Methylphenidate reduces spatial attentional bias by modulating fronto-striatal connectivity

Spatial attention bias reflects tendency to direct attention to specific side in space. This bias reflects asymmetric dopamine (DA) signaling in the striatum. Administration of DA agonists reduces spatial bias, yet the underlying mechanism is not yet clear. To address this, the current study tested whether methylphenidate (MPH; an indirect DA agonist) reduces orienting bias by modulating fronto-striatal connectivity. 54 adults with consistent bias completed the greyscales task which detects subtle biases during fMRI scanning under MPH (20 mg) or placebo, in a double-blind design. As hypothesized, MPH reduced bias by increasing orienting towards non-preferred hemispace, regardless of whether the initial bias was left or right. MPH-induced increases were found in activation of the medial superior frontal gyrus (mSFG: F[1;53] = 4.632, cluster-defining threshold of P < 0.05, minimal cluster size = 0, p_FWE = 0.036, η2 = 0.08) and its functional connectivity with the caudate (left caudate: F[1;53] = 12.664, p_FWE = 0.001, η2 = 0.192; right caudate: F[1;53] = 11.069, p_FWE = 0.002, η2 = 0.172), when orienting towards the non-preferred hemispace. MPH also reduced mSFG activation and fronto-striatal connectivity for the preferred hemispace. Results suggest modulation of frontal excitability due to increased caudate-mSFG functional connectivity. This mechanism may underlie the positive effect of dopaminergic agonists on abnormal patterns of directing attention in space.