Theta Rhythmopathy as a Cause of Cognitive Disability in TLE

Shuman, Tristan; Amendolara, Benjamin; Golshani, Peyman

doi:10.5698/1535-7511.17.2.107

Cited by 40 publications

(55 citation statements)

References 72 publications

(91 reference statements)

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“…The rhythm is also tuned by arousal and anxiety (Jeewajee, Lever, Burton, O'Keefe, & Burgess, 2008;Penley et al, 2013;Wells et al, 2013). Alterations of the pacemaker structure, sprouting connections between oscillators (Christenson et al, 2017;Dudek & Shao, 2004;Houser et al, 1990), changes in neuronal resonance properties (Marcelin et al, 2009;Wolfart & Laker, 2015) or different anxiety or arousal levels thus are potential causes for a frequency reduction (reviewed in Shuman et al, 2017). Worsening of the disease in chronic state might also have an impact on all of these processes and therefore progressively decrease theta frequency.…”

Section: Mechanisms Of Theta Frequency Reductionmentioning

confidence: 99%

“…Furthermore, memory deficits were correlated with changes in theta band oscillations (5–12 Hz, Chauvière et al, ; Inostroza et al, ). Since under healthy conditions these oscillations are tightly coupled to spatial navigation and memory in both, humans (Kahana, Sekuler, Caplan, Kirschen, & Madsen, ; Cornwell, Johnson, Holroyd, Carver, & Grillon, ; Miller et al, ) and rodents (Buzsáki & Moser, ), impairment of theta oscillations has been proposed as a potential cause for memory deficits in MTLE (Shuman, Amendolara, & Golshani, ). The rescue of hippocampal theta oscillation and improvement of spatial memory by septal theta stimulation during epileptogenesis further supported this (Lee et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model

et al. 2018

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Mesial temporal lobe epilepsy is characterized by focal, recurrent spontaneous seizures, sclerosis and granule cell dispersion (GCD) in the hippocampal formation. Changes in theta rhythm properties have been correlated with the severity of hippocampal restructuring and were suggested as a cause of memory deficits accompanying epilepsy. For severe sclerosis, it has even been questioned whether theta band oscillations persist. We asked how theta oscillations change with graded restructuring along the longitudinal hippocampal axis and whether these changes correlate with the overall severity of temporal lobe epilepsy. We recorded local field potentials in the medial entorhinal cortex and along the septo-temporal axis of the dentate gyrus at sites with different degrees of GCD in freely behaving epileptic mice. Theta frequency was decreased at all recording positions throughout the dentate gyrus and in the medial entorhinal cortex, irrespective of the extent of GCD or the rate of severe epileptic events. The frequency reduction by up to 1.7 Hz, corresponding to 1/3 octaves within the theta range, was present during rest, exploration and running. Despite the frequency reduction, theta oscillations remained coherent across the hippocampal formation and were modulated by running speed as in controls. The reduction in theta frequency thus is likely not a consequence of the local restructuring but rather a global phenomenon affecting the hippocampal formation as a whole.

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Section: Mechanisms Of Theta Frequency Reductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model

et al. 2018

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“…In particular, in chronically epileptic mice, new functional inhibitory connections form within the DG 6 , between CA1 and DG 7 , and even across hemispheres 25 . Concurrently, network activity is altered in the hippocampus of epileptic mice, with reductions in the power of theta oscillations that correlate with memory impairments [26][27][28] . In addition, changes in the synchrony of hippocampal rhythms have been hypothesized to underlie cognitive deficits 28,29 .…”

Section: Main Textmentioning

confidence: 99%

Breakdown of spatial coding and neural synchronization in epilepsy

Shuman

Aharoni

et al. 2018

Preprint

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Temporal lobe epilepsy causes significant cognitive deficits in both human patients and rodent models, yet the specific circuit mechanisms that alter cognitive processes remain unknown. There is dramatic and selective interneuron death and axonal reorganization within the hippocampus of both humans and animal models, but the functional consequences of these changes on information processing at the neuronal population level have not been well characterized. To examine spatial representations of epileptic and control mice, we developed a novel wire-free miniature microscope to allow for unconstrained behavior during in vivo calcium imaging of neuronal activity. We found that epileptic mice running on a linear track had severely impaired spatial processing in CA1 within a single session, as place cells were less precise and less stable, and population coding was impaired. Long-term stability of place cells was also compromised as place cells in epileptic mice were highly unstable across short time intervals and completely remapped across a week. Because of the large-scale reorganization of inhibitory circuits in epilepsy, we hypothesized that degraded spatial representations were caused by dysfunctional inhibition. To test this hypothesis, we examined the temporal dynamics of hippocampal interneurons using silicon probes to simultaneously record from CA1 and dentate gyrus during head-fixed virtual navigation. We found that epileptic mice had a profound reduction in theta coherence between the dentate gyrus and CA1 regions and altered interneuron synchronization. In particular, dentate interneurons of epileptic mice had altered phase preferences to ongoing theta oscillations, which decorrelated inhibitory population firing between CA1 and dentate gyrus. To assess the specific contribution of desynchronization on spatial coding, we built a CA1 network model to simulate hippocampal desynchronization.Critically, we found that desynchronized inputs reduced the information content and stability of CA1 neurons, consistent with the experimental data. Together, these results demonstrate that temporally precise intra-hippocampal communication is critical for forming the spatial code and that desynchronized firing of hippocampal neuronal populations contributes to poor spatial processing in epileptic mice. 3 Main Text:Temporal lobe epilepsy (TLE) is associated with disabling cognitive deficits 1,2 , interneuron cell death 3,4 , and large-scale anatomical reorganization of limbic circuits [5][6][7][8] in both human patients and rodent models. Following cell death, surviving interneurons from both CA1 and dentate gyrus (DG) sprout new local and long-range connections leading to altered timing and kinetics of inhibition 8-12 . These alterations are likely to have dramatic effects on spatial processing as the hippocampus relies on the precise timing of diverse interneuron subtypes that control excitatory inputs [13][14][15][16] . Indeed, initial studies have shown degraded spatial representations in epileptic rodents 17-20 , but i...

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“…Finally, given that network theta and gamma activity are often compromised in a variety of neurological and psychiatric disorders [85][86][87][88][89][90][91], and abnormal activities of hippocampal interneurons are often associated with these diseases [92][93][94][95][96][97][98][99][100], future research should also determine if disruption of intrinsic oscillations in one or more of the major interneuron subtypes occurs in neuropathological conditions such as epilepsy. The results from such research will provide new insights into the mechanisms underlying compromised hippocampal rhythmogenesis in various diseases, and could provide a basis for novel interventions to restore compromised hippocampal theta and gamma oscillations.…”

Section: Frequency Specific Hippocampal Interneuronsmentioning

confidence: 99%

The Critical Role of Intrinsic Membrane Oscillations

Lee¹,

Urbano²,

García‐Rill³

2018

Neurosignals

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Intrinsic, rhythmic subthreshold oscillations have been described in neurons of regions throughout the brain and have been found to influence the timing of action potentials induced by synaptic inputs. Some oscillations are sodium channel-dependent while others are calcium channel-dependent. These oscillations allow neurons to fire coherently at preferred frequencies and represent the main mechanism for maintaining high frequency network activity, especially in the cortex. Because cortical circuits are incapable of maintaining high frequency activity in the gamma range for prolonged periods, those processes dependent on continuous gamma band activity are subserved by subthreshold oscillations. As such, intrinsic oscillations, coupled with synaptic circuits, are essential to prolonged maintenance of such functions as sensory perception and “binding”, problem solving, memory, waking, and rapid eye movement (REM) sleep.

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Theta Rhythmopathy as a Cause of Cognitive Disability in TLE

Cited by 40 publications

References 72 publications

Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model

Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model

Breakdown of spatial coding and neural synchronization in epilepsy

The Critical Role of Intrinsic Membrane Oscillations

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