Signatures of Covert Neuron Loss in the Local Field Potential of Motor Cortex.

BACKGROUND

Covert stroke is understudied despite occurring 10 times for every symptomatic stroke and contributing to stroke's enormous global disease burden. For instance, does covert stroke replicate the neuroelectrophysiological spectrum impact of symptomatic stroke? We explored this by using our novel electrolytic lesioning platform to induce covert neuron loss.

METHODS

During a multimonth arm reaching task, electrolytic lesions were delivered to the motor cortex of 2 large animals (U: n=4; H: n=7). Effects on behavioral metrics and local field potential features (bandpowers, aperiodic/periodic parameters, time-frequency tensors) were measured using state space modeling and nonparametric permutation tests.

RESULTS

Task success was unaffected by lesions, but shifts in aperiodic structure reduced next-day γ bandpower (30-100 Hz; U: -1.38 μV2, P<1×10-3; H: -1.66 μV2, P=0.001) and sensorimotor rhythms spanning 8 to 45 Hz (∑SMR) were amplified (U: 8.68 μV2, P<1×10-3; H: 2.40 μV2, P=0.004). Additionally, state space modeling showed that perturbations to γ and ∑SMR outlasted any behavioral impact (Monkey U: Behavior = 1 d, γ= 2 d, ∑SMR = 2 d; Monkey H: Behavior = 0 d, γ= 3 d, ∑SMR = 1 d). Finally, tensor decomposition revealed interpretable, personalized perturbations to time-frequency dynamics.

CONCLUSION

The neural spectrum is more sensitive to neuron loss than previously understood and could be responsive to covert stroke. This work also motivates using electrolytic lesions to bridge covert and symptomatic regimes of neuron loss, advancing our causal understanding of poststroke spectrum and behavior.