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Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis.

Fink CG, Gliske S, Catoni N, Stacey WC - eNeuro (2015 May-Jun)

Bottom Line: Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing.Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner.These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physics & Astronomy and Neuroscience Program, Ohio Wesleyan University, Delaware, OH, USA.

ABSTRACT

High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100-250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very di cult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by di erent mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples.

No MeSH data available.


Related in: MedlinePlus

Effect of diminished inhibition on fast ripple incidence. Simulations were conducted in which 50 separate sharp waves were induced by intermittently activating pyramidal cells with noisy input (using a noise intensity of 0.77 nA2). Inhibitory connections from basket cells to all pyramidal cells were progressively removed. A fast ripple was defined to occur when the peak energy in the fast ripple band (>250 Hz) exceeded the peak energy in the ripple band (100–250 Hz). A, Proportion of sharp waves which exhibited fast ripples, as a function of percent inhibitory connections removed. Fast ripple incidence increased dramatically as inhibitory connections were lost. (Error bars represent SEM over 10 simulations, each with 50 induced sharp waves.) B–D, Example LFP’s and spectrograms for three levels of intact inhibition, each with three example sharp waves. FR, Fast ripple episode; R, ripple episode.
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Figure 5: Effect of diminished inhibition on fast ripple incidence. Simulations were conducted in which 50 separate sharp waves were induced by intermittently activating pyramidal cells with noisy input (using a noise intensity of 0.77 nA2). Inhibitory connections from basket cells to all pyramidal cells were progressively removed. A fast ripple was defined to occur when the peak energy in the fast ripple band (>250 Hz) exceeded the peak energy in the ripple band (100–250 Hz). A, Proportion of sharp waves which exhibited fast ripples, as a function of percent inhibitory connections removed. Fast ripple incidence increased dramatically as inhibitory connections were lost. (Error bars represent SEM over 10 simulations, each with 50 induced sharp waves.) B–D, Example LFP’s and spectrograms for three levels of intact inhibition, each with three example sharp waves. FR, Fast ripple episode; R, ripple episode.

Mentions: Because the model network was unable to generate fast ripples for any level of input when network inhibition was intact (Fig. 3), we investigated the effects of compromising network inhibition on fast ripple generation. Starting from the model shown in Figure 3 with a noise intensity of 0.77 nA2, we randomly disabled a specified percentage of basket-to-pyramidal cell GABAergic connections, then generated 50 consecutive sharp waves by transiently increasing the random synaptic input to pyramidal cells. This enabled determination of the proportion of sharp waves that included fast ripple events. (The peak frequency in the fast ripple band had to have higher spectral power than the peak frequency in the ripple band for at least 25% of the duration of the sharp wave in order to count as a fast ripple event.) From the results shown in Figure 5, disruption of inhibitory connections had a profound impact on the emergence of fast ripples: as more basket cell connections were lost, the same input that had previously generated only sharp wave-ripple events began to produce fast ripples as well. This result is similar to previous findings that decreased GABAergic transmission facilitates the emergence of fast ripples (Bragin et al., 2002a; Demont-Guignard et al., 2012).


Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis.

Fink CG, Gliske S, Catoni N, Stacey WC - eNeuro (2015 May-Jun)

Effect of diminished inhibition on fast ripple incidence. Simulations were conducted in which 50 separate sharp waves were induced by intermittently activating pyramidal cells with noisy input (using a noise intensity of 0.77 nA2). Inhibitory connections from basket cells to all pyramidal cells were progressively removed. A fast ripple was defined to occur when the peak energy in the fast ripple band (>250 Hz) exceeded the peak energy in the ripple band (100–250 Hz). A, Proportion of sharp waves which exhibited fast ripples, as a function of percent inhibitory connections removed. Fast ripple incidence increased dramatically as inhibitory connections were lost. (Error bars represent SEM over 10 simulations, each with 50 induced sharp waves.) B–D, Example LFP’s and spectrograms for three levels of intact inhibition, each with three example sharp waves. FR, Fast ripple episode; R, ripple episode.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487885&req=5

Figure 5: Effect of diminished inhibition on fast ripple incidence. Simulations were conducted in which 50 separate sharp waves were induced by intermittently activating pyramidal cells with noisy input (using a noise intensity of 0.77 nA2). Inhibitory connections from basket cells to all pyramidal cells were progressively removed. A fast ripple was defined to occur when the peak energy in the fast ripple band (>250 Hz) exceeded the peak energy in the ripple band (100–250 Hz). A, Proportion of sharp waves which exhibited fast ripples, as a function of percent inhibitory connections removed. Fast ripple incidence increased dramatically as inhibitory connections were lost. (Error bars represent SEM over 10 simulations, each with 50 induced sharp waves.) B–D, Example LFP’s and spectrograms for three levels of intact inhibition, each with three example sharp waves. FR, Fast ripple episode; R, ripple episode.
Mentions: Because the model network was unable to generate fast ripples for any level of input when network inhibition was intact (Fig. 3), we investigated the effects of compromising network inhibition on fast ripple generation. Starting from the model shown in Figure 3 with a noise intensity of 0.77 nA2, we randomly disabled a specified percentage of basket-to-pyramidal cell GABAergic connections, then generated 50 consecutive sharp waves by transiently increasing the random synaptic input to pyramidal cells. This enabled determination of the proportion of sharp waves that included fast ripple events. (The peak frequency in the fast ripple band had to have higher spectral power than the peak frequency in the ripple band for at least 25% of the duration of the sharp wave in order to count as a fast ripple event.) From the results shown in Figure 5, disruption of inhibitory connections had a profound impact on the emergence of fast ripples: as more basket cell connections were lost, the same input that had previously generated only sharp wave-ripple events began to produce fast ripples as well. This result is similar to previous findings that decreased GABAergic transmission facilitates the emergence of fast ripples (Bragin et al., 2002a; Demont-Guignard et al., 2012).

Bottom Line: Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing.Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner.These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physics & Astronomy and Neuroscience Program, Ohio Wesleyan University, Delaware, OH, USA.

ABSTRACT

High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100-250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very di cult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by di erent mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples.

No MeSH data available.


Related in: MedlinePlus