Memory-related brain potentials for visual objects in early AD show impairment and compensatory mechanisms.

Impaired episodic memory is the primary feature of early Alzheimer's disease (AD), but not all memories are equally affected. Patients with AD and amnestic Mild Cognitive Impairment (aMCI) remember pictures better than words, to a greater extent than healthy elderly. We investigated neural mechanisms for visual object recognition in 30 patients (14 AD, 16 aMCI) and 36 cognitively unimpaired healthy (19 in the "preclinical" stage of AD). Event-related brain potentials (ERPs) were recorded while participants performed a visual object recognition task. Hippocampal occupancy (integrity), amyloid (florbetapir) PET, and neuropsychological measures of verbal & visual memory, executive function were also collected. A right-frontal ERP recognition effect (500-700 ms post-stimulus) was seen in cognitively unimpaired participants only, and significantly correlated with memory and executive function abilities. A later right-posterior negative ERP effect (700-900 ms) correlated with visual memory abilities across participants with low verbal memory ability, and may reflect a compensatory mechanism. A correlation of this retrieval-related negativity with right hippocampal occupancy (r = 0.55), implicates the hippocampus in the engagement of compensatory perceptual retrieval mechanisms. Our results suggest that early AD patients are impaired in goal-directed retrieval processing, but may engage compensatory perceptual mechanisms which rely on hippocampal function.

[Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice].

Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group ( P < 0.01); the peak time, half-wave width, threshold and maximum descending slope of the action potential were significantly higher than those in the control group ( P < 0.01). The time-frequency energy values of LFPs signals in the θ and γ bands of mice in the ischemia and reperfusion groups were significantly reduced ( P < 0.01), and the time-frequency energy values in the reperfusion group were increased compared with the ischemia group ( P < 0.01). The signal complexity of LFPs in the ischemia and reperfusion group was significantly reduced ( P < 0.05), and the signal complexity in the reperfusion group was increased compared with the ischemia group ( P < 0.05). In summary, cerebral ischemia-reperfusion reduced the excitability of nerve cells in the DG area of the mouse hippocampus; cerebral ischemia reduced the discharge activity and signal complexity of nerve cells, and the electrophysiological indicators recovered after reperfusion, but it failed to reach the healthy state during the experiment period.

Contribution of prefrontal cortex and ventral hippocampus to anxiety in young epileptic mice.

Children with epilepsy are particularly vulnerable to anxiety disorders, where these disorders are frequently underdiagnosed and untreated. Despite the high prevalence of anxiety in epilepsy, the underlying neurobiological mechanisms are not fully understood. The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) are key brain regions implicated in the genesis and modulation of anxiety, and their interactions play a crucial role in emotional processing including anxiety. We utilized a pilocarpine-induced epilepsy model in young mice (7 weeks old) to assess anxiety-like behaviors using the open field test (OFT), light/dark box, and elevated plus maze (EPM). Local field potential (LFP) recordings were conducted to examine theta power and coherence between the mPFC and vHPC. LFP recordings revealed significantly altered theta power variation in both the mPFC and vHPC during exposure to anxiogenic contexts, suggesting the involvement of these regions in anxiety in the young epileptic mice. Notably, theta-frequency synchrony between the mPFC and vHPC was not significantly altered in the young epileptic mice, indicating that altered theta power rather than inter-regional synchrony may underlie anxiety behaviors in young epileptic mice. Furthermore, we demonstrated that chemogenetic inhibition of excitatory neurons in the mPFC and vHPC reduced anxiety levels in young epileptic mice. Altogether, our findings highlight the critical contributions of mPFC and vHPC to the pathogenesis of comorbid anxiety in epilepsy. These findings underscore the potential therapeutic significance of modulating the activity in these two regions as means to alleviate anxiety in a youth epilepsy population.

Hippocampal-occipital connectivity reflects autobiographical memory deficits in aphantasia.

Aphantasia refers to reduced or absent visual imagery. While most of us can readily recall decade-old personal experiences (autobiographical memories, AM) with vivid mental images, there is a dearth of information about whether the loss of visual imagery in aphantasics affects their AM retrieval. The hippocampus is thought to be a crucial hub in a brain-wide network underlying AM. One important question is whether this network, especially the connectivity of the hippocampus, is altered in aphantasia. In the current study, we tested 14 congenital aphantasics and 16 demographically matched controls in an AM fMRI task to investigate how key brain regions (i.e. hippocampus and visual-perceptual cortices) interact with each other during AM re-experiencing. All participants were interviewed regarding their autobiographical memory to examine their episodic and semantic recall of specific events. Aphantasics reported more difficulties in recalling AM, were less confident about their memories, and described less internal and emotional details than controls. Neurally, aphantasics displayed decreased hippocampal and increased visual-perceptual cortex activation during AM retrieval compared to controls. In addition, controls showed strong negative functional connectivity between the hippocampus and the visual cortex during AM and resting-state functional connectivity between these two brain structures predicted better visualization skills. Our results indicate that visual mental imagery plays an important role in detail-rich vivid AM, and that this type of cognitive function is supported by the functional connection between the hippocampus and the visual-perceptual cortex.

Association Between Postsurgical Functional Connectivity and Seizure Outcome in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: Despite the success of presurgical network connectivity studies in predicting short-term (1-year) seizure outcomes, later seizure recurrence occurs in some patients with temporal lobe epilepsy (TLE). To uncover contributors to this recurrence, we investigated the relationship between functional connectivity and seizure outcomes at different time points after surgery in these patients. METHODS: Patients included were clinically diagnosed with unilateral mesial TLE after a standard clinical evaluation and underwent selective amygdalohippocampectomy. Healthy controls had no history of seizures or head injury. Using resting-state fMRI, we assessed the postsurgical functional connectivity node strength, computed as the node's total strength to all other nodes, between seizure-free (Engel Ia-Ib) and nonseizure-free (Engel Ic-IV) acquisitions. The change over time after surgery in different outcome groups in these nodes was also characterized. RESULTS: Patients with TLE (n = 32, mean age: 43.1 ± 11.9 years; 46.8% female) and 85 healthy controls (mean age: 37.7 ± 13.5 years; 48.2% female) were included. Resting fMRI was acquired before surgery and at least once after surgery in each patient (range 1-4 scans, 5-60 months). Differences between patients with (n = 30) and without (n = 18) seizure freedom were detected in the posterior insula ipsilateral to the resection (I-PIns: 95% CI -154.8 to -50.1, p = 2.8 × 10-4) and the bilateral central operculum (I-CO: 95% CI -163.2 to -65.1, p = 2.6 × 10-5, C-CO: 95% CI -172.7 to -55.8, p = 2.8 × 10-4). In these nodes, only those who were seizure-free had increased node strength after surgery that increased linearly over time (I-CO: 95% CI 1.0-5.2, p = 4.2 × 10-3, C-CO: 95% CI 1.0-5.2, p = 5.5 × 10-3, I-PIns: 95% CI 1.6-5.5, p = 0.9 × 10-3). Different outcome groups were not distinguished by node strength before surgery. DISCUSSION: The findings suggest that network evolution in the first 5 years after selective amygdalohippocampectomy surgery is related to seizure outcomes in TLE. This highlights the need to identify presurgical and surgical conditions that lead to disparate postsurgical trajectories between seizure-free and nonseizure-free patients to identify potential contributors to long-term seizure outcomes. However, the lack of including other surgical approaches may affect the generalizability of the results.

TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial.

BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.

Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.

Noninvasive closed-loop acoustic brain-computer interface for seizure control.

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. Methods: We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. Conclusions: Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI.

Treating Traumatic Brain Injury with Exercise: Onset Delay and Previous Training as Key Factors Determining its Efficacy.

PURPOSE: Exercise reduces cognitive deficits in traumatic brain injury (TBI), but early post-trauma exercise is often discouraged due to potential harm. The purpose was to evaluate the interaction between pre- and post-injury physical exercise on cognition, neuronal survival and inflammation. METHODS: Rats were either sham-operated and kept sedentary (Sham) or subjected to controlled cortical impact injury and then distributed into sedentary (Tbi), pre-injury exercise (Pre-Tbi), post-injury exercise with early (24 hours, Tbi-early) or late (6 days, Tbi-late) onset, and a combination of pre- and post-injury exercise with early (Pre-Tbi-early) or late (Pre-Tbi-late) onset. Object recognition memory, hippocampal volume, neuronal survival (NeuN+) in the hippocampus and perirhinal cortex, and microglial activity (Iba-1) in the hippocampus were evaluated. RESULTS: All exercise conditions, except TBI-early, attenuated the significant memory impairment at 24-hour retention caused by TBI. Additionally, Pre-TBI-early treatment led to memory improvement at 3-hour retention. Pre-TBI reduced neuronal death and microglial activation in the hippocampus. TBI-late, but not TBI-early, mitigated hippocampal volume loss, loss of mature neurons in the hippocampus, and inflammation. Combining pre-injury and early-onset exercise reduced memory deficits but did not affect neuronal death or microglial activation. Combining pre-injury and late-onset exercise had a similar memory-enhancing effect than late post-injury treatment alone, albeit with reduced effects on neuronal density and neuroinflammation. CONCLUSIONS: Pre-TBI physical exercise reduces the necessary onset delay of post-TBI exercise to obtain cognitive benefits, yet the exact mechanisms underlying this reduction require further research.

Continuous exercise training rescues hippocampal long-term potentiation in the VPA rat model of Autism: Uncovering sex-specific effects.

Long-term potentiation (LTP) impairment has been reported in many studies of autistic models. The aim of the present study was to investigate the effects of interval training (IT) and continuous training (CT) exercises on LTP in the hippocampal dentate gyrus (DG) neurons of valproic acid (VPA) rat model of autism. To induce an autism-like model, pregnant rats were injected 500 mg/kg NaVPA (intraperitoneal) on the embryonic day 12.5. IT and CT aerobic exercises started on postnatal day 56 in the offspring. Four weeks after IT and/or CT exercises, the offspring were urethane-anesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. In the DG region, excitatory post synaptic potentials (EPSP) slope and population spike (PS) amplitude were measured. Sex differences in LTP were evident for control rats but not for VPA-exposed offspring. LTP was significantly smaller in VPA-exposed male offspring compared with control male rats. In contrast to males, there was no difference between VPA-exposed female offspring and control female rats. Interestingly, we observed a sex difference in the response to exercise between VPA-exposed male and female offspring. CT exercise training (but not IT) increased LTP in VPA-exposed male offspring. Both IT and CT exercise trainings had no effect on intact LTP in VPA-exposed female offspring. Our work suggests that there may be differences in the benefits of exercise interventions based on sex, and CT exercise training could be more beneficial for LTP improvements.

Dexamethasone attenuates low-frequency brainwave disturbances following acute seizures induced by pentylenetetrazol in Wistar rats.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. STATE OF THE ART: We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. CLINICAL IMPLICATIONS: We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. FUTURE DIRECTIONS: Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

Altered functional connectivity of primary olfactory cortex-hippocampus-frontal cortex in subjective cognitive decline during odor stimulation.

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.

Mechanical pain sensitivity is associated with hippocampal structural integrity.

ABSTRACT: Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.

Impaired Dynamics of Positional and Contextual Neural Coding in an Alzheimer's Disease Rat Model.

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.

Interictal blood-brain barrier dysfunction in piriform cortex of people with epilepsy.

OBJECTIVE: The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood-brain barrier. We investigated blood-brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry. METHODS: Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1interictal-postictal) and interictal (∆qT1noncontrast-interictal) blood-brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex. RESULTS: In temporal lobe epilepsy (n = 14), ∆qT1noncontrast-interictal was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1noncontrast-interictal was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1noncontrast-interictal (ß = 0.001, p < 0.001) in all regions, while the association was strongest in the piriform cortex. Impaired verbal memory was associated with ∆qT1noncontrast-interictal only in the piriform cortex (p = 0.04). ∆qT1interictal-postictal did not show differences in any region. INTERPRETATION: Interictal blood-brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.

Recent Insights into Hippocampal Dysfunction and Neuroplasticity in Sleep Disorders: An Update from Preclinical Studies.

Sleep disorders are prevalent neurological conditions linked to neurocognitive impairments. Understanding the neuroplasticity changes in the hippocampus, which plays a central role in regulating neurocognitive function, is crucial in the context of sleep disorders. However, research on neurodegenerative disorders and the influence of sleep disorders on hippocampal neuroplasticity remains largely unclear. Therefore, this review aims to highlight the latest advancements regarding hippocampal neuroplasticity and functional changes during sleep disorders, drawing insights from clinical and preclinical research involving sleep-deprived animal models. These articles were gathered through comprehensive literature searches across databases, including Google Scholar, PubMed, Web of Science, and Scopus. Maternal sleep deprivation has been observed to cause neurocognitive impairment in offspring, along with changes in protein expression levels associated with neuroplasticity. Similarly, sleep deprivation in adult mice has been shown to affect several cognitive functions and fear extinction without influencing the acquisition of fear conditioning. While mechanistic research on neurocognitive dysfunction induced by maternal and adult sleep deprivation is limited, it suggests the involvement of several signaling pathways, including neurotrophic factors, synaptic proteins, and inflammatory molecules, which are triggered by sleep deprivation. Further studies are needed to clarify the mechanistic pathways underlying hippocampal dysfunction and synaptic alterations associated with sleep disturbances.

Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex.

Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.