Phase-dependent neuronal coding of objects in short-term memory

Abstract

The ability to hold multiple objects in memory is fundamental to intelligent behavior, but its neural basis remains poorly understood. It has been suggested that multiple items may be held in memory by oscillatory activity across neuronal populations, but yet there is little direct evidence. Here, we show that neuronal information about two objects held in short-term memory is enhanced at specific phases of underlying oscillatory population activity. We recorded neuronal activity from the prefrontal cortices of monkeys remembering two visual objects over a brief interval. We found that during this memory interval prefrontal population activity was rhythmically synchronized at frequencies around 32 and 3 Hz and that spikes carried the most information about the memorized objects at specific phases. Further, according to their order of presentation, optimal encoding of the first presented object was significantly earlier in the 32 Hz cycle than that for the second object. Our results suggest that oscillatory neuronal synchronization mediates a phase-dependent coding of memorized objects in the prefrontal cortex. Encoding at distinct phases may play a role for disambiguating information about multiple objects in short-term memory.

Fig. 1.

Behavioral task, average spike rates, and local field potential (LFP) power. (A) Visual two-object short-term memory task. For each trial, monkeys remembered a sequence of two successively presented target objects. After a blank delay interval, the monkeys were shown an array of three different test objects, two of which were the target objects previously presented. The animals had to report the remembered target objects by saccading to them in the order of their initial display. This required the monkeys to remember the identity of both target objects and their order of presentation. For each trial, the two target objects and the third test object were drawn randomly from a set of four objects. A new and unique set of four objects was chosen for each recording day. The experimental design was fully balanced for object identity, presentation order, and object positions in the test array. (B) Time course of average spike rates (n = 140 sites). The shaded region indicates the SEM across recording sites. (C) Time-frequency representation of the average normalized LFP power (n = 140 sites, normalized by 1/frequency to enhance readability). Broken vertical lines indicate object on- and offsets. (D) Time-frequency representation of the average LFP components phase-locked and non-phase-locked to stimulus presentation (n = 140 sites). The stimulus-locked components are equivalent to the “evoked field” overlaid in white on its time-frequency representation. (Scale bar, 5 μV.)

Fig. 2.

Spike–local field potential (LFP) synchronization. (A) Time-frequency representation of the percentage of spike–LFP pairs that showed significant (P < 0.01) phase synchrony (n = 140 pairs). Any bias of synchrony due to modulations of firing rates was accounted for by stratifying the number of spikes across the time course of the trial. Black triangles mark 3 and 32 Hz. (B) Phase histogram of the preferred phases of spiking relative to the 32-Hz LFP during the entire trial (n = 140 pairs). The red line indicates a fitted von Mises distribution along with the average preferred phase and its bootstrap SEM. (Inset) Average preferred phase on a schematic LFP (standard cosine). (C) Spike-rate modulation by the 32-Hz LFP phase. Circles display the average spike rate for 12 phase bins (relative to the preferred spike phase) normalized by the average rate across all of the bins. The red line indicates a fitted von Mises distribution. (D and E) Preferred LFP phases of spiking and the modulation of spike rates by LFP phase for 3 Hz. For all panels, only synchrony not phase-locked to stimulus presentation was taken into account.

Fig. 3.

Phase-dependent coding. (A) Colored traces display the average information about the two target objects in firing rates measured as the percentage firing rate variance across trials explained by the identity of the first and second presented objects. Shaded regions indicate the SEM across sites (n = 140 sites). (B) Average normalized information in spikes during the second delay interval (2–3 s) about the identity of both objects as a function of local field potential frequency and phase (n = 103 pairs). Information (explained variance) was normalized by the average across phase. (C) Spectra of phase-dependent information for both objects during the second delay interval. Shaded regions indicate the bootstrap SEM across pairs (n = 103). Solid bars indicate significant phase dependence (P < 0.01 corrected, permutation test). Black triangles mark 3 and 32 Hz. Any phase dependence induced by stimulus-locked responses was discounted.

Fig. 4.

Order dependence of optimal phases. (A) Normalized information about the first and second presented object as a function of the 32-Hz LFP phase during the second delay interval (n = 103 pairs). Circles and bars display the normalized information for 12 phase bins and bootstrap SEMs. Solid traces display a cosine fit, the average optimally encoding phase, and its bootstrap SEM (n = 103 pairs). To the right, the optimally encoding phases and SEMs are displayed on a schematic LFP (standard cosine). The large panels display the data for the correct trials. The smaller panels with light colors display the data after replacing the correct trials with error trials. (B) Phase-dependent coding at 3 Hz (n = 103 pairs, same conventions as in A). Any phase dependence induced by stimulus-locked responses was discounted.

Fig. 5.

The 3-to-32-Hz phase–amplitude coupling. (A) Phase histogram of the 3-Hz local field potential (LFP) phases of the peak 32-Hz LFP amplitude (“preferred phase”) during the second delay interval (n = 140 pairs). The red line indicates a fitted von Mises distribution along with the average preferred phase and its bootstrap SEM. (Inset) Average preferred phase on a schematic LFP (standard cosine). (B) Average log-transformed 32-Hz LFP power for 12 bins of the 3-Hz phase (relative to the preferred phase) normalized by the average power across all of the phase bins. The red line indicates a fitted von Mises distribution. Only not stimulus-locked phase–amplitude coupling was taken into account.