Cross-frequency coupling (CFC) is a mechanism by which information is transferred between different spatial and temporal scales in the brain, enabling effective computation and synaptic modification. It involves the statistical relationship between the phase of a low-frequency brain rhythm and the amplitude of a high-frequency component. This coupling plays a functional role in neuronal computation, communication, and learning, as it allows for the integration of activity across multiple scales. Low-frequency rhythms are dynamically entrained by both external sensory input and internal cognitive events, while high-frequency activity reflects local cortical processing. CFC can modulate high-frequency power in response to sensory, motor, and cognitive events, and its strength varies across brain areas and tasks. Phase-amplitude CFC has been observed in various brain regions, including the hippocampus, basal ganglia, and neocortex, and is associated with cognitive functions such as memory and learning. Studies show that CFC strength correlates with performance in learning tasks, suggesting a functional role in learning and memory. For example, in a learning task, hippocampal CFC strength increased over time as performance improved, indicating that CFC may regulate synaptic connections vital for memory and learning. CFC is also involved in attention and sensory processing, with phase-amplitude coupling influencing the timing and synchronization of neuronal activity. This coupling can be modulated by different brain rhythms, such as theta and gamma, and is essential for coordinating fast, spike-based computation with slower, behaviorally-relevant events. The cellular and network origins of CFC involve interactions between different neuronal populations, including inhibitory interneurons and excitatory pyramidal cells. The dynamic regulation of CFC strength suggests that it has the necessary temporal resolution to modulate distinct functional networks. CFC is also involved in the regulation of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), which are critical for learning and memory. Overall, CFC plays a key role in integrating functional systems across multiple spatiotemporal scales, supporting cognitive processes such as attention, learning, and memory.Cross-frequency coupling (CFC) is a mechanism by which information is transferred between different spatial and temporal scales in the brain, enabling effective computation and synaptic modification. It involves the statistical relationship between the phase of a low-frequency brain rhythm and the amplitude of a high-frequency component. This coupling plays a functional role in neuronal computation, communication, and learning, as it allows for the integration of activity across multiple scales. Low-frequency rhythms are dynamically entrained by both external sensory input and internal cognitive events, while high-frequency activity reflects local cortical processing. CFC can modulate high-frequency power in response to sensory, motor, and cognitive events, and its strength varies across brain areas and tasks. Phase-amplitude CFC has been observed in various brain regions, including the hippocampus, basal ganglia, and neocortex, and is associated with cognitive functions such as memory and learning. Studies show that CFC strength correlates with performance in learning tasks, suggesting a functional role in learning and memory. For example, in a learning task, hippocampal CFC strength increased over time as performance improved, indicating that CFC may regulate synaptic connections vital for memory and learning. CFC is also involved in attention and sensory processing, with phase-amplitude coupling influencing the timing and synchronization of neuronal activity. This coupling can be modulated by different brain rhythms, such as theta and gamma, and is essential for coordinating fast, spike-based computation with slower, behaviorally-relevant events. The cellular and network origins of CFC involve interactions between different neuronal populations, including inhibitory interneurons and excitatory pyramidal cells. The dynamic regulation of CFC strength suggests that it has the necessary temporal resolution to modulate distinct functional networks. CFC is also involved in the regulation of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), which are critical for learning and memory. Overall, CFC plays a key role in integrating functional systems across multiple spatiotemporal scales, supporting cognitive processes such as attention, learning, and memory.