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.

Previous studies have reported altered glutamate (Glu) concentrations in the blood and brain of individuals with autism spectrum disorder (ASD) compared to neurotypical controls (NC), but the direction (increased or decreased) of metabolite differences is still unclear. Moreover, the relationship between Glu and both brain function and clinical manifestations of the disorder require further investigation. Within this study, we investigated metabolite concentrations within the dorsal anterior cingulate cortex (dACC), a brain region functionally associated with inhibitory executive control tasks and also part of the salience network. There were 19 participants with ASD and 20 NCs between the ages of 23 and 58 years who participated in this study. A study clinician administered the Autism Diagnostic Observation Schedule (ADOS) to individuals with ASD to further confirm their diagnosis. In addition, all participants in this study completed assessments of general intelligence and attention, which included an inhibitory executive control task. Researchers also acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS) in the dACC to quantify both Glu and combined Glu and glutamine (Glx) concentrations. We hypothesised that these metabolite concentrations would be altered (decreased or increased) in adult participants with ASD compared to NCs and would correlate with inhibitory performance and ASD severity in individuals with ASD. Participants also underwent a resting-state functional magnetic resonance imaging (fMRI) scan to assess the relationship between functional connectivity and Glu and Glx concentrations. We also hypothesised that there would be an altered relationship between local Glu and Glx concentrations and seed-based functional connectivity in adults with ASD compared to NCs. There were no significant group differences in Glu or Glx concentrations between individuals with ASD and NCs. Furthermore, we did not find any relationship between metabolite concentrations and either inhibitory performance or clinical symptoms of the disorder. This evidence suggests that increased or decreased Glu and Glx concentrations were not a core marker of altered brain function in the dACC in this group of adult individuals with ASD. When individuals taking psychotropic medications were excluded from the analysis, there was a significant interaction between age and group for Glx concentrations. This evidence weakly suggests disease-specific variations in Glx concentrations over the lifespan of an individual with ASD. Nevertheless, this result did not survive correction for multiple comparisons and requires further replication. In our final experiment, we reported that Glu concentrations were negatively correlated with right and left dACC seed-based resting-state functional connectivity to the left medial temporal lobe only in individuals with ASD. We also reported an interaction between groups in the association between Glx concentrations and both left and right dACC functional connectivity to other salience network regions including the insular cortex. This evidence suggests that local Glu and Glx concentrations were incongruent with long-distance functional connectivity in individuals with ASD. This analysis was largely exploratory, but further investigation and replication of these relationships may further explain the pathophysiology of the disorder as well as provide a useful marker for therapeutic intervention.

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.

The current study is the first to demonstrate that structural deficits in the Anterior Cingulate Cortex (ACC) of the human brain may play a role in reading ability. Recent imaging work has indicated that the ACC is activated by tasks involving modulation of the fronto-temporal networks during language processing tasks and may be involved in anticipatory reactions and response preparation during reading. This study investigated the relationship between ACC volumetric measurements and reading ability in a sample of 68 individuals nested within 24 families with and without reading disorders. This sample allowed for examination of the effect of the volume of the ACC on reading, while controlling for normally occurring fluctuations in the size of the ACC due to heredity and shared environment. Forty-five linear models were conducted in SPSS on all 68 participants using the brain measurements (ACC, ACC with Paracingulate (PaC), and Putamen, separately) as well as control variables (gender, FSIQ, family membership) as predictors of the outcomes variables related to reading achievement (GORT Passage, rate, and accuracy) and reading processes (CTOPP phonological awareness and rapid naming). The use of family membership as a random effect predictor together with the specific brain volume as a predictor allowed for the effect of family on reading outcomes to be accounted for while, explicitly accounting for any relationships that may exist between family and brain volume. Additional sets of measurements, with PaC, were included in the final analyses to address the inconsistent inclusion of this tertiary structure in earlier research. Finally, a control region (putamen) was included to rule out whole brain effects and improve the specificity of the findings. The most significant findings were that the results varied systematically with inclusion or exclusion of the PaC. Measurements including the PaC were statistically significant for reading achievement for the left side of the ACC as expected. However, for the ACC volume without PaC, it was the right side that was related to reading measures. Neither set of measurements of the ACC were predictive of group membership. The current study supported a role for the ACC in reading and suggests a standardized method for inclusion of the PaC in the volumetric analysis of the ACC. / text