<p>Social phobia is a disabling anxiety disorder characterized by an excessive fear of negative evaluation in social situations. The present thesis explored the epidemiology and neurobiology of the disorder. By means of a mailed questionnaire, the point prevalence of social phobia in the Swedish general population was estimated at 15.6%. However, prevalence rates varied between 1.9 and 20.4% across the different levels of distress and impairment used to define cases. Thus, although social anxiety is widespread within the community, the precise diagnostic boundaries for social phobia are difficult to determine. Social phobia was associated with female gender, low educational attainment, psychoactive medication use, and lack of social support. A cluster analysis revealed that subtypes of social phobia mainly differed dimensionally on a mild-moderate-severe continuum, with number of cases declining with increasing severity. Public speaking was the most common social fear in all groups of social phobics and in the population at large.</p><p>In the neurobiological studies, positron emission tomography was used to examine brain serotonin metabolism and changes in the regional cerebral blood flow (rCBF) response to public speaking stress following treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral group therapy. Social phobics exhibited lowered serotonin turnover, relative to non-phobics, mainly in the medial temporal cortex including the bilateral rhinal and periamygdaloid regions. Symptom improvement with cognitive-behavioral- as well as SSRI-treatment was accompanied by a reduced rCBF-response to public speaking in the amygdala, hippocampus and adjacent temporal cortex, i.e. regions that serve important functions in anxiety. Thorough suppression of rCBF in limbic brain regions was associated with favorable long-term treatment outcome. These results provide neuroimaging evidence for a presynaptic serotonergic dysfunction in social phobia and for a common neural mechanism whereby psychological and pharmacological anti-anxiety treatments act.</p>

Social phobia is a disabling anxiety disorder characterized by an excessive fear of negative evaluation in social situations. The present thesis explored the epidemiology and neurobiology of the disorder. By means of a mailed questionnaire, the point prevalence of social phobia in the Swedish general population was estimated at 15.6%. However, prevalence rates varied between 1.9 and 20.4% across the different levels of distress and impairment used to define cases. Thus, although social anxiety is widespread within the community, the precise diagnostic boundaries for social phobia are difficult to determine. Social phobia was associated with female gender, low educational attainment, psychoactive medication use, and lack of social support. A cluster analysis revealed that subtypes of social phobia mainly differed dimensionally on a mild-moderate-severe continuum, with number of cases declining with increasing severity. Public speaking was the most common social fear in all groups of social phobics and in the population at large. In the neurobiological studies, positron emission tomography was used to examine brain serotonin metabolism and changes in the regional cerebral blood flow (rCBF) response to public speaking stress following treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral group therapy. Social phobics exhibited lowered serotonin turnover, relative to non-phobics, mainly in the medial temporal cortex including the bilateral rhinal and periamygdaloid regions. Symptom improvement with cognitive-behavioral- as well as SSRI-treatment was accompanied by a reduced rCBF-response to public speaking in the amygdala, hippocampus and adjacent temporal cortex, i.e. regions that serve important functions in anxiety. Thorough suppression of rCBF in limbic brain regions was associated with favorable long-term treatment outcome. These results provide neuroimaging evidence for a presynaptic serotonergic dysfunction in social phobia and for a common neural mechanism whereby psychological and pharmacological anti-anxiety treatments act.

Functional neuroimaging techniques such as near-infrared spectroscopy (NIRS) have been studied in brain-computer interface (BCI) development. Previous research has suggested that the addition of a second brain-monitoring modality may improve the accuracy of a NIRS-BCI. The objective of this study was to determine whether the classification accuracies achievable by a multimodal BCI, which combines NIRS and transcranial Doppler ultrasonography (TCD) signals, can exceed those attainable using a unimodal NIRS-BCI or TCD-BCI. Nine able-bodied subjects participated in the study. Simultaneous measurements were made with NIRS and TCD instruments while participants were prompted to perform a verbal fluency task or to remain at rest, within the context of a block-stimulus paradigm. In five of nine (55.6%) participants, classification accuracies with the NIRS-TCD system were significantly higher (p<0.05) than with NIRS or TCD systems alone. Our results suggest that multimodal neuroimaging may be a promising approach towards improving the accuracy of future BCIs.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

Functional neuroimaging techniques such as near-infrared spectroscopy (NIRS) have been studied in brain-computer interface (BCI) development. Previous research has suggested that the addition of a second brain-monitoring modality may improve the accuracy of a NIRS-BCI. The objective of this study was to determine whether the classification accuracies achievable by a multimodal BCI, which combines NIRS and transcranial Doppler ultrasonography (TCD) signals, can exceed those attainable using a unimodal NIRS-BCI or TCD-BCI. Nine able-bodied subjects participated in the study. Simultaneous measurements were made with NIRS and TCD instruments while participants were prompted to perform a verbal fluency task or to remain at rest, within the context of a block-stimulus paradigm. In five of nine (55.6%) participants, classification accuracies with the NIRS-TCD system were significantly higher (p<0.05) than with NIRS or TCD systems alone. Our results suggest that multimodal neuroimaging may be a promising approach towards improving the accuracy of future BCIs.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

Attention biases to trauma-related information contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD); this phenomenon has been observed through various behavioral studies, although findings from studies using a precise, direct bias task, the dot probe, have been mixed. PTSD neuroimaging studies have indicated atypical function in specific brain regions involved with attention bias; when viewing emotionally-salient cues or engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions implicated in cognitive control and attention allocation, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC) and amygdala. However, remarkably few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and include emotionally-salient information. In the current study of attention biases in highly traumatized African-American adults, a version of the dot probe task that includes stimuli that are both salient (threatening facial expressions) and relevant (photographs of African-American faces) was administered to 19 participants with and without PTSD during functional magnetic resonance imaging (fMRI). I hypothesized that: 1) individuals with PTSD would show a significantly greater attention bias to threatening faces than traumatized controls; 2) PTSD symptoms would be associated with a significantly greater attentional bias toward threat expressed in African-American, but not Caucasian, faces; 3) PTSD symptoms would be significantly associated with abnormal activity in the mPFC, dlPFC, and amygdala during presentation of threatening faces. Behavioral data did not provide evidence of attentional biases associated with PTSD. However, increased activation in the dlPFC and regions of the mPFC in response to threat cues was found in individuals with PTSD, relative to traumatized controls without PTSD; this may reflect hyper-engaged cognitive control, attention, and conflict monitoring resources in these individuals. Additionally, viewing threat in same-race, both not other-race, faces was associated with increased activation in the mPFC. These findings have important theoretical and treatment implications, suggesting that PTSD, particularly in those individuals who have experienced chronic or multiple types of trauma, may be characterized less by top-down “deficits” or failures, but by imbalanced neurobiological and cognitive systems that become over-engaged in order to “control” the emotional disruption caused by trauma-related triggers.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.

La voix humaine constitue la partie dominante de notre environnement auditif. Non seulement les humains utilisent-ils la voix pour la parole, mais ils sont tout aussi habiles pour en extraire une multitude d’informations pertinentes sur le locuteur. Cette expertise universelle pour la voix humaine se reflète dans la présence d’aires préférentielles à celle-ci le long des sillons temporaux supérieurs. À ce jour, peu de données nous informent sur la nature et le développement de cette réponse sélective à la voix. Dans le domaine visuel, une vaste littérature aborde une problématique semblable en ce qui a trait à la perception des visages. L’étude d’experts visuels a permis de dégager les processus et régions impliqués dans leur expertise et a démontré une forte ressemblance avec ceux utilisés pour les visages. Dans le domaine auditif, très peu d’études se sont penchées sur la comparaison entre l’expertise pour la voix et d’autres catégories auditives, alors que ces comparaisons pourraient contribuer à une meilleure compréhension de la perception vocale et auditive. La présente thèse a pour dessein de préciser la spécificité des processus et régions impliqués dans le traitement de la voix. Pour ce faire, le recrutement de différents types d’experts ainsi que l’utilisation de différentes méthodes expérimentales ont été préconisés. La première étude a évalué l’influence d’une expertise musicale sur le traitement de la voix humaine, à l’aide de tâches comportementales de discrimination de voix et d’instruments de musique. Les résultats ont démontré que les musiciens amateurs étaient meilleurs que les non-musiciens pour discriminer des timbres d’instruments de musique mais aussi les voix humaines, suggérant une généralisation des apprentissages perceptifs causés par la pratique musicale. La seconde étude avait pour but de comparer les potentiels évoqués auditifs liés aux chants d’oiseaux entre des ornithologues amateurs et des participants novices. L’observation d’une distribution topographique différente chez les ornithologues à la présentation des trois catégories sonores (voix, chants d’oiseaux, sons de l’environnement) a rendu les résultats difficiles à interpréter. Dans la troisième étude, il était question de préciser le rôle des aires temporales de la voix dans le traitement de catégories d’expertise chez deux groupes d’experts auditifs, soit des ornithologues amateurs et des luthiers. Les données comportementales ont démontré une interaction entre les deux groupes d’experts et leur catégorie d’expertise respective pour des tâches de discrimination et de mémorisation. Les résultats obtenus en imagerie par résonance magnétique fonctionnelle ont démontré une interaction du même type dans le sillon temporal supérieur gauche et le gyrus cingulaire postérieur gauche. Ainsi, les aires de la voix sont impliquées dans le traitement de stimuli d’expertise dans deux groupes d’experts auditifs différents. Ce résultat suggère que la sélectivité à la voix humaine, telle que retrouvée dans les sillons temporaux supérieurs, pourrait être expliquée par une exposition prolongée à ces stimuli. Les données présentées démontrent plusieurs similitudes comportementales et anatomo-fonctionnelles entre le traitement de la voix et d’autres catégories d’expertise. Ces aspects communs sont explicables par une organisation à la fois fonctionnelle et économique du cerveau. Par conséquent, le traitement de la voix et d’autres catégories sonores se baserait sur les mêmes réseaux neuronaux, sauf en cas de traitement plus poussé. Cette interprétation s’avère particulièrement importante pour proposer une approche intégrative quant à la spécificité du traitement de la voix. / The human voice is the most meaningful sound category of our auditory environment. Not only is the human voice the carrier of speech, but it is also used to extract a wealth of relevant information on the speaker. Voice-sensitive areas have been identified along the superior temporal sulci of normal adult listeners. Yet little data is available on the nature and development of this selective response to voice. In the visual domain, a vast literature focuses on a similar problem regarding face perception. Several studies have identified processes and regions involved in visual expertise, demonstrating a strong resemblance to those used for faces. In the auditory domain, very few studies have compared voice expertise to expertise for other sound categories. Such comparisons could contribute to a better understanding of voice perception and hearing. This thesis aims to clarify the nature of the processes and regions involved in voice perception. Different types of experts and different experimental methods were used in three separate studies. The first study assessed the influence of musical expertise on timbre voice processing, by using using behavioral voice and musical instrument discrimination tasks. The results showed that amateur musicians performed better than non-musicians in both tasks, suggesting a generalization of auditory abilities associated with musical practice. The second study compared event related potentials evoked by birdsongs in bird experts and non-expert participants. Because a different topographical distribution was observed among bird experts in all sound categories, a definitive interpretation was difficult to make. In the third study, we asked whether the voice-sensitive areas would be recruited by different categories of sounds of expertise in guitar makers, bird experts and non-experts. The behavioral data showed an interaction between the two groups of experts and their respective category of expertise for memory and discrimination tasks. The functional magnetic resonance imaging results showed an interaction of the same type in the left superior temporal sulcus and the left posterior cingulate gyrus. The results show that the voice selective areas do not exclusively process voice stimuli but could also contribute to expert-level processing of other sound categories. Therefore, cortical selectivity to human voice could be due to a prolonged exposure to voice. The data presented demonstrate several behavioral and anatomo-functional similarities between cerebral voice processing and other types of auditory expertise. These common aspects can be explained by a functional and economical brain organization. Consequently, sound processing would rely on shared neural networks unless necessary. This interpretation is particularly important to suggest an integrative approach for studying voice processing specificity.