Bidirectional Frontoparietal Oscillatory Systems Support Working Memory

Abstract

The ability to represent and select information in working memory provides the neurobiological infrastructure for human cognition. For 80 years, dominant views of working memory have focused on the key role of prefrontal cortex (PFC) [1-8]. However, more recent work has implicated posterior cortical regions [9-12], suggesting that PFC engagement during working memory is dependent on the degree of executive demand. We provide evidence from neurological patients with discrete PFC damage that challenges the dominant models attributing working memory to PFC-dependent systems. We show that neural oscillations, which provide a mechanism for PFC to communicate with posterior cortical regions [13], independently subserve communications both to and from PFC-uncovering parallel oscillatory mechanisms for working memory. Fourteen PFC patients and 20 healthy, age-matched controls performed a working memory task where they encoded, maintained, and actively processed information about pairs of common shapes. In controls, the electroencephalogram (EEG) exhibited oscillatory activity in the low-theta range over PFC and directional connectivity from PFC to parieto-occipital regions commensurate with executive processing demands. Concurrent alpha-beta oscillations were observed over parieto-occipital regions, with directional connectivity from parieto-occipital regions to PFC, regardless of processing demands. Accuracy, PFC low-theta activity, and PFC → parieto-occipital connectivity were attenuated in patients, revealing a PFC-independent, alpha-beta system. The PFC patients still demonstrated task proficiency, which indicates that the posterior alpha-beta system provides sufficient resources for working memory. Taken together, our findings reveal neurologically dissociable PFC and parieto-occipital systems and suggest that parallel, bidirectional oscillatory systems form the basis of working memory.

Keywords: directional connectivity; executive control; frontal lesions; graph theory; oscillations; parietal cortex; prefrontal cortex; working memory.

Conflict of interest statement

This work was conducted without any financial or other obligation that might be construed as a potential conflict of interest.

Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1. PFC patient lesion overlap, working memory task design, and accuracy

(A) Reconstruction of the extent of PFC lesion overlap for all 14 patients normalized to the left hemisphere. Color scale = number of patients with lesions at the specified site. See alsoFigures S1–S3 and Tables S1–S2. (B) Single-trial lateralized working memory task design. Following a 2-sec pretrial fixation interval, subjects were cued to focus on either IDENTITY or RELATION information. Then, two common shapes were presented for 200 msec each to the left or right visual hemifield in a specific spatiotemporal configuration (i.e., top/bottom spatial and first/second temporal positions). After a 900- or 1150-msec jittered maintenance fixation interval, the test prompt appeared, followed by an active processing fixation interval of the same length. Working memory was tested in a two-alternative forced choice test, resulting in a 0.5 chance rate. In the identity test (top), subjects indicated whether the pair was the SAME pair they just studied (correct response: no). In the spatiotemporal relation test (bottom), subjects indicated which shape fit the TOP/BOTTOM spatial or FIRST/SECOND temporal relation prompt (correct response for prompt TOP or SECOND: circle). See alsoFigures S2–S3. (C) Mean working memory task accuracy by group. Patient accuracy was attenuated relative to controls (p < 7×10−5). ** = significant result; error bars = SEM; CTRL, controls; PFC, PFC patients; VHF, visual hemifield. See alsoTable S3. (D) Single-subject histograms of working memory task accuracy by visual hemifield presentation. Accuracy did not differ by visual hemifield presentation (uncorrected p > 0.05). DIST, distribution; CTRL, controls; PFC, PFC patients. See alsoTable S3.

Figure 2. Diminished low-theta power in lesioned PFC at active processing

(A) Mean task-induced low-theta (3–4 Hz) hemispheric asymmetry in PFC over active processing by group when stimuli were presented to the lesioned visual hemifield. Low-theta power was diminished in patients in channels over the lesion, relative to the homologous intact-hemisphere channels (Group × Hemisphere pcluster = 0.04). Left panel: Significant effects are marked in black/gray and masked per channel on the BioSemi-64 topography (inset). Right panel: Scalp distributions of power and hemispheric difference z-scores are presented for the period of significant effects. While anterior theta power appears elevated in patients relative to controls, the contrast did not survive statistical testing (Group pcluster > 0.61). Shading = SEM; Z-DIFF, difference between lesioned- and intact-hemisphere z-scored power; VHF, visual hemifield. See alsoFigure S4. (B) Equivalent to (A): Similar low-theta power effects were observed when stimuli were presented to the intact visual hemifield (Group × Hemisphere pcluster = 0.036).

Figure 3. Diminished PFC ➔ parieto-occipital delta-theta PSI in patients

(A) Mean task-induced delta-theta (2–7 Hz) PSI over encoding, maintenance, and active processing by group when stimuli were presented to the lesioned visual hemifield. Left panel: Single-subject analyses revealed parieto-occipital ➔ PFC PSI at the end of encoding in both groups (baseline-corrected z ≤ −10, p < 2×10−23). Controls then exhibited PFC ➔ parieto-occipital PSI at mid-maintenance (z > 1.96, p < 0.05) and early processing (z ≥ 10, p < 2×10−23), while patients exhibited zero directionality (z < 1.96, p > 0.05). Right panel: Group differences were maximal during active processing so that PFC damage impacted the bilateral central-posterior connectome (Group pcluster < 0.05). Significant effects are masked per channel and 100-msec timepoint on the BioSemi-64 topography for the period of significant effects (marked in black/gray on the left). Shading = SEM; CTRL, controls; PFC, PFC patients; ** = significant result. (B) Equivalent to (A): Similar delta-theta PSI effects were observed when stimuli were presented to the intact visual hemifield.

Figure 4. Independent parieto-occipital ➔ PFC alpha-beta PSI

(A) Mean task-induced alpha-beta (9–24 Hz) PSI at encoding, maintenance, and active processing by group when stimuli were presented to the lesioned visual hemifield. Single-subject analyses revealed parieto-occipital ➔ PFC PSI (baseline-corrected z < −1.96, p < 0.05) that did not differ between groups (Group pcluster > 0.05). Shading = SEM; CTRL, controls; PFC, PFC patients. (B) Equivalent to (A): Similar alpha-beta PSI effects were observed when stimuli were presented to the intact visual hemifield. (C) Schematic of neurological dissociations in frontoparietal PSI. PFC ➔ parieto-occipital delta-theta PSI was abolished with PFC damage, while parieto-occipital ➔ PFC alpha-beta PFC was unaffected, revealing a posterior alpha-beta system that is independent of PFC.