Low-beta repetitive transcranial magnetic stimulation to human dorsolateral prefrontal cortex during object recognition memory sample presentation, at a task-related frequency observed in local field potentials in homologous macaque cortex, impairs subsequent recollection but not familiarity

Abstract

According to dual-process signal-detection (DPSD) theories, short- and long-term recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to these processes, but frequency-specific neuronal activities are considered to play a key role. In Experiment 1, nonhuman primate (NHP) local field potential (LFP) electrophysiological recordings in macaque left dorsolateral PFC (dlPFC) revealed performance-related differences in a low-beta frequency range during the sample presentation phase of a visual object recognition memory task. Experiment 2 employed a similar task in humans and targeted left dlPFC (and vertex as a control) with repetitive transcranial magnetic stimulation (rTMS) at 12.5 Hz during occasional sample presentations. This low-beta frequency rTMS to dlPFC decreased DPSD derived indices of recollection, but not familiarity, in subsequent memory tests of the targeted samples after short delays. The same number of rTMS pulses over the same total duration albeit at a random frequency had no effect on either recollection or familiarity. Neither stimulation protocols had any causal effect upon behaviour when targeted to the control site (vertex). In this study, our hypotheses for our human TMS study were derived from our observations in NHPs; this approach might inspire further translational research through investigation of homologous brain regions and tasks across species using similar neuroscientific methodologies to advance the neural mechanism of recognition memory in primates.

Keywords: prefrontal cortex; primate; rTMS; recognition memory; recollection.

FIGURE 1

Nonhuman primate (NHP) recognition memory task structure and recording sites from dlPFC in two NHPs. Panel (a) depicts the structure of one trial in the electrophysiological study in Experiment 1. The NHPs initiated the task by holding the key touch device once the red dot cue appeared, after which a sample object image was shown on the screen behind the red dot cue (encoding phase). The NHPs were required to keep holding the key touch device after which the red key touch cue disappeared, then the NHPs were trained to release their hands from the key touch prompting the commence of the delay (1,000 ms) between sample and choice phases. Then, after the delay period another key touch red dot cue appeared, animals were required to hold the key touch again until the red cue disappeared. After the two choice stimuli (one an object image and the other a black circle) appeared, animals were trained to make a choice to the touchscreen to either the object test‐image stimulus or to the black circle. Just as in the human task in Figure 2 for Experiment 2, in ‘match trials’, the black circle was presented with an identical image to one of the preceding sample, whereas in ‘nonmatch trials’, the black circle was presented with a novel stimulus not seen before. Animals were trained to touch the test item if they remembered the test item was a match but to touch the black circle if they thought the test item was a nonmatch; accordingly, the responses could be separated into hits, misses, correct rejections and false alarms as indicted. Panel (b): recording locations in macaque lateral prefrontal cortex (PFC); both recording sites were anterior to the superior arcuate sulcus (SAR) and inferior arcuate sulcus (IAR), located above the principal sulcus (PS) in Monkey A and around the PS in Monkey B, which were marked by grey areas

FIGURE 2

Human recognition memory task structure. The figure depicts the task structure for one block of trials in the transcranial magnetic stimulation (TMS) study. Twelve sample object images were sequentially presented for 480 ms with an interstimuli interval of 350 ms. Six repetitive TMS (rTMS) pulses (at beta frequency or at random frequency) or no stimulation were given during the sample presentation for four out of the 12 samples in the list (the different stimulation protocols were never intermixed within the same block of trials). Then, after a delay of 1,000 ms, 12 test trials followed (the right half of the figure shows the procedure for one of these 12). Just as in the NHP task in Figure 1a for Experiment 1, in ‘match trials’, the black circle was presented with an identical image to one of the preceding sample; in ‘nonmatch trials’, the black circle was presented with a novel stimulus not seen before. Participants were previously instructed to touch the test item if they remembered the test item was a match but to touch the black circle if they thought the test item was a nonmatch; accordingly, the responses could be separated into hits, misses, correct rejections and false alarms as indicted. Each test trial in this human version of the task lasted maximally 5,000 ms and ended with a confidence judgement indicated by the participant by their making a finger gesture as described in the main text. The intertrial interval was 1,000 ms

FIGURE 3

Time‐frequency spectrogram for induced local field potential (LFP) power and averaged LFP power in alpha/low‐beta band (10–15 Hz) from dorsolateral prefrontal cortex (dlPFC) in the sample presentation epoch in two nonhuman primates (NHPs) in Experiment 1. Panel (a): The areas of statistically significant differences of LFPs between pre‐ and post‐sample periods in macaque dlPFC were highlighted by a black outline in hit–miss contrast LFP difference spectrums; sample onset is indicated by 0 ms on this figure. Panel (b): Average time course of the LFP power in alpha/low beta (10–15 Hz) before and after sample onset (indicated by a vertical black line) in two NHPs. In each panel, blue line reflects averaged LFP power during sample presentation in hit trials; red line reflects averaged LFP power during sample presentation in miss trials. Error bars are the standard errors of the mean (SEMs) of each frequency band. The black line indicates the period when the gradient for each trial type was calculated. * and ** indicate a significant larger gradient for hit trial than miss trial at p < .05 and p < .01, separately

FIGURE 4

Stimulation sites for each group of human participants and within‐block analysis for the effects of transcranial magnetic stimulation (TMS) upon recollection and familiarity in each human participant group in Experiment 2. Panel (a): Lateral and frontal view of the human brain depicting stimulation sites for repetitive TMS (rTMS) to dorsolateral prefrontal cortex (dlPFC) (red) and vertex (blue). Panel (b): Averaged receiver‐operating characteristics (ROCs) fitted for the recognition data under beta frequency stimulation with samples targeted with rTMS (+) or without rTMS (−). Accordingly, the R and F indices were labelled as R+, R−, F+ and F−. The ROCs depict decreased recollection under beta frequency stimulation with rTMS to dlPFC (but no change for vertex). Panels (c) and (d): Raincloud plots presenting the recollection index (Panel c) and familiarity index (Panel d) in dlPFC (red) and vertex (blue) in R+, R−, F+ and F− conditions. Circles are individual data; circles with black edge colour show the average of group data; distributions show probability density function of data points. ** indicates p < .01

FIGURE 5

Between‐block analysis for the effects of transcranial magnetic stimulation (TMS) upon hit rate, recollection and familiarity indices in Experiment 2. Panels (a)–(c): Raincloud plots presenting the hit rate in match choice trials (Panel a), the mean recollection index (Panel b) and familiarity index (Panel c) in dlPFC (red) and vertex (blue) under beta frequency stimulation, random frequency stimulation and no stimulation. Circles are individual data; circles with black edge colour show the average of group data; distributions show probability density function of data points. ** indicates p < .01