The disinhibited cortex as an attractor: Altered burst initiation reveals focal excitatory-inhibitory imbalance

The imbalance between cortical excitation and inhibition (E/I) underlies many neurological disorders; however, its early detection remains challenging. The burst suppression (BS) pattern, characterized by a globally suppressed cortical background punctuated by quasi-periodic bursts, provides a unique functional window. Under the BS state, wide-field imaging showed that bursts originated from discrete, flexible cortical foci and propagated in a stereotyped, highly synchronized manner. Given the established role of E/I imbalance in disrupting cortical synchrony and our prior observation that bursts preferentially arise near seizure focus, we hypothesized that a focal hyperexcitability would exert a concentration-dependent attraction on burst origin sites. To test this, we induced a graded, focal E/I imbalance in the cortex of mice (n = 26) via microinjections of the GABA_A antagonist bicuculline at subconvulsive concentrations during anesthesia-induced BS. Our analyses revealed that focal disinhibition reconfigured BS dynamics across multiple scales. First, at the local level, burst-associated calcium transients at the injection site showed a tendency toward reduced waveform complexity and an increased amplitude of the initial response peak. Second, at the global level, the functional synchrony between the disinhibited focus and the rest of the cortex was disrupted. Critically, burst origin sites were progressively attracted toward the imbalance focus in a concentration-dependent manner. Quantifying this spatial clustering via hemisphere-specific hotspot analysis confirmed a stronger attraction effect in the ipsilateral hemisphere. Together, these results demonstrate that the spatiotemporal pattern of BS serves as a sensitive and quantifiable readout for detecting and localizing focal cortical E/I imbalance.