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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

Effects of synaptic parameters on HFOs. LFPs were constructed as in Figure 9C, except that GABAergic synaptic rise and decay times were modified from their standard values (τrise = 1.5 ms; τdecay = 8.0 ms). A, B, Changing τdecay had little effect on the HFO output. C, D, Very fast τrise time (0.5 ms) enabled IPSPs to produce HFOs more robustly.
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Figure 10: Effects of synaptic parameters on HFOs. LFPs were constructed as in Figure 9C, except that GABAergic synaptic rise and decay times were modified from their standard values (τrise = 1.5 ms; τdecay = 8.0 ms). A, B, Changing τdecay had little effect on the HFO output. C, D, Very fast τrise time (0.5 ms) enabled IPSPs to produce HFOs more robustly.

Mentions: One major goal of this work is to determine the generic mechanisms that produce epileptic and normal HFOs. We sought to answer, independent of any network structure, what type of activity is necessary and sufficient to produce each type of HFO. As it is impossible to simulate all potential network configurations, we developed a more basic method of producing neural signals. We explicitly defined the onset times for a large number of either IPSP or AP waveforms (results shown in ). This model did not include any neuronal structure; it was simply a mathematical reconstruction of a number of IPSP or AP waveforms, using the same waveforms generated by the biophysical model. The goal of this model was to show, under completely controlled conditions, how the LFP would appear if it were generated purely by either type of waveform. The model allowed an explicit demonstration of the differences between these two cases, and also enabled exploration of the relationship between variability in cell firing and network output. To generate this output, we recorded from 200 μm away the LFP voltage produced by an AP in a single pyramidal cell in our biophysical model, as well as that produced by a basket cell IPSP onto a pyramidal cell. These two waveforms, which we denote hAP(t) and hPSP(t), were used as templates for the output of each AP or IPSP. We then simulated a population of cells producing these waveforms at specific times using the process described below. The AP waveform had an amplitude of 0.383 μV and a full-width at half-max duration of 0.65 ms, whereas the PSP waveform had corresponding values of 0.0237 μV and 15.3 ms. These parameters are consistent with those reported in previous studies (Gold et al., 2006; Bazelot et al., 2010).


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)

Effects of synaptic parameters on HFOs. LFPs were constructed as in Figure 9C, except that GABAergic synaptic rise and decay times were modified from their standard values (τrise = 1.5 ms; τdecay = 8.0 ms). A, B, Changing τdecay had little effect on the HFO output. C, D, Very fast τrise time (0.5 ms) enabled IPSPs to produce HFOs more robustly.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Effects of synaptic parameters on HFOs. LFPs were constructed as in Figure 9C, except that GABAergic synaptic rise and decay times were modified from their standard values (τrise = 1.5 ms; τdecay = 8.0 ms). A, B, Changing τdecay had little effect on the HFO output. C, D, Very fast τrise time (0.5 ms) enabled IPSPs to produce HFOs more robustly.
Mentions: One major goal of this work is to determine the generic mechanisms that produce epileptic and normal HFOs. We sought to answer, independent of any network structure, what type of activity is necessary and sufficient to produce each type of HFO. As it is impossible to simulate all potential network configurations, we developed a more basic method of producing neural signals. We explicitly defined the onset times for a large number of either IPSP or AP waveforms (results shown in ). This model did not include any neuronal structure; it was simply a mathematical reconstruction of a number of IPSP or AP waveforms, using the same waveforms generated by the biophysical model. The goal of this model was to show, under completely controlled conditions, how the LFP would appear if it were generated purely by either type of waveform. The model allowed an explicit demonstration of the differences between these two cases, and also enabled exploration of the relationship between variability in cell firing and network output. To generate this output, we recorded from 200 μm away the LFP voltage produced by an AP in a single pyramidal cell in our biophysical model, as well as that produced by a basket cell IPSP onto a pyramidal cell. These two waveforms, which we denote hAP(t) and hPSP(t), were used as templates for the output of each AP or IPSP. We then simulated a population of cells producing these waveforms at specific times using the process described below. The AP waveform had an amplitude of 0.383 μV and a full-width at half-max duration of 0.65 ms, whereas the PSP waveform had corresponding values of 0.0237 μV and 15.3 ms. These parameters are consistent with those reported in previous studies (Gold et al., 2006; Bazelot et al., 2010).

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