Neuromodulation of Mind-Wandering in Depression

The default mode network (DMN) is a network of structurally and functionally connected brain regions that was first identified during "passive" states. Since its initial discovery, the conceptualization of the DMN has evolved over time; the DMN has now been linked with a range of higher-order cognitive processes such as spontaneous, self-generated thoughts (i.e. mind-wandering) and thinking about oneself in the past, future, and in relation to others. Given the DMN's involvement in cognition, researchers have investigated its role in psychiatric disorders associated with cognitive issues, such as Major Depressive Disorder (MDD).

MDD is a mood disorder in which people experience a persistent negative mood or loss of interest or pleasure, thoughts of worthlessness and guilt, and/or suicidal ideation. The majority of literature suggests that currently depressed individuals have increased DMN resting-state functional connectivity at rest and greater DMN activation when processing negative stimuli. Researchers have suggested that this DMN hyperactivity reflects the tendency for depressed individuals to engage in negative cognition, such as maladaptive mind-wandering (i.e. task-irrelevant thought when individuals are supposed to be focused on a task) and rumination (i.e. negative, repetitive, self-focused thinking). Mind-wandering, in general, has been linked to unhappiness. Rumination is associated with the maintenance of a current depressive episode and is a predictor of future depressive episodes. Therefore, changing these forms of negative cognition, via modulation of DMN activity, could be of benefit to individuals with MDD.

One way of modulating DMN activity is to use brain stimulation. The investigators have previously used transcranial Direct Current Stimulation (tDCS) of a DMN brain region to effect a small yet significant reduction in mind-wandering behavior in a community sample. However, tDCS has low spatial specificity and neuroimaging was not used to determine if tDCS was actually changing mind-wandering via changes in DMN activity. Low Intensity Focused Ultrasound Pulsation (LIFUP) is a novel non-invasive brain stimulation method which has high spatial specificity, unlike other non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS) and tDCS. Specifically, LIFUP can deliver acoustic energy to a brain region of a few millimeters in diameter. This method has been applied to the thalamus to restore consciousness to patients in minimally conscious states, and the investigators have been using this method in multiple IRB-approved studies as applied to the amygdala, ventral striatum, and entorhinal cortex.

Specific Aims:

The specific aim of this proposed study is to investigate the feasibility and therapeutic potential of LIFUP in changing negative cognition in depression. Specifically, the investigators will study if modulating DMN activity can change maladaptive mind-wandering. The investigators hypothesize that DOWN-modulation of the posterior cingulate cortex (PCC), a key DMN node, will decrease DMN resting state functional connectivity, perfusion, and activation during a cognitive-affective task (description below). The investigators also hypothesize that DOWN-modulation of the PCC will be associated with decreased mind-wandering and increased mindfulness. Finally, the investigators hypothesize that the opposite will be true for UP-modulation of the PCC.