Yoon Lab News


New Publication: Subthalamic Nucleus Activation Occurs Early during Stopping and Is Associated with Trait Impulsivity

Jong H. Yoon, Edward Dong Bo Cui, Michael J. Minzenberg and Cameron S. Carter

Abstract: The subthalamic nucleus (STN) is thought to be a central regulator of behavioral inhibition, which is thought to be a major determinant of impulsivity. Thus, it would be reasonable to hypothesize that STN function is related to impulsivity. However, it has been difficult to test this hypothesis because of the challenges in noninvasively and accurately measuring this structure's signal in humans. We utilized a novel approach for STN signal localization that entails identifying this structure directly on fMRI images for each individual participant in native space. Using this approach, we measured STN responses during the stop signal task in a sample of healthy adult participants. We confirmed that the STN exhibited selective activation during “Stop” trials. Furthermore, the magnitude of STN activation during successful Stop trials inversely correlated with individual differences in trait impulsivity as measured by a personality inventory. Time course analysis revealed that early STN activation differentiated successful from unsuccessful Stop trials, and individual differences in the magnitude of STN activation inversely correlated with stop signal RT, an estimate of time required to stop. These results are consistent with the STN playing a central role in inhibition and related behavioral proclivities, with implications for both normal range function and clinical syndromes of inhibitory dyscontrol. Moreover, the methods utilized in this study for measuring STN fMRI signal in humans may be gainfully applied in future studies to further our understanding of the role of the STN in regulating behavior and neuropsychiatric conditions.

New Publication: Impaired prefrontal functional connectivity despite intact activations in schizophrenia; associations with WM performance and disorganization.

 

Sripriya Charia, Michael Minzenberg, Marjorie Solomon, J. Daniel Ragland, Cameron S. Carter, Jong H. Yoon

Working memory (WM) deficits are key features of schizophrenia and are associated with significant functional impairment. The precise mechanisms of WM deficits in patients with schizophrenia and the relationship between WM deficits with other clinical symptoms of schizophrenia remain unclear.  Contemporary models propose that WM requires synchronous activity across brain regions within a distributed network, including lateral prefrontal cortex (PFC) and task-relevant posterior sensory cortical regions. This suggests that WM deficits in patients may be due to PFC functional connectivity (FC) impairments rather than activation impairments per se. We tested this hypothesis by measuring the magnitude of FC between lateral PFC and visual cortex and univariate activations within these regions during visual WM. We found decreased FC in patients compared to healthy subjects in the context of similar levels of univariate activity.  Furthermore, this decreased FC was associated with task performance and clinical symptomatology in patients. The magnitude of FC, particularly during the delay period, was positively correlated with WM task accuracy, and inversely correlated with severity of disorganization. Taken together, these results suggest that impairment in PFC FC is a key neural mechanism underlying WM deficits in patients with schizophrenia, and may be a sensitive index of altered neurophysiology.