Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by increased hyperactivity, impulsivity, and inattention. Some theories propose that ADHD is caused by a deficit in inhibitory control, interacting with other executive functions (e.g., emotional control) to lead to behavioural dysfunction. Furthermore, certain brain regions have been found to be involved in executive functions, and several studies have examined the neural correlates of ADHD at broad-based levels. Increased interest has been placed on the Anterior Cingulate Cortex (ACC), which is known to play a role in attention and other complex cognitive processes. Thus, to further clarify the nature of the behavioural and cognitive deficits observed in ADHD, and to elucidate potential relationships between these difficulties and their neural substrates with more specificity, volumetric analyses of the ACC were conducted. For this purpose, 10 children with ADHD and 10 matched controls underwent magnetic resonance imaging and neuropsychological assessment. Manual tracing of ACC subregions was conducted using ANALYZE 9.0 (Mayo Clinic), followed by between-group statistical comparisons. Correlation analyses were used to investigate whether ACC subregions were associated with performance on executive functions tasks. It was hypothesized that there would be significant volumetric groups differences between the two groups, and that subregions would have a differential relationship with executive function performance. Results indicated the ADHD group has marginally larger right dorsal ACC volumes relative to controls. Further, between the two groups, brain-behaviour relationships were different. These results provide support for the hypothesis of a delay in neuronal maturation of the ACC in children with ADHD from Spain. / Graduate

The anterior cingulate cortex (ACC) expresses high density of Gastrin-releasing peptide (GRP) and GRP receptor mRNA. To address possible function, this investigation used patch clamp recordings in mouse brain slice preparations to evaluate intrinsic properties of ACC neurons and neuronal responses to bath-applied GRP peptide. The ACC neurons were divided according to their morphology, the properties of action potentials and their firing pattern in response to depolarizing current pulses. Two physiological groups of interneurons and three groups of pyramidal neurons were defined. Application of the GRP induced depolarization and increased firing of the interneurons while hyperpolarization and reduced firing in pyramidal neurons. Moreover, activation of GRP receptor facilitated GABAergic neurotransmission via a postsynaptic mechanism. The results suggest that GRP receptor is an important regulator of neuronal circuits in the ACC and may consequently play an important role for ACC neurons in the central processing of high brain function.

The anterior cingulate cortex (ACC) expresses high density of Gastrin-releasing peptide (GRP) and GRP receptor mRNA. To address possible function, this investigation used patch clamp recordings in mouse brain slice preparations to evaluate intrinsic properties of ACC neurons and neuronal responses to bath-applied GRP peptide. The ACC neurons were divided according to their morphology, the properties of action potentials and their firing pattern in response to depolarizing current pulses. Two physiological groups of interneurons and three groups of pyramidal neurons were defined. Application of the GRP induced depolarization and increased firing of the interneurons while hyperpolarization and reduced firing in pyramidal neurons. Moreover, activation of GRP receptor facilitated GABAergic neurotransmission via a postsynaptic mechanism. The results suggest that GRP receptor is an important regulator of neuronal circuits in the ACC and may consequently play an important role for ACC neurons in the central processing of high brain function.

Cognitive dissonance is the uncomfortable psychological feeling that arises when something is perceived as contradictory. In 1957, Leon Festinger first developed the theory of cognitive dissonance, which has since continued to be of interest for, among other things, decision-making, moral reasoning, motivation, politics, and science. This systematic review summarises six peer-reviewed studies that use functional magnetic resonance imaging (fMRI) to measure if there is increased activity in the anterior cingulate cortex (ACC) and dorsal anterior cingulate cortex (dACC) during cognitive dissonance in adults. Four studies tested cognitive dissonance during forced choices and two during counter-attitudinal behaviours. The overall fMRI results indicate increased activity in ACC and dACC to dissonance versus control conditions, but with some inconsistency on the exact locations in the brain.

In recent years Social Neuroscience has started to investigate how mood and culture influence social and emotional situations. In the present study differences in elicited emotion and neural activation were investigated when participants viewed films depicting social interactions. Film clips are preferred stimuli for elicitation of emotion in laboratory studies, but given the lack of standardised film sets in the literature, two behavioural studies were conducted prior to imaging. The first study (147 females, 30 males; 98.8% 18 to 24 years) identified a set of clips that elicited emotion profiles in which the target emotion (happy, sad) was strongest, as well as neutral clips, and demonstrated an effect of participants’ stable mood. The second study (143 females, 19 males; mean age 19.2 years) optimised the stimulus set and demonstrated effects of self-reported ethnic origin, mood and interest on profiles of elicited emotion. In the fMRI investigation 33 female and 8 male participants (mean age 19.2 years) viewed film clips in a block design experiment with loose and tight t-contrasts and retrospective ratings of elicited emotion. Across all-participants, social interaction depicting sadness activated key emotion-related structures such as left amygdala and insula, and medial frontal cortex that were not significantly activated with social interaction depicting happiness. However, greater activation was observed for Europeans than for non-Europeans in orbitofrontal cortex, anterior and posterior cingulate for happy social interaction and in hippocampus, precuneus and retrosplenial cortex for sad social interaction. Individual differences in trait emotions and stable mood were measured with PANAS-X. For high fatigue participants greater activation was observed in the left amgydala for happy social interaction. For participants with high positive stable mood greater activation was observed in the insula for happy and sad social interaction. The research described here indicates that self-reported ethnic origin and mood are potentially significant influences on elicited emotion and brain reactivity to positive and negative social and emotional situations.

This thesis introduces a new theoretical framework from which to view the factors that contribute to stuttering variability. The speech and monitoring interaction (SAMI) framework proposes that there are two systems that account for stuttering variability: the speech production system and the monitoring system. Each system has unique factors that modulate them. Within SAMI, the interaction of these two categories of factors is formalized in a mathematical equation. What is particularly novel about SAMI is the use of a mathematical equation to formalize the interaction between these systems and the specific proposal of the biological substrates of the monitoring system and its interaction with the speech system. The focus of this thesis is on the anticipation of stuttering, which is one of the factors from SAMI that modulates the monitoring system. The goals of the studies were to 1) characterize the degree to which people who stutter (PWS) anticipate stuttering and how accurately they can predict actual stuttering, 2) investigate the correlation between stuttering expectancy on words and the verbal response time to say those word in word naming tasks, and 3) make a qualitative comparison of the behavioral results and the results from a neural network model. Utilizing the SAMI framework it was hypothesized that stuttering expectancy would be positively correlated with the response time and the results from the simulations would qualitatively match the behavioral results. The key finding was that across the group of PWS, there was positive correlation between stuttering expectancy scores and relative reaction times on those words. The degree to which stuttering expectancy was correlated with reaction time within subjects was positively correlated with stuttering severity. A qualitative comparison showed a good fit in between results of the simulations and the behavioral study. This is the first study to show that the expectation of stuttering has an effect on fluent speech production, providing evidence that the anticipation of stuttering is not only correlated with moments of stuttering but may also be a contributing factor to stuttering. The model provides a means of hypothesizing and testing specific neural substrates associated with anticipation of stuttering and its effects on the speech production process.

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.

Neurabin, a cytoskeletal protein, has been shown to be required for normal dopamine signalling, and dopaminergic systems have been previously implicated in the pathophysiology of anxiety disorders, including generalized social anxiety disorder. And results from neuroimaging studies have implicated the anterior cingulate cortex (ACC) in depression and anxiety disorders. However, lesion studies have failed to produce the expected deficits. Here, we demonstrate that the injections of muscimol and midazolam into the ACC reduced anxiety- and depression-like behaviours, and that complete absence of neurabin reduced anxiety-like behaviour but increased depression-like behaviour. However, reduction of neurabin by injecting neurabin-targeted siRNA into the ACC reduced anxiety-like behaviour but did not affect depression-like behaviour. This study provides evidence that the imbalance of excitatory and inhibitory activity in the ACC alters affective disorders, and that neurabin may be critical for the modulation of these behaviours.

Neurabin, a cytoskeletal protein, has been shown to be required for normal dopamine signalling, and dopaminergic systems have been previously implicated in the pathophysiology of anxiety disorders, including generalized social anxiety disorder. And results from neuroimaging studies have implicated the anterior cingulate cortex (ACC) in depression and anxiety disorders. However, lesion studies have failed to produce the expected deficits. Here, we demonstrate that the injections of muscimol and midazolam into the ACC reduced anxiety- and depression-like behaviours, and that complete absence of neurabin reduced anxiety-like behaviour but increased depression-like behaviour. However, reduction of neurabin by injecting neurabin-targeted siRNA into the ACC reduced anxiety-like behaviour but did not affect depression-like behaviour. This study provides evidence that the imbalance of excitatory and inhibitory activity in the ACC alters affective disorders, and that neurabin may be critical for the modulation of these behaviours.

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.