Mechanisms of cognitive impairment in temporal lobe epilepsy: A systematic review of resting-state functional connectivity studies

Ives‐Deliperi, Victoria; Butler, James

doi:10.1016/j.yebeh.2020.107686

Cited by 43 publications

(41 citation statements)

References 55 publications

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“…Collectively, it is reasonable to consider that the functional disconnection between these regions within two subsystems of the DMN could give rise to the disruption and inefficiency of essential processes involved in VSWM, which would manifest as worse VSWM performances in rTLE patients. This is consistent with the review of Ives-Deliperi and Butler ( 35 ) concerning about the resting state functional connectivity alteration in rTLE patients with VSWM deficit, in which they found significant decline of RSFC between medial temporal network and DMN, as well as within the frontal-insula parietal network.…”

Section: Discussionsupporting

confidence: 92%

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy

Chen

et al. 2021

Front. Neurol.

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Visuospatial working memory (VSWM) impairment is common in patients with right temporal lobe epilepsy (rTLE). The posterior hippocampus is critical for spatial memory, but the contributions of the different subfields to VSWM deficits remain unclear. Forty-six rTLE patients and 42 healthy controls (HCs) were recruited. Resting-state fMRI (rsfMRI) and structural MRI scans were administered, followed by a VSWM_Nback test. The right posterior hippocampus was automatically segmented, and the surface-based functional connectivity (SBFC) of the subiculum (Sub), CA1, CA3, dentate gyrus (DG), hippocampal tail, and right entorhinal cortex (EC) were compared between groups. Correlation analysis was performed between the altered SBFC and VSWM_Nback scores for rTLE patients. The results showed that rTLE patients underperformed in the VSWM_Nback test, with longer mean reaction time of accurate response (ACCmeanRT) in 0back and 2back condition, lower hit rate (HR) and higher false alarm rate (FAR) in 2back condition. Compared with HCs, the rCA3 in the rTLE group exhibited decreased SBFC with inferior parietal cortex (IPC), temporal lateral cortex (TLC), and posterior visual cortex (PVC) in the right hemisphere as well as the bilateral dorsolateral prefrontal cortex (DLPFC). The SBFC of the rEC and right anterior cingulate cortex (rACC) increased in the rTLE group. Within the rTLE group, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC were correlated with worse VSWM performance. Therefore, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC might be the critical aberrant FC pattern reflecting VSWM impairment in rTLE patients. The mechanism might involve functional disruption between the core subsystem and the medial temporal subsystem of the default mode network (DMN).

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Section: Discussionsupporting

confidence: 92%

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy

Chen

et al. 2021

Front. Neurol.

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Section: Introductionmentioning

confidence: 99%

“…Temporal lobe epilepsy (TLE) is a type of focal epilepsy that is commonly drug-resistant ( 1 ) and is highly comorbid with cognitive deficits ( 2 ). Cognitive comorbidities, including deficits in memory, attention, and executive function have been reported in 40–95% of patients with TLE ( 2 ). Unfortunately, currently available anti-seizure mediations do not address cognitive defects and in some cases can aggravate intellectual decline in individuals with epilepsy ( 3 ), supporting the need for novel therapies.…”

Section: Introductionmentioning

confidence: 99%

“…In TLE, the hippocampus is often damaged as evidenced by the presence of extensive gliosis and severe neuronal loss, also known as hippocampal sclerosis. These disruptions to the hippocampal circuitry interfere with essential functions such as processing and consolidation of short- and long-term memories thereby resulting in learning and memory dysfunctions ( 2 ). Extensive research in animal models of acquired TLE, typically induced with a single episode of status epilepticus (SE), a long-lasting seizure (>1 h), support that SE-induced hippocampal injury in an otherwise healthy system contributes to epileptogenesis, as well as memory decline ( 4 ); though the mechanisms underlying memory loss after SE and TLE are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of Microgliosis With the Colony-Stimulating Factor 1 Receptor Inhibitor PLX3397 Does Not Attenuate Memory Defects During Epileptogenesis in the Rat

et al. 2021

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Events of status epilepticus (SE) trigger the development of temporal lobe epilepsy (TLE), a type of focal epilepsy that is commonly drug-resistant and is highly comorbid with cognitive deficits. While SE-induced hippocampal injury, accompanied by gliosis and neuronal loss, typically disrupts cognitive functions resulting in memory defects, it is not definitively known how. Our previous studies revealed extensive hippocampal microgliosis that peaked between 2 and 3 weeks after SE and paralleled the development of cognitive impairments, suggesting a role for reactive microglia in this pathophysiology. Microglial survival and proliferation are regulated by the colony-stimulating factor 1 receptor (CSF1R). The CSF1R inhibitor PLX3397 has been shown to reduce/deplete microglial populations and improve cognitive performance in models of neurodegenerative disorders. Therefore, we hypothesized that suppression of microgliosis with PLX3397 during epileptogenesis may attenuate the hippocampal-dependent spatial learning and memory deficits in the rat pilocarpine model of SE and acquired TLE. Different groups of control and SE rats were fed standard chow (SC) or chow with PLX3397 starting immediately after SE and for 3 weeks. Novel object recognition (NOR) and Barnes maze (BM) were performed to determine memory function between 2 and 3 weeks after SE. Then microglial populations were assessed using immunohistochemistry. Control rats fed with either SC or PLX3397 performed similarly in both NOR and BM tests, differentiating novel vs. familiar objects in NOR, and rapidly learning the location of the hidden platform in BM. In contrast, both SE groups (SC and PLX3397) showed significant deficits in both NOR and BM tests compared to controls. Both PLX3397-treated control and SE groups had significantly decreased numbers of microglia in the hippocampus (60%) compared to those in SC. In parallel, we found that PLX3397 treatment also reduced SE-induced hippocampal astrogliosis. Thus, despite drastic reductions in microglial cells, memory was unaffected in the PLX3397-treated groups compared to those in SC, suggesting that remaining microglia may be sufficient to help maintain hippocampal functions. In sum, PLX3397 did not improve or worsen the memory deficits in rats that sustained pilocarpine-induced SE. Further research is required to determine whether microglia play a role in cognitive decline during epileptogenesis.

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“…However, the transient activation of c-Fos may, in most instances, be too short-lasting to mitigate a palpable degree of progression of epileptogenesis to chronic epilepsy. A c-Fos deficit at later stages of epileptogenesis could contribute to impaired cognition and memory, the well-documented associates of advanced epilepsy [72,73]. A correlation coefficient was considered statistically significant at the two-tailed p-value <0.05.…”

Section: C-fos: a Potential Target For Antiepileptic Treatmentmentioning

confidence: 99%

Selected Molecular Targets for Antiepileptogenesis

Pawlik

Miziak

Walczak

et al. 2021

IJMS

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The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies.

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Mechanisms of cognitive impairment in temporal lobe epilepsy: A systematic review of resting-state functional connectivity studies

Cited by 43 publications

References 55 publications

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy

Suppression of Microgliosis With the Colony-Stimulating Factor 1 Receptor Inhibitor PLX3397 Does Not Attenuate Memory Defects During Epileptogenesis in the Rat

Selected Molecular Targets for Antiepileptogenesis

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