BACKGROUND: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. OBJECTIVE: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. METHODS: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. RESULTS: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. CONCLUSIONS: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.
- MeSH
- Alzheimerova nemoc * patofyziologie MeSH
- amyloidový prekurzorový protein beta genetika MeSH
- hipokampální oblast CA1 patofyziologie MeSH
- hipokampus patofyziologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- poruchy paměti etiologie patofyziologie MeSH
- potkani inbrední F344 MeSH
- potkani transgenní * MeSH
- prostorová paměť fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Numerous physiological processes are cyclical, but sampling these processes densely enough to perform frequency decomposition and subsequent analyses can be challenging. Mathematical approaches for decomposition and reconstruction of sparsely and irregularly sampled signals are well established but have been under-utilized in physiological applications. We developed a basis pursuit denoising with polynomial detrending (BPWP) model that recovers oscillations and trends from sparse and irregularly sampled timeseries. We validated this model on a unique dataset of long-term inter-ictal epileptiform discharge (IED) rates from human hippocampus recorded with a novel investigational device with continuous local field potential sensing. IED rates have well established circadian and multiday cycles related to sleep, wakefulness, and seizure clusters. Given sparse and irregular samples of IED rates from multi-month intracranial EEG recordings from ambulatory humans, we used BPWP to compute narrowband spectral power and polynomial trend coefficients and identify IED rate cycles in three subjects. In select cases, we propose that random and irregular sampling may be leveraged for frequency decomposition of physiological signals. Trial Registration: NCT03946618.
- MeSH
- algoritmy MeSH
- elektroencefalografie metody MeSH
- elektrokortikografie metody MeSH
- epilepsie * patofyziologie diagnóza MeSH
- hipokampus patofyziologie fyziologie MeSH
- lidé MeSH
- modely neurologické MeSH
- počítačové zpracování signálu MeSH
- výpočetní biologie metody MeSH
- záchvaty patofyziologie diagnóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
PURPOSE: Despite documented clinical effectiveness, deep brain stimulation (DBS) therapy for drug-resistant epilepsy rarely yields long-term seizure free outcomes. METHODS: This pilot study in five patients investigated circuit of Papez evoked potentials (EPs) using hippocampal sensing during anterior nucleus of the thalamus (ANT) electrical stimulation. We hypothesize that hippocampal EP is a potential biomarker that could be useful for ANT electrode targeting and improving seizure reduction. We obtained bilateral circuit of Papez EPs in five patients with bilateral temporal lobe epilepsy (TLE). The circuit of Papez EPs were measured and assessed by signal amplitude. Volumetric analysis of relevant mesial temporal structures and ANT stimulation analysis was performed on immediate post-implantation images. RESULTS: The patient with the most favorable seizure outcome, which meant long-term seizure reduction greater than 50 % compared to baseline, had strong bilateral EPs and normal hippocampal structure. Conversely, those without clinical benefit with ANT DBS had absent or weak bilateral EPs as well as MRI findings consistent with mesial temporal sclerosis (MTS). CONCLUSION: The data support the hypothesis that hippocampal EPs with ANT stimulation may be used to as a surrogate marker to probe circuit of Papez and predict ANT DBS efficacy.
- MeSH
- dospělí MeSH
- elektrická stimulace MeSH
- epilepsie temporálního laloku patofyziologie MeSH
- evokované potenciály fyziologie MeSH
- hipokampus patofyziologie MeSH
- lidé MeSH
- nervové dráhy patofyziologie MeSH
- nuclei anteriores thalami patofyziologie MeSH
- pilotní projekty MeSH
- záchvaty patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi. The similarity of HFOs properties recorded at rest in epileptic and non-epileptic hippocampi suggests that they cannot be used alone to distinguish between hippocampi. However, both ripples and fast ripples were observed with higher rates, higher relative amplitudes and longer durations at rest as well as during a cognitive task in epileptic compared with non-epileptic hippocampi. Moreover, during a cognitive task, significant reductions of HFOs rates were found in epileptic hippocampi. These reductions were not observed in non-epileptic hippocampi. Our results indicate that although both hippocampi generate HFOs with similar features that probably reflect non-pathological phenomena, it is possible to differentiate between epileptic and non-epileptic hippocampi using a simple odd-ball task.
- MeSH
- dospělí MeSH
- elektroencefalografie přístrojové vybavení MeSH
- epilepsie temporálního laloku diagnóza patofyziologie terapie MeSH
- hipokampus patofyziologie MeSH
- implantované elektrody MeSH
- kognice fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozkové vlny fyziologie MeSH
- neuropsychologické testy MeSH
- refrakterní epilepsie diagnóza patofyziologie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Neuroactive steroid 20-oxo-5β-pregnan-3α-yl L-glutamyl 1-ester (PA-Glu), a synthetic analogue of naturally occurring 20-oxo-5β-pregnan-3α-yl sulfate (pregnanolone sulfate, PA-S), inhibits N-methyl-D-aspartate (NMDA) receptors and possesses neuroprotective properties and minimal adverse effects. Herein, we report in vivo effects of new structural modifications of the PA-S molecule: a nonpolar modification of the steroid D-ring (5β-androstan-3α-yl L-glutamyl 1-ester, AND-Glu), attachment of a positively charged group to C3 (20-oxo-5β-pregnan-3α-yl L-argininate dihydrochloride salt, PA-Arg) and their combination (5β-androstan-3α-yl L-argininate dihydrochloride salt, AND-Arg). The first aim of this study was to determine the structure-activity relationship for neuroprotective effects in a model of excitotoxic hippocampal damage in rats, based on its behavioral correlate in Carousel maze. The second aim was to explore side effects of neuroprotective steroids on motor functions, anxiety (elevated plus maze) and locomotor activity (open field) and the effect of their high doses in mice. The neuroprotective properties of PA-Glu and AND-Glu were proven, with the effect of the latter appearing to be more pronounced. In contrast, neuroprotective efficacy failed when positively charged molecules (PA-Arg, AND-Arg) were used. AND-Glu and PA-Glu at the neuroprotective dose (1 mg/kg) did not unfavorably influence motor functions of intact mice. Moreover, anxiolytic effects of AND-Glu and PA-Glu were ascertained. These findings corroborate the value of research of steroidal inhibitors of NMDA receptors as potential neuroprotectants with slight anxiolytic effect and devoid of behavioral adverse effects. Taken together, the results suggest the benefit of the nonpolar D-ring modification, but not of the attachment of a positively charged group to C3.
- MeSH
- agonisté excitačních aminokyselin toxicita MeSH
- antagonisté excitačních aminokyselin chemická syntéza farmakologie MeSH
- bludiště - učení účinky léků MeSH
- chování zvířat účinky léků MeSH
- hipokampus účinky léků metabolismus patologie patofyziologie MeSH
- lokomoce účinky léků MeSH
- molekulární struktura MeSH
- myši MeSH
- N-methylaspartát toxicita MeSH
- neuroprotektivní látky chemická syntéza farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Long-Evans MeSH
- pregnanolon analogy a deriváty chemická syntéza farmakologie MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory metabolismus MeSH
- sírany chemická syntéza farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- nedeklarativní paměť,
- MeSH
- afázie klasifikace patologie MeSH
- agnozie klasifikace MeSH
- Alzheimerova nemoc patofyziologie MeSH
- apraxie klasifikace MeSH
- delirium MeSH
- dlouhodobá paměť klasifikace MeSH
- duševní poruchy patofyziologie MeSH
- exekutivní funkce MeSH
- hipokampus patofyziologie MeSH
- kognice MeSH
- kognitivní dysfunkce * diagnóza etiologie klasifikace patofyziologie patologie MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- neurovývojové poruchy klasifikace MeSH
- paměť klasifikace MeSH
- percepční poruchy etiologie klasifikace patologie MeSH
- poruchy paměti etiologie klasifikace patofyziologie MeSH
- pozornost MeSH
- stupeň závažnosti nemoci MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVE: The main aim of this study was to investigate the potential differences in terms of interictal high frequency oscillations (HFOs) between both hippocampi in unilateral (U-MTLE) and bilateral mesial temporal lobe epilepsy (B-MTLE). METHODS: Sixteen patients with MTLE underwent bilateral hippocampal depth electrode implantation as part of epilepsy surgery evaluation. Interictal HFOs were detected automatically. The analyses entail comparisons of the rates and spatial distributions of ripples and fast ripples (FR) in hippocampi and amygdalae, with respect to the eventual finding of hippocampal sclerosis (HS). RESULTS: In U-MTLE, higher ripple and FR rates were found in the hippocampi ipsilateral to the seizure onset than in the contralateral hippocampi. Non-epileptic hippocampi in U-MTLE were distinguished by significantly lower ripple rate than in the remaining analyzed hippocampi. There were not differences between the hippocampi in B-MTLE. In the hippocampi with proven HS, higher FR rates were observed in the ventral than in the dorsal parts. CONCLUSIONS: Non-epileptic hippocampi in U-MTLE demonstrated significantly lower ripple rates than those epileptic in U-MTLE and B-MTLE. SIGNIFICANCE: Low interictal HFO occurrence might be considered as a marker of the non-epileptic hippocampi in MTLE.
- MeSH
- amygdala patofyziologie MeSH
- dospělí MeSH
- elektroencefalografie metody MeSH
- epilepsie temporálního laloku patologie patofyziologie MeSH
- hipokampus patologie patofyziologie MeSH
- implantované elektrody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- spánkový lalok patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hippocampal and basal forebrain (BF) atrophy is associated with allocentric navigation impairment in Alzheimer's disease (AD) and may lead to recruitment of compensatory navigation strategies. We examined navigation strategy preference, its association with allocentric navigation, and the role of hippocampal and BF volumes in this association in early clinical stages of AD. Sixty nine participants-amnestic mild cognitive impairment (aMCI) due to AD (n = 28), AD dementia (n = 21), and cognitively normal (CN) older adults (n = 20)-underwent virtual Y-maze strategy assessment, real-space navigation testing, cognitive assessment, and hippocampal and BF volumetry. Preference for egocentric over allocentric strategy increased with AD severity (aMCI: 67% vs. 33%; dementia: 94% vs. 6%), which contrasted with preference in the CN group (39% vs. 61%). Those with aMCI who preferred egocentric strategy had worse allocentric navigation. Among those with aMCI, hippocampal and BF atrophy explained up to 25% of the association between strategy preference and allocentric navigation. The preference for egocentric strategy in AD may reflect recruitment of compensatory extrahippocampal navigation strategies as adaptation to hippocampal and BF neurodegeneration.
- MeSH
- Alzheimerova nemoc patologie psychologie MeSH
- atrofie MeSH
- bludiště - učení MeSH
- degenerace nervu MeSH
- hipokampus patologie patofyziologie MeSH
- kognitivní dysfunkce patologie psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- pars basalis telencephali patologie patofyziologie MeSH
- prostorová navigace fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- velikost orgánu MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.
- MeSH
- elektroencefalografie MeSH
- hipokampální oblast CA1 patofyziologie MeSH
- hipokampus patofyziologie MeSH
- lidé MeSH
- nervová síť patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- potkani Wistar MeSH
- synapse fyziologie MeSH
- záchvaty patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
