Neural network functional connectivity (FC)

Neural network functional connectivity (FC) is defined as the temporal correlation of neurophysiological events between spatially distributed brain regions [12]. It represents a systems-level emergent property of the brain, reflecting how distinct areas integrate information and communicate to support complex cognitive and behavioral functions [2, 12]. Rather than being a single molecule or receptor, FC serves as a functional architecture that is often disrupted in various neurodegenerative and psychiatric conditions, such as Alzheimer's disease, schizophrenia, and bipolar disorder [1, 3, 4]. Pharmacological agents do not bind to functional connectivity directly; instead, they modulate it indirectly by acting on molecular targets like receptors and transporters that regulate synaptic plasticity and neurotransmitter systems [4, 8]. Furthermore, FC is increasingly used as a therapeutic target for neuromodulation techniques like transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS), where interventions are specifically designed to normalize aberrant connectivity patterns [5, 13]. As a biomarker, it offers significant potential for early diagnosis, patient stratification, and monitoring treatment efficacy in central nervous system drug development [2, 6, 13].

Other names

Functional connectivityIntrinsic functional connectivityResting-state functional connectivityBrain network connectivityNeural connectivity

Pharmacological agents modulate neural network functional connectivity indirectly by altering synaptic transmission, neurotransmitter levels (e.g., acetylcholine, dopamine, glutamate), and neuronal excitability, which shifts the temporal synchronization of activity between spatially distinct brain regions [4, 8].