Levels of γ-Aminobutyric acid in the ventral lateral prefrontal cortex as a predictor of underdetermined selection ability

The inhibitory neurotransmitter γ-Aminobutyric acid (GABA) and the excitatory neurotransmitter glutamate are the most abundant neurotransmitters in the brain. Together these neurotransmitter systems have been implicated in brain regions related to executive function, specifically, in the ventral lateral prefrontal cortex (VLPFC) and the dorsal lateral prefrontal cortex (DLPFC). One measure of executive function that these systems influence, is the process of obtaining a winning option amongst competing alternatives, known as selection. Selection can be split into two categories; underdetermined selection and prepotent selection. Underdetermined selection refers to selection amongst many task related options while prepotent selection refers to the ability to select relevant information in the face of a dominant option that is task irrelevant. Moreover, previous studies have shown a relationship between selection and traits related to psychopathology, such as anxiety and depression. The current study seeks to examine the pathways linking GABA to regional brain activation in the prefrontal cortex to performance on selection based cognitive tasks and to traits related to psychopathology. Using MR spectroscopy, GABA levels were measured in the VLPFC and fMRI was used to measure brain activation during a selection based, verb generation task. Levels of anxiety and depression were measured through the Penn State Worry Questionnaire (PSWQ) and the Mood and Anxiety Symptoms Questionnaire (MASQ). The results show a significant negative correlation between VLPFC GABA concentration and performance on underdetermined selection tasks suggesting that levels of neurotransmitter in the prefrontal cortex can influence the degree to which an individual exerts executive control

Influences of glutamine administration on response selection and sequence learning: a randomized-controlled trial

Article / Letter to editorCognitieve Psychologi

Influences of glutamine administration on response selection and sequence learning: a randomized-controlled trial

Article / Letter to editorCognitieve Psychologi

Prediction of adolescent substance use by individual differences in GABA and glutamate levels in the lateral prefrontal cortex: A preliminary exploration

Adolescence is a period of time associated with lower levels of impulse control and is often the time during which youth begin to engage in substance use. Prior research has found that higher levels of impulsivity are associated with increased adolescent substance use. The brain structure responsible for impulse control, the prefrontal cortex (PFC), is underdeveloped in adolescents, which may help to explain increased levels of impulsivity observed during adolescence. As such, research has been conducted on the neural correlates of impulsivity in the PFC, including magnetic resonance spectroscopy (MRS) studies that measure levels of relevant neurotransmitters in relation to levels of impulsivity. However, the majority of this research has been focused on neurotransmitter levels in the medial PFC in adult populations &ndash; no previous studies have assessed the relationship between&nbsp;lateral&nbsp;PFC neurotransmitter levels and substance use in adolescents. This exploratory study examines whether individual differences in lateral PFC neurotransmitters &gamma;-aminobutyric acid (GABA) and glutamate can significantly predict the age of onset and frequency of alcohol use in a nonclinical adolescent population. MRS was used to measure proxy values for GABA (GABA+) and glutamate (Glx; glutamate + glutamine) levels in the lateral PFC, and data on disinhibition and substance use were collected via self-report questionnaires. Results showed that higher levels of impulsivity were associated with earlier and more frequent substance use, as predicted per extensive prior literature. While the hypothesized relationship with GABA+ was not observed, higher Glx levels were associated with earlier onset of substance use while accounting for the joint relationships between both Glx and substance use with impulsivity. As a result, we concluded that the relationship between excitatory-inhibitory signaling in the lPFC and impulsivity levels is likely different in the developing adolescent brain than in adults, and future research in this area will help to expand upon the findings of this preliminary study.</p

Brain Neurotransmitters, Cognitive Control, and Resting Heart Rate Variability (rHRV) in the MRI Environment

Determining reliable measures that show how the brain can regulate the body and its physiological states could offer insight into how mental health and wellbeing is related to physiology and self-regulation. This study investigates how heart rate variability (HRV) at rest (rHRV), a measure of autonomic nervous system activity according to several studies (Thayer 2009, Colzato 2017, Shaffer & Ginsberg, 2017), relates to neurotransmitter levels in the prefrontal cortex (PFC), cognitive control over emotional material, and individual traits involved in psychopathology. Resting heart rate (HR) measures were taken via pulse rate measurements in an MRI scanner, and processed into rHRV. Prior research has suggested that increased heart rate variability is associated with a) better emotional regulation and b) individual differences in GABAergic function. We investigated these relationships in a novel manner by examining whether GABAergic function of the prefrontal cortex, which is known to be involved in emotion regulation, is associated with rHRV. No significant correlations were found between rHRV and any of the main measures: prefrontal GABA concentration, emotional regulation or measures related to psychopathology. Potential reasons for these null findings include a) that the GABA concentrations were obtained 20-24 months earlier, b) that the method used to assess rHRV is not as robust as standard measures which are difficult to implement in the magnet, c) the size of our current sample is small and hence may be underpowered to detect such relationships

Choosing our words: Neural mechanisms supporting cognitive control during language processing

When we speak, we must constantly retrieve and select words in the face of multiple competing alternatives. Previous research has left many questions unanswered about how we achieve these fundamental cognitive control processes. This dissertation contributes to answering these questions at three levels. First, using well-controlled tasks and measures, we ask what specific aspects of language production drive cognitive control demands, as indexed by slower RTs to produce a verbal response. Second, we apply these unconfounded measures to fMRI experiments, to ask what neural substrates support cognitive control during language production. Third, we ask how these brain areas support cognitive control processes, by first simulating possible mechanisms in a neural network model and then empirically testing model predictions using pharmacological and clinical methods. In sum, the dissertation research suggests that cognitive control is needed during language production when responses compete with alternative task-relevant response options (underdetermined selection), compete with prepotent responses (prepotent selection), or are difficult to retrieve from semantic memory (controlled retrieval), and these demands interact both behaviorally and neurally. Shared neural substrates in left ventrolateral prefrontal cortex (VLPFC) support both underdetermined selection and controlled retrieval, while left VLPFC is not activated by prepotent selection demands. In contrast, an area of left dorsolateral prefrontal cortex (DLPFC) is sensitive to both underdetermined and prepotent competition. Neural network simulations suggest that competitive lateral inhibition in VLPFC is key for underdetermined selection, while other mechanisms subserved by VLPFC support controlled retrieval, and top-down biasing from DLPFC is critical for prepotent selection. As predicted by the model, increased inhibition under the GABA agonist midazolam improved selection, while anxiety (linked to reduced GABAergic function) was associated with impaired selection and reduced engagement of left VLPFC during selection. These findings enable a synthesis and reinterpretation of prior evidence, and suggest that language production is affected by both selection and retrieval mechanisms subserved by left VLPFC and DLPFC, and these processes interact in meaningful ways. Better understanding these fundamental aspects of language production may ultimately have implications for better understanding and treating impairments associated with prefrontal damage, as well as anxiety and depression

Influences of glutamine administration on response selection and sequence learning: a randomized-controlled trial

Action Contro

Brain adaptation and alternative developmental trajectories

Resilience and adaptation in the face of early genetic or environmental risk has become a major interest in child psychiatry over recent years. However, we still remain far from an understanding of how developing human brains as a whole adapt to the diffuse and widespread atypical synaptic function that may be characteristic of some common developmental disorders. The first part of this paper discusses four types of whole-brain adaptation in the face of early risk: redundancy, reorganization, niche construction, and adjustment of developmental rate. The second part of the paper applies these adaptation processes specifically to autism. We speculate that key features of autism may be the end result of processes of early brain adaptation, rather than the direct consequences of ongoing neural pathology

Understanding emotions: origins and roles of the amygdala

Emotions arise from activations of specialized neuronal populations in several parts of the cerebral cortex, notably the anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as the amygdala, ventral striatum, putamen, caudate nucleus, and ventral tegmental area. Feelings are conscious, emotional experiences of these activations that contribute to neuronal networks mediating thoughts, language, and behavior, thus enhancing the ability to predict, learn, and reappraise stimuli and situations in the environment based on previous experiences. Contemporary theories of emotion converge around the key role of the amygdala as the central subcortical emotional brain structure that constantly evaluates and integrates a variety of sensory information from the surroundings and assigns them appropriate values of emotional dimensions, such as valence, intensity, and approachability. The amygdala participates in the regulation of autonomic and endocrine functions, decision-making and adaptations of instinctive and motivational behaviors to changes in the environment through implicit associative learning, changes in short- and long-term synaptic plasticity, and activation of the fight-or-flight response via efferent projections from its central nucleus to cortical and subcortical structures