Working memory (WM) is crucial for retaining and manipulating a limited amount of information for short periods. It underpins a wide range of cognitive functions, including reasoning, learning, and comprehension. Cognitive control is essential for protecting the persistent activity in the hippocampus required for WM. This study investigates how theta-gamma phase-amplitude coupling (TG-PAC) coordinates the interactions between frontal control and hippocampal activity to regulate WM storage. Understanding these mechanisms can shed light on fundamental processes of cognition and potential targets for interventions in cognitive disorders.
Methods
Participants
The study involved 36 patients undergoing neurosurgery, who performed a WM task while single-neuron and local field potential (LFP) activity were recorded from the medial frontal cortex and medial temporal lobe (MTL). These patients provided a unique opportunity to directly measure neuronal activity in these regions, offering insights that are not possible through non-invasive methods.
Behavioral Task
Participants were shown one (load 1) or three (load 3) pictures sequentially and asked to maintain them in WM for 2.5-2.8 seconds. They were then presented with a probe stimulus to identify if it matched the memorized items. This task design allowed for the assessment of WM under varying cognitive loads, providing a robust framework for examining how neural mechanisms scale with task demands.
Data Recording and Analysis
- Recorded 1,454 single neurons and 1,922 microwire channels with LFP across the hippocampus, amygdala, pre-supplementary motor area (pre-SMA), dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC).
- Estimated PAC as a function of low-frequency (2-14 Hz) phase and high-frequency (30-150 Hz) power, focusing on how these signals interact to support WM.
- Analyzed the modulation indices for theta to low-gamma and theta to high-gamma PAC to determine the strength and significance of these interactions.
Results
Behavioral Findings
Participants showed higher accuracy and faster response times in load 1 trials compared to load 3 trials, indicating increased cognitive control demand with higher memory load. This suggests that as the number of items held in WM increases, the cognitive system requires more robust control mechanisms to maintain performance.
Hippocampal PAC and Memory Load
Theta-high-gamma PAC was strongest in the hippocampus and was significantly reduced in load 3 compared to load 1 trials. Faster reaction times were associated with stronger single-trial estimates of TG-PAC. This indicates that effective WM maintenance relies on the synchronization of theta and gamma rhythms in the hippocampus, with disruptions in this coupling leading to performance deficits.
Category Cells and WM Maintenance
Identified category neurons in the hippocampus, amygdala, and vmPFC that exhibited stimulus-specific persistent activity during the WM maintenance period. Category neurons in the MTL, but not the vmPFC, showed higher firing rates (FRs) for preferred stimuli during WM maintenance, highlighting the role of these neurons in encoding and maintaining specific information within WM.
PAC Neurons
Selected PAC neurons based on their firing rates being modulated by the interaction between theta-phase and gamma amplitude. A subset of these PAC neurons overlapped with category neurons in the hippocampus and amygdala, suggesting that these neurons play a dual role in encoding specific WM content and coordinating the temporal dynamics necessary for maintaining this information.
Spike-Field Coherence (SFC)
High-gamma-band SFC was stronger in preferred trials for category neurons in the hippocampus, indicating synchronization with gamma LFPs. This effect was absent in non-preferred trials and in the amygdala, suggesting that hippocampal neurons specifically synchronize their activity to gamma rhythms when encoding preferred WM content.
Cross-Regional SFC
Hippocampal PAC neurons showed stronger theta-band SFC with vmPFC LFPs in load 3 trials, suggesting enhanced cognitive control. This effect was not observed for other frontal regions or for amygdala PAC neurons, indicating a specific interaction between the hippocampus and vmPFC in managing high WM loads.
Discussion
Mechanisms of Cognitive Control
The study demonstrates that TG-PAC in the hippocampus integrates cognitive control and WM storage across brain areas. Hippocampal PAC neurons modulate the population code through noise correlations with persistently active neurons, enhancing WM fidelity. This mechanism allows for the fine-tuning of neuronal activity to support the precise maintenance of information within WM.
Implications for Working Memory Models
The findings support a multicomponent model of WM, where frontal control processes regulate the maintenance of WM content in storage-related areas like the hippocampus. TG-PAC provides a mechanism for top-down control over sensory-driven processes, ensuring that relevant information is maintained and irrelevant information is suppressed.
Future Directions
Future research should explore the detailed mechanisms of PAC-mediated cognitive control and its role in other cognitive functions like attention, decision-making, and long-term memory retrieval. Understanding these mechanisms could inform the development of interventions for cognitive disorders involving WM deficits, such as ADHD and schizophrenia.
Conclusion
This study provides strong evidence that theta-gamma PAC in the hippocampus plays a critical role in integrating cognitive control and WM storage. The dynamic interactions between frontal and hippocampal neurons, mediated by TG-PAC, enhance the fidelity of WM representations. These findings highlight the importance of cross-frequency coupling in supporting cognitive functions and offer potential targets for therapeutic interventions in cognitive disorders.
References
For further details, you can access the full study here.
