Differential correlation of frontal and parietal activity with the number of alternatives for cued choice saccades

The time taken to choose a response appropriate for a cue increases with the number of potential response options (Hick's law). We used this temporal constraint of choice behavior in event-related fMRI experiments to identify brain areas carrying out the translation from a cue stimulus to response: Since the process takes longer with more alternatives, the activity of the areas would increase in correlation with the number of alternatives (NA) available at the time of choice decision. During a choice saccade task in which one target is selected among many alternatives based on the color of a cue in the center, the frontal eye fields (FEF) and intraparietal sulcus (IPS) were activated. Within these regions, signals were correlated with NA at the medial part of the FEF and the posterior part of the IPS, but not at the lateral FEF and anterior IPS. This suggests a functional differentiation within each cortical region. Furthermore, given the separate fronto-parietal projections linking sub-regions that are alike in NA-correlation, cognitive steps for choice decision may occur in different networks of the sub-regions: i.e., the stimulus-response translation step in a network of the posterior IPS and medial FEF, and response execution in the anterior IPS/lateral FEF network.This work was supported by a grant (M103KV010021- 03K2201-02120) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea and by P30_EY006883 and the Smith-Kettlewell Eye Research Institute

BRAIN CONNECTIVITY AND TREATMENT RESPONSE IN ADULT ADHD:understanding the relationship between individual differences in fronto-parietal and fronto-striatal brain networks and response to chronic treatment with methylphenidate

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterised by disrupted anatomical and/or functional connectivity, mainly in the fronto-striatal and fronto-parietal networks. Stimulants, such as methylphenidate (MPH), represent a first-line treatment in ADHD, but one third of patients fail to respond, with severe consequences for the individual and the society at large. Hence, a comprehensive understanding of the relationship between individual differences in brain abnormalities and treatment response is needed.This thesis focused on two main brain networks: the fronto-striatal network, a central theme in ADHD research, and the fronto-parietal attentive network, formed by the three branches of the superior longitudinal fasciculus (SLF). The SLF branches have been only recently described in humans, and there is no detailed analysis of their distinct functional roles and involvement in disorders such as ADHD. Therefore, I first investigated the functional anatomy of the SLF branches by combining a meta-analytic approach with tractography, and revealed novel findings about the anatomical and functional segregation and integration of brain functions within fronto-parietal networks. Then, I showed, for the first time, that the three SLF branches are all significantly right-lateralised in ADHD patients but not in controls, and provided preliminary evidence that the pattern of lateralisation of the SLF I may be related to poor attentive performance in ADHD patients.Finally, I conducted functional and structural connectivity analysis to test whether a relationship exists between brain abnormalities and treatment response in adult ADHD. I employed a longitudinal crossover follow-up design. 60 non-medicated adult ADHD patients were recruited and underwent behavioural assessment (Qb test) and magnetic resonance imaging (MRI) scanning twice, once under placebo and once under a clinically effective dose of MPH. Clinical and behavioural response was measured after two months of treatment with MPH. I demonstrated for the first time that there is a relationship between ‘connectivity’ abnormalities within fronto-parietal networks and treatment response in adult ADHD, both at the anatomical and functional level.Ultimately, my investigation contributed towards the identification of potential biomarkers of treatment response, which in the future may help clinicians deliver more individualised treatments.<br/