Sustained neural activity patterns during working memory in the human medial temporal lobe

Abstract

In contrast to classical findings that the medial temporal lobe (MTL) specifically underlies long-term memory, previous data suggest that MTL structures may also contribute to working memory (WM). However, the neural mechanisms by which the MTL supports WM have remained unknown. Here, we exploit intracranial EEG to identify WM-specific sustained activity patterns with the highest temporal and spatial resolution currently available in humans. Using a serial Sternberg paradigm, we found a positive shift of the direct current (DC) potential and a long-lasting decrease in MTL gamma-band activity during maintenance of a single item, reflective of a sustained reduction in neural activity. Maintenance of an increasing number of items elicited an incrementally negative shift of the DC potential and an increase in MTL gamma-band activity. In addition, the paradigm was conducted in healthy control subjects using functional magnetic resonance imaging. This confirmed that our results were not caused by pathological processes within the MTL, and that this region was indeed specifically activated during the task. Our results thus provide direct evidence for sustained neural activity patterns during working memory maintenance in the MTL, and show that these patterns depend on WM load.

Figure 1.

Overview of the paradigm.

Figure 2.

Behavioral results. Top, Accuracy of the entire group of 34 subjects, of the 11 patients, and of the 23 normal subjects as a function of memory load. Bottom, Reaction time. Error bars indicate SEM.

Figure 3.

Positive shift of the DC potential during maintenance of a single item turning increasingly negative during maintenance of multiple items. Left column, Averaged hippocampal contacts; right column, averaged rhinal contacts in trials with one (light gray), two (dark gray), and four items (black).

Figure 4.

Build-up of the negative shift of the DC potential during encoding of subsequent items in trials with four items. Left column, Averaged hippocampal contacts; right column, averaged rhinal contacts. Darker shades of gray indicate items later in the trial.

Figure 5.

Decreased gamma power during maintenance of a single item and increasing gamma power during maintenance of multiple items. Trials with one item (left), two items (medium), and four items (right column). a, b, Power of iEEG from hippocampal (a) and rhinal (b) contacts. The plots on the right display normalized power values in the gamma frequency range (20–98 Hz) for trials with one item (light gray), two items (dark gray), and four items (black). Error bars indicate SEM.

Figure 6.

Activation during encoding and maintenance period regardless of memory load. a, During encoding, we observed bilateral activation in the prefrontal cortex as well as in higher visual regions. Parameter estimates for different memory loads are shown for the contrast estimates in the most activated voxel in the left middle frontal gyrus (mean ± SD). b, Activation pattern during maintenance compared with rest. Parameter estimates are shown for the contrast estimates in the most activated voxel in the left inferior occipital gyrus (mean ± SD). In none of these contrasts did we observe an activation of MTL regions.

Figure 7.

Memory load-dependent activation during processing of an increasing number of items during encoding and maintenance. a, b, Memory load-dependent hippocampal activation during encoding (a) and maintenance (b). The right column shows parameter estimates for contrast estimates of the most activated voxel in the left MTL in each condition (mean ± SD).