Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training.

A major challenge in the cognitive training field is inducing broad, far-transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision-based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non-learners) and a subset of participants in the MLA (i.e., MLA non-learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.

The neuroprotective effect of NeuroAid on morphine-induced amnesia with respect to the expression of TFAM, PGC-1α, ΔfosB and CART genes in the hippocampus of male Wistar rats.

Morphine is a natural alkaloid which derived from the opium poppy Papaver somniferum. Many studies have reported the effect of morphine on learning, memory and gene expression. CART (cocaine-amphetamine regulated transcript)is an important neuropeptide which has a critical role in physiological processes including drug dependence and antioxidant activity. ΔfosB is a transcription factor which modulates synaptic plasticity and affects learning and memory. TFAM (the mitochondrial transcription factor A) and PGC-1α (Peroxisome proliferator-activated receptor γ coactivator-1α) are critically involved in mitochondrial biogenesis and antioxidant pathways. NeuroAid is a Chinese medicine that induces neuroprotective and anti-apoptotic effects. In this research, we aimed to investigate the effect of NeuroAid on morphine-induced amnesia with respect to the expression of TFAM, PGC-1α, ΔfosB and CART in the rat's hippocampus. In this study, Morphine sulfate (at increasing doses), Naloxone hydrochloride (2.5 mg/kg) and NeuroAid (2.5 mg/kg) were administered intraperitoneal and real-time PCR reactions were done to assess gene expression. The results showed, morphine impaired memory of step-through passive avoidance, while NeuroAid had no effect. NeuroAid attenuated (but not reversed) morphine-induced memory impairment in morphine-addicted rats. Morphine increased the expression of PGC-1α and decreased the expression of CART. However, NeuroAid increased the expression of TFAM, PGC-1α, ΔfosB and CART. NeuroAid restored the effect of morphine on the expression of CART and PGC-1α. In conclusion, morphine impaired memory of step-through passive avoidance and NeuroAid attenuated this effect. The effect of NeuroAid on morphine-induced memory impairment/gene expression may be related to its anti-apoptotic and neuroprotective effects.

Evaluation of the Memory Enhancing Activity of Dichloromethane Fraction of the Methanolic Extract of Pycnanthus angolensis Stem Bark on Experimental Models of Memory Impairment.

Pycnanthus angolensis (Welw) Warb., Myristicaceae, is used extensively in ethnomedicine. Numerous health benefits have been ascribed to the use of different parts of P. angolensis including its role in cognitive function and inflammatory conditions. Hence, this study was undertaken to investigate the effect of stem bark of the plant on memory function in mice.The plant material was pulverized into powder and extracted by maceration with 80% methanol at room temperature for 48 h. This was subsequently fractionated using N-hexane, Dichloromethane (DCM) and Ethyl acetate. The Dichloromethane fraction which is the most potent fraction (25, 50 and 100 mg/kg) was evaluated for memory enhancing activity using the Y-maze (YMT), morris water maze (MWM) and the elevated plus maze (EPM) on D-galactose plus scopolamine and ketamine induced amnesia. The antioxidant markers and acetylcholinesterase (AChE) inhibiting effect of DCM were also investigated.The results obtained from the behavioural study indicates that the DCM fraction significantly (p<0.05) increased alternation behaviour of mice in the YMT, decreased the escape latency in the MWM paradigm and decreased the transfer latency in the EPM. Biochemically, DCM increased glutathione, and superoxide dismutase, but decreased malondialdehyde and AChE activity in the brain.The findings therefore suggests that the DCM possesses significant memory enhancing activity, which may be due to enhancement of antioxidant activity and cholinergic transmission. The attenuation of the effect of ketamine by the DCM may possibly result from an increase in NMDA receptor mediated neurotransmission and attenuation of oxidative stress.

Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition.

Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of ß amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.

Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice.

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.

Patients with hippocampal amnesia successfully integrate gesture and speech.

During conversation, people integrate information from co-speech hand gestures with information in spoken language. For example, after hearing the sentence, "A piece of the log flew up and hit Carl in the face" while viewing a gesture directed at the nose, people tend to later report that the log hit Carl in the nose (information only in gesture) rather than in the face (information in speech). The cognitive and neural mechanisms that support the integration of gesture with speech are unclear. One possibility is that the hippocampus - known for its role in relational memory and information integration - is necessary for integrating gesture and speech. To test this possibility, we examined how patients with hippocampal amnesia and healthy and brain-damaged comparison participants express information from gesture in a narrative retelling task. Participants watched videos of an experimenter telling narratives that included hand gestures that contained supplementary information. Participants were asked to retell the narratives and their spoken retellings were assessed for the presence of information from gesture. For features that had been accompanied by supplementary gesture, patients with amnesia retold fewer of these features overall and fewer retellings that matched the speech from the narrative. Yet their retellings included features that contained information that had been present uniquely in gesture in amounts that were not reliably different from comparison groups. Thus, a functioning hippocampus is not necessary for gesture-speech integration over short timescales. Providing unique information in gesture may enhance communication for individuals with declarative memory impairment, possibly via non-declarative memory mechanisms.

Ameliorative potential of desalted Salicornia europaea L. extract in multifaceted Alzheimer's-like scopolamine-induced amnesic mice model.

The Salicornia europaea L. (SE) plant is a halophyte that has been widely consumed as a seasoned vegetable, and it has been recently reported to counteract chronic diseases related to oxidative and inflammatory stress. In this study, we performed an initial phytochemical analysis with in vitro biochemical tests and chromatographic profiling of desalted and enzyme-digested SE ethanol extract (SE-EE). Subsequently, we evaluated the anti-neuroinflammatory and ameliorative potential of SE-EE in LPS-inflicted BV-2 microglial cells and scopolamine-induced amnesic C57/BL6N mice, respectively. SE-EE possess considerable polyphenols and flavonoids that are supposedly responsible to improve its bio-efficacy. SE-EE dose-dependently attenuated LPS-induced inflammation in BV-2 cells, significantly repressed behavioural/cognitive impairment, dose-dependently regulated the cholinergic function, suppressed oxidative stress markers, regulated inflammatory cytokines/associated proteins expression and effectively ameliorated p-CREB/BDNF levels, neurogenesis (DCX stain), neuron proliferation (Ki67 stain) in scopolamine-administered mice. Thus, SE-EE extract shows promising multifactorial disease modifying activities and can be further developed as an effective functional food, drug candidate, or supplemental therapy to treat neuroinflammatory mediated disorders.

COGNITIVE-ENHANCING PROPERTIES OF MORINDA LUCIDA (RUBIACEAE) AND PELTOPHORUM PTEROCARPUM (FABACEAE) IN SCOPOLAMINE-INDUCED AMNESIC MICE.

BACKGROUND: Cognitive disorders associated with aging have been successfully managed by African traditional medical practitioners using various plants. This study evaluated the cognitive enhancing potentials of Morinda lucida (L) Rubiaceae and Peltophorum pterocarpum (DC) ex. K Heyne in scopolamine induced amnesic animals. MATERIALS AND METHODS: The anti-amnesic activity of the ethyl acetate extracts of Morinda lucida and Peltophorum pterocarpum at doses of 4 mg/kg, 6 mg/kg and 8 mg/kg were assessed in scopolamine induced amnesic mice using Morris water maze test model. Effect of the extracts on the histology of the hippocampus was also evaluated. RESULTS: The ethyl acetate extract of Morinda lucida and Peltophorum pterocarpum ameliorated scopolamine induced memory deficit in the animals under study. There was no effect of the extract on the histology of the hippocampus. However, there was an increase in the density of cells in the hippocampus of treated group as compared to the untreated. CONCLUSION: Morinda lucida and Peltophorum pterocarpum showed considerable enhancement of cognition in scopolamine induced amnesic mice.

Effect of Gingko biloba extract on scopolamine-induced apoptosis in the hippocampus of rats.

Apoptosis, known as programmed cell death, plays a crucial role in normal development and tissue homeostasis. Apoptosis is also involved in neurodegenerative diseases such as Alzheimer's disease. Amnesia refers to the loss of memory and can also be a warning sign of neurodegenerative diseases. The antioxidant properties of Ginkgo biloba extract was known previously. Therefore, the aim of this study was to examine the effects of Ginkgo biloba extract on the rat's hippocampal apoptotic neurons number after Scopolamine based amnesia. Thirty-six adult male Wistar rats were used. Rats were randomly divided into control, sham, protective and treatment groups. The rats in the sham group received only scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received Ginkgo biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before/after scopolamine injection. Then 48 h after the last injection, the brains of rats were withdrawn and fixed with paraformaldehyde, and then, after histological processing, the slices were stained with the TUNEL kit for apoptotic neurons. Data were compared by the ANOVA Post Hoc Tukey test; P < 0.05 was considered significant. Our results showed that Scopolamine (in the sham group) increased significantly the number of apoptotic neurons in all areas of the hippocampus compared with the control. Whereas, Ginkgo biloba extract reduce the neuronal apoptosis in the hippocampus before and/or after encounter with scopolamine. We concluded that pretreatment and treatment injection of Ginkgo biloba extract can have a protective effect for neurons and it can limit apoptosis in all area of the hippocampus.

Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety.

The study aims at formulation and optimization brain targeted nanoparticles (NP) of Rivastigmine (RT) to improve its therapeutic potential and to verify its safety profile. The NP were optimized using a two factor three level (3(2)) central composite design aiming to minimize particle size; maximize zeta potential and drug entrapment efficiency of NP. The optimized formulation (cRTNP) was evaluated using in vitro drug release study; in vivo behavioral, and biochemical and maximum tolerated dose (MTD) study. The optimized formulation evidenced a significant reversal of scopolamine-induced amnesia by Tween 80(®) coated nanoparticles as compared to both pure RT as well as uncoated nanoparticles. The MTD of RT was increased by 10% by formulating them as cRTNP. Thus, formulation of RT as cRTNP improved the therapeutic and safety profile of RT.

Learning and memory promoting effects of crude garlic extract.

Chronic administration of aged garlic extract has been shown to prevent memory impairment in mice. Acute and chronic (21 days) effects of marketed formulation of crude garlic extract (Lasuna) were evaluated on learning and memory in mice using step down latency (SDL) by passive avoidance response and transfer latency (TL) using elevated plus maze. Scopolamine (0.4 mg/kg, ip) was used to induce amnesia in mice and piracetam (200 mg/kg, ip) served as positive control. In the acute study, Lasuna (65 mg/kg, po) partially reversed the scopolamine-induced amnesia but failed to improve learning and memory in untreated animals. Chronic administration of Lasuna (40 mg/kg/day for 21 days) significantly improved learning both in control and scopolamine induced amnesic animals. Influence of Lasuna on central cholinergic activity and its antioxidant properties were also studied by estimating the cortical acetylcholinesterase (AchE) activity and reduced glutathione (GSH) levels respectively. Chronic administration of Lasuna inhibited AchE, while increasing GSH levels. Thus the results indicate that long-term administration of crude garlic extract may improve learning and memory in mice while the underlying mechanism of action may be attributed to the anti-AchE activity and anti-oxidant property of garlic.

Can complex visual discrimination deficits in amnesia be attributed to the medial temporal lobe? An investigation into the effects of medial temporal lobe damage on brain connectivity.

It has been suggested that complex visual discrimination deficits in patients with medial temporal lobe (MTL) damage may be explained by damage or dysfunction beyond the MTL. We examined the resting functional networks and white matter connectivity of two amnesic patients who have consistently demonstrated discrimination impairments for complex object and/or spatial stimuli across a number of studies. Although exploratory analyses revealed some significant differences in comparison with neurologically healthy controls (more specifically in the patient with a larger MTL lesion), there were no obvious findings involving posterior occipital or posterior temporal regions, which can account entirely for their discrimination deficits. These findings converge with previous work to support the suggestion that the MTL does not subserve long-term declarative memory exclusively.

Neuroprotective effect of Alpinia galanga (L.) fractions on Aß(25-35) induced amnesia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Alpinia galanga (L.) Willd (Zingiberaceae), a ginger substitute for flavouring food was traditionally used as nervine tonic and stimulant. AIM OF THE STUDY: This investigation is designed to screen cognitive improvement of Alpinia galanga (AG) fractions in Alzheimer's type of amnesia in mice induced by Aß((25-35)). MATERIALS AND METHODS: Alzheimer's disease induced mice treated with fractions (n-hexane, chloroform and ethyl acetate) of AG in 200 and 400mg/kg. Neurotoxicity was induced by intracerebroventricular injection of Aß((25-35)) on the 14th day of 21 days drug treatment. Open field and water maze were carried to determine habituation memory and hippocampal memory. Na(+)/K(+)-ATPase, acetylcholinesterase (AChE) and antioxidant enzymes (SOD, GPx, catalase and vitamin C) were determined in brain tissue homogenate to estimate the brain biochemical changes and its anti-amnesic potential with intensity of oxidative stress signaling. Further bioactive (chloroform) fraction was eluted through column chromatography to identify the lead molecules. RESULTS: Increased habituation memory and decreased escape latency in behavioral parameter are the indicative of the cognitive enhancement after treatment with Alpinia galanga fractions. Increment in Na(+)/K(+)-ATPase and antioxidant activity depicts brain membrane integrity improvement and free radical scavenging property. AChE level was decreased to improve the cognition by enhancing cholinergic transmission. CONCLUSION: Anti-amnesic effect was exerted by various fractions of Alpinia galanga. Among all fractions, preeminent neuroprotection was exerted by chloroform fraction, which has compound, 1'δ-1'-acetoxyeugenol acetate and it may be a potential therapeutic agent for Alzheimer's type of amnesia. These results further motivate us to explore the activity of lead compound's anti-amnesic effect on transgenic mice model of AD.

Neuroprotective potential of ethanolic extract of Pseudarthria viscida (L) Wight and Arn against beta-amyloid(25-35)-induced amnesia in mice.

The neuroprotective potential of ethanolic extract of roots of Pseudarthria viscida (L) Wight and Arn (EEPV) was investigated against beta-amyloid(25-35)-induced amnesia in mice which is a suitable animal model for Alzheimer's disease (AD). The senile plaques of beta-amyloid (Abeta) are major constituents accumulated during the progression of AD as a potent neurotoxicant. In our investigation, intracerebroventricular injection of Abeta(25-35) in mice induced the neurodegeneration, exhibited the increased time of escape latency in behavioral pattern using water maze and decreased the levels of antioxidants namley superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and vitamin C with elevated level of acetylcholinesterase enzyme (AChE). The neuroprotective potential of EEPV was determined by behavioral pattern using water maze and biochemical parameters such as SOD, CAT and GPx and vitamin C content as well as AChE. Mice were treated with EEPV at 200 and 400 mg/kg doses for 21 days. Except control, all animals received a single injection of neurotoxicant Abeta(25-35) on 14th day. In behavioural assessment, treatment with ethanolic extract improved the cognitive function in the water maze and attenuated the elevated levels of AChE with increase in antioxidant enzymes, indicating the neuroprotection with increased levels of vitamin C. These findings suggest that ethanolic extract of P. viscida exerts anti-amnesiac effects and enhances cognitive function.

Vascular thalamic amnesia: a reappraisal.

In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided lesions and 41 with bilateral lesions). We aimed to find answers to the following questions concerning the vascular thalamic amnesia syndrome: (i) Which qualitative pattern of memory impairment (and associated cognitive and behavioral deficits) do these patients present? (ii) Which lesioned intrathalamic structures are primarily responsible for the amnesic syndrome? (iii) Are the recollection and familiarity components of declarative memory underlain by the same or by different thalamic structures? Results of the review indicate that, similar to patients with amnesic syndromes due to mesio-temporal lobe damage, patients with vascular thalamic amnesia display a prevalent deficit of declarative anterograde long-term memory, a less consistent deficit of declarative retrograde long-term memory and substantially spared short-term and implicit memory. Unlike mesio-temporal lobe patients, however, vascular thalamic amnesics often present dysexecutive and behavioral deficits similar to those observed in patients with frontal damage. The presence of an amnesic syndrome in patients with thalamic lacunar infarcts is strongly predicted by involvement of the mammillo-thalamic tract, which connects the anterior nuclei complex to the hippocampus proper via the fornix and the mammillary bodies. Finally, data reported in a few single cases provide support for the hypothesis that thalamic regions connected to distinct areas of the mesio-temporal lobe play differential roles in recollection and familiarity processes. The mammillo-thalamic tract/anterior nuclei axis seems primarily implicated in recollective processes, whereas the ventroamygdalofugal pathway/medio-dorsal axis primarily underlies familiarity processes.

Effects of Nelumbo nucifera rhizome extract on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model.

A large aquatic herb, Nelumbo nucifera Gaertn, has psychopharmacological effects similar to minor tranquillizers and antistress agents. This study examined the effects of Nelumbo nucifera rhizome extracts (NRE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of a rat model of scopolamine-induced amnesia. Immunohistochemical markers included Ki67, an endogenous marker for active cell cycle, and doublecortin (DCX), a marker for immature neurons and migratory neuroblasts. Scopolamine was administered for 28 days via an ALzet minipump (44 mg/mL delivered at 2.5 µL/h). NRE was administered by gavage, 1 g/kg per day for 28 days. The administration of scopolamine significantly reduced the number of Ki67- and DCX-immunoreactive cells in the DG, whereas scopolamine did not induce any significant changes in mature neurons in the DG. The administration of NRE significantly ameliorated the scopolamine-induced reduction of Ki67- and DCX-immunoreactive cells in the DG. In addition, the administration of NRE significantly restored the scopolamine-induced reduction of brain-derived neurotrophic factor in DG homogenates. These results suggest that NRE can ameliorate the scopolamine-induced reductions of cell proliferation, neuroblast differentiation and BDNF levels.

MR imaging texture analysis of the corpus callosum and thalamus in amnestic mild cognitive impairment and mild Alzheimer disease.

BACKGROUND AND PURPOSE: TA is a branch of image processing that seeks to reduce image information by extracting texture descriptors from the image. TA of MR images of anatomic structures in mild AD and aMCI is not well-studied. Our objective was to attempt to find differences among patients with aMCI and mild AD and normal-aging subjects, by using TA applied to the MR images of the CC and the thalami of these groups of subjects. MATERIALS AND METHODS: TA was applied to the MR images of 17 patients with aMCI, 16 patients with mild AD, and 16 normal-aging subjects. The TA approach was based on the GLCM. MR images were T1-weighted and were obtained in the sagittal and axial planes. The CC and thalami were manually segmented for each subject, and 44 texture parameters were computed for each of these structures. RESULTS: TA parameters showed differences among the 3 groups for the CC and thalamus. A pair-wise comparison among groups showed differences for AD-control and aMCI-AD for the CC; and for AD-control, aMCI-AD, and aMCI-control for the thalamus. CONCLUSIONS: TA is a useful technique to aid in the detection of tissue alterations in MR images of mild AD and aMCI and has the potential to become a helpful tool in the diagnosis and understanding of these pathologies.

Prospective memory in thalamic amnesia.

The contribution of the thalamus to the functioning of prospective memory (PM) is currently unknown. Here we report an experimental investigation of the performance of two patients with bilateral infarcts in the anterior-mesial regions of the thalami on an event-based PM paradigm. One patient, G.P., had a pervasive declarative memory impairment but no significant executive deficit. The other patient, R.F., had a memory deficit limited to verbal material with associated behavioral abnormalities (inertia and apathy); she performed poorly on tests of executive functions. Although both patients performed poorly on the PM task, a qualitative analysis of performance revealed different mechanisms at the base of their impaired PM. G.P. had reduced declarative memory for target words compared with normal controls; but, unforgotten words were normally able to elicit his recall of the prospective intention. Conversely, R.F.'s declarative memory for target words was as accurate as that of normal controls, but she presented a dramatically reduced ratio between the number of target words she recalled and the number of times she activated the prospective intention on the PM task, suggesting that her deficit consisted of difficulty in activating the intention despite normal declarative memory for the target events. In conclusion, results of the present study demonstrate that thalamic structures have an important role in PM processes. They also document that damage to the anterior-mesial regions of the thalami affects PM abilities by two different mechanisms, respectively based on the relative disruption of declarative memory or executive processes functioning, which, in turn, is related to the specific intrathalamic structures involved by the lesions. Indeed, while G.P.'s pervasive declarative memory deficit was underlain by bilateral involvement of the mammillo-thalamic tract, R.F.'s executive and behavioral abnormalities were likely related to bilateral damage of the midline, intralaminar, and medio-dorsal nuclei.

Dissociation in hysteria and hypnosis: evidence from cognitive neuroscience.

Jean-Martin Charcot proposed the radical hypothesis that similar brain processes were responsible for the unexplained neurological symptoms of 'hysteria', now typically diagnosed as 'conversion disorder' or 'dissociative (conversion) disorder', and the temporary effects of hypnosis. While this idea has been largely ignored, recent cognitive neuroscience studies indicate that (i) hypnotisability traits are associated with a tendency to develop dissociative symptoms in the sensorimotor domain; (ii) dissociative symptoms can be modelled with suggestions in highly hypnotisable subjects; and (iii) hypnotic phenomena engage brain processes similar to those seen in patients with symptoms of hysteria. One clear theme to emerge from the findings is that 'symptom' presentation, whether clinically diagnosed or simulated using hypnosis, is associated with increases in prefrontal cortex activity suggesting that intervention by the executive system in both automatic and voluntary cognitive processing is common to both hysteria and hypnosis. Nevertheless, while the recent literature provides some compelling leads into the understanding of these phenomena, the field still lacks well controlled systematically designed studies to give a clear insight into the neurocognitive processes underlying dissociation in both hysteria and hypnosis. The aim of this review is to provide an agenda for future research.

Hippocampal, retrosplenial, and prefrontal hypoactivity in a model of diencephalic amnesia: Evidence towards an interdependent subcortical-cortical memory network.

The medial diencephalon is vital for memory, but it is not known why. The present study tested between the predictions of current hypotheses as to why this region is critical for memory. Lesions were made in the rat mammillothalamic tract, the only diencephalic structure consistently associated with amnesia in humans after ischemia. Decreased activity, as measured by immediate-early gene expression (c-fos), was found in three key sites associated with memory function: the hippocampus, the prefrontal cortex, and the retrosplenial cortex. The specificity of these changes was confirmed by the qualitatively different patterns of immediately-early gene changes seen after amygdala lesions, e.g., hypoactivity in the hippocampus and retrosplenial cortex following mammillothalamic tract lesions but not following amygdala lesions. The mammillothalamic lesion results unify substrates linked to diencephalic and temporal lobe amnesia, and thereby support a new account of diencephalic amnesia that emphasizes multiple dysfunctions across hippocampal, retrosplenial, and prefrontal areas. This account suggests a role for the mammillary bodies that is independent of their hippocampal inputs.