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Aims: In this study, the anticonvulsant action of closed‐loop, low‐frequency deep brain stimulation (DBS) was investigated. In addition, the changes in brain rhythms and functional connectivity of the hippocampus and prefrontal cortex were evaluated. Methods: Epilepsy was induced by pilocarpine in male Wistar rats. After the chronic phase, a tripolar electrode was implanted in the right ventral hippocampus and a monopolar electrode in medial prefrontal cortex (mPFC). Subjects' spontaneous seizure behaviors were observed in continuous video recording, while the local field potentials (LFPs) were recorded simultaneously. In addition, spatial memory was evaluated by the Barnes maze test. Results: Applying hippocampal DBS, immediately after seizure detection in epileptic animals, reduced their seizure severity and duration, and improved their performance in Barnes maze test. DBS reduced the increment in power of delta, theta, and gamma waves in pre‐ictal, ictal, and post‐ictal periods. Meanwhile, DBS increased the post‐ictal‐to‐pre‐ictal ratio of theta band. DBS decreased delta and increased theta coherences, and also increased the post‐ictal‐to‐pre‐ictal ratio of coherence. In addition, DBS increased the hippocampal‐mPFC coupling in pre‐ictal period and decreased the coupling in the ictal and post‐ictal periods. Conclusion: Applying closed‐loop, low‐frequency DBS at seizure onset reduced seizure severity and improved memory. In addition, the changes in power, coherence, and coupling of the LFP oscillations in the hippocampus and mPFC demonstrate low‐frequency DBS efficacy as an antiepileptic treatment, returning LFPs to a seemingly non‐seizure state in subjects that received DBS. [ABSTRACT FROM AUTHOR]

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS' inhibitory mechanisms is lacking. Here, α1 and α2 adrenergic receptors' roles in mediating LFS inhibitory action on high-K+ induced epileptiform activity (EA) was examined in rat hippocampal slices. Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons' excitability. By applying high-K+ on hippocampal slices, EA was induced, and neuronal excitability increased. Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α1 adrenergic receptor antagonist) and yohimbine (5 µM, an α2 adrenergic receptor antagonist), LFS' typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K+ washout; These antagonists did not have a significant effect on LFS' inhibitory action on spike firing during EA. Conclusion: These findings suggest that LFS' anticonvulsant effect, on neuronal hyperexcitability following high-K+ EA, may be mediated partly through α adrenergic receptors in hippocampal slices. [ABSTRACT FROM AUTHOR]

Aims: Deep brain electrical stimulation (DBS), as a potential therapy for drug resistive epileptic patients, has inhibitory action on epileptogenesis. In the present investigation, the role of dopamine D2‐like receptors in the antiepileptogenic action of DBS was studied. Methods: Seizures were induced in adult rats by stimulating the perforant path in a semi‐rapid kindling method. Five minutes after the last kindling stimulation, daily DBS was applied to the perforant path at the pattern of low frequency stimulation (LFS; 1 Hz; pulse duration: 0.1 ms; intensity: 50–150 μA; 4 trains of 200 pulses at 5 min intervals). Sulpiride (10 μg/1 μl, i.c.v.), a selective dopamine D2‐like receptor antagonist, was administered prior to the daily LFS application. Results: Kindling stimulations increased cumulative daily behavioral seizure stages, daily afterdischarge duration (dADD), and population spike amplitude (PS) in dentate gyrus following perforant path stimulation, while applying LFS decreased the kindled seizures' parameters. In addition, kindling potentiated the early (at 10–50 ms inter‐pulse interval) and late (at 150–1000 ms inter‐pulse interval) paired‐pulse inhibition and decreased the paired‐pulse facilitation (at 70–100 ms inter‐pulse interval). These effects were also inhibited by applying LFS. All inhibitory effects of LFS on kindling procedure were prevented by sulpiride administration. Conclusion: These data may suggest that LFS exerts its preventive effect on kindling development, at least partly, through the receptors on which sulpiride acts which are mainly dopamine D2‐like (including D2, D3, and D4) receptors. [ABSTRACT FROM AUTHOR]

Patients with Capgras syndrome (CS) adopt the delusional belief that persons well-known to them have been replaced by an imposter. Several current theoretical models of CS attribute such misidentification problems to deficits in covert recognition processes related to the generation of appropriate affective autonomic signals. These models assume intact overt recognition processes for the imposter and, more broadly, for other individuals. As such, it has been suggested that CS could reflect the "mirror-image" of prosopagnosia. The purpose of the current study was to determine whether overt person recognition abilities are indeed always spared in CS. Furthermore, we examined whether CS might be associated with any impairments in overt affective judgments of facial expressions. We pursued these goals by studying a patient with Dementia with Lewy bodies (DLB) who showed clear signs of CS, and by comparing him to another patient with DLB who did not experience CS, as well as to a group of healthy control participants. Clinical magnetic resonance imaging scans revealed medial prefrontal cortex (mPFC) atrophy that appeared to be uniquely associated with the presence CS. We assessed overt person recognition with three fame recognition tasks, using faces, voices, and names as cues. We also included measures of confidence and probed pertinent semantic knowledge. In addition, participants rated the intensity of fearful facial expressions. We found that CS was associated with overt person recognition deficits when probed with faces and voices, but not with names. Critically, these deficits were not present in the DLB patient without CS. In addition, CS was associated with impairments in overt judgments of affect intensity. Taken together, our findings cast doubt on the traditional view that CS is the mirror-image of prosopagnosia and that it spares overt recognition abilities. These findings can still be accommodated by models of CS that emphasize deficits in autonomic responding, to the extent that the potential role of interoceptive awareness in overt judgments is taken into account. [ABSTRACT FROM AUTHOR]

We have shown that when subjects reach with continuous, misaligned visual feedback of their hand, their reaches are adapted and proprioceptive sense of hand position is recalibrated to partially match the visual feedback (Salomonczyk et al., 2011). It is unclear if similar changes arise after reaching with visual feedback that is provided only at the end of the reach (i.e., terminal feedback), when there are shorter temporal intervals for subjects to experience concurrent visual and proprioceptive feedback. Subjects reached to targets with an aligned hand-cursor that provided visual feedback at the end of each reach movement across a 99-trial training block, and with a rotated cursor over three successive blocks of 99 trials each. After each block, no cursor reaches, to measure aftereffects, and felt hand positions were measured. Felt hand position was determined by having subjects indicate the position of their unseen hand relative to a reference marker. We found that subjects adapted their reaches following training with rotated terminal visual feedback, yet slightly less (i.e., reach aftereffects were smaller), than subjects from a previous study who experienced continuous visual feedback. Nonetheless, current subjects recalibrated their sense of felt hand position in the direction of the altered visual feedback, but this proprioceptive change increased incrementally over the three rotated training blocks. Final proprioceptive recalibration levels were comparable to our previous studies in which subjects performed the same task with continuous visual feedback. Thus, compared to reach training with continuous, but altered visual feedback, subjects who received terminal altered visual feedback of the hand produced significant but smaller reach aftereffects and similar changes in hand proprioception when given extra training. Taken together, results suggest that terminal feedback of the hand is sufficient to drive motor adaptation, and also proprioceptive recalibration. [ABSTRACT FROM AUTHOR]

The classic view holds that the medial temporal lobes (MTL) are dedicated to declarative memory functioning. Recent evidence, however, suggests that perirhinal cortex (PrC), a structure within the anterior MTL, may also play a role in perceptual discriminations when representations of complex conjunctions of features, or of gestalt-characteristics of objects must be generated. Interestingly, neuroimaging and electrophysiological recordings in nonhuman primates have also revealed a face patch in the anterior collateral sulcus with preferential responses to face stimuli in various task contexts. In the present fMRI study, we investigated the representational demands that influence PrC involvement in different types of judgments on human faces. Holding stimulus complexity constant, we independently manipulated the nature of the task and the orientation of the stimuli presented (through face inversion). Aspects of right PrC showed increased responses in a forced-choice recognition-memory and a perceptual-oddity task, as compared to a feature-search task that was included to probe visual detection of an isolated face feature. Effects of stimulus orientation in right PrC were observed when the recognition-memory condition for upright faces was compared with all other experimental conditions, including recognition-memory for inverted faces-a result that can be related to past work on the role of PrC in object unitization. Notably, both effects in right PrC paralleled activity patterns in broader networks of regions that also included the right fusiform gyrus and the amygdala, regions frequently implicated in face processing in prior research. As such, the current findings do not support the view that reference to a prior study episode clearly distinguishes the role of PrC from that of more posterior ventral visual pathway regions. They add to a growing body of evidence suggesting that the functional role of specific MTL structures may be best understood in terms of the representations that are required by the task and the stimuli at hand. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

• Kindled animals show impairment in learning & memory. • Low-frequency electrical stimulation (LFS) improves learning & memory impairment. • LFS induced memory improvement is reduced by hippocampal 5-HT 1A antagonist. • LFS also prevented the kindling-induced increase in 5-HT 1A receptors. In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT 1A receptors in mediating LFS' improving effect on spatial learning and memory was investigated in amygdala-kindled rats. Amygdala kindling was conducted in a semi-rapid kindling stimulations (12 stimulations per day) in male Wistar rats. LFS (4 trains of 0.1 ms pulse duration at 1 Hz, 200 pulses, 50–150 μA, at 5 min intervals) was applied after termination of kindling stimulations. NAD-299 (a selective 5-HT 1A receptor antagonist; 2.5 and 5 μg/μl) was microinjected into the hippocampal CA1 before applying LFS. The Morris water maze, and novel object recognition tests were conducted after the last kindling stimulation. Hippocampal samples were also prepared, and 5-HT 1A receptor gene expression levels were assessed using quantitative RT-PCR. In kindled animals, LFS reduced impairments in spatial learning and memory in the Morris water maze and novel object recognition tests. Microinjection of NAD doses of 5 μg/μl reduced the effects of LFS on learning and memory. The gene expression level of 5-HT 1A receptors increased significantly in the hippocampus of amygdala-kindled rats. However, LFS applied after kindling stimulations inhibited this effect. It seems that activation of 5-HT 1A receptors in the CA1 field is necessary for LFS' improving effects on spatial learning and memory in kindled animals; although surprisingly, LFS application prevented the elevation in gene expression of 5-HT 1A receptors in kindled animals. [ABSTRACT FROM AUTHOR]

Aims: Deep brain electrical stimulation (DBS), as a potential therapy for drug resistive epileptic patients, has inhibitory action on epileptogenesis. In the present investigation, the role of dopamine D 2 -like receptors in the antiepileptogenic action of DBS was studied., Methods: Seizures were induced in adult rats by stimulating the perforant path in a semi-rapid kindling method. Five minutes after the last kindling stimulation, daily DBS was applied to the perforant path at the pattern of low frequency stimulation (LFS; 1 Hz; pulse duration: 0.1 ms; intensity: 50-150 μA; 4 trains of 200 pulses at 5 min intervals). Sulpiride (10 μg/1 μl, i.c.v.), a selective dopamine D 2 -like receptor antagonist, was administered prior to the daily LFS application., Results: Kindling stimulations increased cumulative daily behavioral seizure stages, daily afterdischarge duration (dADD), and population spike amplitude (PS) in dentate gyrus following perforant path stimulation, while applying LFS decreased the kindled seizures' parameters. In addition, kindling potentiated the early (at 10-50 ms inter-pulse interval) and late (at 150-1000 ms inter-pulse interval) paired-pulse inhibition and decreased the paired-pulse facilitation (at 70-100 ms inter-pulse interval). These effects were also inhibited by applying LFS. All inhibitory effects of LFS on kindling procedure were prevented by sulpiride administration., Conclusion: These data may suggest that LFS exerts its preventive effect on kindling development, at least partly, through the receptors on which sulpiride acts which are mainly dopamine D 2 -like (including D 2 , D 3 , and D 4 ) receptors., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Epileptic seizures are accompanied by learning and memory impairments. In this study, the effect of low frequency stimulation (LFS) on spatial learning and memory was assessed in kindled animals and followed for one month. Fully kindled rats received LFS at 4 times (immediately, 6 h, 24 h and 30 h following the final kindling stimulation). Applying LFS improved kindled animals' performance in the Barnes maze test. This LFS action was accompanied by a decrease in NR2B gene expression, an increase in the gene expression of the α subunit of calcineurin A and an increased NR2A/NR2B ratio in kindled animals. In addition, the gene expression of the GABA A receptor γ 2 subunit increased at 2-3 h after applying LFS. The increase in NR2A/NR2B ratio was also observed 1 week after LFS. No significant changes were observed one month after LFS administration. Field potential recordings in the hippocampal CA1 area showed that kindling-induced potentiation of the field EPSP slope returned to near baseline when measured 2-3 h after applying LFS. Therefore, it may be postulated that applying LFS in kindled animals reduced the seizure-induced learning and memory impairments, albeit time-dependently. In tandem, LFS prevented kindling-induced alterations in gene expression of the described proteins, which are potentially important for synaptic transmission and/or potentiation. Moreover, a depotentiation-like phenomenon may be a possible mechanism underlying the LFS action., Epileptic seizures are accompanied by learning and memory impairments. In this study, the effect of low frequency stimulation (LFS) on spatial learning and memory was assessed in kindled animals and followed for one month. Fully kindled rats received LFS at 4 times (immediately, 6 h, 24 h and 30 h following the final kindling stimulation). Applying LFS improved kindled animals’ performance in the Barnes maze test. This LFS action was accompanied by a decrease in NR2B gene expression, an increase in the gene expression of the α subunit of calcineurin A and an increased NR2A/NR2B ratio in kindled animals. In addition, the gene expression of the GABA A receptor γ 2 subunit increased at 2–3 h after applying LFS. The increase in NR2A/NR2B ratio was also observed 1 week after LFS. No significant changes were observed one month after LFS administration. Field potential recordings in the hippocampal CA1 area showed that kindling-induced potentiation of the field EPSP slope returned to near baseline when measured 2–3 h after applying LFS. Therefore, it may be postulated that applying LFS in kindled animals reduced the seizure-induced learning and memory impairments, albeit time-dependently. In tandem, LFS prevented kindling-induced alterations in gene expression of the described proteins, which are potentially important for synaptic transmission and/or potentiation. Moreover, a depotentiation-like phenomenon may be a possible mechanism underlying the LFS action.