Effect of the closed-loop hippocampal low-frequency stimulation on seizure severity, learning, and memory in pilocarpine epilepsy rat model.

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.

Comparing the synaptic potentiation in schaffer collateral-CA1 synapses in dorsal and intermediate regions of the hippocampus in normal and kindled rats.

There is growing evidence that the hippocampus comprises diverse neural circuits that exhibit longitudinal variation in their properties, however, the intermediate region of the hippocampus has received comparatively little attention. Therefore, this study was designed to compared short- and long-term synaptic plasticity between the dorsal and intermediate regions of the hippocampus in normal and PTZ-kindled rats. Short-term plasticity was assessed by measuring the ratio of field excitatory postsynaptic potentials' (fEPSPs) slope in response to paired-pulse stimulation at three different inter-pulse intervals (20, 80, and 160 ms), while long-term plasticity was assessed using primed burst stimulation (PBS). The results showed that the basal synaptic strength differed between the dorsal and intermediate regions of the hippocampus in both control and kindled rats. In the control group, paired-pulse stimulation of Schaffer collaterals resulted in a significantly lower fEPSP slope in the intermediate part of the hippocampus compared to the dorsal region. Additionally, the magnitude of long-term potentiation (LTP) was significantly lower in the intermediate part of the hippocampus compared to the dorsal region. In PTZ-kindled rats, both short-term facilitation and long-term potentiation were impaired in both regions of the hippocampus. Interestingly, there was no significant difference in synaptic plasticity between the dorsal and intermediate regions in PTZ-kindled rats, despite impairments in both regions. This suggests that seizures eliminate the regional difference between the dorsal and intermediate parts of the hippocampus, resulting in similar electrophysiological activity in both regions in kindled animals. Future studies should consider this when investigating the responses of the dorsal and intermediate regions of the hippocampus following PTZ kindling.

Alpha adrenergic receptors have role in the inhibitory effect of electrical low frequency stimulation on epileptiform activity in rats.

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.

Involvement of dopamine D2 -like receptors in the antiepileptogenic effects of deep brain stimulation during kindling in rats.

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.

Effect of low frequency stimulation of olfactory bulb on seizure severity, learning, and memory in kindled rats.

Low frequency deep brain electrical stimulation (LFS) is a potential therapeutic strategy to control seizures in epilepsy patients. Given the functional connection of the olfactory bulb with the hippocampal formation, in this study the effect of applying LFS in the olfactory bulb on seizure severity, and learning and memory was investigated in hippocampal kindling. In male Wistar rats (250-300 g), a tripolar electrode was inserted in the CA1 region of the right hippocampus to apply kindling stimulations and record the afterdischarges (ADs). Two bipolar electrodes were also inserted bilaterally into the olfactory bulbs for applying LFS. In the kindled group, the animals received daily kindling stimulations to produce stage 5 seizures for three consecutive days. In one group of subjects, LFS was administered 2-3 min after the last kindling stimulation. Within this group, subjects were divided into two subgroups: one subgroup received two and the other subgroup received four packages of LFS protocol. Obtained data showed that bilateral LFS application to the left and right olfactory bulb reduced seizure severity. Among the protocols, applying four packages of LFS had a greater anticonvulsant effect compared to applying two packages LFS. Applying LFS in the olfactory bulb of kindled subject restored performance on measures that test short- and long-term memory - the Y maze and Morris water maze test - and applying four packages of LFS was more effective than two. These results indicated that applying LFS to the olfactory bulb had anticonvulsant effects and ameliorated the seizure-induced impairment of working and spatial memory. These effects appear to be depended on the number of applied LFS and were greater by increasing the number of LFS.

A corollary discharge mediates saccade-related inhibition of single units in mnemonic structures of the human brain.

Despite the critical link between visual exploration and memory, little is known about how neuronal activity in the human mesial temporal lobe (MTL) is modulated by saccades. Here, we characterize saccade-associated neuronal modulations, unit-by-unit, and contrast them to image onset and to occipital lobe neurons. We reveal evidence for a corollary discharge (CD)-like modulatory signal that accompanies saccades, inhibiting/exciting a unique population of broad-/narrow-spiking units, respectively, before and during saccades and with directional selectivity. These findings comport well with the timing, directional nature, and inhibitory circuit implementation of a CD. Additionally, by linking neuronal activity to event-related potentials (ERPs), which are directionally modulated following saccades, we recontextualize the ERP associated with saccades as a proxy for both the strength of inhibition and saccade direction, providing a mechanistic underpinning for the more commonly recorded saccade-related ERP in the human brain.

Group I metabotropic glutamate receptors contribute to the antiepileptic effect of electrical stimulation in hippocampal CA1 pyramidal neurons.

Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS inhibitory action on epileptiform activity (EA) was investigated. EA was induced by increasing the K+ concentration in artificial cerebrospinal fluid (ACSF) up to 12 mM in hippocampal slices of male Wistar rats. LFS (1 Hz, 900 pulses) was delivered to the bundles of Schaffer collaterals at the beginning of EA. The excitability of CA1 pyramidal neurons was assayed by intracellular whole-cell recording. Applying LFS reduced the firing frequency during EA and substantially moved the membrane potential toward repolarization after a high-K+ ACSF washout. In addition, LFS attenuated the EA-generated neuronal hyperexcitability. A blockade of both mGluR 1 and mGluR 5 prevented the inhibitory action of LFS on EA-generated neuronal hyperexcitability. Activation of mGluR I mimicked the LFS effects and had similar inhibitory action on excitability of CA1 pyramidal neurons following EA. However, mGluR I agonist's antiepileptic action was not as strong as LFS. The observed LFS effects were significantly attenuated in the presence of a PKC inhibitor. Altogether, the LFS' inhibitory action on neuronal hyperexcitability following EA relies, in part, on the activity of mGluR I and a PKC-related signaling pathway.

Deep brain stimulation effects on learning, memory and glutamate and GABAA receptor subunit gene expression in kindled rats.

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 GABAA receptor γ2 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 GABAA receptor γ2 subunit increased at 2­3 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 2­3 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.

The role of α adrenergic receptors in mediating the inhibitory effect of electrical brain stimulation on epileptiform activity in rat hippocampal slices.

The Inhibitory effect of electrical low-frequency stimulation (LFS) on neuronal excitability and seizure occurrence has been indicated in experimental models, but the precise mechanism has not established. This investigation was intended to figure out the role of α1 and α2 adrenergic receptors in LFS' inhibitory effect on neuronal excitability. Epileptiform activity induced in an in vitro rat hippocampal slice preparation by high K+ ACSF and LFS (900 square wave pulses at 1 Hz) was administered at the beginning of epileptiform activity to the Schaffer collaterals. In CA1 pyramidal neurons, the electrophysiological properties were measured at the baseline, before high K+ ACSF washout, and at 15 min after high K+ ACSF washout using whole-cell, patch-clamp recording. Results indicated that after high K+ ACSF washout, prazosine (10 µM; α1 adrenergic receptor antagonist) and yohimbine (5 µM; α2 adrenergic receptor antagonist) suppressed the LFS' effect of reducing rheobase current and utilization time following depolarizing ramp current, the latency to the first spike following a depolarizing current and latency to the first rebound action potential following hyperpolarizing current pulses. Thus, it may be proposed that LFS' inhibitory action on the neuronal hyperexcitability, in some way, is mediated by α1 and α2 adrenergic receptors.

Allergic rhinitis impairs working memory in association with drop of hippocampal - Prefrontal coupling.

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the activity and coupling of these brain areas, which consequently may impair working memory. The current study aimed to examine alterations of the vHipp-plPFC circuit in a rat model of AR. Our results show decreased working memory performance in AR animals, accompanied by a reduction of theta and gamma oscillations in plPFC. Also, AR reduces coherence between vHipp and plPFC in both theta and gamma frequency bands. Cross-frequency coupling analyses confirmed a reduced interaction between hippocampal theta and plPFC gamma oscillations. Granger causality analysis revealed a reduction in the causal effects of vHipp activity on plPFC oscillations and vice versa. A significant correlation was found between working memory performance with disruption of functional connectivity in AR animals. In summary, our data show that in AR, there is a deficit of functional coupling between hippocampal and prefrontal network, and suggest that this mechanism might contribute to working memory impairment in individuals with AR.

The role of dopamine D2-like receptors in a "depotentiation-like effect" of deep brain stimulation in kindled rats.

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, Gi-protein-coupled receptors, including D2-like receptors, may have a role in mediating these effects. In the present study, the role of D2-like receptors in LFS' anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 min intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D2-like receptors antagonist, 2 µm) and/or bromocriptine (D2-like receptors agonist 2 µg/µlit) were microinjected into the lateral ventricle immediately after the last kindling, before applying LFS. Obtained results showed that applying LFS in fully-kindled subjects led to a depotentiation-like decrease in kindling-induced potentiation and reduced the amplitude and rise slope of excitatory and inhibitory post-synaptic currents in whole-cell recordings from CA1 pyramidal neurons. In addition, LFS restored the kindling-induced, spatial learning and memory impairments in the Barnes maze test. A D2-like receptor antagonist inhibited these effects of LFS, while a D2-like receptor agonist mimicked these effects. In conclusion, a depotentiation-like mechanism may be involved in restoring LFS' effects on learning and memory, and synaptic plasticity. These effects depend on D2-like receptors activity.

Allergen-induced anxiety-like behavior is associated with disruption of medial prefrontal cortex - amygdala circuit.

Anxiety is prevalent in asthma, and is associated with disease severity and poor quality of life. However, no study to date provides direct experimental evidence for the effect of allergic inflammation on the structure and function of medial prefrontal cortex (mPFC) and amygdala, which are essential regions for modulating anxiety and its behavioral expression. We assessed the impact of ovalbumin (OVA)-induced allergic inflammation on the appearance of anxiety-like behavior, mPFC and amygdala volumes using MRI, and the mPFC-amygdala circuit activity in sensitized rats. Our findings exhibited that the OVA challenge in sensitized rats induced anxiety-like behavior, and led to more activated microglia and astrocytes in the mPFC and amygdala. We also found a negative correlation between anxiety-like behavior and amygdala volume. Moreover, OVA challenge in sensitized rats was associated with increases in mPFC and amygdala activity, elevation of amygdala delta-gamma coupling, and the enhancement of functional connectivity within mPFC-amygdala circuit - accompanied by an inverted direction of information transferred from the amygdala to the mPFC. We indicated that disrupting the dynamic interactions of the mPFC-amygdala circuit may contribute to the induction of anxiety-related behaviors with asthma. These findings could provide new insight to clarify the underlying mechanisms of allergic inflammation-induced psychiatric disorders related to asthma.

Intrahippocampal 5-HT1A receptor antagonist inhibits the improving effect of low-frequency stimulation on memory impairment in kindled rats.

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-HT1A 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-HT1A 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-HT1A 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-HT1A 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-HT1A 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-HT1A receptors in kindled animals.

Low-Frequency Electrical Stimulation Reduces the Impairment in Synaptic Plasticity Following Epileptiform Activity in Rat Hippocampal Slices through α1, But Not α2, Adrenergic Receptors.

Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented this impairment. Then, we investigated the involvement of α-adrenergic receptors in this effect of LFS. EA was induced by increasing the extracellular K+ concentration to 12 mM and EPSPs were recorded from CA1 neurons in whole cell configuration. EA increased EPSP amplitude from 6.9 ±â€¯0.7 mV to 9.6 ±â€¯0.6 mV. For LTP induction, the Schaffer collaterals were stimulated by high frequency stimulation (HFS; two trains of 100 pulses, 100 Hz at the interval of 20 s). The application of HFS resulted in 40.9 ±â€¯2.3% increase in the amplitude of EPSPs. However, following EA, HFS could not produce any significant changes in EPSP amplitude. Administration of LFS (1 Hz, 900 pulses) to Schaffer collaterals at the beginning of EA restored LTP induction to the hippocampal slices and HFS increased the EPSPs amplitude up to 41.7 ±â€¯3.1% of baseline. When slices were perfused by prazosin (α1-adrenergic receptor antagonist; 10 µM) before and during LFS application, LFS improvement on LTP induction was reduced significantly. Perfusion of slices by yohimbine (α2-adrenergic receptor antagonist; 5 µM) had no effect on LFS action. Therefore, it may be concluded that following epileptiform activity, LFS can improve the impairment of LTP generation through α1, but not α2, adrenergic receptor activity.

The inhibitory effect of different patterns of low frequency stimulation on neuronal firing following epileptiform activity in rat hippocampal slices.

Low frequency stimulation (LFS) has inhibitory effect on hyperexcitability during epileptic states. However, knowledge is lacking about LFS patterns that can exert an optimal antiepileptic effect. In this study, the effect of different numbers of pulses and current intensities of 1 Hz LFS applied at various time points of epileptiform activity was evaluated in high-K+ model of epileptiform activity (EA). LFS was applied to the Schaffer collaterals, and changes in the excitability of CA1 pyramidal neurons were measured using whole-cell patch-clamp recording. Six hundred and 900 pulses of LFS at two current intensities (equal to and 1.5 times greater than the current intensity sufficient to elicit a 5 mV EPSP) administered at the beginning of EA revealed a stronger LFS inhibitory effect on EA-induced neuronal hyperexcitability when applied at higher pulse number and current intensity. LFS900 (high intensity) significantly hyperpolarized the membrane potential after a high-K+ ACSF washout, reduced the frequency of spontaneous action potentials during EA, and attenuated neuronal firing frequency after high-K+ ACSF washout. Moreover, applying LFS900 (high intensity) before EA induction and 8-10 min after EA initiation could not significantly affect neuronal hyperexcitability, compared to its application at the beginning of EA. This study's findings also offered long-term depression (LTD) as a probable mechanism for LFS' inhibitory role on EA-induced neuronal hyperexcitability. Therefore, the application of LFS (1 Hz) at 900 pulses and greater current intensity at the beginning of EA can exert a strong inhibitory effect on EA-induced neuronal hyperexcitability.

The role of 5-HT1A receptors of hippocampal CA1 region in anticonvulsant effects of low-frequency stimulation in amygdala kindled rats.

Low frequency stimulation (LFS) has been proposed as a method in the treatment of epilepsy, but its anticonvulsant mechanism is still unknown. In the current study, the hippocampal CA1 region was microinjected with NAD-299 (a selective 5-HT1A antagonist), and its role in mediating the inhibitory action of LFS on amygdala kindling was investigated. Male Wistar rats were kindled by amygdala stimulation in a semi-rapid kindling manner (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, 50-150 µA) was applied at 5 min after termination of daily kindling stimulations. NAD (a selective 5-HT1A antagonist) was microinjected into the CA1 region of the hippocampus at the doses of 2.5 and 5 µg/1 µl. An open field test was also run to determine the motor activity of animals in different experimental groups. The application of LFS following daily kindling stimulations reduced the behavioral seizure stages, afterdischarge duration, and stage 5 seizure duration and increased the latency to stage 4 seizure compared to the kindled group. However, microinjection of NAD at the doses of 5 µg/1 µl, but not 2.5 µg/1 µl, blocked the inhibitory effect of LFS on behavioral and electrophysiological parameters in kindled animals. It could be presumed that 5-HT1A receptors in the CA1 area are involved in mediating the antiepileptic effects of LFS.

Nature and extent of person recognition impairments associated with Capgras syndrome in Lewy body dementia.

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.

Reach adaptation and proprioceptive recalibration following terminal visual feedback of the hand.

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.

Representational demands modulate involvement of perirhinal cortex in face processing.

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.