The time course of ventrolateral prefrontal cortex involvement in memory formation

Abstract

Human neuroimaging studies have implicated a number of brain regions in long-term memory formation. Foremost among these is ventrolateral prefrontal cortex. Here, we used double-pulse transcranial magnetic stimulation (TMS) to assess whether the contribution of this part of cortex is crucial for laying down new memories and, if so, to examine the time course of this process. Healthy adult volunteers performed an incidental encoding task (living/nonliving judgments) on sequences of words. In separate series, the task was performed either on its own or while TMS was applied to one of two sites of experimental interest (left/right anterior inferior frontal gyrus) or a control site (vertex). TMS pulses were delivered at 350, 750, or 1,150 ms following word onset. After a delay of 15 min, memory for the items was probed with a recognition memory test including confidence judgments. TMS to all three sites nonspecifically affected the speed and accuracy with which judgments were made during the encoding task. However, only TMS to prefrontal cortex affected later memory performance. Stimulation of left or right inferior frontal gyrus at all three time points reduced the likelihood that a word would later be recognized by a small, but significant, amount (approximately 4%). These findings indicate that bilateral ventrolateral prefrontal cortex plays an essential role in memory formation, exerting its influence between > or = 350 and 1,150 ms after an event is encountered.

Fig. 1.

Outline of the study phase of the experiment. Volunteers viewed sequences of words, presented one at a time and separated by 2–3 s. A living/nonliving judgment had to be made on each word. In different blocks, the task was either performed on its own or while transcranial magnetic stimulation (TMS) was administered to one of 3 sites (left anterior inferior frontal gyrus, right anterior inferior frontal gyrus, or vertex). The vertex served as a control site to assess nonspecific effects of TMS. The order of blocks was randomized across volunteers. During the TMS blocks, neural activity was disrupted on each trial with two consecutive TMS pulses separated by 40 ms (double-pulse TMS). Stimulation started at 350, 750, or 1,150 ms, randomly allocated across trials. Following all 4 blocks, volunteers performed a surprise recognition memory test incorporating confidence judgments.

Fig. 2.

Study task performance. Response times (bars; left axis) and response accuracy (squares; right axis) of living/nonliving judgments made while the task was performed on its own or while TMS was applied to the left inferior frontal gyrus (IFG), right IFG, or a control site (the vertex). Values are collapsed across time of stimulation. Error bars represent SEs.

Fig. 3.

Memory test performance. Recognition accuracy Pr (bars; left axis) and response bias Br (squares; right axis) for words studied without TMS or while TMS was applied to the left inferior frontal gyrus (IFG), right IFG, or a control site (the vertex). Values are collapsed across time of stimulation. Error bars represent SEs.