Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD

Abstract

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder.

Chemogenetic Stimulation of Tonic Locus Coeruleus Activity Strengthens the Default Mode Network

“…S8, C and D), a key node of the salience network that may causally suppress DMN (54). This enhanced polarization among networks also supports the plausible mechanism by which NEtargeting pharmacological agents like atomoxetine, clonidine and guanfacine are effective in treating ADHD patients since they strengthen the FC within the Frontal DMN module, resulting in improved attention (79,80). Additionally, abnormally heightened FC in Frontal DMN regions have been associated with anxiety and depression (81,82), which coincide with anxiety-like behavioral phenotypes such as reduced locomotor activity when placed in a novel environment and anhedonia following chemogenetic-evoked LC-NE activation in awake mice (30).…”

Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD

“…Our results corroborate the essential role of the striatum in mediating responses to methylphenidate in ADHD [16,23]. The present study also highlights newly-reported, but not surprising, evidence, indicating the involvement of the DMN in methylphenidate mechanisms [30,31,34]. Most of the regions, which were identified to be able to help differentiate clinically good and poor responders, are functionally or structurally linked with striatum.…”

“…Through increasing dopamine and norepinephrine, methylphenidate has been consistently reported to suppress DMN activities in patients with ADHD while engaging in cognitive tasks (i.e., reducing the DMN-taskpositive network connection) [30][31][32][33]. Reduction in DMN activity or connectivity with task-positive networks also is associated with methylphenidate-related improvements in core symptoms of individuals with ADHD [34]. The medial prefrontal cortex, which is thinner in poor responders at baseline, as shown in the aforementioned naturalistic study [17], partially corresponds to the one hub region of the DMN.…”

Psychiatric neuroimaging research in Brazil: historical overview, current challenges, and future opportunities

“…Liaising with radiologists, physicists, radiopharmacists, and computer data analysts, our psychiatric teams have gained access to sophisticated imaging technology, developed the capacity to acquire and analyze quality data from unique, large-sized populations, and established a tradition of collaboration both nationally and internationally with leading institutions. This has allowed our neuroimaging labs to make scientific contributions in several fronts over the past decades, including the reporting of original findings of brain changes in samples of subjects with prevalent psychiatric disorders recruited in our environment before any exposure to treatment 26,79 ; original findings of brain changes associated with subtypes of psychiatric disorders rarely or never previously evaluated in other countries 28,207 ; the use of cross-sectional and longitudinal epidemiological designs to assess specific populations and address relationships with relevant risk factors for mental disorders 82,176,219 ; development of novel intervention studies using imaging markers as outcome measures and predictors of treatment response 220,221 ; production of original findings evaluating brain effects of relevant psychopharmacological agents 57,108 ; the use of fMRI in studies applying innovative tasks of interest to psychiatry [95][96][97] ; publishing well-cited reviews of neuroimaging issues in top international journals 222,223 ; and participation in worldwide consortia organized to analyze neuroimaging data from samples of unprecedented size. 183,184 Additionally, we have developed awareness of the need to work in close collaboration with experts from other fields of neuroscience to devising studies that integrate neuroimaging indices with other biomarkers of interest to psychiatry.…”

“…77,78 In the state of Rio Grande do Sul, knowledgeable clinical and basic science research groups based at the Federal University of Rio Grande do Sul (UFRGS) and the Pontifical Catholic University (PUC) have adopted the first model outlined in the previous section of this article, testing original hypotheses in a number of psychiatric neuroimaging studies carried out in collaboration with teams of imaging experts either from the local Clinics Hospital of Porto Alegre (HCPA), the PUC-based Brain Institute (InsCer), or Sã o Paulo-based centers. These groups have contributed to the development of the field of psychiatric neuroimaging in Brazil by leading studies on attention-deficit/hyperactivity disorder (ADHD), [79][80][81] child and adolescent development, 82,83 psychosis, 84 mood and anxiety disorders, [85][86][87] and autism (Table 1). 88 The same collaborative model has been applied by research groups based at other universities in Brazil.…”