As disfonias neurológicas são distúrbios vocais que acompanham lesões ou alterações no sistema nervoso. O Acidente Vascular Encefálico (AVE) é a segunda causa de morte no mundo e os danos cerebrais causados podem afetar a comunicação do indivíduo em diversos aspectos. As alterações de voz características dessas lesões são pouco descritas quanto à localização e extensão do acometimento cerebral. Desta forma, torna-se importante compreender a interferência das alterações no Sistema Nervoso Central (SNC) na produção da voz, visando maior substrato para reabilitação. Os objetivos do trabalho foram caracterizar a população de pacientes acometidos por AVE conforme a topografia da lesão observada ao exame de Tomografia Computadorizada (TC) e relacionar tais achados com as características fonatórias encontradas. Participaram do estudo 10 idosos acometidos por AVE. Foram realizadas avaliação perceptivo-auditiva da voz por meio d o protocolo CAPE-V, análise do Tempo Máximo de Fonação e avaliação da diadococinesia (DDC) laríngea, por meio do programa Motor Speech Profile Advanced, da KayPentax. Os exames de neuroimagem foram classificados quanto a localização, extensão, lateralidade e território de vascularização da lesão cerebral. Foi observado um grupo homogêneo de cinco sujeitos que apresentaram AVEs extensos de acometimento da artéria cerebral média e outros cinco sujeitos que apresentaram AVEs de menor extensão e com localização variada no cérebro. Os resultados da avaliação de voz foram relacionados com os achados dos exames de imagem e foi observado que não houve relação entre a localização e extensão da lesão cerebral com as alterações vocais dos indivíduos. As vozes dos sujeitos mostraram predominantemente presença de rugosidade, instabilidade e pastosidade, além de velocidade reduzida e instabilidade na repetição de vogais, indicativas de alteração no controle motor laríngeo, bem como redução dos tempos máximos de fonação, indicativos de alteração no controle do fluxo aéreo. / Neurological dysphonias are vocal disorders accompanying injuries or changes in the nervous system. The Cerebrovascular accident is the second leading cause of death worldwide and the brain damage caused by it can affect an individual\'s communication in several aspects. The voice changes characteristical of these lesions are poorly described as location and extent of cerebral involvement. Thus, it becomes important to understand the influence of changes in central nervous system on voice production, aiming to increase the substrate for rehabilitation. The objectives were to characterize the population of patients who had stroke according to the topography of the lesion to the cerebral computed tomography and correlate these findings with the phonatory characteristics found. The study included 10 elderly patients whit stroke. The perceptual voice analysis through the CAPE-V protocol, the Maximum Phonation Time and larynx diadochosinesis (DDK), through the program Advanced Motor Speech Profile of Kay Pentax, were evaluated. Neuroimaging studies were classified according to location, extent and laterality of the vascular territory of brain injury. Were observed imaging studies from a homogeneous group of five patients who had strokes extensive involvement of the middle cerebral artery and another five patients who had less extensive strokes and varied location in the brain. The results of the voice analysis were related to the fidings of imaging studies. It was found no relationship between the location and extent of brain injury with individuals vocal changes. The voices of the subjects showed presence of roughness, instability and pastiness, changes in larynx motor control and air flow control.

The neurocognitive model of antidepressant treatment action states that antidepressants work by producing relatively immediate positive shifts in emotional processing, which translate into clinical improvement with time. Short-term or even acute doses of antidepressants can, for example, increase memory for positive self-referent words or decrease amygdala activation to fearful faces, and these early changes correlate with later clinical improvement. However, there are a number of ways in which the model needs further probing. The aim of this thesis was to test the neurocognitive model by: 1) investigating whether changes in emotional processing occur in an antidepressant with a novel mechanism of action, St John's wort, as the model predicts; and 2) examining whether there is a comparable pattern of neuropsychological changes to citalopram in a population of high neurotic volunteers, whose baseline emotional biases may make them a more ideal group in which to study drug effects. We found that seven days of St John's wort produced similar changes to other antidepressants, for example reducing recognition of disgusted faces and attention to fearful faces while increasing memory for positive words. The drug did not affect other aspects of cognition including working memory and reward learning. These findings support the theory that early psychological changes are a common feature of all antidepressants. On the other hand, four weeks of citalopram treatment produced apparently contradictory effects in high neurotics, increasing memory for positive words but also increasing recognition of negative facial expressions. Neuroimaging data showed that high neurotics had greater response to neutral faces in emotional processing areas compared to low neurotics, which was reduced with citalopram. High neurotics also showed increased resting state connectivity in default mode network areas and between amygdala and cortical areas, which was again reduced with citalopram. We suggest that in this group citalopram corrects general negative emotional processing biases, but also works to decrease a natural aversion to particularly threatening socially-relevant stimuli. Overall this thesis supports the idea that early changes in emotional processing are vital for antidepressant action, but also suggests that in certain groups such as high neurotics, some changes may be more nuanced than previously reported and warrant further scrutiny.

在亞洲人群包括中國人群中，顱內動脈粥樣硬化（ICAS）發病率很高，是缺血性卒中和短暫性腦缺血發作（TIA）的首要病因。然而，目前ICAS 並未被深入研究。因此我們在一系列研究中通過運用傳統及創新的神經影像學方法，來研究ICAS 的臨床及血流動力學特徵，以期促進其全面評價及危險分層。 / 既往研究發現亞洲人群和西方人群在頭頸部動脈粥樣硬化的發生和發展上存在種族差異。爲了進一步驗證這些種族差異，我們開展了一項社區研究，以探索無癥狀性顱內外動脈粥樣硬化在中國社區成年居民中的發病情況，以及二者之間的相互關係。在該研究中，我們分別採用經顱多普勒（TCD）和頸部血管超聲（CD）來評價顱內和顱外動脈的粥樣硬化。在研究納入的537 例研究對象中，我們發現顱內動脈粥樣硬化的發展優先於頸動脈粥樣硬化，而且不同階段的頸動脈粥樣硬化與顱內動脈粥樣硬化並無獨立相關關係。該結果提示，在中國人群的全身系統性粥樣硬化的過程中，顱內動脈粥樣硬化可能是一個比較早期而且相對獨立的過程，這與西方人群的情況不同。本研究結果進一步支持東西方人群在顱內外動脈粥樣硬化進程上存在的種族差異。 / 根據既往研究結果，病因為癥狀性ICAS的缺血性卒中或TIA患者卒中復發的風險很高。目前，癥狀性ICAS患者的危險分層大多基於其動脈管腔的狹窄程度。然而，管腔的解剖學狹窄程度並不一定與其血流動力學的嚴重程度成比例，而後者也可能影響相關患者的卒中復發風險。因此，我們進行了以下的一系列研究， 以評價癥狀性ICAS的血流動力學特徵，同時初步探索其在相關患者危險分層中的應用價值。 / 我們首先進行了三項研究，採用一種基於磁共振血管成像（MRA）的創新方法來評價癥狀性ICAS的血流動力學嚴重程度。基於時間飛躍法（TOF）MRA的信號對比機制，我們提出了一項名為信號強度比值（SIR）的參數來定量地評價癥狀性ICAS 的血流動力學效應；該參數代表TOF MRA 影像上經過背景信號強度校正后的ICAS 病變后和病變前的信號強度比值。在一項初步研究中，我們確定了該參數的評價和計算方法。在26例癥狀性ICAS病變中，我們發現該參數的計算操作簡便，在臨床上可行，且在同一評價者的兩次評價中具有很高的可重複性。在隨後的一項研究中，我們在102例癥狀性ICAS病變中發現該參數在兩位評價者之間具有顯著的可重複性。在第三項研究中，我們在36例具有癥狀性ICAS的缺血性卒中患者中發現SIR與患者的急性梗死灶體積顯著相關，但我們並未發現該參數與患者1年的卒中復發風險相關，可能由於該研究的樣本量過小。以上三項研究證實，SIR作為一種基於TOF MRA的評價癥狀性ICAS血流動力學嚴重程度的方法，具有可重複性及臨床可行性；而其對於相關患者危險分層的價值需要在前瞻性的較大型研究中進一步驗證。 / 在如下的另外兩項研究中，我們採用計算機流體動力學（CFD）技術對癥狀性ICAS患者的計算機斷層掃描血管成像（CTA）影像進行重建，從而評價其ICAS 病變的血流動力學特徵。首先，在一項初步研究中，我們探索了採用臨床常規CTA影像進行CFD模型重建的可行性。在10例癥狀性ICAS病變中，9例病變的CTA原始圖像成功重建為CFD模型。重建的CFD模型可以定量地反映ICAS病變的各種血流動力學特徵。該初步研究證實了基於臨床常規CTA進行CFD建模從而評價ICAS血流動力學特徵的可行性。在隨後的一項研究中，我們探索了CFD 模型反映的癥狀性ICAS 的血流動力學特徵對於相關患者卒中復發的預測價值。在32例具有70-99%管腔狹窄的癥狀性ICAS病例中，我們發現病變前後血流動力學參數的變化（包括壓力，剪切應變率及血流速度）可能預測患者的卒中復發風險。以上兩項研究證實，基於臨床常規CTA進行CFD模型重建從而定量評價癥狀性ICAS的血流動力學特徵具可行性，同時，這些血流動力學特徵可能對相關患者的卒中復發風險具有預測價值。 / 綜上所述，通過以上研究，我們進一步證實了亞洲人群和西方人群在顱內外動脈粥樣硬化的進程上存在的種族差異。更重要的是，我們的研究證實評價癥狀性ICAS病變的血流動力學特徵具有臨床意義。對於相關患者，採用以上研究中的兩種方法評價癥狀性ICAS的血流動力學特徵，可能對患者的危險分層具有潛在的指導意義。在未來的前瞻性大樣本研究中，上述方法對癥狀性ICAS患者卒中復發風險的預測價值需要進一步證實，以期促進相關的臨床決策，從而在長遠目標上降低相關患者的卒中復發風險。 / Intracranial atherosclerosis (ICAS) is of high prevalence in Asia, which is the leading cause for ischemic stroke and transient ischemic attack (TIA) in Asians, including the Chinese. However, it has not been fully appreciated or adequately investigated in relevant studies. In this thesis, we tried to delineate the hemodynamics and clinical implications of ICAS, by using several traditional and novel neuroimaging methods. / Previous studies had suggested differences in atherogenesis of intra- and extracranial arteries between Asians and Caucasians. To find further evidence, we performed a study to investigate asymptomatic ICAS and carotid atherosclerosis and their correlations in community-dwelling Chinese adults, by using transcranial Doppler and carotid duplex ultrasonography, respectively. For the 537 subjects studied, we found more advanced asymptomatic ICAS than carotid atherosclerosis, and there were no independent correlations between different stages of carotid atherosclerosis and presence of ICAS. The results suggested that atherogenesis of intracranial arteries might be a relatively independent course in systemic atherosclerosis in the Chinese population, which is unlike the case in Caucasians. By combing with previous findings, results of this study further supported the existence of racial differences in cervicocerebral atherogenesis between Asians and Caucasians. / According to previous studies, stroke patients with symptomatic ICAS are at high risk of recurrence. Currently, risk stratification of symptomatic ICAS are usually based on the percentage of luminal stenosis. However, the anatomic severity does not always proportionate to its hemodynamic significance, which may also impact on the risk of stroke recurrence in symptomatic ICAS. Therefore, we performed a series of studies as follows to evaluate the hemodynamics of symptomatic ICAS, and to assess its value in risk stratification of those with such lesions. / We first performed three studies based on time-of-flight (TOF) magnetic resonance angiography (MRA), to gauge the hemodynamic significance of symptomatic ICAS. Based on the signal contrast mechanism of TOF MRA, we developed a novel index, signal intensity ratio (SIR), representing changes of signal intensities (SI) across an ICAS on maximum intensity projections of TOF MRA, to quantify its hemodynamic significance: SIR = (mean post-stenotic SI - mean background SI) / (mean pre-stenotic SI - mean background SI). In a pilot study to establish the methodology of this index, we found it easy to perform, and highly reproducible between repetitive measurements by a same observer in 26 symptomatic ICASs. In a subsequent study, we also found this index to be substantially reproducible between measurements from two observers in 102 symptomatic ICAS lesions. In a third study, we tried to investigate the relationships between SIR of ICAS, other imaging features, and 1 year outcomes of patients with symptomatic ICAS. In the 36 patients enrolled, SIR was found to be significantly, linearly and negatively correlated to acute infarct volume on diffusion-weighted MR images. However, we did not establish a definite correlation between SIR and recurrent ischemic stroke, probably due to the small sample size. These studies suggested that SIR as evaluated on MRA was a feasible and reproducible method to gauge the hemodynamic and functional significance of ICAS. The role of this index in predicting further recurrent risks in those with symptomatic ICAS needs to be verified in future studies. / In another two studies, we applied the computational fluid dynamics (CFD) modeling technique in processing computed tomography angiography (CTA) images, to evaluate the hemodynamic characteristics of ICAS. In a pilot study, we tested the feasibility of CFD modeling of ICAS based on CTA images. Among 10 cases of symptomatic ICAS identified on CTA, the CTA source images of 9 were successfully processed to CFD models, which were able to quantitatively delineate the hemodynamic environment across the lesions. This pilot study demonstrated the feasibility of constructing CFD models of ICAS out of routinely obtained CTA source images. Then in a second study, we preliminarily explored the values of hemodynamics of ICAS revealed by such CFD models, in predicting recurrent risks in patients with symptomatic ICAS of 70-99% luminal stenosis. In the 32 cases evaluated, we found that changes of hemodynamic features across an ICAS lesion, including the changes of pressure, shear strain rate, and blood flow velocity, may be able to predict the recurrent risk in this patient subset. Therefore, it was feasible to model hemodynamics of symptomatic ICAS based on CTA images, and future prospective studies with larger sample sizes are warranted to further validate the role of CFD modeling in risk stratification of affected patients. / In conclusion, in this thesis we found further evidence to support the existence of racial differences in atherogenesis of cervicocerebral arteries between Caucasians and Asians. More importantly, we demonstrated that hemodynamics of symptomatic ICAS could be of clinical significance in characterization of such lesions. In patients with symptomatic ICAS, the two methods to evaluate hemodynamic features of ICAS as used in this thesis, may yield potential values in predicting the recurrent risk of these patients. In the near future, prospective studies enrolling more patients are warranted to further validate findings in this thesis, to embrace more reasonable and comprehensive evaluation of symptomatic ICAS, so as to facilitate decision making in clinical scenarios and patient selection in clinical studies, which in the long run may help reduce the risk of stroke recurrence in affected patients. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Leng, Xinyi. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 131-146). / Abstracts also in Chinese.

Personality neuroscience is a rapidly expanding field of study fueled by a growing interest in understanding the structural brain correlates of individual differences in personality. Data on the structural brain correlates of personality are especially lacking from large-scale studies, and are nearly nonexistent in the adolescent age group. Furthermore, the role of sex differences in structural brain changes associated with personality are rarely considered. To address this gap in knowledge, this thesis investigates the structural brain correlates of personality and sex differences in structure at age fourteen. A large sample of adolescents (N = 2000) were drawn from the IMAGEN project. Data on adolescents’ puberty status, IQ, and personality were collected through adolescent-reported questionnaires and interviews. The structural brain correlates of personality were examined utilizing personality variables from the NEO Five Factor Inventory (NEO-FFI) and Voxel-Based Morphometry (VBM). Our results showed few correlations between any dimension of the NEO-FFI and regional grey matter volume (GMV). In the total sample, a negative correlation was found for agreeableness and bilateral supplementary motor area (SMA), which was also present in the male subsample. The female sample showed a significant negative correlation between extraversion and the right SMA, and a positive correlation in the left cerebellum. A non-linear effect of extraversion positively correlated with the right precuneus in females. The present study suggests personality traits are not strongly reflected in GMV during adolescence. This thesis includes a discussion on future directions and suggestions for assessing the brain correlates of personality.

This research is primarily focused on laser-based non-invasive photoacoustic tomography of small animal brains. Photoacoustic tomography, a novel imaging modality, was applied to visualize the distribution of optical absorptions in small-animal brains through the skin and skull. This technique combines the high-contrast advantage of optical imaging with the high-resolution advantage of ultrasonic imaging. Based on the intrinsic optical contrast, this imaging system successfully visualized three-dimensional tissue structures in intact brains, including lesions and tumors in brain cerebral cortex. Physiological changes and functional activities in brains, including cerebral blood volume and blood oxygenation in addition to anatomical information, were also satisfactorily monitored. This technique successfully imaged the dynamic distributions of exogenous contrast agents in small-animal brains. Photoacoustic angiography in small-animal brains yielding high contrast and high spatial resolution was implemented noninvasively using intravenously injected absorbing dyes. In the appendix, the theory of Monte Carlo simulation of polarized light propagation in scattering media was briefly summarized.

Gilles de la Tourette syndrome (GTS) is a chronic neuropsychiatric disorder characterized by multiple motor and vocal tics, affecting approximately 1% of the population. The precise neuropathology of GTS has not yet been delineated, but current models implicate subcortical and cortical areas - the cortico-striato-thalamo-cortical (CSTC) circuit. The majority of studies in the literature have either dealt with GTS with comorbid conditions and/or children with GTS. As these factors are known to affect brain structure and function, it unknown what the neurobiological underpinnings of pure adult GTS are. The objective of this body of work was to use functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize differences in brain function and structure in pure adult GTS patients versus age- and sex-matched controls. I employed a series of three distinct analyses for this purpose, based upon current models of CSTC circuit-related dysfunction in GTS. In the first, GTS patients and control participants executed three finger-tapping paradigms that varied in both complexity and memory requirements. These finger-tapping tasks were modeled after previous studies that showed CSTC circuit-related activity in healthy individuals. Using a multivariate statistical technique to assess task-related patterns of activation across the whole brain, I found that, while there was much overlap in brain activation patterns between groups, sensorimotor cortical regions were differentially recruited by GTS patients compared to controls. In the second fMRI analysis, I measured low-frequency spontaneous fluctuations of the blood oxygen level dependent signal during rest, and found that GTS patients exhibited greater resting state functional connectivity with the left putamen compared to controls. In the final analysis, DTI was used to provide a whole-brain assessment of regional diffusion anisotropy in GTS patients and healthy volunteers and to investigate the fractional anisotropy in predetermined ROIs. This analysis found no differences between GTS patients and controls. Overall, my findings indicated that several CSTC-related regions shown to be atypical in GTS patients previously, are also atypical in pure adult GTS, and that sensorimotor cortical regions and the putamen may be regions of functional disturbance in pure adult GTS.

Emotion processing involves specialised brain regions allowing for effective evaluation of the social environment and for the acquisition of social skills that emerge over childhood. In humans, an important aspect of normal development is the ability to understand the facial expressions of others that signal the nature and safety of the environment. Existing functional data, however, have not characterised the developmental trajectories associated with the differing neural and cognitive-behavioural development. The current thesis investigates the functional specialisation and development of the spatial and temporal patterns in neural activities during implicit processing of facial emotions from early childhood through adulthood. The first study identified brain regions engaged in implicit processing of emotional expressions using a simple emotion-processing paradigm (target detection task) with fourteen healthy adults using magnetoencephalography (MEG) recordings. Participants responded to a non-face target (a scrambled pattern) while ignoring the emotional face presented in a different hemifield. Results showed ACC and right-lateralised amygdala activations in early latencies in response to the unattended emotional faces related to rapid and implicit attention to the task-irrelevant facial emotions, specifically during the processing of the fearful emotion. Based on the findings in the first study, the second study investigated the developmental patterns and age-related differences in brain activities associated with the rapid and automatic processing of the emotional expressions in MEG with twelve children 7 – 10 years old, twelve adolescents 12 – 15 years old and twelve young adults (mean age 24.4 years) using the same paradigm. The results showed that emotion processing developed early in childhood in the amygdalae, whereas the processing of fear had later maturation engaging the ACC. The results further demonstrated an age-correlated increase in development in ACC activity and an age-related laterality shift in the amygdalae related to fear processing. The present thesis provides new evidence contributing to the understanding of the protracted but differing normal development in the emotional brain over the childhood into adulthood, and offers critical insights into understanding possible dysfunctions of these brain regions during development.

The term working memory (WM) refers to a set of cognitive processes that allows for the temporary storage and manipulation of information. Neural correlates of the N- back task, a well-established WM measure used in neuroimaging, have been studied extensively in adults but less so in developmental populations. This thesis determines the effect of age on brain activations that mediate cognitive processes for remembering non- verbal/visual stimuli. Block-design fMRI was used to record activity in 84 subjects (6-35 years) during a visual-patterns 0- and 1-back task. Regions activated during the 1-back condition were largely common to all age groups, with adults displaying the largest extent of activations. Children and adolescents showed similar 0-back activations (distinct from 1-back) while adults engaged an analogous 1-back activation pattern during 0-back, suggesting that brain mechanisms underlying memory and attentional processes required for this task in children and adolescents are not yet mature and that strategy usage is still developing.

The term working memory (WM) refers to a set of cognitive processes that allows for the temporary storage and manipulation of information. Neural correlates of the N- back task, a well-established WM measure used in neuroimaging, have been studied extensively in adults but less so in developmental populations. This thesis determines the effect of age on brain activations that mediate cognitive processes for remembering non- verbal/visual stimuli. Block-design fMRI was used to record activity in 84 subjects (6-35 years) during a visual-patterns 0- and 1-back task. Regions activated during the 1-back condition were largely common to all age groups, with adults displaying the largest extent of activations. Children and adolescents showed similar 0-back activations (distinct from 1-back) while adults engaged an analogous 1-back activation pattern during 0-back, suggesting that brain mechanisms underlying memory and attentional processes required for this task in children and adolescents are not yet mature and that strategy usage is still developing.

Emotion processing involves specialised brain regions allowing for effective evaluation of the social environment and for the acquisition of social skills that emerge over childhood. In humans, an important aspect of normal development is the ability to understand the facial expressions of others that signal the nature and safety of the environment. Existing functional data, however, have not characterised the developmental trajectories associated with the differing neural and cognitive-behavioural development. The current thesis investigates the functional specialisation and development of the spatial and temporal patterns in neural activities during implicit processing of facial emotions from early childhood through adulthood. The first study identified brain regions engaged in implicit processing of emotional expressions using a simple emotion-processing paradigm (target detection task) with fourteen healthy adults using magnetoencephalography (MEG) recordings. Participants responded to a non-face target (a scrambled pattern) while ignoring the emotional face presented in a different hemifield. Results showed ACC and right-lateralised amygdala activations in early latencies in response to the unattended emotional faces related to rapid and implicit attention to the task-irrelevant facial emotions, specifically during the processing of the fearful emotion. Based on the findings in the first study, the second study investigated the developmental patterns and age-related differences in brain activities associated with the rapid and automatic processing of the emotional expressions in MEG with twelve children 7 – 10 years old, twelve adolescents 12 – 15 years old and twelve young adults (mean age 24.4 years) using the same paradigm. The results showed that emotion processing developed early in childhood in the amygdalae, whereas the processing of fear had later maturation engaging the ACC. The results further demonstrated an age-correlated increase in development in ACC activity and an age-related laterality shift in the amygdalae related to fear processing. The present thesis provides new evidence contributing to the understanding of the protracted but differing normal development in the emotional brain over the childhood into adulthood, and offers critical insights into understanding possible dysfunctions of these brain regions during development.