High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

The Dynamic Brain in Action: Cortical Oscillations and Coordination Dynamics

Cortical oscillations are electrical activities with rhythmic and/or repetitive nature generated spontaneously and in response to stimuli. Study of cortical oscillations has become an area of converging interests since the last two decades and has deepened our understanding of its physiological basis across different behavioral states. Experimental and modeling work has taught us that there is a wide diversity of cellular and circuit mechanisms underlying the generation of cortical rhythms. A wildly diverse set of functions has pertained to synchronous oscillations but their significance in cognition should be better appraised in the more general framework of correlation between spike times of neurons. Oscillations are the core mechanism in adjusting neuronal interactions and shaping temporal coordination of neural activity. In the first part of this thesis, we review essential feature of cortical oscillations in membrane potentials and local field potentials recorded from turtle ex vivo preparation. Then we develop a simple computational model that reproduces the observed features. This modeling investigation suggests a plausible underlying mechanism for rhythmogenesis through cellular and circuit properties. The second part of the thesis is about temporal coordination dynamics quantified by signal and noise correlations. Here, again, we present a computational model to show how temporal coordination and synchronous oscillations can be sewn together. More importantly, what biophysical ingrediants are necessary for a network to reproduce the observed coordination dynamics

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback

청 감각제어를 위한 parvalbumin 인터뉴론의 흥분성 시냅스 조절기전을 매개하는 PV 의존적 adenylate cyclase 5 신호전달

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2021.8. 김상정.Parvalbumin-expressing (Pv) interneuron dysfunction has been increasingly implicated in cognitive deficits and disruption of auditory sensorimotor gating, but how the cellular substrates for Pv interneuron abnormality have remained elusive. Here, I report that modulation of PPI measured as a psychophysiological index of pre-pulse inhibition (PPI) in mPFC depends on parvalbumin (PV)-mediated adenylate cyclase isoform 5 (AC 5) regulation to coordinate synaptic changes of AMPA receptor (AMPAR), which is adaptive to NMDA receptor (NMDAR) function at glutamatergic synapses onto Pv interneurons. Studies in mPFC of NMDAR antagonism and PV shRNA-silencing models demonstrated downregulation of AMPAR in Pv interneurons and PPI deficits associated with aberrant network activity. Furthermore, deletion of AC 5 impaired PPI without affecting other behavioral effects. Overexpression of PV and reactivation of AC 5 signaling promoted to improve Pv interneuronal synaptic activity in line with PPI effects, which is comparable to PPI rescue by optogenetic stimulation of Pv interneurons. These results suggest that PV-AC 5 signaling is the novel Pv interneuronal mechanisms for mediating synaptic changes of AMPAR and thus NMDAR hypofunction-induced disruption of this signaling impairs synaptic regulation of AMPAR, leading to PPI deficits with abnormal network activity.Parvalbumin 인터뉴론의 기능 장애는 인지 기능 및 청각 감각 운동 동기의 악화에 연루되어 있음이 많은 이전 연구들에서 진행되었다. 하지만, parvalbumin 인터뉴론에 대한 구체적인 분자적 및 세포학적 수준에서의 기질연구는 여전히 많은 부분이 탐구되지 않았다. 본 연구에서 나는 mPFC에서 청각 감각 운동 동기의 정신생리학적 측정 지표인 Prepulse 억제 (PPI)의 조절이 AMPA 수용체 (AMPAR)의 시냅스 변화에 의해서 기저하며, 이러한 AMPA 수용체는 Parvalbumin 단백질 (PV) 매개된 adenylate cyclase 이소형 5 (AC 5) 조절에 의존된다고 보고한다. 이러한 parvalbumin 중간게재 세포 특이적인 신호전달 경로는 NMDA 수용체 (NMDAR)의 기능에 따라 적응적으로 조절됨을 시사한다. NMDAR 길항작용 및 PV shRNA 억제 (silencing) 모델의 mPFC에 대한 연구는 비정상적인 네트워크 활동과 관련된 parvalbumin 인터뉴론에서의 하향 조절된 AMPA 수용체의 기능 및 PPI 결핍이 나타남을 입증했다. 또한, AC 5의 유전자 제거 모델에서는 다른 행동 효과에는 영향을 미치지 않으면서 특이적으로 PPI의 결핍만이 나타남을 발견하였다. Parvalbumin 단백질의 과발현과 AC 5 신호전달의 재활성화는 PPI에 대한 효과와 일치하여 parvalbumin 인터뉴론의 시냅스 활성을 개선하도록 촉진시키는데 기여하였으며, 이는 parvalbumin 인터뉴론을 직접적으로 광유전학적 자극을 함으로서 회복되어지는 PPI 정도와 유사한 수준의 개선임을 밝혔다. 이러한 결과는 parvalbumin 단백질 (PV)에서 AC 5로 연결되어지는 신호가 AMPA 수용체의 시냅스 변화를 매개하기 위한 새로운 parvalbumin 인터뉴론안의 특이적인 신경 메커니즘이며 따라서 NMDA 수용체 기능저하로 야기되어지는 이 신호의 방해가 AMPA 수용체의 조절을 손상시켜 비정상적인 네트워크 활동과 함께 PPI 결손을 초래함을 시사한다.Preface 1 Abstract 2 Abstract in Korean 4 Graphical Abstract 6 Chapter Ⅰ. PV deficiency induced by NMDAR hypofunction in Pv interneurons causes AMPAR downregulation associated with sensorimotor gating deficits 10 Introduction 11 Materials and Methods 15 Results 21 Figures 33 Discussion 75 Chapter Ⅱ. Distinctive AMPAR regulation by PV-mediated AC 5 signaling in Pv interneurons is required for sensorimotor gating 80 Introduction 80 Materials and Methods 83 Results 92 Figures 99 Discussion 122 Bibliography 127박

The Correlation between Astrocytic Calcium and fMRI Signals is Related to the Thalamic Regulation of Cortical States

BOLD fMRI has been wildly used for mapping brain activity, but the cellular contribution of BOLD signals is still controversial. In this study, we investigated the correlation between neuronal/astrocytic calcium and the BOLD signal using simultaneous GCaMP-mediated calcium and BOLD signal recording, in the event-related state and in resting state, in anesthetized and in free-moving rats. To our knowledge, the results provide the first demonstration that evoked and intrinsic astrocytic calcium signals could occur concurrently accompanied by opposite BOLD signals which are associated with vasodilation and vasoconstriction. We show that the intrinsic astrocytic calcium is involved in brain state changes and is related to the activation of central thalamus. First, by simultaneous LFP and fiber optic calcium recording, the results show that the coupling between LFP and calcium indicates that neuronal activity is the basis of the calcium signal in both neurons and astrocytes. Second, we found that evoked neuronal and astrocytic calcium signals are always positively correlated with BOLD responses. However, intrinsic astrocytic calcium signals are accompanied by the activation of the central thalamus followed by a striking negative BOLD signal in cortex, which suggests that central thalamus may be involved in the initiation of the intrinsic astrocytic calcium signal. Third, we confirmed that the intrinsic astrocytic calcium signal is preserved in free moving rats. Moreover, the occurrences of intrinsic astrocytic calcium spikes are coincident with the transition between different sleep stages, which suggests intrinsic astrocytic calcium spikes reflect brain state transitions. These results demonstrate that the correlation between astrocytic calcium and fMRI signals is related to the thalamic regulation of cortical states. On the other hand, by studying the relationship between vessel–specific BOLD signals and spontaneous calcium activity from adjacent neurons, we show that low frequency spontaneous neuronal activity is the cellular mechanism of the BOLD signal during resting state

Neural Processing in the Three Layer Turtle Visual Cortex

In this thesis we investigate neural processing in turtle visual cortex. To this end, we characterize the nature of both spontaneous, ongoing neural activity as well as activity evoked by visual stimulation. Data are collected from whole brain eye-attached preparations, recording with extracellular and intracellular electrodes. We investigate the activity of action potentials as well as the slower local field potential activity. To investigate response properties, we explore spatial properties of receptive fields, temporal properties of spontaneous and evoked activity, response adaptation, and correlations between different types of activity as well as between activity recorded in different regions. To study the roles of rhythmic oscillations in the local field potential, we examine temporal and spectral properties of oscillations. We look at the distributions of durations of oscillatory bursts as well as the distributions of the dominant frequencies within those oscillations. We also investigate the variability of these features and produce similar results in a model simulation. Lastly, we investigate criticality and the statistics of neural activity over a range of scales in the turtle visual cortex. We use neuronal avalanches to reveal scale-free cortical dynamics and power-law statistics, which have been hypothesized to optimize information processing