The current project investigated the brain-behavior relationships between fusiform volume and orthographic processing in children with Reading Disability (RD) and Attention-Deficit/Hyperactivity Disorder (ADHD). It was hypothesized that there would be differences in fusiform volume between those with and without RD. Individuals with and without ADHD were not expected to differ in fusiform volume and an interaction in the RD/ADHD group was not expected. Children with RD/ADHD were expected to have similar volumes to children who have RD. It also was hypothesized that size of the left fusiform segments would be correlated with three orthographic processing tasks and tests of reading achievement (i.e., Orthographic Choice, Homophone/Pseudohomophone Choice and the Colorado Perceptual Speed Task; Letter Word Identification, Word Attack, and Reading Fluency). Results indicated that there were no group differences in fusiform volume between children with and without RD as well as with and without ADHD. There were also no relationships between the left fusiform and any of the orthographic or reading achievement measures. However, all three measures of orthographic processing were significantly related to the right posterior fusiform. Additionally, Homophone/Pseudohomophone Choice and Reading Fluency demonstrated a trend with the right anterior fusiform. The findings reported in this study were largely unexpected and suggest that further research examining the relationship between right fusiform volume and orthographic processing is warranted.

Age-related hearing loss, presbycusis, is a complex disorder involving the interaction of both peripheral and central neurological deficits. Central auditory dysfunction may contribute to poor temporal discrimination of complex sounds such as speech. This research is timely since our population over 60 years old is increasing rapidly due to advances in medicine and nutrition as well as the advancing age of baby boomers. This study was designed to provide a better understanding of age-related changes in dorsal cochlear nucleus (DCN) physiology. DCN was chosen because it receives direct input from the auditory nerve and much is known about its neuronal morphology, physiology and circuitry. In young animals, DCN output neurons, fusiform cells, receive excitatory inputs from the acoustic nerve, which is modulated and shaped by inhibitory glycinergic inputs from nearby vertical cells. A number of studies in rodents suggested an age-related impairment of glycinergic neurotransmission. To access the functional impact of reduced putative glycinergic input in the central auditory system, this study compared the physiological responses of DCN neurons from young adult and aged rats in response set of simple and more complex acoustic stimuli. Single-unit extracellular recordings were made from two groups of DCN neurons: fusiform cells and cartwheel cells. Fusiform cells reflect the culmination of DCN processing, therefore were good candidates for studying the effect of aging on one ascending auditory stream. Two specific aims were directed at fusiform cell: SA1) Examine the effects of aging on fusiform cell response properties to simple tone burst stimuli; SA2) Examine the effect of aging on DCN output neuron response to complex temporal stimuli. A third aim, SA3) Examine the impact of aging on the response properties of cartwheel cells, a DCN inhibitory interneuron. Fusiform cells recorded from aged rats displayed significantly higher maximum discharge rates to characteristic frequency (CF) tones, fewer nonmonotonic CF rate-level functions and more wide-chopper type post-stimulus time histograms (PSTHs) when compared to neurons from young adult rats. These findings were consistent with an age-related loss of inhibitory glycinergic input. To elucidate how loss of inhibition could lead to functional deficits in temporal processing, fusiform cells were challenged to encode sinusoidally amplitude modulated (SAM) tones. DCN output neurons were presented with SAM tones at three modulation depths at 30 dB above hearing level/response threshold with the carrier frequency set to each unit’s CF. Temporal synchronicity to the SAM envelope was measured using vector strength from temporal modulation transfer functions (tMTFs). Firing rate to SAM tones was also assessed in rate modulation transfer functions (rMTFs). DCN output neurons from aged rats showed no loss of rate response (rMTF) but displayed a selective loss of temporal precision to SAM tones with significant age-related changes in peak vector strength (best modulation frequency), and the shape and category of tMTF. Wide-chopper PSTH types had significantly lower vector strength values than buildup and pauser PSTHs in both young and aged fusiform cells. Since a significantly greater proportion of aged neurons exhibited wide-chopper responses, this could explain, in part, the loss of temporal processing. The age-related response changes in the present study mimicked results from earlier studies were glycine inhibition onto young adult fusiform cells was pharmacologically blocked. Cartwheel cells receive excitatory inputs from granule cell parallel fibers as well as somatosensory dorsal column nucleus and project glycinergic inputs onto DCN output neurons. They appear to play a role in the integration of auditory and somatosensory inputs such as sensing head position. Aged cartwheel neurons exhibited signs of disinhibition showing increased spontaneous activity, increased maximum discharge rates and altered rate-level functions. The observed age-related changes in cartwheel cells are consistent with deafferentation studies using acoustic trauma. Collectively, the changes in DCN output neurons and cartwheel cells reflect a potentially maladaptive age-related neuroplasticity in response to a loss of excitatory acoustic nerve input. These in vivo extracellular findings were consistent with a global downregulation of glycinergic input within the DCN of aged rats. This reduced inhibition may contribute to functional deficits, particularly in activities that require precise timing of events such as response to speech-like stimuli.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19272号 / 医博第4036号 / 新制||医||1011(附属図書館) / 32274 / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 村井 俊哉, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The objective of this study was to expand on a method previously established in the lab for predicting subcortical structures using functional magnetic resonance imaging (fMRI) data restricted to the cortical surface. Our goal is to enhance the utility of low cost, portable imaging modalities, such as functional near infrared spectroscopy (fNIRS), which is limited in signal penetration depth. Previous work in the lab successfully employed functional connectivity to predict ten resting state networks and six anatomically de fined structures from the outer 10 mm layer of cortex using resting state fMRI data. The novelty of this study was two-fold: we chose to predict the functionally de fined region fusiform face area (FFA), and we utilized the functional connectivity of both resting state and task activation. Right FFA was identi ed for 27 subjects using a general linear model of a functional localizer tasks, and the average time series were extracted from right FFA and used as training and testing labels in support vector regression (SVR) models. Both resting state and task data decoded activity in right FFA above chance, both within and between run types. Our method is not specific to resting state, potentially broadening the scope of research questions depth-limited techniques can address. We observed a similarity in our accuracy cross-validation to previous work in the lab. We characterized this relationship between prediction accuracy and spatial signal-to-noise (SNR). We found that this relationship varied between resting state and task, as well as the functionality of features included in SVR modeling. / Master of Science / We used functional magnetic resonance imaging (fMRI) to predict activity in a deep brain region based on activity along the brain surface. This would increase the type of brain function a person could study using alternative methods that are less costly and easier to use, but can only detect signals along the surface. We were able to use this method to predict the fusiform face are, a region in the brain that responds more strongly to face images than other types of images. We also found a relationship between the quality of spatial information in the brain and the accuracy of predictions. This relationship differed depending on the types of brain regions were used to build the models, as well as whether the subjects were performing a task or rest scan.

Can the brain register the emotional valence of brief exposures of complex natural stimuli under conditions of forward and backward masking, and under conditions of attentional competition between foveal and peripheral stimuli? To address this question, three experiments were conducted. The first, a behavioural experiment, measured subjective valence of response (pleasant vs unpleasant) to test the perception of the valence of natural images in brief, masked exposures in a forward and backward masking paradigm. Images were chosen from the International Affective Picture System (IAPS) series. After correction for response bias, responses to the majority of target stimuli were concordant with the IAPS ratings at better than chance, even when the presence of the target was undetected. Using functional magnetic resonance imaging (fMRI), the effects of IAPS valence and stimulus category were objectively measured on nine regions of interest (ROIs) using the same strict temporal restrictions in a similar masking design. Evidence of affective processing close to or below conscious threshold was apparent in some of the ROIs. To further this line of enquiry, a second fMRI experiment mapping the same ROIs and using the same stimuli were presented in a foveal (‘attended’) peripheral (‘to-be-ignored’) paradigm (small image superimposed in the centre of a large image of the same category, but opposite valence) to investigate spatial parameters and limitations of attention. Results are interpreted as showing both valence and category specific effects of ‘to-be-ignored’ images in the periphery. These results are discussed in light of theories of the limitations of attentional capacity and the speed in which we process natural images, providing new evidence of the breadth of variety in the types of affective visual stimuli we are able to process close to the threshold of conscious perception.

Die Verarbeitung unbekannter und visuell vertrauter Gesichter wurde mittels simultaner Messung von Elektroenzephalogramm (EEG), Magnetoenzephalogramm (MEG) und Verhaltensreaktionen untersucht. Dipollokalisationen zeigten, dass MEG und EEG bei 170 ms und 400 bis 500 ms nach Beginn von Gesichterdarbietungen Aktivierung der posterioren Gyri fusiformes (GF) abbilden. Damit konnten beide Zeitbereiche als Aktivität des fusiformen Gesichterareals interpretiert werden. In einem Primingparadigma wurde bei viermaliger Wiederholung unbekannter Gesichter ein Reaktionszeitpriming gezeigt, das für Wiederholungen mit einem Zeitabstand (Lag) von Sekunden stärker als für mehrere Minuten war. Im EEG bewirkten nur Wiederholungen mit kurzem Lag einen Wiederholungseffekt von 300 ms bis 600 ms an posterioren und zentralen Elektroden. Dieser wurde als Korrelat impliziter Gedächtnisverarbeitung von Gesichtern im GF interpretiert. Ein frontaler Wiederholungseffekt ab 700 ms wurde als Ausdruck inzidentellen Erkennens der Gesichterwiederholungen angesehen. Das MEG zeigte posterior einen Wiederholungseffekt ab 800 ms für das kurze Lag. Für das lange Lag wurden keine MEG- oder EEG-Effekte gefunden. Die Wiederholung des Primingexperimentes mit den in einem Lerntraining vertraut gewordenen Gesichtern erzeugte eine generelle Verkürzung der Reaktionszeiten, aber eine Abschwächung des Primingeffektes für das kurze Lag und einen Verlust der Abhängigkeit der Primingstärke vom Zeitabstand. Diese Veränderungen gingen im EEG mit dem Trend zur Verstärkung des posterioren Wiederholungseffektes ab 500 ms einher. Im MEG konnte für die vertrauten Gesichter ein dem EEG in Zeit und Entstehungsort analoger Wiederholungseffekt gezeigt werden. Die Ergebnisse der Untersuchung von Priming bringen Evidenz für die Existenz von Primingeffekten für unbekannte Gesichter. Sie zeigen die Abhängigkeit der Primingeffekte vom Wiederholungsabstand und die Veränderung von Primingeffekten beim Erwerb visueller Vertrautheit. / The processing of unfamiliar and visually familiar faces was examined in a simultaneous measurement of Electroencephalogram (EEG), Magnetoencephalogram (MEG) and behavioural reactions during the presentation of a priming task. Dipole modelling on the EEG and MEG data localized activity in posterior fusiform gyri around 170 ms and between 400 and 500 ms post stimulus onset. Both time ranges were interpreted as activity correlates of the fusiform face area. In the priming paradigm unfamiliar faces were repeated four times. A reaction time priming effect could be shown. This effect was stronger for a short lag (seconds) between repetitions than for minutes. In EEG, only repetitions with short lag evoked a repetition effect at posterior and central electrodes between 300 and 600 ms. This effect was interpreted as a correlate of implicit memory processes presumably generated in the fusiform gyrus. A frontal repetition effect starting around 700 ms was considered a reflection of the incidental recognition of the face repetitions. The MEG data showed a repetition effect for the short lag starting at 800 ms. No electrophysiological effects of face repetition were found for the long lag. Some months later, the same subjects were visually familiarized with the faces in three learning sessions and the priming experiment was repeated. An overall shortening of reaction times was found together with a weakening of the priming effect for the short lag and an absence of the lag’s influence on the strength of the priming effects. In the EEG data a trend for a strengthening of the posterior repetition effect from 500 ms onward emerged. The MEG data yielded a repetition effect for the familiar faces that was analogous to the EEG effect. The results of the priming task give evidence for the existence of priming effects for unfamiliar and familiar faces. They furthermore demonstrate the dependency of priming effects on the lag between repetitions and the visual familiarity of the faces.

Synchronized oscillations of ensembles of neurons in the brain underlie human cognition and behaviors. Neuronal network oscillations can be described by the physics of coupled dynamical systems. This dissertation examines the dynamic network activities in two distinct neurocognitive networks, the salience network (SN) and the ventral temporal cortex-dorsolateral prefrontal cortex (VTC-DLPFC) network, during perceptual decision-making (PDM). The key nodes of the SN include the right anterior insula (rAI), left anterior insula (lAI), and dorsal anterior cingulate cortex (dACC) in the brain. When and how a sensory signal enters and organizes within the SN before reaching the central executive network including the prefrontal cortex has been a mystery. Second, prior studies also report that perception of visual objects (face and house) involves a network of the VTC—the fusiform face area (FFA) and para-hippocampal place area (PPA)—and the DLPFC. How sensory information enters and organizes within the VTC-DLPFC network is not well understood, in milliseconds time-scale of human’s perception and decision-making. We used clear and noisy face/house image categorization tasks and scalp electroencephalography (EEG) recordings to study the dynamics of these networks. We demonstrated that beta (13–30 Hz) oscillation bound the SN, became most active around 100 ms after the stimulus onset, the rAI acted as a main outflow hub within the SN, and the SN activities were negatively correlated with the difficult tasks. We also uncovered that the VTC-DLPFC network activities were mediated by beta (13-30 Hz) and gamma (30-100 Hz) oscillations. Beta activities were enhanced in the time frame 125-250 ms after stimulus onset, the VTC acted as main outflow hub, and network activities were negatively correlated with the difficult tasks. In contrast, gamma activities were elevated in the time frame 0-125 ms, the DLPFC acted as a main outflow hub, and network activities—specifically the FFA-PPA pair—were positively correlated with the difficult tasks. These findings significantly enhance our understanding of how sensory information enters and organizes within the SN and the VTC-DLPFC network, respectively in PDM.

No description available.

A inferência do curso temporal da atividade neural a partir do efeito BOLD é um importante problema, ainda em aberto. A forma da curva BOLD não reflete diretamente as características temporais da atividade eletrofisiológica dos neurônios. Nessa tese, é introduzido o conceito de tempo de processamento neural (TPN) como um dos parâmetros do modelo biofísico da função de resposta hemodinâmica (HRF). O objetivo da introdução desse conceito é obter estimativas mais acuradas da duração da atividade neural a partir do efeito BOLD, que possui auto grau de nãolinearidade. Duas formas de estimar os parâmetros do modelo do efeito BOLD foram desenvolvidas. A validade e aplicabilidade do conceito de TPN e das rotinas de estimação foram avaliadas por simulações computacionais e análise de séries temporais experimentais. Os resultados das simulações e da aplicação foram comparados com medidas da forma da HRF. O experimento analisado consistiu em um paradigma de tomada de decisão na presença de distratores emocionais. Esperase que o TPN em áreas sensoriais primárias seja equivalente ao tempo de apresentação de estímulos. Por outro lado, o TPN em áreas relacionadas com a tomada de decisão deve ser menor que a duração dos estímulos. Além disso, o TPN deve depender da condição experimental em áreas relacionadas ao controle de distratores emocionais. Como predito, o valores estimados do TPN no giro fusiforme foram equivalentes à duração dos estímulos e o TPN no giro do cíngulo dorsal variou com a presença de distrator emocional. Observou-se ainda lateralidade do TPN no córtex pré-frontal dorsolateral. As medidas da forma da HRF obtidas por um método convencional não dectectaram as variações observadas no TPN / The extraction of information about neural activity dynamics related to the BOLD signal is a challenging task. The temporal evolution of the BOLD signal does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. We describe two routines to estimate the parameters of the HRF model. The face validity and applicability of the concept of NPT and the estimation procedures are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. We analysed an experiment based on a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas is approximately the stimulus presentation duration. On the other hand, the NPT in brain areas related to decisionmaking processes should be less than the stimulus duration. Moreover, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the estimated NPTs in the dorsolateral prefrontal cortex indicate functional laterality of this region. The analysis using standard measures of HRF did not detect the variations observed in our method (NPT)

A inferência do curso temporal da atividade neural a partir do efeito BOLD é um importante problema, ainda em aberto. A forma da curva BOLD não reflete diretamente as características temporais da atividade eletrofisiológica dos neurônios. Nessa tese, é introduzido o conceito de tempo de processamento neural (TPN) como um dos parâmetros do modelo biofísico da função de resposta hemodinâmica (HRF). O objetivo da introdução desse conceito é obter estimativas mais acuradas da duração da atividade neural a partir do efeito BOLD, que possui auto grau de nãolinearidade. Duas formas de estimar os parâmetros do modelo do efeito BOLD foram desenvolvidas. A validade e aplicabilidade do conceito de TPN e das rotinas de estimação foram avaliadas por simulações computacionais e análise de séries temporais experimentais. Os resultados das simulações e da aplicação foram comparados com medidas da forma da HRF. O experimento analisado consistiu em um paradigma de tomada de decisão na presença de distratores emocionais. Esperase que o TPN em áreas sensoriais primárias seja equivalente ao tempo de apresentação de estímulos. Por outro lado, o TPN em áreas relacionadas com a tomada de decisão deve ser menor que a duração dos estímulos. Além disso, o TPN deve depender da condição experimental em áreas relacionadas ao controle de distratores emocionais. Como predito, o valores estimados do TPN no giro fusiforme foram equivalentes à duração dos estímulos e o TPN no giro do cíngulo dorsal variou com a presença de distrator emocional. Observou-se ainda lateralidade do TPN no córtex pré-frontal dorsolateral. As medidas da forma da HRF obtidas por um método convencional não dectectaram as variações observadas no TPN / The extraction of information about neural activity dynamics related to the BOLD signal is a challenging task. The temporal evolution of the BOLD signal does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. We describe two routines to estimate the parameters of the HRF model. The face validity and applicability of the concept of NPT and the estimation procedures are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. We analysed an experiment based on a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas is approximately the stimulus presentation duration. On the other hand, the NPT in brain areas related to decisionmaking processes should be less than the stimulus duration. Moreover, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the estimated NPTs in the dorsolateral prefrontal cortex indicate functional laterality of this region. The analysis using standard measures of HRF did not detect the variations observed in our method (NPT)