Voltage Dependency of fMRI BOLD signal.

<p>A) Comparison of data from left unilateral NAc stimulation at 3 V 130 Hz 500 µs (i; n = 7) with stimulation at 5 V 130 Hz 500 µs (ii; n = 7). Both voltages showed regions of activation in the prefrontal cortex and insula as well as an area of deactivation in the dorsal region of the thalamus. B) i. Region of interest cluster sizes (mm³) comparing the percent size of areas of activation with 3 V 130 Hz 500 µs (yellow; n = 7) and 5 V 130 Hz 500 µs (red; n = 7), represented by the relative size of the two circles. ii. Event-related time course of percent change in BOLD signal from baseline with 1 V (blue; n = 5), 3 V (yellow; n = 7), and 5 V at 130 Hz (red; n = 7), 500 µs pulse width. C) Unilateral stimulation to the left (left) right (middle) and bilateral (right) NAc (n = 1). Stimulation of the right NAc activated areas corresponding to those of left NAc stimulation, including prefrontal cortex and insula, ipsilateral to the side of stimulation.</p

Significant Clusters in the General Linear Model comparing Stimulation “on” periods to baseline.

<p>I = Ipsilateral, AP = Anterior/Posterior, ML = Medial/Lateral; DV = Dorsal/Ventral.</p><p>Stimulation Parameters = 5 V 130 Hz 500 µs.</p

Pulse Width dependency of fMRI BOLD signal.

<p>A) Comparison of data from left unilateral NAc stimulation at 5 V 130 Hz 500 µs (i; n = 3) with stimulation at 3 V 130 Hz 100 µs (ii; n = 3). Both pulse widths showed regions of activation in the prefrontal cortex, insula, dorsal anterior cingulate, caudate. There was an additional area of activation in parahippocampal cortex present only with stimulation at 5 V 130 Hz 500 µs. B) i. Region of interest cluster sizes (mm³) comparing the percent size of areas of activation with 5 V 130 Hz 100 µs (yellow; n = 3) and 5 V 130 Hz 500 µs (red; n = 3), represented by the relative size of the two circles. ii. Event-related time course of percent change in BOLD signal from baseline with 100 µs (yellow; n = 3) and 500 µs (red; n = 3) pulse widths at 5 V and 130 Hz.</p

DBS surgery and Lead Confirmation.

<p>A) Custom designed MRI-compatible head frame. B) Screenshot of MR-image based targeting procedure using modified COMPASS software. C) Surgical introduction of the Medtronic 3389 DBS electrode using the Lexsell stereotactic arc. D) fMRI Experimental Setup. Extension wiring connected the externalized DBS lead with a pulse generator located outside the scan room. E) Representative pre-surgical anatomical MP-RAGE scan. F) Post-surgical CT scan demonstrating electrode location in the left NAc G) MR-CT fusion with atlas overlay <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056640#pone.0056640-Felix1" target="_blank">[45]</a>demonstrating the location of the electrode tip in the left NAc. H) Diagram plotting the location of the 0 contact in each animal (red asterisks), as determined by the MR-CT fusion on a stereotaxic pig brain atlas, sagittal slice (lateral 2.00 mm from midline) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056640#pone.0056640-Felix1" target="_blank">[45]</a>.</p

NAc DBS elicits distal network BOLD changes.

<p>A–C) Areas of activation with left unilateral NAc stimulation at 5 V 130 Hz 500 µs (n = 7), normalized to a 3D pig brain template <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056640#pone.0056640-Saikali1" target="_blank">[44]</a> Significant activation q(FDR)<0.001 was observed in the anterior and dorsolateral prefrontal (red), insula (brown), parahippocampal (green) and cingulate cortex (blue). Decrease in BOLD signal was observed in the dorsal region of the thalamus (tan). Slice locations are presented in distance (mm) from the posterior commissure. D) Event-related analysis of the average time course for each region of interest was plotted as average percent change in BOLD signal from baseline vs. time (one scan is equal to TR = 3 seconds) using ten frames (30 seconds) prior to stimulation onset as the baseline. Duration of stimulation is marked by the vertical purple lines. In all regions of interest, there is a clear peak in percent change associated with stimulation.</p