neurons, and their inhibitory postsynaptic potentials are phase-locked to gamma oscillations (Guan et al., 2022). Gamma oscillations are proposed to play a key role in maintaining homeostatic brain processes including synchronization of other oscillatory bands, inter- and intra-regional communication,and maintenance of excitatory and inhibitory activation within the brain (Guan et al., 2022). Disruption of gamma oscillations occurs in several pathological and non-pathological conditions which can lead to disruption of metabolic,cognitive, and behavioral processes. New evidence has proposed that entrainment of these oscillations may facilitate functional recovery,making this a promising target for therapeutic intervention (Adaikkan and Tsai, 2020; Balbi et al.,2021; Wang et al., 2023). Following ischemic stroke, there is an increased disruption of low gamma oscillations (30–50 Hz) in the region surrounding the ischemic core (Hazimeet al., 2021). Optogenetic targeting of fast-spiking parvalbumin inhibitory neurons at 40 Hz has been shown to increase the power of gamma oscillations (Cardin et al., 2009), and in the context of ischemic stroke, stimulation of inhibitory neurons at this frequency has shown remarkable improvements to functional recovery (Balbi etal., 2021). The precise mechanism by which the targeted modulation of inhibitory neuronal activity through gamma oscillations contributes to enhanced recovery following a stroke remains elusive.In this perspective, we discuss our recent findings proposing that this phenomenon can be attributed to facilitating interregional communication between brain regions and inducing functional plasticity (Wang et al., 2023).Gamma frequency stimulation of inhibitory neurons regulates the inhibitory-excitatory balance: Targeting oscillatory dynamics using brain stimulation techniques is an emerging toolfor promoting recovery post stroke, however,has had varying results (reviewed in Storch etal., 2021). Gamma oscillations in particular are thought to be key in order to maintain a healthy balance between excitatory and inhibitory activity within the brain, which is essential for information processing. Targeting inhibitory neurons either ipsi- or contra-lesionally within the gamma frequency preferentially facilitates behavioral recovery following stroke (Balbi et al.,2021). Ipsilesional 40 Hz stimulation immediately following stroke also aided in restoration of blood flow and reduced lesion size, whilst optogenetic stimulation at 10 Hz or whisker stimulation at 4 Hz did not improve outcomes (Balbi et al., 2021). While investigating how gamma oscillations modulate neuronal assemblies, we found that 40Hz stimulation of interneurons leads to synaptic current changes in pyramidal neurons, meaning that they receive direct inputs from interneurons to regulate their activity (Wang et al., 2023). We observed synchronized but anticorrelated activity of excitatory and inhibitory signals whereby interneuron firing occurred during the peak phase of the gamma rhythm, and pyramidal neurons fired during the trough phase. These modulatory effects were observed exclusively during 40 Hz stimulation where the firing rate of both pyramidal neurons and interneurons was affected, whilst10 Hz stimulation of interneurons had no effect on the firing rate of either cell type (Wang etal., 2023). By stimulating inhibitory neurons at their resonating frequency, we are therefore able to increase their activity whilst simultaneously reducing possible over-excitation caused by stroke.Thus, this induction of gamma oscillations may restore the harmony between inhibitory and excitatory activity in the brain. We hypothesize that by rescuing this balance in local networks,we may be able to mitigate damage to long-range connections between brain regions.Induction of gamma oscillations leads to improved inter-regional communication: Theta-gamma coupling refers to the synchronization between neuronal oscillatory rhythms in the theta (4–8 Hz) and gamma range. This coupling showcases the regulatory role of low-frequency brain activity in orchestrating information exchange between different brain regions by modulating the amplitude of high-frequency oscillations. This dynamic interplay between theta and gamma oscillations is thought to play a crucial role in coordinating cognitive functions by enhancing communication between different brain regions.Theta-gamma cross-frequency coupling is disrupted following stroke, making it a clear target for improving recovery (Zheng et al.,2020; Rustamov et al., 2022; Wang et al., 2023).Furthermore, this coupling is increased during the generation and execution of motor functions,Montana Samantzis#, Cong Wang#, Matilde Balbi*and an improvement of theta-gamma coupling has been reported as a potential biomarker of recovery in patients during the chronic phase of stroke, correlating with improved motor performance (Rustamov et al., 2022). Deficits in theta-gamma coupling that are observed within two weeks following hippocampal ischemia can be rescued following repeated 40 Hz visual stimulation (Zheng et al., 2020). Interestingly, our recent work builds upon this evidence and shows that 40 Hz stimulation also enhances theta-gamma coupling and motor performance in the acute phase following stroke, suggesting that this may also be a useful biomarker for recovery of motor function acutely following injury (Balbi et al., 2021;Wang et al., 2023).On a wider scale, gamma oscillations facilitate inter-regional communication, potentially through enhancing the coherence of gamma oscillations between regions. Following stroke,there is a decrease in evoked gamma synchronicity which has been shown to correlate with worse clinical outcomes (Pellegrino et al., 2019). By optogenetically targeting inhibitory neurons at 40 Hz in the acute phase after stroke, we recently demonstrated increased interregional communication between the primary motor cortex and the posterior temporal area. Interestingly,this increase in functional connectivity was still observed 24 hours following stimulation (Wang etal., 2023). This restoration of coordinated network activity between regions is a key for facilitating communication following stroke and may allow for compensation of lost activity within the stroke core, thus helping to promote motor function.Functional plasticity following ischemia can be facilitated by inducing gamma oscillations: Neuroplasticity refers to the nervous system’s ability to change itself by reorganizing its connections, functions, or structures in response to internal or external stimuli. Following ischemia,there is damage to one or more brain regions,causing the brain to compensate for lost functions and reorganize its network structure. As gamma oscillations are heavily involved in the coordination of network activity, they may also play a key role in the regulation of plasticity processes following disruption to natural communication patterns.As previously mentioned, we have demonstrated that induced gamma oscillations phase locks the activity of both inhibitory and excitatory activity,which we postulate can synchronize the timing of both pre- and post-synaptic activities (Wang et al.,2023). The physiological process underlying the link between synchronous neuronal activity and neuroplasticity may be an instance of Hebbian theory such as spike-timing-dependent plasticity(Dan and Poo, 2004).We also recently observed a decrease in the number of pairwise functional synaptic connections as determined by cross correlogram analysis following ischemic stroke (Wang et al.,2023). Remarkably, following 40 Hz stimulation this functional connectivity is rescued to baseline levels 24 hours following ischemia (Wang et al., 2023).40 Hz visual stimulation has also been shown to increase postsynaptic long-term potentiations,  presynaptic short-term plasticity, and spine density following hippocampal ischemia (Zheng et al.,2020). In addition to functional changes, several key proteins related to synaptic plasticity have changes to expression levels as a result of 40 Hz stimulation, namely, postsynaptic density protein95, glutamate transport ATP-binding protein,and regulator of G protein signaling 12 (Zhenget al., 2020; Wang et al., 2023). Increases in these protein levels further support the idea that gamma frequency stimulation may have effects on both pre- and post-synaptic plasticity. However,further exploration of potential pathways of action is needed in order to fully understand the role of these oscillations in this fundamental plasticity process. In future studies, it will also be important to ascertain the extent to which 40 Hz stimulation can affect pre- and post-synaptic plasticity when the stimulation site is not directly next to the stroke region.

 

Conclusion and perspective: 

 

There is currently substantial evidence that gamma frequency stimulation may be beneficial in a range of neurodegenerative disorders; however, our understanding of the mechanisms of action is lacking. Recent findings show that entraining inhibitory activity in the gamma frequency range leads to synchronicity and functional plasticity following stroke (Figure 1). This evidence suggests that entrainment of gamma oscillations may be a promising treatment for other neurological disorders where gamma therapies are disrupted.The neurovascular unit encapsulates the highly complex synchronization between brain cells and the vasculature. Communication between different components of the neurovascular unit is a cornerstone for healthy brain functioning,including the generation of oscillatory activity.The coupling of the components of this unit is an intricate process involving a series of coordinated responses to changes in blood flow or neuronal activity, and disruption to either of these processes can be detrimental to the function of the unit as a whole. In addition to interneurons, astrocytes are a key component of the neurovascular unit that plays a role in the maintenance of gamma oscillations (Lee et al., 2014). The loss of blood flow following ischemia interferes with the activity within these crucial components and disrupts neurovascular function. We propose that induction and restoration of oscillatory activity in the gamma range in the stroke region can provide a substitute for naturally occurring oscillatory activity that is needed during a critical time window.This work was supported by the Brazil Family Program for Neurology (to MB), Alastair Rushworth Research Fund (to MS), Australian Government Research Training Program Scholarship (to MS),the National Natural Science Foundation of China(82202787) (to CW). Montana Samantzis#, Cong Wang#,Matilde Balbi*Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia(Samantzis M, Wang C, Balbi M)Engineering Research Centre of Traditional ChineseMedicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China (Wang C)*Correspondence to: Matilde Balbi, PhD,m.balbi@uq.edu.au.https://orcid.org/0000-0003-4590-5447(Matilde Balbi)#Both authors contributed equally to this article.Date of submission: January 31, 2024Date of decision: March 4, 2024Date of acceptance: March 20, 2024Date of web publication: April 16, 2024https://doi.org/10.4103/NRR.NRR-D-24-00127How to cite this article: Samantzis M, Wang C,Balbi M (2024) Gamma oscillations and their role in orchestrating balance and communication following stroke. Neural Regen Res 19(0):000-000