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Figure 1. (A) The panel illustrates the encoding block design. Vagus nerve stimulation (VNS) was set to a 30 second ‘on’ / 66 second ‘off’ cycle as the patient viewed randomized 1 second presentations of positive, negative, and neutral words (representing discrete non-overlapping events). During the first of three encoding blocks, the patient was scanned using fMRI, signaling the onset of the VNS before scanning by a button press. (B) Across recognition memory blocks performed 20 minutes after each of the three encoding blocks, the patient made significantly more recognition errors to words encoded when the stimulator was active (i.e., in the 30 second ‘on’ period). This effect was almost entirely attributable to interference with the encoding of negative words (which, compared with normative data were relatively enhanced when the stimulator was ‘off’). The bar chart depicts the patient’s recognition memory performance for each word category across all recognition blocks (filled = stimulator ‘on’ at encoding). (C) Activity in a discrete set of brain regions reflected the selective behavioral impact of VNS on the encoding of negative words. VNS enhanced the activity brain stem (pons) ventromedial prefrontal cortex, right anterior insula/lateral orbitofrontal (area 47) cortex, and frontal pole during the processing of negative (but not positive or neutral) words that were subsequently recognized. Interestingly, activity within these regions, particularly area 47 and frontal pole, also predicted subsequent forgetting of words during the first encoding task, illustrated in a conjunction analysis depicted in 2 panels on the right. Significant activity relating to this interaction is plotted on a normalized T2*weighted echoplanar volume from the patient to illustrate fully the field of view. Data are presented at p < .001, uncorrected for clusters of 10 or more contiguous voxels. Peak coordinates and magnitudes of the effects are given in Table 1.
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