Cortical Orchestra Conducted by Purpose and Function

학위논문(박사)--서울대학교 대학원 :자연과학대학 협동과정 뇌과학전공,2020. 2. 정천기.촉각과 자기수용감각은 우리의 생존 및 일상생활에 절대적인 영향을 미치는 중요한 감각 기능이다. 말초신경계에서 이 두 가지 기능들에 필요한 정보를 수집하고 전달하는 기계적 수용기 및 그 구심성 신경들에 대한 신호 전달 메커니즘 및 그 특징들은 상대적으로 잘 알려져 있는 편이다. 그러나, 촉각과 자기수용감각을 형성하기 위한 인간 뇌의 피질에서의 정보 처리 메커니즘에 대하여 우리가 현재 알고 있는 바는 극히 일부분이다. 이 논문에서 제시하는 일련의 연구들은 인간 뇌 피질 단계에서 촉각과 자기수용감각의 지각적 처리과정에 대한 거시적 신경계 정보처리 메커니즘을 다룬다. 첫 번째 연구에서는 뇌피질뇌파를 이용하여 인간 일차 및 이차 체성감각 피질에서 인공적인 자극과 일상생활에서 접할 수 있는 자극을 포함하는 다양한 진동촉감각 및 질감 자극에 대한 거시적 신경계 정보처리 특성을 밝혔다. 이 연구에서는 일차 및 이차 체성감각 피질의 촉감각 주파수 특이적인 하이-감마 영역 신경활동이 자극 주파수에 따라 각각 상이한 시간적 다이나믹스를 가지고 변화하는 것을 확인하였다. 또한, 이러한 하이-감마 활동은 성긴 질감과 미세한 입자감을 가진 자연스러운 질감 자극에 대해서도 진동촉감각의 경우와 유사한 패턴을 보였다. 이러한 결과들은 인간의 진동촉감각이 매우 단순한 형태에 자극일지라도 대뇌 체성감각 시스템에 있어 거시적인 다중 영역에서의 계층적 정보처리를 동반한다는 점을 시사한다. 두 번째 연구에서는 인간의 움직임과 관련된 두정엽 영역에서의 하이-감마 뇌활성이 자기수용감각과 같은 말초신경계로부터의 체성감각 피드백을 주로 반영하는지, 아니면 움직임 준비 및 제어를 위한 피질 간 신경 프로세스에 대한 활동을 반영하는지를 조사하였다. 연구 결과, 자발적 운동 중 대뇌 운동감각령에서의 하이-감마 활동은 일차 체성감각피질이 일차 운동피질보다 더 지배적인 것으로 나타났다. 또한 이 연구에서는, 움직임과 관련된 일차 체성감각피질에서의 하이-감마 뇌활동은 말초신경계로부터의 자기수용감각과 촉각에 대한 신경계 정보처리를 주로 반영하는 것을 밝혔다. 이러한 연구들을 바탕으로, 마지막 연구에서는 인간 대뇌에서의 체성감각 지각 프로세스에 대한 거시적 피질 간 네트워크를 규명하고자 하였다. 이를 위해, 51명의 뇌전증 환자에게서 체성감각을 유발했던 뇌피질전기자극 데이터와 46명의 환자에게서 촉감각 자극 및 운동 수행 중에 측정한 뇌피질뇌파 하이-감마 매핑 데이터를 종합적으로 분석하였다. 그 결과, 체성감각 지각 프로세스는 대뇌에서 넓은 영역에 걸쳐 분포하는 체성감각 관련 네트워크의 신경 활성을 수반한다는 것을 알아냈다. 또한, 뇌피질전기자극을 통한 대뇌 지도와 하이-감마 매핑을 통한 대뇌 지도는 서로 상당한 유사성을 보였다. 흥미롭게도, 뇌피질전기자극과 하이-감마 활동을 종합한 뇌지도들로부터 체성감각 관련 뇌 영역의 공간적 분포가 체성감각 기능에 따라 서로 달랐고, 그에 해당하는 각 영역들은 서로 뚜렷하게 다른 시간적 다이나믹스를 가지고 순차적으로 활성화되었다. 이러한 결과들은 체성감각에 대한 거시적 신경계 프로세스가 그 지각적 기능에 따라 뚜렷이 다른 계층적 네트워크를 가진다는 점을 시사한다. 더 나아가, 본 연구에서의 결과들은 체성감각 시스템의 지각-행동 관련 신경활동 흐름에 관한 이론적인 가설에 대하여 설득력 있는 증거를 제시하고 있다.Tactile and proprioceptive perceptions are crucial for our daily life as well as survival. At the peripheral level, the transduction mechanisms and characteristics of mechanoreceptive afferents containing information required for these functions, have been well identified. However, our knowledge about the cortical processing mechanism for them in human is limited. The present series of studies addressed the macroscopic neural mechanism for perceptual processing of tactile and proprioceptive perception in human cortex. In the first study, I investigated the macroscopic neural characteristics for various vibrotactile and texture stimuli including artificial and naturalistic ones in human primary and secondary somatosensory cortices (S1 and S2, respectively) using electrocorticography (ECoG). I found robust tactile frequency-specific high-gamma (HG, 50–140 Hz) activities in both S1 and S2 with different temporal dynamics depending on the stimulus frequency. Furthermore, similar HG patterns of S1 and S2 were found in naturalistic stimulus conditions such as coarse/fine textures. These results suggest that human vibrotactile sensation involves macroscopic multi-regional hierarchical processing in the somatosensory system, even during the simplified stimulation. In the second study, I tested whether the movement-related HG activities in parietal region mainly represent somatosensory feedback such as proprioception from periphery or primarily indicate cortico-cortical neural processing for movement preparation and control. I found that sensorimotor HG activities are more dominant in S1 than in M1 during voluntary movement. Furthermore, the results showed that movement-related HG activities in S1 mainly represent proprioceptive and tactile feedback from periphery. Given the results of previous two studies, the final study aimed to identify the large-scale cortical networks for perceptual processing in human. To do this, I combined direct cortical stimulation (DCS) data for eliciting somatosensation and ECoG HG band (50 to 150 Hz) mapping data during tactile stimulation and movement tasks, from 51 (for DCS mapping) and 46 patients (for HG mapping) with intractable epilepsy. The results showed that somatosensory perceptual processing involves neural activation of widespread somatosensory-related network in the cortex. In addition, the spatial distributions of DCS and HG functional maps showed considerable similarity in spatial distribution between high-gamma and DCS functional maps. Interestingly, the DCS-HG combined maps showed distinct spatial distributions depending on the somatosensory functions, and each area was sequentially activated with distinct temporal dynamics. These results suggest that macroscopic neural processing for somatosensation has distinct hierarchical networks depending on the perceptual functions. In addition, the results of the present study provide evidence for the perception and action related neural streams of somatosensory system. Throughout this series of studies, I suggest that macroscopic somatosensory network and structures of our brain are intrinsically organized by perceptual function and its purpose, not by somatosensory modality or submodality itself. Just as there is a purpose for human behavior, so is our brain.PART I. INTRODUCTION 1 CHAPTER 1: Somatosensory System 1 1.1. Mechanoreceptors in the Periphery 2 1.2. Somatosensory Afferent Pathways 4 1.3. Cortico-cortical Connections among Somatosensory-related Areas 7 1.4. Somatosensory-related Cortical Regions 8 CHAPTER 2: Electrocorticography 14 2.1. Intracranial Electroencephalography 14 2.2. High-Gamma Band Activity 18 CHAPTER 3: Purpose of This Study 24 PART II. EXPERIMENTAL STUDY 26 CHAPTER 4: Apparatus Design 26 4.1. Piezoelectric Vibrotactile Stimulator 26 4.2. Magnetic Vibrotactile Stimulator 29 4.3. Disc-type Texture Stimulator 33 4.4. Drum-type Texture Stimulator 36 CHAPTER 5: Vibrotactile and Texture Study 41 5.1. Introduction 42 5.2. Materials and Methods 46 5.2.1. Patients 46 5.2.2. Apparatus 47 5.2.3. Experimental Design 49 5.2.4. Data Acquisition and Preprocessing 50 5.2.5. Analysis 51 5.3. Results 54 5.3.1. Frequency-specific S1/S2 HG Activities 54 5.3.2. S1 HG Attenuation during Flutter and Vibration 62 5.3.3. Single-trial Vibration Frequency Classification 64 5.3.4. S1/S2 HG Activities during Texture Stimuli 65 5.4. Discussion 69 5.4.1. Comparison with Previous Findings 69 5.4.2. Tactile Frequency-dependent Neural Adaptation 70 5.4.3. Serial vs. Parallel Processing between S1 and S2 72 5.4.4. Conclusion of Chapter 5 73 CHAPTER 6: Somatosensory Feedback during Movement 74 6.1. Introduction 75 6.2. Materials and Methods 79 6.2.1. Subjects 79 6.2.2. Tasks 80 6.2.3. Data Acquisition and Preprocessing 82 6.2.4. S1-M1 HG Power Difference 85 6.2.5. Classification 86 6.2.6. Timing of S1 HG Activity 86 6.2.7. Correlation between HG and EMG signals 87 6.3. Results 89 6.3.1. HG Activities Are More Dominant in S1 than in M1 89 6.3.2. HG Activities in S1 Mainly Represent Somatosensory Feedback 94 6.4. Discussion 100 6.4.1. S1 HG Activity Mainly Represents Somatosensory Feedback 100 6.4.2. Further Discussion and Future Direction in BMI 102 6.4.3. Conclusion of Chapter 6 103 CHAPTER 7: Cortical Maps of Somatosensory Function 104 7.1. Introduction 106 7.2. Materials and Methods 110 7.2.1. Participants 110 7.2.2. Direct Cortical Stimulation 114 7.2.3. Classification of Verbal Feedbacks 115 7.2.4. Localization of Electrodes 115 7.2.5. Apparatus 116 7.2.6. Tasks 117 7.2.7. Data Recording and Processing 119 7.2.8. Mapping on the Brain 120 7.2.9. ROI-based Analysis 122 7.3. Results 123 7.3.1. DCS Mapping 123 7.3.2. Three and Four-dimensional HG Mapping 131 7.3.3. Neural Characteristics among Somatosensory-related Areas 144 7.4. Discussion 146 7.4.1. DCS on the Non-Primary Areas 146 7.4.2. Two Streams of Somatosensory System 148 7.4.3. Functional Role of ventral PM 151 7.4.4. Limitation and Perspective 152 7.4.5. Conclusion of Chapter 7 155 PART III. CONCLUSION 156 CHAPTER 8: Conclusion and Perspective 156 8.1. Perspective and Future Work 157 References 160 Abstract in Korean 173Docto

Functional Imaging of Central Mechanisms Underlying Human Pain Perception

Investigations of human somatosensory perception have demonstrated robust interactions between the submodalities of pain and touch, and there is increasing recognition that the systematic assessment of somatosensory perception in disorders characterized by persistent pain such as Temporomandibular Disorder (TMD) would greatly aid diagnosis and evaluation of treatment efficacy. To better understand the pathophysiological mechanisms underlying TMD, we investigated cortical processing interactions that occur between innocuous and noxious cutaneous input using functional magnetic resonance imaging (fMRI). Innocuous vibrotactile stimulation and noxious skin heating were delivered separately and concurrently to the hand of women with TMD and to pain-free, gender-matched controls (HC). Cortical responses evoked by innocuous vibrotactile stimulation alone differentiated TMDs from HCs, and the differences between the groups suggest cortical plasticity in TMD which primes areas to respond to innocuous vibrotactile input that normally would not, including parts of the pain matrix and auditory cortex. In contrast, pain ratings and cortical responses to noxious heat alone did not differ significantly between TMDs and HCs. However, additional group differences emerged in the cortical patterns characterizing interactions between somatosensory submodalities in subjects with and without TMD during concurrent stimulation that could not be explained exclusively by group differences in the response to innocuous vibrotactile stimulation. Some of these differences in the interaction of innocuous and noxious somatosensory inputs were correlated with the severity of the TMD patients' clinical pain despite the fact that no significant correlations were observed between TMD pain and responses to vibrotactile or noxious heat stimulation alone. This suggests that cortical processing interactions between somatosensory submodalities more closely reflect individual experiences of persistent clinical pain than does the unimodal processing of innocuous vibrotactile or noxious heat input alone

The temporal pattern of impulses in primary afferents analogously encodes touch and hearing information

An open question in neuroscience is the contribution of temporal relations between individual impulses in primary afferents in conveying sensory information. We investigated this question in touch and hearing, while looking for any shared coding scheme. In both systems, we artificially induced temporally diverse afferent impulse trains and probed the evoked perceptions in human subjects using psychophysical techniques. First, we investigated whether the temporal structure of a fixed number of impulses conveys information about the magnitude of tactile intensity. We found that clustering the impulses into periodic bursts elicited graded increases of intensity as a function of burst impulse count, even though fewer afferents were recruited throughout the longer bursts. The interval between successive bursts of peripheral neural activity (the burst-gap) has been demonstrated in our lab to be the most prominent temporal feature for coding skin vibration frequency, as opposed to either spike rate or periodicity. Given the similarities between tactile and auditory systems, second, we explored the auditory system for an equivalent neural coding strategy. By using brief acoustic pulses, we showed that the burst-gap is a shared temporal code for pitch perception between the modalities. Following this evidence of parallels in temporal frequency processing, we next assessed the perceptual frequency equivalence between the two modalities using auditory and tactile pulse stimuli of simple and complex temporal features in cross-sensory frequency discrimination experiments. Identical temporal stimulation patterns in tactile and auditory afferents produced equivalent perceived frequencies, suggesting an analogous temporal frequency computation mechanism. The new insights into encoding tactile intensity through clustering of fixed charge electric pulses into bursts suggest a novel approach to convey varying contact forces to neural interface users, requiring no modulation of either stimulation current or base pulse frequency. Increasing control of the temporal patterning of pulses in cochlear implant users might improve pitch perception and speech comprehension. The perceptual correspondence between touch and hearing not only suggests the possibility of establishing cross-modal comparison standards for robust psychophysical investigations, but also supports the plausibility of cross-sensory substitution devices

Novel sensory testing methods for the quantitative assessment of cortical-cortical interactions

Traditional tactile sensory testing has relied heavily on delivery of single-site stimuli to the skin and querying test subjects on various qualities of those stimuli. While these methods are effective in making measures that characterize the peripheral nervous system, they lack in quantitatively assessing centrally mediated disorders of the nervous system. Additionally, the models from which the developments of such peripherally-based protocols originate are based more on historical precedence of prior techniques than on a characterization of the central nervous system. This thesis describes the development of not only novel methods for delivering multi-site tactile stimuli, but a novel approach for sensory testing based on models derived from measures of neural population response yielded from in-vivo and in-vitro animal experimentation. During the course of this study, two separate stimulators were designed and fabricated. The first, referred to as the "Two-Point Stimulator" (TPS), was a prototype developed to improve upon previously existing methods for delivering vibrotaction during psychophysical and physiological experimentation. To test the device, tracking protocols were used to assess the ability of human subjects to discriminate and localize between two near-adjacent skin sites under stimulus conditions of varying amplitude, frequency, location, and duration. Data collected were consistent with previously published reports, suggesting that one possible use of the device would be to provide a means for improved measures of spatio-tactile acuity. These studies were repeated on subjects with autism resulting in significant differences in performance from that of the normal population. Correlating data obtained from these psychophysical experiments with cortical measures, acquired primarily with optical imaging and neural recording techniques in animal experimentation, has allowed us to develop a better understanding of the cortical dynamics involved in somatosensory processing. A second stimulator fabricated during this period, the CM-1 (Cortical Metrics - Model #1), improves considerably upon the TPS, most notably in portability, cost, and functional capability. Current ongoing experimentation using this novel device allows an improved means for measuring tactile sensibility and assessing differences in cortical information-processing strategies between normal healthy control populations and populations with various neurological disorders, in both research and clinical settings

Temporomandibular Disorder Modifies Cortical Response to Tactile Stimulation

Individuals with temporomandibular disorder (TMD) suffer from persistent facial pain and exhibit abnormal sensitivity to tactile stimulation. To better understand the pathophysiological mechanisms underlying TMD, we investigated cortical correlates of this abnormal sensitivity to touch. Using functional magnetic resonance imaging (fMRI), we recorded cortical responses evoked by low frequency vibration of the index finger in subjects with TMD and in healthy controls (HC). Distinct subregions of contralateral SI, SII, and insular cortex responded maximally for each group. Although the stimulus was inaudible, primary auditory cortex was activated in TMDs. TMDs also showed greater activation bilaterally in anterior cingulate cortex and contralaterally in the amygdala. Differences between TMDs and HCs in responses evoked by innocuous vibrotactile stimulation within SI, SII, and the insula paralleled previously reported differences in responses evoked by noxious and innocuous stimulation, respectively, in healthy individuals. This unexpected result may reflect a disruption of the normal balance between central resources dedicated to processing innocuous and noxious input, manifesting itself as increased readiness of the pain matrix for activation by even innocuous input. Activation of the amygdala in our TMD group could reflect the establishment of aversive associations with tactile stimulation due to the persistence of pain

The in vivo functional neuroanatomy and neurochemistry of vibrotactile processing

Touch is a sense with which humans are able to actively explore the world around them. Primary somatosensory cortex (S1) processing has been studied to differing degrees at both the macroscopic and microscopic levels in both humans and animals. Both levels of enquiry have their advantages, but attempts to combine the two approaches are still in their infancy. One mechanism that is possibly involved in determining the reponse properties of neurons that are involved in sensory discrimination is inhibition by γ-aminobutyric acid (GABA). Several studies have shown that inhibition is an important mechanism to “tune” the response of neurons. Recently it has become possible to measure the concentration of GABA in vivo using edited Magnetic Resonance Spectroscopy (MRS), whereas magnetoencephalography (MEG) offers the possibility to look at changes in neuromagnetic activation with millisecond accuracy. With these methods we aimed to establish whether in vivo non-invasive neuroimaging can elucidate the underlying neuronal mechanisms of human tactile behaviour and to determine how such findings can be integrated with what is currently known from invasive methods. Edited GABA-MRS has shown that individual GABA concentration in S1 correlates strongly with tactile frequency discrimination. MEG was used to investigate the neuromagnetic correlates of a frequency discrimination paradigm in which we induced adaptation to a 25 Hz frequency. We showed that S1 is driven by the adapting stimulus and shows that neural rhythms are modulated as a result of adaptation. This is the first time that behavioural psychophysics of tactile adaptation has been investigated using complimentary neuroimaging methods. We combined different methods to complement both physiological and behavioural studies of tactile processing in S1 to investigate the factors involved in the neural dynamics of tactile processing and we show that non-invasive studies on humans can be used to understand physiological underpinnings of somatosensory processing.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Encoding tactile frequency and intensity information in the temporal pattern of afferent nerve impulses

Using our hands to interact with the world around us produces complex vibrations travelling across the skin. These complex waves are transduced by tactile afferent neurons whose impulse patterns convey information about the external world. A major question in this field is how important the timing of these afferent impulses is in shaping perception. We have the means to investigate this question by artificially inducing impulse patterns using brief mechanical and electrical stimuli, allowing us to study the neural coding of vibrotactile sensory information. Our lab has used this to show that when mechanical pulses evoked impulse trains grouped into periodic bursts, perceived frequency corresponded to the duration of the silent inter-burst gap interval, rather than the periodicity or the mean impulse rate. In this thesis, we induced controlled impulse trains, while measuring the perceptual responses of human subjects using psychophysical methods to assess the dimensions of frequency and intensity. As electrical stimulation has broad utility in prosthetic applications, we first verified that the same perceived frequency as predicted by the burst gap was elicited with electrical pulses in subjects within the low frequency flutter range. We then tested whether this same coding mechanism also applied outside the flutter frequency range by conducting further experiments with higher pulse rates. We found that burst gap coding correctly predicted perceived frequencies above flutter, suggesting a generalised temporal processing strategy that operates on tactile afferent inputs spanning a broad range of frequencies. Next, we investigated perceived intensity where stimulus pulse rate was varied without changes in afferent population recruitment or in perceived frequency by using bursts of pulsatile stimuli. Increasing the number of pulses within a burst caused a significant increase in perceived intensity when electrical stimulation was used. Mechanical pulses with the same burst groupings did not produce a comparable intensity increase, possibly due to minimal variations in the population firing rate. These new insights into the encoding of tactile information through temporal patterning in peripheral impulse patterns may allow the multiplexing of frequency and intensity sensations with a fixed stimulation amplitude for use in neural interfaces to deliver sensory feedback information

Regionally specific human GABA concentration correlates with tactile discrimination thresholds

The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al., 2009). In the present study, we used magnetic resonance spectroscopy of GABA and psychophysical testing of vibrotactile frequency thresholds to investigate whether individual differences in tactile frequency discrimination performance are correlated with GABA concentration in sensorimotor cortex. Behaviorally, individuals showed a wide range of discrimination thresholds ranging from 3 to 7.6 Hz around the 25 Hz standard. These frequency discrimination thresholds were significantly correlated with GABA concentration (r = −0.58; p < 0.05) in individuals' sensorimotor cortex, but not with GABA concentration in an occipital control region (r = −0.04). These results demonstrate a link between GABA concentration and frequency discrimination in vivo, and support the hypothesis that GABAergic mechanisms have an important role to play in sensory discrimination

Towards Establishing Age-Related Cortical Plasticity on the Basis of Somatosensation.

Age-related somatosensory processing appears to remain intact where tasks engage centrally- as opposed to peripherally-mediated mechanisms. This distinction suggests that insight into alterations in neural plasticity could be derived via metrics of vibrotactile performance. Such an approach could be used to support the early detection of global changes in brain health but current evidence is limited. Knowledge of the precise conditions in which older adults are expected to sustain somatosensory performance is largely unknown. For this purpose, the study aimed to characterize age-related performance on tactile detection and discrimination-based tests. Accordingly, a group of young and older adult participants took part in simple reaction time and amplitude discrimination tasks. Participants' ability to distinguish between stimuli on the basis of amplitude was assessed with and without dual-site adaptation, which has been proposed to refine cortical responses and improve behavioral performance. The results show that while older adults exhibited significantly prolonged (p < .001, d = 1.116) and more variable (p = .022, d = 0.578) information processing speed compared to young adults, they were able to achieve similar scores in baseline discrimination (p = .179, d = 0.336). We also report, for the first time, that older adults displayed similar performance improvements to young adults, under conditions of dual-site adaptation (p = .948, d = 0.016). The findings support the argument that centrally-mediated mechanisms remain intact in the ageing population. Accordingly, dual-site adaptation data provide compelling new evidence of somatosensation in ageing that will contribute towards the development of an assessment tool to ascertain pre-clinical, age-related changes in the status of cortical function