The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults

Abstract

By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-state functional connectivity of the dorsal striatum and thalamus, areas each with dense dopaminergic and noradrenergic innervations, as well as global cerebral connectivity. We administered a single, oral dose (45 mg) to 24 healthy adults and compared resting-state connectivity to 24 demographically matched adults who did not receive any medication. The results showed that methylphenidate alters seed-based and global connectivity between the thalamus/dorsal striatum with primary motor cortex, amygdala/hippocampus and frontal executive areas (p<0.05, corrected). Specifically, while methylphenidate at this dosage enhances connectivity to the motor cortex and memory circuits, it dampens prefrontal cortical connectivity perhaps by increasing catecholaminergic signalling past the ‘optimal’ level. These findings advance our understanding of a critical aspect of the multifaceted effects of methylphenidate on brain functions. The results may also facilitate future studies of the aetiology and treatment of neurological and psychiatric disorders that implicate catecholaminergic dysfunction.

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood

“…VTA/SN (Figure 1f) showed positive connectivity with SMA, ACC, vmPFC, superior temporal cortex, posterior cingulate cortex, thalamus, basal ganglia, insula and cerebellum, and negative connectivity with occipital, parietal and somatomotor cortices. These results largely replicate those of previous work (Di Martino et al, 2008; Barnes et al, 2010; Farr et al, 2014). …”

“…Before discussing the age-related changes in functional connectivity in detail, we confirmed that cerebral connectivity of the striatum and VTA/SN are consistent with previous reports (Di Martino et al, 2008; Barnes et al, 2010; Farr et al, 2014). The caudate nucleus showed positive connectivity with a wide area of the frontal cortex and negative connectivity with somatomotor and occipital cortices.…”

Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study

“…Additional studies are needed to evaluate MPH effects on DLPFC connectivity, which in the current study showed a similar, albeit nonsignificant, pattern of effects as the task data. Indeed, little work has examined the effects of MPH on DLPFC connectivity during resting-state, though one study in healthy controls reported that thalamic-DLPFC connectivity was reduced with MPH (Farr et al 2014), which is the pattern we observed here for CUD. Importantly, the combined DLPFC modulation by MPH (i.e., tasks and resting state) was further correlated with the frequency of recent cocaine use.…”

Characterizing Attention with Predictive Network Models

“…Specifically, high- and low-attention network strength were examined in a new group of healthy adults who had been administered a single dose of methylphenidate (trade name: Ritalin), a drug used to treat ADHD symptoms [72], and a group of unmedicated control participants (dataset from [73,74]). As predicted a priori , individuals given methylphenidate showed connectivity signatures of strong attentional abilities: they had stronger high-attention networks and weaker low-attention networks than unmedicated controls as they rested and performed a stop-signal task [71].…”