Network asynchrony underlying increased broadband gamma power

Abstract

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike “contamination”) affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor.

Response outcome gates the effect of spontaneous cortical state fluctuations on perceptual decisions

“…Optical pulsatile activation (30 Hz) of the ACC to VC projection resulted in decreases in low-frequency LFP power (consistent with a decrease in our Synch measure, Fig. 1h,i) and increases in high-frequency power (consistent with an increase in FR 44,45 ) in the visual cortex -akin to our favorable state for accuracy after errors. Inter-estingly, a behavioral effect of either excitation or suppression of this projection was only observed when the manipulation was performed in the baseline period after errors.…”

Sensory processing dysregulations as reliable translational biomarkers inSYNGAP1haploinsufficiency

“…First, PV cells play a key role in generating and maintaining gamma oscillations in the brain 83,84 . In particular, recent studies have also shown that deficiency in PV interneuron-mediated inhibition contribute to increased baseline cortical gamma rhythm 79,85,86 , a phenotype we observed in both mutant mice and SYNGAP1-ID patients (Figure 2). Second, auditory habituation has been shown to involve an increase in inhibition 87,88 .…”

Broadband Dynamics Rather than Frequency-Specific Rhythms Underlie Prediction Error in the Primate Auditory Cortex

“…Contrary to the oscillatory narrow-band signals, such as alpha rhythm, broadband activity recorded with ECoG primarily reflects asynchronous neuronal firing (Buzsáki et al, 2012; Guyon et al, 2021; Henrie and Shapley, 2005; Hwang and Andersen, 2011; Li et al, 2019; Mukamel et al, 2005). Likewise, our earlier modeling of power-law changes in Broadband PCS suggests they reflect a change in mean population-averaged firing rate (Miller et al, 2009a; Miller, 2010).…”

“…Likewise, our earlier modeling of power-law changes in Broadband PCS suggests they reflect a change in mean population-averaged firing rate (Miller et al, 2009a; Miller, 2010). The association between broadband signals and neuronal spikes has been demonstrated both during passive tasks (Guyon et al, 2021; Manning et al, 2009) as well as in response to sensory stimulation (Henrie and Shapley, 2005; Hwang and Andersen, 2011; Li et al, 2019; Medvedev and Kanwal, 2004). While most of the evidence comes from visual neuroscience (e.g.…”

“…Post-synaptic potentials contribute to the rhythmic oscillations of different frequency bands (Buzsaki et al, 2012), reflecting neural synchrony at specific timescales. Contrary to this, empirical data analysis and modeling suggest that the average neuronal firing rate produces asynchronous, broadband changes across a wide frequency range (Buzsáki et al, 2012; Guyon et al, 2021; Henrie and Shapley, 2005; Hwang and Andersen, 2011; Li et al, 2019; Medvedev and Kanwal, 2004; Mukamel et al, 2005). Such rhythmic and broadband components of LFP signal can be decomposed using spectral principal component analysis (spectral PCA) (Miller et al, 2009a, 2009b, 2017; Miller, 2019), this way separating synchronous and asynchronous neural activity.…”