Residual cortical responses and network reorganization in inherited retinal degeneration: electrophysiological evidence
Retinitis pigmentosa (RP) progressively deprives the retina of input, but whether the responsiveness of the visual cortex declines in parallel, remains preserved, or increases through compensatory gain remains unclear. Indeed, a weaker visually evoked response cannot, on its own, distinguish these possibilities, since it is equally compatible with a passively degraded input and with an actively recalibrated cortex. We combined spatially resolved steady-state visual evoked potentials (SSVEPs), which index stimulus-driven activity, with transcranial magnetic stimulation combined with electroencephalography (TMS-EEG), which probes cortical reactivity independently of vision, in patients with RP and in healthy controls. Nine patients (PTs) with RP (five women, age range 28 to 69 years) and nineteen sex-, age-, and handedness-matched healthy controls (thirteen women, mean age 42.6 years) were tested. They underwent SSVEP recordings to stimuli presented at three eccentricities (central, intermediate, peripheral) and single-pulse TMS-EEG over the left and right occipital cortex and, as a non-visual control site, the dominant motor cortex. We quantified SSVEP amplitude and phase at 12 Hz, early TMS-evoked potentials, oscillatory power, inter-trial phase synchrony, and functional connectivity and graph-theoretical network measures derived from the weighted phase lag index. SSVEP amplitude followed the expected central-to-peripheral gradient: PTs were comparable to healthy controls at the center, reduced but still above their own resting baseline at intermediate eccentricity, and no longer distinguishable from baseline in the periphery; phase differed from controls in a quarter of the central and half of the intermediate sectors. Occipital stimulation elicited a larger early negative deflection after left-hemisphere stimulation in PTs compared to controls, a stronger beta-band event-related spectral perturbation after stimulation of either hemisphere, and stronger, more efficiently distributed post-stimulus connectivity, despite comparable pre-stimulus connectivity, resting motor threshold, and most early evoked components. The pattern was site- and hemisphere-specific: left occipital stimulation produced widespread, mainly contralateral effects; right occipital stimulation a more circumscribed ipsilateral one, and motor cortex stimulation showed altered alpha-band activity without the bilateral occipital beta effect. Together, these results show that progressive retinal deafferentation in RP does not produce a parallel decline in cortical responsiveness. Visually driven activity weakens with eccentricity, while direct cortical perturbation reveals preserved and, at selected sites, enhanced reactivity. This dissociation is consistent with a homeostatic increase in cortical gain rather than a uniform loss of cortical function, and indicates that the deafferented cortex retains, and in places strengthens, its capacity to respond as retinal input deteriorates.