Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report.

PubMed

Reneman, L; Majoie, C B; Schmand, B; van den Brink, W; den Heeten, G J

2001-10-01

3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy") is known to damage brain serotonin neurons in animals and possibly humans. Because serotonergic damage may adversely affect memory, we compared verbal memory function between MDMA users and MDMA-naïve control subjects and evaluated the relationship between verbal memory function and neuronal dysfunction in the MDMA users. An auditory verbal memory task (Rey Auditory Verbal Learning Test) was used to study eight abstinent MDMA users and seven control subjects. In addition 1H-MRS was used in different brain regions of all MDMA users to measure N-acetylaspartate/creatine (NAA/Cr) ratios, a marker for neuronal viability. The MDMA users recalled significantly fewer words than control subjects on delayed (p =.03) but not immediate recall (p =.08). In MDMA users, delayed memory function was strongly associated with NAA/Cr only in the prefrontal cortex (R(2) =.76, p =.01). Greater decrements in memory function predicted lower NAA/Cr levels-and by inference greater neuronal dysfunction-in the prefrontal cortex of MDMA users.

Uninformative memories will prevail: the storage of correlated representations and its consequences.

PubMed

Kropff, Emilio; Treves, Alessandro

2007-11-01

Autoassociative networks were proposed in the 80's as simplified models of memory function in the brain, using recurrent connectivity with Hebbian plasticity to store patterns of neural activity that can be later recalled. This type of computation has been suggested to take place in the CA3 region of the hippocampus and at several levels in the cortex. One of the weaknesses of these models is their apparent inability to store correlated patterns of activity. We show, however, that a small and biologically plausible modification in the "learning rule" (associating to each neuron a plasticity threshold that reflects its popularity) enables the network to handle correlations. We study the stability properties of the resulting memories (in terms of their resistance to the damage of neurons or synapses), finding a novel property of autoassociative networks: not all memories are equally robust, and the most informative are also the most sensitive to damage. We relate these results to category-specific effects in semantic memory patients, where concepts related to "non-living things" are usually more resistant to brain damage than those related to "living things," a phenomenon suspected to be rooted in the correlation between representations of concepts in the cortex.

Intensive working memory training: a single case experimental design in a patient following hypoxic brain damage.

PubMed

Hynes, S M; Fish, J; Manly, T

2014-01-01

Recent reports suggest that intensive, progressive training on working memory tasks can lead to generalized cognitive gains. A patient, following hypoxic brain damage, showed significant difficulties in working memory and time-perception. This study examined the impact and specificity of any benefits resulting from automated working memory training (AWMT) in comparison with the effects of an equivalent programme that emphasized automated novel problem-solving (APST) which served as an active control. Following initial assessment, the patient trained for 4 weeks (20 days), 20-30 minutes a day on the APST tasks before repeating key outcome measures. He then trained for an identical period on AWMT. There were no cognitive gains apparent following APST. Furthermore, there were no disproportionate gains on digit span following AWMT. AWMT was, however, associated with improvement in time-perception that had previously been resistant to rehabilitation. In line with previous reports, AWMT was also followed by gains on a measure of planning. The results provide encouraging evidence that AWMT may have generalized benefits in the context of impaired WM capacity following brain injury.

Categorization skills and recall in brain damaged children: a multiple case study.

PubMed

Mello, Claudia Berlim de; Muszkat, Mauro; Xavier, Gilberto Fernando; Bueno, Orlando Francisco Amodeo

2009-09-01

During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.

31 CFR 346.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2014 CFR

2014-07-01

... transportation, or doing small chores. (iv) Cancer which is inoperable and progressive. (v) Damage to the brain or brain abnormality which has resulted in severe loss of judgment, intellect, orientation, or memory...

Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.

PubMed

Brand, Matthias; Eggers, Carsten; Reinhold, Nadine; Fujiwara, Esther; Kessler, Josef; Heiss, Wolf-Dieter; Markowitsch, Hans J

2009-10-30

Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.

REM sleep rescues learning from interference

PubMed Central

McDevitt, Elizabeth A.; Duggan, Katherine A.; Mednick, Sara C.

2015-01-01

Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: protection against acetylcholinesterase activity and neuronal oxidative damage.

PubMed

Ghasemi, Simagol; Moradzadeh, Malihe; Hosseini, Mahmoud; Beheshti, Farimah; Sadeghnia, Hamid Reza

2018-05-10

This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3-5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p < 0.01-p <0.001). Treatment by the extract reversed all the effects of scopolamine (p < 0.05-p <0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity.

Cortisol Excess and the Brain.

PubMed

Resmini, Eugenia; Santos, Alicia; Webb, Susan M

2016-01-01

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages.

PubMed

He, Xiao-Fei; Lan, Yue; Zhang, Qun; Liu, Dong-Xu; Wang, Qinmei; Liang, Feng-Ying; Zeng, Jin-Sheng; Xu, Guang-Qing; Pei, Zhong

2016-08-01

Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine (DFX), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57BL6 and Thy-1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two-photon laser irradiation. DFX (100 mg/kg) was administered 6 h after microhemorrhage induction, followed by every 12 h for three consecutive days. The water maze task was conducted 7 days after induction of microhemorrhages, followed by measurement of blood-brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser-induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX, supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment. Irons accumulation after intracranial hemorrhage induced a serious secondary damage to the brain. We proposed that irons accumulation after parietal microhemorrhages impaired spatial cognition. After parietal multiple microhemorrhages, increased irons and ferritin contents induced blood-brain barrier disruption, microglial activation, and further induced dendrites loss, eventually impaired the water maze, deferoxamine treatment protected from these damages. © 2016 International Society for Neurochemistry.

Retinal Atherosclerosis, Ophthalmologically Reported and Documented with OSA in 1987, is now Totally Reversed, and Recorded, Photographically. The Supposition then was that Equivalent Cortical Damage could Respond to the same Healing Protocol.

NASA Astrophysics Data System (ADS)

Niemi, Paul N.; O., D.; Mc Leod, David M.; Mc Leod, Roger D.

2007-10-01

Documented retinal atherosclerosis, ``silver streaking'' of retinal capillaries, was reported and documented with OSA, in October 1987. That retinal damage, despite claims it usually progresses and is nonreversible, is now completely cleared. The original OSA presentation proposed that equivalent cortical damage was probably present throughout the brain at that time, as attested by failing short-term memory performance and transient ischemic attacks, TIAs, brief vision strokes. The supposition then was that ophthalmologic access to the retina, by some accounts the progenitor of all brain evolution, could provide a means of monitoring the actual circulatory state of inaccessible parts of the brain. To the extent that retinal health was naturopathically restored, and memory performance seems also to have significantly kept pace, is it a tenable premise that such protocols have rather general importance? Can applied optics help establish more appropriate diagnoses, and evaluate treatments for dementia and Alzheimer's disease?

Superficial white matter damage in anti-NMDA receptor encephalitis.

PubMed

Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

2018-05-01

Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

PubMed

Raffa, R B

2013-08-01

Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. © 2013 John Wiley & Sons Ltd.

On Common Ground: Jost's (1897) Law of Forgetting and Ribot's (1881) Law of Retrograde Amnesia

ERIC Educational Resources Information Center

Wixted, John T.

2004-01-01

T. Ribot's (1881) law of retrograde amnesia states that brain damage impairs recently formed memories to a greater extent than older memories, which is generally taken to imply that memories need time to consolidate. A. Jost's (1897) law of forgetting states that if 2 memories are of the same strength but different ages, the older will decay more…

Judo as a possible cause of anoxic brain damage. A case report.

PubMed

Owens, R G; Ghadiali, E J

1991-12-01

The rules of judo provide for strangulation techniques in which the blood supply to the brain is blocked by pressure on the carotid arteries; such techniques produce anoxia and possible unconsciousness if the victim fails to submit. A case is presented of a patient with signs of anoxic brain damage, with psychometric investigation showing memory disturbance consistent with a left temporal lobe lesion. This patient had been frequently strangled during his career as a judo player; it is suggested that such frequent strangulation was the cause of the damage. Such an observation indicates the need for caution in the use of such techniques.

Psychogenic amnesia--a malady of the constricted self.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J; Brand, Matthias

2010-09-01

Autobiographical-episodic memory is the conjunction of subjective time, autonoetic consciousness and the experiencing self. Understanding the neural correlates of autobiographical-episodic memory might therefore be essential for shedding light on the neurobiology underlying the experience of being an autonoetic self. In this contribution we illustrate the intimate relationship between autobiographical-episodic memory and self by reviewing the clinical and neuropsychological features and brain functional imaging correlates of psychogenic amnesia - a condition that is usually characterized by severely impaired retrograde memory functioning, in absence of structural brain damage as detected by standard imaging. We demonstrate that in this disorder the autobiographical-episodic memory deficits do not exist in isolation, but occur with impairments of the autonoetic self-consciousness, emotional processing, and theory of mind or executive functions. Furthermore functional and metabolic brain alterations involving regions that are agreed upon to exert crucial roles in memory processes were frequently found to accompany the psychogenic memory "loss". Copyright © 2010 Elsevier Inc. All rights reserved.

Dissociations in cognitive memory: the syndrome of developmental amnesia.

PubMed

Vargha-Khadem, F; Gadian, D G; Mishkin, M

2001-09-29

The dearth of studies on amnesia in children has led to the assumption that when damage to the medial temporal lobe system occurs early in life, the compensatory capacity of the immature brain rescues memory functions. An alternative view is that such damage so interferes with the development of learning and memory that it results not in selective cognitive impairments but in general mental retardation. Data will be presented to counter both of these arguments. Results obtained from a series of 11 amnesic patients with a history of hypoxic ischaemic damage sustained perinatally or during childhood indicate that regardless of age at onset of hippocampal pathology, there is a pronounced dissociation between episodic memory, which is severely impaired, and semantic memory, which is relatively preserved. A second dissociation is characterized by markedly impaired recall and relatively spared recognition leading to a distinction between recollection-based versus familiarity-based judgements. These findings are discussed in terms of the locus and extent of neuropathology associated with hypoxic ischaemic damage, the neural basis of 'remembering' versus 'knowing', and a hierarchical model of cognitive memory.

Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer's disease

PubMed Central

Mistridis, Panagiota; Taylor, Kirsten I.; Kissler, Johanna M.; Monsch, Andreas U.; Kressig, Reto W.; Kivisaari, Sasa L.

2014-01-01

Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g., autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer's disease (AD), which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14), patients with AD (n = 15) and its putative prodrome amnestic mild cognitive impairment (n = 11) completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies. PMID:24478669

Memory-For-Designs Test: Comparison of Performance of Young and Old Adults.

ERIC Educational Resources Information Center

Dustman, Robert E.; Beck, Edward C.

1980-01-01

No significant decline in performance occurred before age 50. Decline in Memory-For-Designs Test performance after age 60 is sufficient to suggest caution in the use of the test for evaluation of brain damage in the older patient. (Author)

Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats.

PubMed

Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

2014-06-01

Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage.

Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

PubMed

Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

2016-07-01

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

Interaction between emotion and memory: importance of mammillary bodies damage in a mouse model of the alcoholic Korsakoff syndrome.

PubMed

Béracochéa, Daniel

2005-01-01

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalic damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiamine-deficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS.

Interaction Between Emotion and Memory: Importance of Mammillary Bodies Damage in a Mouse Model of the Alcoholic Korsakoff Syndrome

PubMed Central

Béracochéa, Daniel

2005-01-01

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalie damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiaminedeficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS. PMID:16444899

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

PubMed

Ghasemi, Simagol; Hosseini, Mahmoud; Feizpour, Azadeh; Alipour, Fatemeh; Sadeghi, Akram; Vafaee, Farzaneh; Mohammadpour, Toktam; Soukhtanloo, Mohammad; Ebrahimzadeh Bideskan, Alireza; Beheshti, Farimah

2017-04-01

The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

The self-imagination effect: benefits of a self-referential encoding strategy on cued recall in memory-impaired individuals with neurological damage.

PubMed

Grilli, Matthew D; Glisky, Elizabeth L

2011-09-01

Knowledge of oneself is preserved in many memory-impaired individuals with neurological damage. Therefore, cognitive strategies that capitalize on mechanisms related to the self may be particularly effective at enhancing memory in this population. The present study investigated the effect of "self-imagining," imagining an event from a personal perspective, on short and long delayed cued recall in memory-impaired individuals with neurological damage. Sixteen patients intentionally encoded word pairs under four separate conditions: visual imagery, semantic elaboration, other person imagining, and self-imagining. The results revealed that self-imagining led to better performance than other-imagining, semantic elaboration, and visual imagery. Furthermore, the "self-imagination effect" (SIE) was preserved after a 30-min delay and was independent of memory functioning. These findings indicate that self-imagining provides a mnemonic advantage in brain-injured individuals, even those with relatively poor memory functioning, and suggest that self-imagining may tap into mnemonic mechanisms related to the self.

Varnish poisoning

MedlinePlus

... lack of responsiveness) Dizziness Impaired memory Insomnia Irritability Loss of coordination Sensation of being drunk Severe brain damage Sleepiness Stupor (decreased level of consciousness) Walking difficulties SKIN Burns Irritation

Extra virgin olive oil improves learning and memory in SAMP8 mice.

PubMed

Farr, Susan A; Price, Tulin O; Dominguez, Ligia J; Motisi, Antonio; Saiano, Filippo; Niehoff, Michael L; Morley, John E; Banks, William A; Ercal, Nuran; Barbagallo, Mario

2012-01-01

Polyphenols are potent antioxidants found in extra virgin olive oil (EVOO); antioxidants have been shown to reverse age- and disease-related learning and memory deficits. We examined the effects of EVOO on learning and memory in SAMP8 mice, an age-related learning/memory impairment model associated with increased amyloid-β protein and brain oxidative damage. We administered EVOO, coconut oil, or butter to 11 month old SAMP8 mice for 6 weeks. Mice were tested in T-maze foot shock avoidance and one-trial novel object recognition with a 24 h delay. Mice which received EVOO had improved acquisition in the T-maze and spent more time with the novel object in one-trial novel object recognition versus mice which received coconut oil or butter. Mice that received EVOO had improve T-maze retention compared to the mice that received butter. EVOO increased brain glutathione levels suggesting reduced oxidative stress as a possible mechanism. These effects plus increased glutathione reductase activity, superoxide dismutase activity, and decreased tissue levels of 4-hydroxynoneal and 3-nitrotyrosine were enhanced with enriched EVOO (3 × and 5 × polyphenols concentration). Our findings suggest that EVOO has beneficial effects on learning and memory deficits found in aging and diseases, such as those related to the overproduction of amyloid-β protein, by reversing oxidative damage in the brain, effects that are augmented with increasing concentrations of polyphenols in EVOO.

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

DTIC Science & Technology

2010-01-01

mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

NASA Astrophysics Data System (ADS)

Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

2015-04-01

The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

A virtual shopping test for realistic assessment of cognitive function

PubMed Central

2013-01-01

Background Cognitive dysfunction caused by brain injury often prevents a patient from achieving a healthy and high quality of life. By now, each cognitive function is assessed precisely by neuropsychological tests. However, it is also important to provide an overall assessment of the patients’ ability in their everyday life. We have developed a Virtual Shopping Test (VST) using virtual reality technology. The objective of this study was to clarify 1) the significance of VST by comparing VST with other conventional tests, 2) the applicability of VST to brain-damaged patients, and 3) the performance of VST in relation to age differences. Methods The participants included 10 patients with brain damage, 10 age-matched healthy subjects for controls, 10 old healthy subjects, and 10 young healthy subjects. VST and neuropsychological tests/questionnaires about attention, memory and executive function were conducted on the patients, while VST and the Mini-Mental State Examination (MMSE) were conducted on the controls and healthy subjects. Within the VST, the participants were asked to buy four items in the virtual shopping mall quickly in a rational way. The score for evaluation included the number of items bought correctly, the number of times to refer to hints, the number of movements between shops, and the total time spent to complete the shopping. Results Some variables on VST correlated with the scores of conventional assessment about attention and everyday memory. The mean number of times referring to hints and the mean number of movements were significantly larger for the patients with brain damage, and the mean total time was significantly longer for the patients than for the controls. In addition, the mean total time was significantly longer for the old than for the young. Conclusions The results suggest that VST is able to evaluate the ability of attention and everyday memory in patients with brain damage. The time of VST is increased by age. PMID:23777412

A virtual shopping test for realistic assessment of cognitive function.

PubMed

Okahashi, Sayaka; Seki, Keiko; Nagano, Akinori; Luo, Zhiwei; Kojima, Maki; Futaki, Toshiko

2013-06-18

Cognitive dysfunction caused by brain injury often prevents a patient from achieving a healthy and high quality of life. By now, each cognitive function is assessed precisely by neuropsychological tests. However, it is also important to provide an overall assessment of the patients' ability in their everyday life. We have developed a Virtual Shopping Test (VST) using virtual reality technology. The objective of this study was to clarify 1) the significance of VST by comparing VST with other conventional tests, 2) the applicability of VST to brain-damaged patients, and 3) the performance of VST in relation to age differences. The participants included 10 patients with brain damage, 10 age-matched healthy subjects for controls, 10 old healthy subjects, and 10 young healthy subjects. VST and neuropsychological tests/questionnaires about attention, memory and executive function were conducted on the patients, while VST and the Mini-Mental State Examination (MMSE) were conducted on the controls and healthy subjects. Within the VST, the participants were asked to buy four items in the virtual shopping mall quickly in a rational way. The score for evaluation included the number of items bought correctly, the number of times to refer to hints, the number of movements between shops, and the total time spent to complete the shopping. Some variables on VST correlated with the scores of conventional assessment about attention and everyday memory. The mean number of times referring to hints and the mean number of movements were significantly larger for the patients with brain damage, and the mean total time was significantly longer for the patients than for the controls. In addition, the mean total time was significantly longer for the old than for the young. The results suggest that VST is able to evaluate the ability of attention and everyday memory in patients with brain damage. The time of VST is increased by age.

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

PubMed

Di Paola, Margherita; Phillips, Owen; Costa, Alberto; Ciurli, Paola; Bivona, Umberto; Catani, Sheila; Formisano, Rita; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-01-01

Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. Neuropsychological scores and hippocampal volumes. We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

Episodic memory, semantic memory, and amnesia.

PubMed

Squire, L R; Zola, S M

1998-01-01

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

Neuropsychological outcome after traumatic temporal lobe damage.

PubMed

Formisano, R; Schmidhuber-Eiler, B; Saltuari, L; Cigany, E; Birbamer, G; Gerstenbrand, F

1991-01-01

The most frequent sequelae after severe brain injury include changes in personality traits, disturbances of emotional behaviour and impairment of cognitive functions. In particular, emotional changes and/or verbal and non verbal dysfunctions were found in patients with bilateral or unilateral temporal lobe lesions. The aim of our study is to correlate the localization of the brain damage after severe brain injury, in particular of the temporal lobe, with the cognitive impairment and the emotional and behavioural changes resulting from these lesions. The patients with right temporal lobe lesions showed significantly better scores in verbal intelligence and verbal memory in comparison with patients with left temporal lobe lesions and those with other focal brain lesions or diffuse brain damage. In contradistinction, study of the personality and the emotional changes (MMPI and FAF) failed to demonstrate pathological scores in the 3 groups with different CT lesions, without any significant difference being found between the groups with temporal lesions and those with other focal brain lesions or diffuse brain damage. The severity of the brain injury and the prolongation of the disturbance of consciousness could, in our patients, account for prevalence of congnitive impairment on personality and emotional changes.

Brain and cognitive-behavioural development after asphyxia at term birth.

PubMed

de Haan, Michelle; Wyatt, John S; Roth, Simon; Vargha-Khadem, Faraneh; Gadian, David; Mishkin, Mortimer

2006-07-01

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has been implicated in two different long-term outcomes, cognitive memory impairment and the psychiatric disorder schizophrenia. Factors in addition to the acute episode of asphyxia likely contribute to these specific outcomes, making prediction difficult. Future studies that better document long-term cognitive-behavioural outcome, quantitatively identify patterns of brain injury over development and consider additional variables that may modulate the impact of asphyxia on cognitive and behavioural function will forward the goals of predicting long-term outcome and understanding the mechanisms by which it unfolds.

NMDA receptor antagonist MK-801 reduces neuronal damage and preserves learning and memory in a rat model of traumatic brain injury.

PubMed

Han, Rui-Zhang; Hu, Jin-Jia; Weng, Yuan-Chi; Li, Ding-Feng; Huang, Yi

2009-12-01

NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury (TBI). The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Forty Sprague-Dawley rats (weighing approximately 200 g) were randomized into 5 groups (n = 8 in each group): control group, model group, low-dose group (MK-801 0.5 mg/kg), middle-dose group (MK-801 2 mg/kg), and high-dose group (MK-801 10 mg/kg). TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase (nNOS)-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.

A Report Generator Volume 2

DTIC Science & Technology

1988-01-01

her Nicholle) ( korsakoffs (proper-noun singlp neuter) korsakoffs korekoffs) (huntingtons (proper-noun sing3p neuter) huntingtons huntingtons...hemisphere)) (sub-class (value gerstmann- syndrome 1-constructional-dyspraxia reading-coup aphasia)) (type (value lobe)) (dda (value (location...class)) (dda (value (function damage memory) (location brain))) (importance (value 10)) (damage (value 8))) ( korsakoffs (super-class (value stm)) (sub

From Contextual Fear to a Dynamic View of Memory Systems

PubMed Central

Fanselow, Michael S

2009-01-01

The brain does not learn and remember in a unitary fashion. Rather, different circuits specialize in certain classes of problems and encode different types of information. Damage to one of these systems typically results in amnesia only for the form of memory that is the affected region's specialty. How does the brain allocate a specific category of memory to a particular circuit? This question has received little attention. The currently dominant view, Multiple Memory Systems Theory, assumes that such abilities are hard-wired. Using fear conditioning as a paradigmatic case, I propose an alternative model in which mnemonic processing is allocated to specific circuits through a dynamic process. Potential circuits compete to form memories with the most efficient circuits emerging as winners. However, alternate circuits compensate when these “primary” circuits are compromised. PMID:19939724

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study

PubMed Central

Karolis, Vyacheslav; Caldinelli, Chiara; Brittain, Philip J.; Kroll, Jasmin; Rodríguez-Toscano, Elisa; Tesse, Marcello; Colquhoun, Matthew; Howes, Oliver; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murray, Robin M.; Williams, Steven C.R.; Nosarti, Chiara

2015-01-01

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI. SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI. PMID:26631462

Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA.

PubMed

Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

2017-10-01

To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic Neuroplasticity after Human Prefrontal Cortex Damage

PubMed Central

Voytek, Bradley; Davis, Matar; Yago, Elena; Barceló, Francisco; Vogel, Edward K.; Knight, Robert T.

2010-01-01

Summary Memory and attention deficits are common after prefrontal cortex (PFC) damage, yet people generally recover some function over time. Recovery is thought to be dependent upon undamaged brain regions but the temporal dynamics underlying cognitive recovery are poorly understood. Here we provide evidence that the intact PFC compensates for damage in the lesioned PFC on a trial-by-trial basis dependent on cognitive load. The extent of this rapid functional compensation is indexed by transient increases in electrophysiological measures of attention and memory in the intact PFC, detectable within a second after stimulus presentation and only when the lesioned hemisphere is challenged. These observations provide evidence supporting a dynamic and flexible model of compensatory neural plasticity. PMID:21040843

Prefrontal Engagement during Source Memory Retrieval Depends on the Prior Encoding Task

PubMed Central

Kuo, Trudy Y.; Van Petten, Cyma

2008-01-01

The prefrontal cortex is strongly engaged by some, but not all, episodic memory tests. Prior work has shown that source recognition tests—those that require memory for conjunctions of studied attributes—yield deficient performance in patients with prefrontal damage and greater prefrontal activity in healthy subjects, as compared to simple recognition tests. Here, we tested the hypothesis that there is no intrinsic relationship between the prefrontal cortex and source memory, but that the prefrontal cortex is engaged by the demand to retrieve weakly encoded relationships. Subjects attempted to remember object/color conjunctions after an encoding task that focused on object identity alone, and an integrative encoding task that encouraged attention to object/color relationships. After the integrative encoding task, the late prefrontal brain electrical activity that typically occurs in source memory tests was eliminated. Earlier brain electrical activity related to successful recognition of the objects was unaffected by the nature of prior encoding. PMID:16839287

Deer Bone Extract Prevents Against Scopolamine-Induced Memory Impairment in Mice

PubMed Central

Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun

2015-01-01

Abstract Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine. PMID:25546299

Neuronal substrates of Corsi Block span: Lesion symptom mapping analyses in relation to attentional competition and spatial bias.

PubMed

Chechlacz, Magdalena; Rotshtein, Pia; Humphreys, Glyn W

2014-11-01

Spatial working memory problems are frequently reported following brain damage within both left and right hemispheres but with the severity often being grater in individuals with right hemisphere lesions. Clinically, deficits in spatial working memory have also been noted in patients with visuospatial disorders such as unilateral neglect. Here, we examined neural substrates of short-term memory for spatial locations based on the Corsi Block tapping task and the relationship with the visuospatial deficits of neglect and extinction in a group of chronic neuropsychological patients. Principal Component Analysis (PCA) was used to distinguish shared and dissociate functional components. The neural substrates of spatial short-term memory deficits and the components identified by PCA were examined using whole brain voxel-based morphometry and tract-wise lesion deficits analyses. We found that bilateral lesions within occipital cortex (middle occipital gyrus) and right posterior parietal cortex, along with disconnection of the right parieto-temporal segment of arcuate fasciculus, were associated with low spatial memory span. A single component revealed by PCA accounted for over half of the variance and was linked to damage to right posterior brain regions (temporo-parietal junction, the inferior parietal lobule and middle temporal gyrus extending into middle occipital gyrus). We also found link to disconnections within several association pathways including the superior longitudinal fasciculus, arcuate fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. These results indicate that different visuospatial deficits converge into a single component mapped within posterior parietal areas and fronto-parietal white matter pathways. Furthermore, the data presented here fit with the role of posterior parietal cortex/temporo-parietal junction in maintaining a map of salient locations in space, with Corsi Block performance being impaired when the spatial map is damaged. Copyright © 2014 Elsevier Ltd. All rights reserved.

Memory-guided reaching in a patient with visual hemiagnosia.

PubMed

Cornelsen, Sonja; Rennig, Johannes; Himmelbach, Marc

2016-06-01

The two-visual-systems hypothesis (TVSH) postulates that memory-guided movements rely on intact functions of the ventral stream. Its particular importance for memory-guided actions was initially inferred from behavioral dissociations in the well-known patient DF. Despite of rather accurate reaching and grasping movements to visible targets, she demonstrated grossly impaired memory-guided grasping as much as impaired memory-guided reaching. These dissociations were later complemented by apparently reversed dissociations in patients with dorsal damage and optic ataxia. However, grasping studies in DF and optic ataxia patients differed with respect to the retinotopic position of target objects, questioning the interpretation of the respective findings as a double dissociation. In contrast, the findings for reaching errors in both types of patients came from similar peripheral target presentations. However, new data on brain structural changes and visuomotor deficits in DF also questioned the validity of a double dissociation in reaching. A severe visuospatial short-term memory deficit in DF further questioned the specificity of her memory-guided reaching deficit. Therefore, we compared movement accuracy in visually-guided and memory-guided reaching in a new patient who suffered a confined unilateral damage to the ventral visual system due to stroke. Our results indeed support previous descriptions of memory-guided movements' inaccuracies in DF. Furthermore, our data suggest that recently discovered optic-ataxia like misreaching in DF is most likely caused by her parieto-occipital and not by her ventral stream damage. Finally, multiple visuospatial memory measurements in HWS suggest that inaccuracies in memory-guided reaching tasks in patients with ventral damage cannot be explained by visuospatial short-term memory or perceptual deficits, but by a specific deficit in visuomotor processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistence of Gender Related-Effects on Visuo-Spatial and Verbal Working Memory in Right Brain-Damaged Patients.

PubMed

Piccardi, Laura; Matano, Alessandro; D'Antuono, Giovanni; Marin, Dario; Ciurli, Paola; Incoccia, Chiara; Verde, Paola; Guariglia, Paola

2016-01-01

The aim of the present study was to verify if gender differences in verbal and visuo-spatial working memory would persist following right cerebral lesions. To pursue our aim we investigated a large sample (n. 346) of right brain-damaged patients and healthy participants (n. 272) for the presence of gender effects in performing Corsi and Digit Test. We also assessed a subgroup of patients (n. 109) for the nature (active vs. passive) of working memory tasks. We tested working memory (WM) administering the Corsi Test (CBT) and the Digit Span (DS) using two different versions: forward (fCBT and fDS), subjects were required to repeat stimuli in the same order that they were presented; and backward (bCBT and bDS), subjects were required to repeat stimuli in the opposite order of presentation. In this way, passive storage and active processing of working memory were assessed. Our results showed the persistence of gender-related effects in spite of the presence of right brain lesions. We found that men outperformed women both in CBT and DS, regardless of active and passive processing of verbal and visuo-spatial stimuli. The presence of visuo-spatial disorders (i.e., hemineglect) can affect the performance on Corsi Test. In our sample, men and women were equally affected by hemineglect, therefore it did not mask the gender effect. Generally speaking, the persistence of the men's superiority in visuo-spatial tasks may be interpreted as a protective factor, at least for men, within other life factors such as level of education or kind of profession before retirement.

Brain Metabolism Correlates of the Free and Cued Selective Reminding Test in Mild Cognitive Impairment.

PubMed

Caffarra, Paolo; Ghetti, Caterina; Ruffini, Livia; Spallazzi, Marco; Spotti, Annamaria; Barocco, Federica; Guzzo, Caterina; Marchi, Massimo; Gardini, Simona

2016-01-01

Free and Cued Selective Reminding Test (FCSRT) measures immediate and delayed episodic memory and cueing sensitivity and is suitable to detect prodromal Alzheimer's disease (AD). The present study aimed at investigating the segregation effect of FCSRT scores on brain metabolism of memory-related structures, usually affected by AD pathology, in the Mild Cognitive Impairment (MCI) stage. A cohort of forty-eight MCI patients underwent FCSRT and 18F-FDG-PET. Multiple regression analysis showed that Immediate Free Recall correlated with brain metabolism in the bilateral anterior cingulate and delayed free recall with the left anterior cingulate and medial frontal gyrus, whereas semantic cueing sensitivity with the left posterior cingulate. FCSRT in MCI is associated with neuro-functional activity of specific regions of memory-related structures connected to hippocampal formation, such as the cingulate cortex, usually damaged in AD.

Protective role of taurine in developing offspring affected by maternal alcohol consumption

PubMed Central

Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

2015-01-01

Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

Toxicological aspects of interesterified fat: Brain damages in rats.

PubMed

D'avila, Lívia Ferraz; Dias, Verônica Tironi; Vey, Luciana Taschetto; Milanesi, Laura Hautrive; Roversi, Karine; Emanuelli, Tatiana; Bürger, Marilise Escobar; Trevizol, Fabíola; Maurer, H Luana

2017-07-05

In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous system (CNS) were performed. Rats from first generation born and maintained under supplementation (3g/Kg, p.o.) of soybean-oil or IF until adulthood were assessed on memory, biochemical and molecular markers in the hippocampus. IF group showed higher saturated fatty acids and linoleic acid and lower docosahexaenoic acid incorporation in the hippocampus. In addition, IF supplementation impaired short and long-term memory, which were related to increased reactive species generation and protein carbonyl levels, decreased catalase activity, BDNF and TrkB levels in the hippocampus. To the best of our knowledge, this is the first study to show that lifelong IF consumption may be related to brain oxidative damage, memory impairments and neurotrophins modifications, which collectively may be present indifferent neurological disorders. In fact, the use of IF in foods was intended to avoid damage from HVF consumption; however this substitute should be urgently reviewed, since this fat can be as harmful as trans fat. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance.

PubMed

Su, Hui-Min

2010-05-01

Docosahexaenoic acid (DHA, 22:6n-3) is specifically enriched in the brain and mainly anchored in the neuronal membrane, where it is involved in the maintenance of normal neurological function. Most DHA accumulation in the brain takes place during brain development in the perinatal period. However, hippocampal DHA levels decrease with age and in the brain disorder Alzheimer's disease (AD), and this decrease is associated with reduced hippocampal-dependent spatial learning memory ability. A potential mechanism is proposed by which the n-3 fatty acids DHA and eicosapentaenoic acid (20:5n-3) aid the development and maintenance of spatial learning memory performance. The developing brain or hippocampal neurons can synthesize and take up DHA and incorporate it into membrane phospholipids, especially phosphatidylethanolamine, resulting in enhanced neurite outgrowth, synaptogenesis and neurogenesis. Exposure to n-3 fatty acids enhances synaptic plasticity by increasing long-term potentiation and synaptic protein expression to increase the dendritic spine density, number of c-Fos-positive neurons and neurogenesis in the hippocampus for learning memory processing. In aged rats, n-3 fatty acid supplementation reverses age-related changes and maintains learning memory performance. n-3 fatty acids have anti-oxidative stress, anti-inflammation, and anti-apoptosis effects, leading to neuron protection in the aged, damaged, and AD brain. Retinoid signaling may be involved in the effects of DHA on learning memory performance. Estrogen has similar effects to n-3 fatty acids on hippocampal function. It would be interesting to know if there is any interaction between DHA and estrogen so as to provide a better strategy for the development and maintenance of learning memory. Copyright 2010 Elsevier Inc. All rights reserved.

Functional (dissociative) retrograde amnesia.

PubMed

Markowitsch, H J; Staniloiu, A

2016-01-01

Retrograde amnesia is described as condition which can occur after direct brain damage, but which occurs more frequently as a result of a psychiatric illness. In order to understand the amnesic condition, content-based divisions of memory are defined. The measurement of retrograde memory is discussed and the dichotomy between "organic" and "psychogenic" retrograde amnesia is questioned. Briefly, brain damage-related etiologies of retrograde amnesia are mentioned. The major portion of the review is devoted to dissociative amnesia (also named psychogenic or functional amnesia) and to the discussion of an overlap between psychogenic and "brain organic" forms of amnesia. The "inability of access hypothesis" is proposed to account for most of both the organic and psychogenic (dissociative) patients with primarily retrograde amnesia. Questions such as why recovery from retrograde amnesia can occur in retrograde (dissociative) amnesia, and why long-term new learning of episodic-autobiographic episodes is possible, are addressed. It is concluded that research on retrograde amnesia research is still in its infancy, as the neural correlates of memory storage are still unknown. It is argued that the recollection of episodic-autobiographic episodes most likely involves frontotemporal regions of the right hemisphere, a region which appears to be hypometabolic in patients with dissociative amnesia. © 2016 Elsevier B.V. All rights reserved.

Low level light in combination with metabolic modulators for effective therapy

NASA Astrophysics Data System (ADS)

Dong, Tingting; Zhang, Qi; Hamblin, Michael R.; Wu, Mei X.

2015-03-01

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced ATP generation, and increased formation of reactive oxygen species (ROS) and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). LLL illumination sustained the mitochondrial membrane potential, constrained cytochrome C leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas those treated with LLL or pyruvate alone, or sham light displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by a combination of LLL and pyruvate, in marked contrast to the severe loss of hippocampal tissue due to secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissues like injured brain. Keywords:

Hand gestures support word learning in patients with hippocampal amnesia.

PubMed

Hilverman, Caitlin; Cook, Susan Wagner; Duff, Melissa C

2018-06-01

Co-speech hand gesture facilitates learning and memory, yet the cognitive and neural mechanisms supporting this remain unclear. One possibility is that motor information in gesture may engage procedural memory representations. Alternatively, iconic information from gesture may contribute to declarative memory representations mediated by the hippocampus. To investigate these alternatives, we examined gesture's effects on word learning in patients with hippocampal damage and declarative memory impairment, with intact procedural memory, and in healthy and in brain-damaged comparison groups. Participants learned novel label-object pairings while producing gesture, observing gesture, or observing without gesture. After a delay, recall and object identification were assessed. Unsurprisingly, amnesic patients were unable to recall the labels at test. However, they correctly identified objects at above chance levels, but only if they produced a gesture at encoding. Comparison groups performed well above chance at both recall and object identification regardless of gesture. These findings suggest that gesture production may support word learning by engaging nondeclarative (procedural) memory. © 2018 Wiley Periodicals, Inc.

Cerebralcare Granule(®), a Chinese Herb Compound Preparation, Attenuates D-Galactose Induced Memory Impairment in Mice.

PubMed

Qu, Zhuo; Yang, Honggai; Zhang, Jingze; Huo, Liqin; Chen, Hong; Li, Yuming; Liu, Changxiao; Gao, Wenyuan

2016-09-01

Cerebralcare granule(®) (CG) is a preparation of Traditional Chinese Medicine that widely used in China. It was approved by the China State Food and Drug Administration for treatment of headache and dizziness associated with cerebrovascular diseases. In the present study, we aimed to investigate whether CG had protective effect against D-galactose (gal)-induced memory impairment and to explore the mechanism of its action. D-gal was administered (100 mg/kg, subcutaneously) once daily for 8 weeks to induced memory deficit and neurotoxicity in the brain of aging mouse and CG (7.5, 15, and 30 g/kg) were simultaneously administered orally. The present study demonstrates that CG can alleviate aging in the mouse brain induced by D-gal through improving behavioral performance and reducing brain cell damage in the hippocampus. CG prevents aging mainly via suppression of oxidative stress response, such as decreasing NO and MDA levels, renewing activities of SOD, CAT, and GPx, as well as decreasing AChE activity in the brain of D-gal-treated mice. In addition, CG prevents aging through inhibiting NF-κB-mediated inflammatory response and caspase-3-medicated neurodegeneration in the brain of D-gal treated mice. Taken together, these data clearly demonstrates that subcutaneous injection of D-gal produced memory deficit, meanwhile CG can protect neuron from D-gal insults and improve memory ability.

Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy.

PubMed

Helmstaedter, C; Van Roost, D; Clusmann, H; Urbach, H; Elger, C E; Schramm, J

2004-02-01

Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach. To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH). 34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning. Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery. Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Neuropsychological rehabilitation in alcohol-related brain damage: a systematic review.

PubMed

Svanberg, Jenny; Evans, Jonathan J

2013-01-01

The evidence base for rehabilitating alcohol-related brain damage (ARBD) is still in its infancy. The aim of this review was to collate evidence of intervention studies for ARBD and Wernicke-Korsakoff syndrome (WKS), to offer some indication of methodological quality, and to suggest directions for future research in this area. A comprehensive search strategy resulted in systematic review of 16 studies investigating neurorehabilitation of cognitive impairment relating to ARBD. Most studies addressed rehabilitation of the memory impairments associated with Korsakoff's syndrome, although one study seeking to remediate executive functioning impairment was also included. Three studies outlining service models or approaches were included, with the aim of generating advances in service development for this population. The reviewed studies were of varying methodology, allowing only tentative conclusions. However, the available evidence suggested benefits of a number of memory rehabilitation strategies. Options for practice are suggested.

[Developmental amnesia and early brain damage: neuropsychology and neuroimaging].

PubMed

Crespo-Eguilaz, N; Dominguez, P D; Vaquero, M; Narbona, J

2018-03-01

To contribute to neuropsychological profiling of developmental amnesia subsequent to bilateral damage to both hippocampi in early age. The total sample of 24 schoolchildren from both sexes is distributed in three groups: perinatal hypoxic-ischaemic encephalopathy and everyday complaints of memory in school age (n = 8); perinatal hypoxic-ischaemic encephalopathy without memory complaints (n = 7); and a group of typically developing (n = 9). All participants in every groups did have normal general intelligence and attention. Both clinical groups had, as another clinical consequence, spastic cerebral palsy (diplegia). Neuropsychological exam consisted on tests of general intelligence, attentional abilities, declarative memory and semantic knowledge. All participants had a brain magnetic resonance image and spectroscopy of hippocampi. Scheltens criteria were used for visual estimation of hippocampal atrophy. Parametric and non-parametric statistical contrasts were made. Despite preservation of semantic and procedural learning, declarative-episodic memory is impaired in the first group versus the other two groups. A significant proportion of bilateral hippocampal atrophy is only present in the first group versus the other two non-amnesic groups using Scheltens estimation on MRI. Two cases without evident atrophy did have diminished NAA/(Cho + Cr) index in both hippocampi. Taken together, these results contribute to delineate developmental amnesia as an specific impairment due to early partial bihippocampal damage, in agreement with previous studies. After diagnosis of developmental amnesia, a specific psychoeducational intervention must be made; also this impairment could be candidate for pharmacological trials in the future.

Age-related cognitive decline in hypercholesterolemic LDL receptor knockout mice (LDLr-/-): evidence of antioxidant imbalance and increased acetylcholinesterase activity in the prefrontal cortex.

PubMed

Moreira, Eduardo Luiz Gasnhar; de Oliveira, Jade; Nunes, Jean Costa; Santos, Danúbia Bonfanti; Nunes, Fernanda Costa; Vieira, Daniella Serafim Couto; Ribeiro-do-Valle, Rosa Maria; Pamplona, Fabrício Alano; de Bem, Andreza Fabro; Farina, Marcelo; Walz, Roger; Prediger, Rui Daniel

2012-01-01

There is increasing evidence that hypercholesterolemia during midlife may represent a predictor of subsequent mild cognitive impairments and dementia decades later. However, the exact mechanism underlying this phenomenon remains unknown since plasmatic cholesterol is not able to cross the blood-brain barrier. In the present study, we evaluated the hypothesis that cognitive impairments triggered by hypercholesterolemia during aging may be related to brain oxidative stress and altered brain acetylcholinesterase (AChE) activity. We also performed a neuropathological investigation in order to analyze whether the cognitive impairments may be associated with stroke-related features. To address these questions we used three- and fourteen-month-old low-density lipoprotein receptor-deficient mice (LDLr-/-). The current findings provide new evidence that aged LDLr-/- mice, exposed to over three-fold cholesterol levels from early life, show working, spatial reference, and procedural memory impairments, without alterations in motor function. Antioxidant imbalance and oxidative damage were evidenced by a marked increase in lipid peroxidation (thiobarbituric acid reactive substances levels) and glutathione metabolism (increase in glutathione levels, glutathione reductase, and glutathione peroxidase activities) together with a significant increase in the AChE activity in the prefrontal cortex of aged hypercholesterolemic LDLr-/- mice. Notably, hypercholesterolemia was not related to brain infarcts and neurodegeneration in mice, independent of their age. These observations provide new evidence that hypercholesterolemia during aging triggers cognitive impairments on different types of learning and memory, accompanied by antioxidant imbalance, oxidative damage, and alterations of cholinergic signaling in brain areas associated with learning and memory processes, particularly in the prefrontal cortex.

Effects of penetrating traumatic brain injury on event segmentation and memory.

PubMed

Zacks, Jeffrey M; Kurby, Christopher A; Landazabal, Claudia S; Krueger, Frank; Grafman, Jordan

2016-01-01

Penetrating traumatic brain injury (pTBI) is associated with deficits in cognitive tasks including comprehension and memory, and also with impairments in tasks of daily living. In naturalistic settings, one important component of cognitive task performance is event segmentation, the ability to parse the ongoing stream of behavior into meaningful units. Event segmentation ability is associated with memory performance and with action control, but is not well assessed by standard neuropsychological assessments or laboratory tasks. Here, we measured event segmentation and memory in a sample of 123 male military veterans aged 59-81 who had suffered a traumatic brain injury as young men, and 34 demographically similar controls. Participants watched movies of everyday activities and segmented them to identify fine-grained or coarse-grained events, and then completed tests of recognition memory for pictures from the movies and of memory for the temporal order of actions in the movies. Lesion location and volume were assessed with computed tomography (CT) imaging. Patients with traumatic brain injury were impaired on event segmentation. Those with larger lesions had larger impairments for fine segmentation and also impairments for both memory measures. Further, the degree of memory impairment was statistically mediated by the degree of event segmentation impairment. There was some evidence that lesions to the ventromedial prefrontal cortex (vmPFC) selectively impaired coarse segmentation; however, lesions outside of a priori regions of interest also were associated with impaired segmentation. One possibility is that the effect of vmPFC damage reflects the role of prefrontal event knowledge representations in ongoing comprehension. These results suggest that assessment of naturalistic event comprehension can be a valuable component of cognitive assessment in cases of traumatic brain injury, and that interventions aimed at event segmentation could be clinically helpful. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

PubMed

Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

2017-04-01

To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (p<0.01) and longer than that of sham-operated group. The piercing indexes of 3 treated groups were higher than that of HIBD control group (p<0.01). Hyperbaric oxygen and nerve growth factor treatments may improve learning and memory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

PubMed

Denis, I; Potier, B; Vancassel, S; Heberden, C; Lavialle, M

2013-03-01

The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet. An optimal diet may therefore be a practical way of delaying the onset of age-related cognitive decline. Nutritional investigations indicate that the ω-3 poyunsaturated fatty acid (PUFA) content of western diets is too low to provide the brain with an optimal supply of docosahexaenoic acid (DHA), the main ω-3 PUFA in cell membranes. Insufficient brain DHA has been associated with memory impairment, emotional disturbances and altered brain processes in rodents. Human studies suggest that an adequate dietary intake of ω-3 PUFA can slow the age-related cognitive decline and may also protect against the risk of senile dementia. However, despite the many studies in this domain, the beneficial impact of ω-3 PUFA on brain function has only recently been linked to specific mechanisms. This review examines the hypothesis that an optimal brain DHA status, conferred by an adequate ω-3 PUFA intake, limits age-related brain damage by optimizing endogenous brain repair mechanisms. Our analysis of the abundant literature indicates that an adequate amount of DHA in the brain may limit the impact of stress, an important age-aggravating factor, and influences the neuronal and astroglial functions that govern and protect synaptic transmission. This transmission, particularly glutamatergic neurotransmission in the hippocampus, underlies memory formation. The brain DHA status also influences neurogenesis, nested in the hippocampus, which helps maintain cognitive function throughout life. Although there are still gaps in our knowledge of the way ω-3 PUFA act, the mechanistic studies reviewed here indicate that ω-3 PUFA may be a promising tool for preventing age-related brain deterioration. Copyright © 2013 Elsevier B.V. All rights reserved.

Imagery mnemonics and memory remediation.

PubMed

Richardson, J T

1992-02-01

This paper evaluates the claim that imagery mnemonic techniques are useful in remediation of memory disorders in brain-damaged patients. Clinical research has confirmed that such techniques can lead to improved performance on formal testing in a number of neurologic disease populations and following lesions of either the left or right hemisphere. However, those patients with more severe forms of amnesia and those with medial or bilateral damage do not improve unless the learning task is highly structured. Even among patients who show improvement on formal testing, there is little evidence that they maintain the use of these techniques in similar learning tasks or generalize the use to new learning situations. Imagery mnemonics also appear to be of little practical value in the daily activities that are of most concern to brain-damaged patients themselves. The effectiveness of imagery mnemonics appears to depend upon the patients' motivation and insight rather than upon their intelligence or educational level. Instead of training patients in specific mnemonic techniques, clinicians should promote the development of "meta-cognitive" skills and the acquisition of knowledge about domains of practical significance.

Hypothesis on two different functionalities co-existing in frontal lobe of human brains.

PubMed

Wang, Jue

2013-09-01

Human frontal lobe is a key area from where our cognition, memory and emotion display or function. In medical case study, there are patients with social dysfunctions, lack of passion or emotion as result of their frontal lobe damage caused by pathological changes, traumatic damage, and brain tumor remove operations. The syndrome of frontal lobe damage remains at large unanswered medically. From early stage of pregnancy, there exists lobe layers, nerve combine, and neurons synaptic, indicating a completion of growth of functionality inside frontal lobe. However, this completion of growth does not match the growth of human intelligence. Human infants only start and complete their cognition and memory functionality one full year after their birth which is marked by huge amount of neurons synaptic inside their frontal lobe, which is not part of a continual growth of originally developed functions. By reasoning on pathological changes of frontal lobe, a hypothesis was established that two individually functional mechanisms co-existed inside one frontal lobe. This neuron system is particularly for human beings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pragmatic and executive functions in traumatic brain injury and right brain damage: An exploratory comparative study

PubMed Central

Zimmermann, Nicolle; Gindri, Gigiane; de Oliveira, Camila Rosa; Fonseca, Rochele Paz

2011-01-01

Objective To describe the frequency of pragmatic and executive deficits in right brain damaged (RBD) and in traumatic brain injury (TBI) patients, and to verify possible dissociations between pragmatic and executive functions in these two groups. Methods The sample comprised 7 cases of TBI and 7 cases of RBD. All participants were assessed by means of tasks from the Montreal Communication Evaluation Battery and executive functions tests including the Trail Making Test, Hayling Test, Wisconsin Card Sorting Test, semantic and phonemic verbal fluency tasks, and working memory tasks from the Brazilian Brief Neuropsychological Assessment Battery NEUPSILIN. Z-score was calculated and a descriptive analysis of frequency of deficits (Z< -1.5) was carried out. Results RBD patients presented with deficits predominantly on conversational and narrative discursive tasks, while TBI patients showed a wider spread pattern of pragmatic deficits. Regarding EF, RBD deficits included predominantly working memory and verbal initiation impairment. On the other hand, TBI individuals again exhibited a general profile of executive dysfunction, affecting mainly working memory, initiation, inhibition, planning and switching. Pragmatic and executive deficits were generally associated upon comparisons of RBD patients and TBI cases, except for two simple dissociations: two post-TBI cases showed executive deficits in the absence of pragmatic deficits. Discussion Pragmatic and executive deficits can be very frequent following TBI or vascular RBD. There seems to be an association between these abilities, indicating that although they can co-occur, a cause-consequence relationship cannot be the only hypothesis. PMID:29213762

[Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].

PubMed

Feng, Er-Cui; Jiang, Li

2017-12-01

To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P<0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P>0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P<0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P<0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P<0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P<0.05), while there was no significant difference between the leptin intervention and sham-operation groups. Leptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

PubMed Central

Nelson, P. Austin; Sage, Jennifer R.; Wood, Suzanne C.; Davenport, Christopher M.; Anagnostaras, Stephan G.; Boulanger, Lisa M.

2013-01-01

Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that specific immune proteins, members of the major histocompatibility complex class I (MHC class I), are essential for normal hippocampus-dependent memory, and are specifically required for NMDAR-dependent forms of long-term depression (LTD) in the healthy adult hippocampus. In β2m−/−TAP−/−mice, which lack stable cell-surface expression of most MHC class I proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished, while NMDAR-independent forms of potentiation, facilitation, and depression are unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of β2m−/−TAP−/−mice is accompanied by pervasive deficits in hippocampus-dependent memory, including contextual fear memory, object recognition memory, and social recognition memory. Thus normal MHC class I expression is essential for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent memory. These results suggest that changes in MHC class I expression could be an unexpected cause of disrupted synaptic plasticity and cognitive deficits in the aging, damaged, and diseased brain. PMID:23959708

The influence of the hippocampus and declarative memory on word use: Patients with amnesia use less imageable words

PubMed Central

Hilverman, Caitlin; Cook, Susan Wagner; Duff, Melissa C.

2018-01-01

Hippocampal functioning contributes to our ability to generate multifaceted, imagistic event representations. Patients with hippocampal damage produce event narratives that contain fewer details and fewer imagistic features. We hypothesized that impoverished memory representations would influence language at the word level, yielding words lower in imageability and concreteness. We tested this by examining language produced by patients with bilateral hippocampal damage and severe declarative memory impairment, and brain-damaged and healthy comparison groups. Participants described events from the real past, imagined past, imagined present, and imagined future. We analyzed the imageability and concreteness of words used. Patients with amnesia used words that were less imageable than those of comparison groups across time periods, even when accounting for the amount of episodic detail in narratives. Moreover, all participants used words that were relatively more imageable when discussing real past events than other time periods. Taken together, these findings suggest that the memory that we have for an event affects how we talk about that event, and this extends all the way to the individual words that we use. PMID:28970108

Effectiveness of a Computer-Based Training Program of Attention and Memory in Patients with Acquired Brain Damage

PubMed Central

Fernandez, Elizabeth; Bergado Rosado, Jorge A.; Rodriguez Perez, Daymi; Salazar Santana, Sonia; Torres Aguilar, Maydane; Bringas, Maria Luisa

2017-01-01

Many training programs have been designed using modern software to restore the impaired cognitive functions in patients with acquired brain damage (ABD). The objective of this study was to evaluate the effectiveness of a computer-based training program of attention and memory in patients with ABD, using a two-armed parallel group design, where the experimental group (n = 50) received cognitive stimulation using RehaCom software, and the control group (n = 30) received the standard cognitive stimulation (non-computerized) for eight weeks. In order to assess the possible cognitive changes after the treatment, a post-pre experimental design was employed using the following neuropsychological tests: Wechsler Memory Scale (WMS) and Trail Making test A and B. The effectiveness of the training procedure was statistically significant (p < 0.05) when it established the comparison between the performance in these scales, before and after the training period, in each patient and between the two groups. The training group had statistically significant (p < 0.001) changes in focused attention (Trail A), two subtests (digit span and logical memory), and the overall score of WMS. Finally, we discuss the advantages of computerized training rehabilitation and further directions of this line of work. PMID:29301194

Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.

PubMed

Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G

2001-01-01

The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

PubMed

He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

2014-11-15

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

PubMed

Zhu, Chun-Min; Ma, Ye; Xie, Lei; Huang, Jin-Zhuang; Sun, Zong-Bo; Duan, Shou-Xing; Lin, Zhi-Rong; Yin, Jing-Jing; Le, Hong-Bo; Sun, Dan-Miao; Xu, Wen-Can; Ma, Shu-Hua

2017-02-01

Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.

Persistence of Gender Related-Effects on Visuo-Spatial and Verbal Working Memory in Right Brain-Damaged Patients

PubMed Central

Piccardi, Laura; Matano, Alessandro; D’Antuono, Giovanni; Marin, Dario; Ciurli, Paola; Incoccia, Chiara; Verde, Paola; Guariglia, Paola

2016-01-01

The aim of the present study was to verify if gender differences in verbal and visuo-spatial working memory would persist following right cerebral lesions. To pursue our aim we investigated a large sample (n. 346) of right brain-damaged patients and healthy participants (n. 272) for the presence of gender effects in performing Corsi and Digit Test. We also assessed a subgroup of patients (n. 109) for the nature (active vs. passive) of working memory tasks. We tested working memory (WM) administering the Corsi Test (CBT) and the Digit Span (DS) using two different versions: forward (fCBT and fDS), subjects were required to repeat stimuli in the same order that they were presented; and backward (bCBT and bDS), subjects were required to repeat stimuli in the opposite order of presentation. In this way, passive storage and active processing of working memory were assessed. Our results showed the persistence of gender-related effects in spite of the presence of right brain lesions. We found that men outperformed women both in CBT and DS, regardless of active and passive processing of verbal and visuo-spatial stimuli. The presence of visuo-spatial disorders (i.e., hemineglect) can affect the performance on Corsi Test. In our sample, men and women were equally affected by hemineglect, therefore it did not mask the gender effect. Generally speaking, the persistence of the men’s superiority in visuo-spatial tasks may be interpreted as a protective factor, at least for men, within other life factors such as level of education or kind of profession before retirement. PMID:27445734

Duration and numerical estimation in right brain-damaged patients with and without neglect: Lack of support for a mental time line.

PubMed

Masson, Nicolas; Pesenti, Mauro; Dormal, Valérie

2016-08-01

Previous studies have shown that left neglect patients are impaired when they have to orient their attention leftward relative to a standard in numerical comparison tasks. This finding has been accounted for by the idea that numerical magnitudes are represented along a spatial continuum oriented from left to right with small magnitudes on the left and large magnitudes on the right. Similarly, it has been proposed that duration could be represented along a mental time line that shares the properties of the number continuum. By comparing directly duration and numerosity processing, this study investigates whether or not the performance of neglect patients supports the hypothesis of a mental time line. Twenty-two right brain-damaged patients (11 with and 11 without left neglect), as well as 11 age-matched healthy controls, had to judge whether a single dot presented visually lasted shorter or longer than 500 ms and whether a sequence of flashed dots was smaller or larger than 5. Digit spans were also assessed to measure verbal working memory capacities. In duration comparison, no spatial-duration bias was found in neglect patients. Moreover, a significant correlation between verbal working memory and duration performance was observed in right brain-damaged patients, irrespective of the presence or absence of neglect. In numerical comparison, only neglect patients showed an enhanced distance effect for numerical magnitude smaller than the standard. These results do not support the hypothesis of the existence of a mental continuum oriented from left to right for duration. We discuss an alternative account to explain the duration impairment observed in right brain-damaged patients. © 2015 The British Psychological Society.

Memory repression: brain mechanisms underlying dissociative amnesia.

PubMed

Kikuchi, Hirokazu; Fujii, Toshikatsu; Abe, Nobuhito; Suzuki, Maki; Takagi, Masahito; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

2010-03-01

Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.

Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

PubMed

Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

2015-11-01

The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

PubMed

Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

2013-09-01

Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

Intracranial recordings and human memory.

PubMed

Johnson, Elizabeth L; Knight, Robert T

2015-04-01

Recent work involving intracranial recording during human memory performance provides superb spatiotemporal resolution on mnemonic processes. These data demonstrate that the cortical regions identified in neuroimaging studies of memory fall into temporally distinct networks and the hippocampal theta activity reported in animal memory literature also plays a central role in human memory. Memory is linked to activity at multiple interacting frequencies, ranging from 1 to 500Hz. High-frequency responses and coupling between different frequencies suggest that frontal cortex activity is critical to human memory processes, as well as a potential key role for the thalamus in neocortical oscillations. Future research will inform unresolved questions in the neuroscience of human memory and guide creation of stimulation protocols to facilitate function in the damaged brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroprotective Actions of Dietary Choline

PubMed Central

Blusztajn, Jan Krzysztof; Slack, Barbara E.; Mellott, Tiffany J.

2017-01-01

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, the methyl group donor S-adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer’s disease (AD), and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline. PMID:28788094

Neuroprotective Actions of Dietary Choline.

PubMed

Blusztajn, Jan Krzysztof; Slack, Barbara E; Mellott, Tiffany J

2017-07-28

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, the methyl group donor S -adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer's disease (AD), and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline.

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

PubMed

Kaur, Shamsherjit; Singh, Satinderpal; Chahal, Karan Singh; Prakash, Atish

2014-11-01

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys.

PubMed

Chareyron, Loïc J; Banta Lavenex, Pamela; Amaral, David G; Lavenex, Pierre

2017-12-01

Hippocampal damage in adult humans impairs episodic and semantic memory, whereas hippocampal damage early in life impairs episodic memory but leaves semantic learning relatively preserved. We have previously shown a similar behavioral dissociation in nonhuman primates. Hippocampal lesion in adult monkeys prevents allocentric spatial relational learning, whereas spatial learning persists following neonatal lesion. Here, we quantified the number of cells expressing the immediate-early gene c-fos, a marker of neuronal activity, to characterize the functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion. Ninety minutes before brain collection, three control and four adult monkeys with bilateral neonatal hippocampal lesions explored a novel environment to activate brain structures involved in spatial learning. Three other adult monkeys with neonatal hippocampal lesions remained in their housing quarters. In unlesioned monkeys, we found high levels of c-fos expression in the intermediate and caudal regions of the entorhinal cortex, and in the perirhinal, parahippocampal, and retrosplenial cortices. In lesioned monkeys, spatial exploration induced an increase in c-fos expression in the intermediate field of the entorhinal cortex, the perirhinal, parahippocampal, and retrosplenial cortices, but not in the caudal entorhinal cortex. These findings suggest that different regions of the medial temporal lobe memory system may require different types of interaction with the hippocampus in support of memory. The caudal perirhinal cortex, the parahippocampal cortex, and the retrosplenial cortex may contribute to spatial learning in the absence of functional hippocampal circuits, whereas the caudal entorhinal cortex may require hippocampal output to support spatial learning.

Tool use disorders after left brain damage.

PubMed

Baumard, Josselin; Osiurak, François; Lesourd, Mathieu; Le Gall, Didier

2014-01-01

In this paper we review studies that investigated tool use disorders in left-brain damaged (LBD) patients over the last 30 years. Four tasks are classically used in the field of apraxia: Pantomime of tool use, single tool use, real tool use and mechanical problem solving. Our aim was to address two issues, namely, (1) the role of mechanical knowledge in real tool use and (2) the cognitive mechanisms underlying pantomime of tool use, a task widely employed by clinicians and researchers. To do so, we extracted data from 36 papers and computed the difference between healthy subjects and LBD patients. On the whole, pantomime of tool use is the most difficult task and real tool use is the easiest one. Moreover, associations seem to appear between pantomime of tool use, real tool use and mechanical problem solving. These results suggest that the loss of mechanical knowledge is critical in LBD patients, even if all of those tasks (and particularly pantomime of tool use) might put differential demands on semantic memory and working memory.

Tool use disorders after left brain damage

PubMed Central

Baumard, Josselin; Osiurak, François; Lesourd, Mathieu; Le Gall, Didier

2014-01-01

In this paper we review studies that investigated tool use disorders in left-brain damaged (LBD) patients over the last 30 years. Four tasks are classically used in the field of apraxia: Pantomime of tool use, single tool use, real tool use and mechanical problem solving. Our aim was to address two issues, namely, (1) the role of mechanical knowledge in real tool use and (2) the cognitive mechanisms underlying pantomime of tool use, a task widely employed by clinicians and researchers. To do so, we extracted data from 36 papers and computed the difference between healthy subjects and LBD patients. On the whole, pantomime of tool use is the most difficult task and real tool use is the easiest one. Moreover, associations seem to appear between pantomime of tool use, real tool use and mechanical problem solving. These results suggest that the loss of mechanical knowledge is critical in LBD patients, even if all of those tasks (and particularly pantomime of tool use) might put differential demands on semantic memory and working memory. PMID:24904487

relationship between diffusion tensor imaging findings and cognitive outcomes following adult traumatic brain injury: A meta-analysis.

PubMed

Wallace, E J; Mathias, J L; Ward, L

2018-05-24

Cognitive impairments are common following a traumatic brain injury (TBI) and frequently result from white matter (WM) damage. This damage can be quantified using diffusion tensor imaging (DTI), which measures the directionality (fractional anisotropy: FA) and amount (mean diffusivity/apparent diffusion coefficient: MD/ADC) of water diffusion in WM, with high FA and low MD/ADC thought to indicate greater WM integrity. However, the relationship between DTI and cognitive outcomes is currently unclear. The data from 20 studies that examined the relationship between WM integrity (measured using DTI) and cognition (categorised into seven domains) following mild-severe adult TBI were meta-analysed. Overall, high FA and low MD/ADC in most brain regions was associated with better cognitive performance, with memory and attention most strongly related to DTI findings. Specifically, memory and/or attention were very strongly related to DTI findings in the corpus callosum, fornix, internal capsule, arcuate and uncinate fasciculi. However, most findings were based on single studies and therefore await replication. Larger-scale, longitudinal studies are now needed to determine the predictive utility of DTI. Copyright © 2018. Published by Elsevier Ltd.

Brain MRI fiber-tracking reveals white matter alterations in hypertensive patients without damage at conventional neuroimaging.

PubMed

Carnevale, Lorenzo; D'Angelosante, Valentina; Landolfi, Alessandro; Grillea, Giovanni; Selvetella, Giulio; Storto, Marianna; Lembo, Giuseppe; Carnevale, Daniela

2018-06-12

Hypertension is one of the main risk factor for dementia. The subtle damage provoked by chronic high blood pressure in the brain is usually evidenced by conventional magnetic resonance imaging (MRI), in terms of white matter (WM) hyperintensities or cerebral atrophy. However, it is clear that by the time brain damage is visible, it may be too late hampering neurodegeneration. Aim of this study was to characterize a signature of early brain damage induced by hypertension, before the neurodegenerative injury manifests. This work was conducted on hypertensive and normotensive subjects with no sign of structural damage at conventional neuroimaging and no diagnosis of dementia revealed by neuropsychological assessment. All individuals underwent cardiological clinical examination in order to define the hypertensive status and the related target organ damage. Additionally, patients were subjected to DTI-MRI scan to identify microstructural damage of WM by probabilistic fiber-tracking. To gain insights in the neurocognitive profile of patients a specific battery of tests was administered. As primary outcome of the study we aimed at finding any specific signature of fiber-tracts alterations in hypertensive patients, associated with an impairment of the related cognitive functions. Hypertensive patients showed significant alterations in three specific WM fiber-tracts: the anterior thalamic radiation, the superior longitudinal fasciculus and the forceps minor. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those WM fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and paired associative learning tasks. Overall, WM fiber-tracking on MRI evidenced an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. In perspective, this approach could allow identifying those patients that are in initial stages of brain damage and could benefit of therapies aimed at limiting the transition to dementia and neurodegeneration.

Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

PubMed

He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun

2008-06-01

Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

White matter integrity of the medial forebrain bundle and attention and working memory deficits following traumatic brain injury.

PubMed

Owens, Jacqueline A; Spitz, Gershon; Ponsford, Jennie L; Dymowski, Alicia R; Ferris, Nicholas; Willmott, Catherine

2017-02-01

The medial forebrain bundle (MFB) contains ascending catecholamine fibers that project to the prefrontal cortex (PFC). Damage to these fibers following traumatic brain injury (TBI) may alter extracellular catecholamine levels in the PFC and impede attention and working memory ability. This study investigated white matter microstructure of the medial MFB, specifically the supero-lateral branch (slMFB), following TBI, and its association with performance on attention and working memory tasks. Neuropsychological measures of attention and working memory were administered to 20 moderate-severe participants with TBI (posttraumatic amnesia M  = 40.05 ± 37.10 days, median time since injury 10.48 months, range 3.72-87.49) and 20 healthy controls. Probabilistic tractography was used to obtain fractional anisotropy (FA) and mean diffusivity (MD) values for 17 participants with TBI and 20 healthy controls. When compared to controls, participants with TBI were found to have significantly lower FA ( p  < .001) and higher MD ( p  < .001) slMFB values, and they were slower to complete tasks including Trail Making Task-A, Hayling, selective attention task, n -back, and Symbol Digit Modalities Test. This study was the first to demonstrate microstructural white matter damage within the slMFB following TBI. However, no evidence was found for an association of alterations to this tract and performance on attentional tasks.

Involvement of Cholinergic Dysfunction and Oxidative Damage in the Effects of Simulated Weightlessness on Learning and Memory in Rats

PubMed Central

Wang, Qiong; Lv, Ke; Wang, Tingmei; Wang, Yanli; Ji, Guohua; Cao, Hongqing; Kan, Guanghan

2018-01-01

The present study aimed to determine how the learning and memory gradually change with the prolonged hindlimb unloading (HU) treatment in rats. Different HU durations (7 d, 14 d, 21 d, and 28 d) in Sprague-Dawley (SD) rats were implemented. Cognitive function was assessed using the Morris water maze (MWM) and the shuttle box test. Additionally, parameters about cholinergic activity and oxidative stress were tested. Results showed that longer-than-14 d HU led to the inferior performances in the behavioral tasks. Besides, acetylcholine esterase (AChE) activity, malondialdehyde (MDA) level in brain, reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG) concentrations of HU rats were significantly increased. Furthermore, choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) activity in brain were notably attenuated. Most of these effects were more pronounced after longer exposure (21 d and 28 d) to HU, although some indicators had their own characteristics of change. These results indicate that cholinergic dysfunction and oxidative damage were involved in the learning and memory impairments induced by longer-than-14 d HU. Moreover, the negative effects of HU tend to be augmented as the HU duration becomes longer. The results may be helpful to present possible biochemical targets for countermeasures development regarding the memory deficits under extreme environmental conditions. PMID:29581965

Visuo-spatial memory deficits following medial temporal lobe damage: A comparison of three patient groups.

PubMed

Esfahani-Bayerl, Nazli; Finke, Carsten; Braun, Mischa; Düzel, Emrah; Heekeren, Hauke R; Holtkamp, Martin; Hasper, Dietrich; Storm, Christian; Ploner, Christoph J

2016-01-29

The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in non-associative memory tasks likely reflect damage of regions outside the MTL. Importantly, the choice of a patient model in human lesion studies of the MTL significantly influences overall performance patterns in visuo-spatial memory tasks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

PubMed

Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

2002-12-01

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Psychogenic and organic amnesia: a multidimensional assessment of clinical, neuroradiological, neuropsychological and psychopathological features.

PubMed

Serra, Laura; Fadda, Lucia; Buccione, Ivana; Caltagirone, Carlo; Carlesimo, Giovanni A

2007-01-01

Psychogenic amnesia is a complex disorder characterised by a wide variety of symptoms. Consequently, in a number of cases it is difficult distinguish it from organic memory impairment. The present study reports a new case of global psychogenic amnesia compared with two patients with amnesia underlain by organic brain damage. Our aim was to identify features useful for distinguishing between psychogenic and organic forms of memory impairment. The findings show the usefulness of a multidimensional evaluation of clinical, neuroradiological, neuropsychological and psychopathological aspects, to provide convergent findings useful for differentiating the two forms of memory disorder.

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

PubMed Central

Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

2016-01-01

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

The von Restorff effect in amnesia: the contribution of the hippocampal system to novelty-related memory enhancements.

PubMed

Kishiyama, M M; Yonelinas, A P; Lazzara, M M

2004-01-01

The ability to detect novelty is a characteristic of all mammalian nervous systems (Sokolov, 1963), and it plays a critical role in memory in the sense that items that are novel, or distinctive, are remembered better than those that are less distinct (von Restorff, 1933). Although several brain areas are sensitive to stimulus novelty, it is not yet known which regions play a role in producing novelty-related effects on memory. In the current study, we investigated novelty effects on recognition memory in amnesic patients and healthy control subjects. The control subjects demonstrated better recognition for items that were novel (i.e., presented in an infrequent color), and this effect was found for both recollection and familiarity-based responses. However, the novelty advantage was effectively eliminated in patients with extensive medial temporal lobe damage, mild hypoxic patients expected to have relatively selective hippocampal damage, and in a patient with thalamic lesions. The results indicate that the human medial temporal lobes play a critical role in producing normal novelty effects in memory.

Prenatal Exposure to DEHP Induces Neuronal Degeneration and Neurobehavioral Abnormalities in Adult Male Mice.

PubMed

Barakat, Radwa; Lin, Po-Ching; Park, Chan Jin; Best-Popescu, Catherine; Bakery, Hatem H; Abosalum, Mohamed E; Abdelaleem, Nabila M; Flaws, Jodi A; Ko, CheMyong

2018-04-23

Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus. Pregnant CD-1 female mice were orally administered 200μg, 500mg, or 750mg/kg/day DEHP or vehicle from gestational day 11 until birth. The neurobehavioral impact of the prenatal DEHP exposure was assessed at the ages of 16 to 22 months. Elevated plus maze and open field tests were used to measure anxiety levels. Y-maze and novel object recognition tests were employed to measure memory function. The oxidative damage in the hippocampus was measured by the levels of oxidative DNA damage and by SLIM microscopic counting of hippocampal neurons. Adult male mice that were prenatally exposed to DEHP exhibited anxious behaviors and impaired spatial and short-term recognition memory. The number of hippocampal pyramidal neurons was significantly decreased in the DEHP mice. Furthermore, DEHP mice expressed remarkably high levels of cyclooxygenase-2, 8-hydroxyguanine, and thymidine glycol in their hippocampal neurons. DEHP mice also had lower circulating testosterone concentrations and displayed a weaker immunoreactivity than the control mice to androgen receptor expression in the brain. This study found that prenatal exposure to DEHP caused elevated anxiety behavior and impaired recognition memory. These behavioral changes may originate from neurodegeneration caused by oxidative damage and inflammation in the hippocampus. Decreased circulating testosterone concentrations and decreased expression of androgen receptor in the brain also may be factors contributing to the impaired neurobehavior in the DEHP mice.

Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism.

PubMed

Kaundal, Madhu; Deshmukh, Rahul; Akhtar, Mohd

2018-06-01

The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats. STZ (3mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5mg/kg/day po), used as standard, and BA (5, 10 and 15mg/kg/day po) were administered after 1h of 1st STZ infusion up to 21days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis. STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine's level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain. The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Coexisting cholinergic and parahippocampal degeneration: a key to memory loss in dementia and a challenge for transgenic models?

PubMed

Cassel, Jean-Christophe; Mathis, Chantal; Majchrzak, Monique; Moreau, Pierre-Henri; Dalrymple-Alford, John C

2008-01-01

One century after Alzheimer's initial report, a variety of animal models of Alzheimer's disease (AD) are being used to mimic one or more pathological signs viewed as critical for the evolution of cognitive decline in dementia. Among the most common are, (a) traditional lesion models aimed at reproducing the degeneration of one of two key brain regions affected in AD, namely the cholinergic basal forebrain (CBF) and the transentorhinal region, and (b) transgenic mouse models aimed at reproducing AD histopathological hallmarks, namely amyloid plaques and neurofibrillary tangles. These models have provided valuable insights into the development and consequences of the pathology, but they have not consistently reproduced the severity of memory deficits exhibited in AD. The reasons for this lack of correspondence with the severity of expected deficits may include the limited replication of multiple neuropathology in potentially key brain regions. A recent lesion model in the rat found that severe memory impairment was obtained only when the two traditional lesions were combined together (i.e. conjoint CBF and entorhinal cortex lesions), indicative of a dramatic impact on cognitive function when there is coexisting, rather than isolated, damage in these two brain regions. It is proposed that combining AD transgenic mouse models with additional experimental damage to both the CBF and entorhinal regions might provide a unique opportunity to further understand the evolution of the disease and improve treatments of severe cognitive dysfunction in neurodegenerative dementias. (c) 2008 S. Karger AG, Basel

Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice

PubMed Central

Kossatz, Elk; Silva-Peña, Daniel; Suárez, Juan; de Fonseca, Fernando R.; Maldonado, Rafael; Robledo, Patricia

2018-01-01

The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg). Behavioral, motor, and cognitive tests were carried out 24 h and 7 days after the HI. The levels of microglia, reactive astrocytes and neuronal nuclei were studied using immunofluorescence, and the expression of genes related to the N-acyl-ethanolamides/endocannabinoid signaling systems was determined by qRT-PCR at the end of the experimental sequence. HI induced brain damage in the ipsilateral hippocampus and cortex, which lead to severe memory impairments, and motor coordination deficits. Significant neuronal loss, increased microglia and reactive astrocytes, and compensatory changes in genes associated with the inflammation/immune and endocannabinoid systems were observed in these brain structures of lesioned mice. SUL reversed the memory and motor deficits, decreased the overexpression of microglia and astrocytes, and reduced neurodegeneration induced by HI. Cnr1 and Cnr2 gene expression was modulated by SUL in both sham and HI mice, while Pparα and Faah expression was regulated in HI mice. GW completely blocked the beneficial actions of SUL. These findings suggest that treatment with SUL reduces brain damage and the associated motor and memory deficits induced by HI probably by normalizing the changes in neuroinflammation/immune system mediators. PMID:29725299

Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice.

PubMed

Kossatz, Elk; Silva-Peña, Daniel; Suárez, Juan; de Fonseca, Fernando R; Maldonado, Rafael; Robledo, Patricia

2018-01-01

The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg). Behavioral, motor, and cognitive tests were carried out 24 h and 7 days after the HI. The levels of microglia, reactive astrocytes and neuronal nuclei were studied using immunofluorescence, and the expression of genes related to the N -acyl-ethanolamides/endocannabinoid signaling systems was determined by qRT-PCR at the end of the experimental sequence. HI induced brain damage in the ipsilateral hippocampus and cortex, which lead to severe memory impairments, and motor coordination deficits. Significant neuronal loss, increased microglia and reactive astrocytes, and compensatory changes in genes associated with the inflammation/immune and endocannabinoid systems were observed in these brain structures of lesioned mice. SUL reversed the memory and motor deficits, decreased the overexpression of microglia and astrocytes, and reduced neurodegeneration induced by HI. Cnr1 and Cnr2 gene expression was modulated by SUL in both sham and HI mice, while Ppar α and Faah expression was regulated in HI mice. GW completely blocked the beneficial actions of SUL. These findings suggest that treatment with SUL reduces brain damage and the associated motor and memory deficits induced by HI probably by normalizing the changes in neuroinflammation/immune system mediators.

Interaction between lexical and grammatical language systems in the brain

NASA Astrophysics Data System (ADS)

Ardila, Alfredo

2012-06-01

This review concentrates on two different language dimensions: lexical/semantic and grammatical. This distinction between a lexical/semantic system and a grammatical system is well known in linguistics, but in cognitive neurosciences it has been obscured by the assumption that there are several forms of language disturbances associated with focal brain damage and hence language includes a diversity of functions (phoneme discrimination, lexical memory, grammar, repetition, language initiation ability, etc.), each one associated with the activity of a specific brain area. The clinical observation of patients with cerebral pathology shows that there are indeed only two different forms of language disturbances (disturbances in the lexical/semantic system and disturbances in the grammatical system); these two language dimensions are supported by different brain areas (temporal and frontal) in the left hemisphere. Furthermore, these two aspects of the language are developed at different ages during child's language acquisition, and they probably appeared at different historical moments during human evolution. Mechanisms of learning are different for both language systems: whereas the lexical/semantic knowledge is based in a declarative memory, grammatical knowledge corresponds to a procedural type of memory. Recognizing these two language dimensions can be crucial in understanding language evolution and human cognition.

A new selective developmental deficit: Impaired object recognition with normal face recognition.

PubMed

Germine, Laura; Cashdollar, Nathan; Düzel, Emrah; Duchaine, Bradley

2011-05-01

Studies of developmental deficits in face recognition, or developmental prosopagnosia, have shown that individuals who have not suffered brain damage can show face recognition impairments coupled with normal object recognition (Duchaine and Nakayama, 2005; Duchaine et al., 2006; Nunn et al., 2001). However, no developmental cases with the opposite dissociation - normal face recognition with impaired object recognition - have been reported. The existence of a case of non-face developmental visual agnosia would indicate that the development of normal face recognition mechanisms does not rely on the development of normal object recognition mechanisms. To see whether a developmental variant of non-face visual object agnosia exists, we conducted a series of web-based object and face recognition tests to screen for individuals showing object recognition memory impairments but not face recognition impairments. Through this screening process, we identified AW, an otherwise normal 19-year-old female, who was then tested in the lab on face and object recognition tests. AW's performance was impaired in within-class visual recognition memory across six different visual categories (guns, horses, scenes, tools, doors, and cars). In contrast, she scored normally on seven tests of face recognition, tests of memory for two other object categories (houses and glasses), and tests of recall memory for visual shapes. Testing confirmed that her impairment was not related to a general deficit in lower-level perception, object perception, basic-level recognition, or memory. AW's results provide the first neuropsychological evidence that recognition memory for non-face visual object categories can be selectively impaired in individuals without brain damage or other memory impairment. These results indicate that the development of recognition memory for faces does not depend on intact object recognition memory and provide further evidence for category-specific dissociations in visual recognition. Copyright © 2010 Elsevier Srl. All rights reserved.

Ventromedial Prefrontal Cortex Is Necessary for Normal Associative Inference and Memory Integration.

PubMed

Spalding, Kelsey N; Schlichting, Margaret L; Zeithamova, Dagmar; Preston, Alison R; Tranel, Daniel; Duff, Melissa C; Warren, David E

2018-04-11

The ability to flexibly combine existing knowledge in response to novel circumstances is highly adaptive. However, the neural correlates of flexible associative inference are not well characterized. Laboratory tests of associative inference have measured memory for overlapping pairs of studied items (e.g., AB, BC) and for nonstudied pairs with common associates (i.e., AC). Findings from functional neuroimaging and neuropsychology suggest the ventromedial prefrontal cortex (vmPFC) may be necessary for associative inference. Here, we used a neuropsychological approach to test the necessity of vmPFC for successful memory-guided associative inference in humans using an overlapping pairs associative memory task. We predicted that individuals with focal vmPFC damage ( n = 5; 3F, 2M) would show impaired inferential memory but intact non-inferential memory. Performance was compared with normal comparison participants ( n = 10; 6F, 4M). Participants studied pairs of visually presented objects including overlapping pairs (AB, BC) and nonoverlapping pairs (XY). Participants later completed a three-alternative forced-choice recognition task for studied pairs (AB, BC, XY) and inference pairs (AC). As predicted, the vmPFC group had intact memory for studied pairs but significantly impaired memory for inferential pairs. These results are consistent with the perspective that the vmPFC is necessary for memory-guided associative inference, indicating that the vmPFC is critical for adaptive abilities that require application of existing knowledge to novel circumstances. Additionally, vmPFC damage was associated with unexpectedly reduced memory for AB pairs post-inference, which could potentially reflect retroactive interference. Together, these results reinforce an emerging understanding of a role for the vmPFC in brain networks supporting associative memory processes. SIGNIFICANCE STATEMENT We live in a constantly changing environment, so the ability to adapt our knowledge to support understanding of new circumstances is essential. One important adaptive ability is associative inference which allows us to extract shared features from distinct experiences and relate them. For example, if we see a woman holding a baby, and later see a man holding the same baby, then we might infer that the two adults are a couple. Despite the importance of associative inference, the brain systems necessary for this ability are not known. Here, we report that damage to human ventromedial prefrontal cortex (vmPFC) disproportionately impairs associative inference. Our findings show the necessity of the vmPFC for normal associative inference and memory integration. Copyright © 2018 the authors 0270-6474/18/383767-09$15.00/0.

An Informal Paper: Teaching the Profoundly Handicapped Child.

ERIC Educational Resources Information Center

Silverrain, Ann

The paper outlines the operative principles for understanding learning and discusses how these principles can help in planning a functional program for a severely or profoundly brain-damaged child. Discussed are: (1) the role of memory in learning; (2) simple associative learning (Pavlovian Conditioning and Operant Conditioning); (3) Piaget's…

The role of the basal ganglia in learning and memory: Insight from Parkinson's disease

PubMed Central

2013-01-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. PMID:21945835

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Classic and recent advances in understanding amnesia.

PubMed

Allen, Richard J

2018-01-01

Neurological amnesia has been and remains the focus of intense study, motivated by the drive to understand typical and atypical memory function and the underlying brain basis that is involved. There is now a consensus that amnesia associated with hippocampal (and, in many cases, broader medial temporal lobe) damage results in deficits in episodic memory, delayed recall, and recollective experience. However, debate continues regarding the patterns of preservation and impairment across a range of abilities, including semantic memory and learning, delayed recognition, working memory, and imagination. This brief review highlights some of the influential and recent advances in these debates and what they may tell us about the amnesic condition and hippocampal function.

Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.

PubMed

Amen, Daniel G; Wu, Joseph C; Taylor, Derek; Willeumier, Kristen

2011-01-01

Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.

Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning.

PubMed

Kádár, Elisabet; Ramoneda, Marc; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

2014-11-01

Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Contribution of visuospatial attention, short-term memory and executive functions to performance in number interval bisection.

PubMed

Ranzini, Mariagrazia; Carbè, Katia; Gevers, Wim

2017-05-01

Number interval bisection consists of estimating the mid-number within a pair (1-9=>5). Healthy adults and right-brain damage patients can show biased performance in this task, underestimating and overestimating the mid-number, respectively. The role of visuospatial attention during this task, and its interplay with other cognitive abilities (e.g., working memory) is still object of debate. In this study we explored the relation between visuospatial attention and individual differences in working memory and executive functions during number interval bisection. To manipulate the deployment of visuospatial attention, healthy participants tracked a dot moving to the left or moving to the right while bisecting numerical intervals. We also collected information concerning verbal and visuospatial short-term memory span, and concerning verbal and visuospatial fluency scores. Beside replicating what is typically observed in this task (e.g., underestimation bias), a correlation was observed between verbal short-term memory and bisection bias, and an interesting relation between performance in the number interval bisection, verbal short-term memory, and visuospatial attention. Specifically, performance of those participants with low verbal span was affected by the direction of the moving dot, underestimating at a larger extent when the dot moved leftward than rightward. Finally, it was also observed that participants' verbal fluency ability contributed in the generation of biases in the numerical task. The finding of the involvement of abilities belonging to the verbal domain contributes to unveil the multi-componential nature of number interval bisection. Considering the debate on the nature of number interval bisection and its use in the clinical assessment of deficits following brain damage, this finding may be interesting also from a clinical perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

PubMed

Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

2011-08-01

Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food Technologists®

Applications of the Morris water maze in translational traumatic brain injury research.

PubMed

Tucker, Laura B; Velosky, Alexander G; McCabe, Joseph T

2018-05-01

Acquired traumatic brain injury (TBI) is frequently accompanied by persistent cognitive symptoms, including executive function disruptions and memory deficits. The Morris Water Maze (MWM) is the most widely-employed laboratory behavioral test for assessing cognitive deficits in rodents after experimental TBI. Numerous protocols exist for performing the test, which has shown great robustness in detecting learning and memory deficits in rodents after infliction of TBI. We review applications of the MWM for the study of cognitive deficits following TBI in pre-clinical studies, describing multiple ways in which the test can be employed to examine specific aspects of learning and memory. Emphasis is placed on dependent measures that are available and important controls that must be considered in the context of TBI. Finally, caution is given regarding interpretation of deficits as being indicative of dysfunction of a single brain region (hippocampus), as experimental models of TBI most often result in more diffuse damage that disrupts multiple neural pathways and larger functional networks that participate in complex behaviors required in MWM performance. Published by Elsevier Ltd.

Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujibayashi, Y.; Yamamoto, S.; Waki, A.

DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies.more » In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.« less

Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment.

PubMed

Horng, Lin-Yea; Hsu, Pei-Lun; Chen, Li-Wen; Tseng, Wang-Zou; Hsu, Kai-Tin; Wu, Chia-Ling; Wu, Rong-Tsun

2015-10-01

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Distinct roles of hippocampus and medial prefrontal cortex in spatial and nonspatial memory.

PubMed

Sapiurka, Maya; Squire, Larry R; Clark, Robert E

2016-12-01

In earlier work, patients with hippocampal damage successfully path integrated, apparently by maintaining spatial information in working memory. In contrast, rats with hippocampal damage were unable to path integrate, even when the paths were simple and working memory might have been expected to support performance. We considered possible ways to understand these findings. We tested rats with either hippocampal lesions or lesions of medial prefrontal cortex (mPFC) on three tasks of spatial or nonspatial memory: path integration, spatial alternation, and a nonspatial alternation task. Rats with mPFC lesions were impaired on both spatial and nonspatial alternation but performed normally on path integration. By contrast, rats with hippocampal lesions were impaired on path integration and spatial alternation but performed normally on nonspatial alternation. We propose that rodent neocortex is limited in its ability to construct a coherent spatial working memory of complex environments. Accordingly, in tasks such as path integration and spatial alternation, working memory cannot depend on neocortex alone. Rats may accomplish many spatial memory tasks by relying on long-term memory. Alternatively, they may accomplish these tasks within working memory through sustained coordination between hippocampus and other cortical brain regions such as mPFC, in the case of spatial alternation, or parietal cortex in the case of path integration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Stress and binge drinking: A toxic combination for the teenage brain.

PubMed

Goldstein, Aaron; Déry, Nicolas; Pilgrim, Malcolm; Ioan, Miruna; Becker, Suzanna

2016-09-01

Young adult university students frequently binge on alcohol and have high stress levels. Based on findings in rodents, we predicted that heavy current alcohol use and elevated stress and depression scores would be associated with deficits on high interference memory tasks, while early onset, prolonged binge patterns would lead to broader cognitive deficits on tests of associative encoding and executive functions. We developed the Concentration Memory Task, a novel computerized version of the Concentration card game with a high degree of interference. We found that young adults with elevated stress, depression, and alcohol consumption scores were impaired in the Concentration Memory Task. We also analyzed data from a previous study, and found that higher alcohol consumption scores were associated with impaired performance on another high interference memory task, based on Kirwan and Stark's Mnemonic Similarity Test. On the other hand, adolescent onset of binge drinking predicted poorer performance on broader range of memory tests, including a more systematic test of spatial recognition memory, and an associative learning task. Our results are broadly consistent with findings in rodents that acute alcohol and stress exposure suppress neurogenesis in the adult hippocampus, which in turn impairs performance in high interference memory tasks, while adolescent onset binge drinking causes more extensive brain damage and cognitive deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

"Brain-specific" nutrients: a memory cure?

PubMed

McDaniel, Mark A; Maier, Steven F; Einstein, Gilles O

2003-01-01

We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

Memory deficits due to brain injury: unique PET findings and dream alterations

PubMed Central

Nishida, Masaki; Nariai, Tadashi; Hiura, Mikio; Ishii, Kenji; Nishikawa, Toru

2011-01-01

The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings. PMID:22674950

Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury.

PubMed

Spain, Aisling; Daumas, Stephanie; Lifshitz, Jonathan; Rhodes, Jonathan; Andrews, Peter J D; Horsburgh, Karen; Fowler, Jill H

2010-08-01

Mild traumatic brain injury (TBI) accounts for up to 80% of clinical TBI and can result in cognitive impairment and white matter damage that may develop and persist over several years. Clinically relevant models of mild TBI for investigation of neurobiological changes and the development of therapeutic strategies are poorly developed. In this study we investigated the temporal profile of axonal and somal injury that may contribute to cognitive impairments in a mouse model of mild TBI. Neuronal perikaryal damage (hematoxylin and eosin and Fluoro-Jade C), myelin integrity (myelin basic protein and myelin-associated glycoprotein), and axonal damage (amyloid precursor protein), were evaluated by immunohistochemistry at 4 h, 24 h, 72 h, 4 weeks, and 6 weeks after mild lateral fluid percussion brain injury (0.9 atm; righting time 167 +/- 15 sec). At 3 weeks post-injury spatial reference learning and memory were tested in the Morris water maze (MWM). Levels of damage to neuronal cell bodies were comparable in the brain-injured and sham groups. Myelin integrity was minimally altered following injury. Clear alterations in axonal damage were observed at various time points after injury. Axonal damage was localized to the cingulum at 4 h post-injury. At 4 and 6 weeks post-injury, axonal damage was evident in the external capsule, and was seen at 6 weeks in the dorsal thalamic nuclei. At 3 weeks post-injury, injured mice showed an impaired ability to learn the water maze task, suggesting injury-induced alterations in search strategy learning. The evolving localization of axonal damage points to ongoing degeneration after injury that is concomitant with a deficit in learning.

Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders.

PubMed

Poon, H Fai; Farr, Susan A; Thongboonkerd, Visith; Lynn, Bert C; Banks, William A; Morley, John E; Klein, Jon B; Butterfield, D Allan

2005-01-01

Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with alpha-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, alpha-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and alpha-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, alpha-enolase, ubiquitous mitochondrial creatine kinase, lactate dehydrogenase B, and dihydropyrimidinase-like protein 2 in process associated with learning and memory of SAMP8 mice.

Bilateral limbic system destruction in man

PubMed Central

Feinstein, Justin S.; Rudrauf, David; Khalsa, Sahib S.; Cassell, Martin D.; Bruss, Joel; Grabowski, Thomas J.; Tranel, Daniel

2010-01-01

We report here a case study of a rare neurological patient with bilateral brain damage encompassing a substantial portion of the so-called “limbic system.” The patient, Roger, has been studied in our laboratory for over 14 years and the current article presents his complete neuroanatomical and neuropsychological profiles. The brain damage occurred in 1980 following an episode of herpes simplex encephalitis. The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral. Despite the magnitude of his brain damage, Roger has a normal IQ, average to above average attention, working memory, and executive functioning skills, and very good speech and language abilities. In fact, his only obvious presenting deficits are a dense global amnesia and a severe anosmia and ageusia. Roger's case presents a rare opportunity to advance our understanding of the critical functions underlying the human limbic system, and the neuropsychological and neuroanatomical data presented here provide a critical foundation for such investigations. PMID:19763994

Accelerated Long-Term Forgetting Is Not Epilepsy Specific: Evidence from Childhood Traumatic Brain Injury.

PubMed

Lah, Suncica; Black, Carly; Gascoigne, Michael B; Gott, Chloe; Epps, Adrienne; Parry, Louise

2017-09-01

Accelerated long-term forgetting (ALF) is characterized by adequate recall after short, but not long delays. ALF is not detected by standardized neuropsychological memory tests. Currently, the prevailing conceptualization of ALF is of a temporal lobe seizure-related phenomenon. Nevertheless, Mayes and colleagues (2003) proposed that ALF may occur when any of the components of the brain network involved in long-term memory formation, or their interaction, is disrupted. This disruption does not have to be caused by temporal lobe seizures for ALF to occur. Here, we investigate this possibility in a group of school-age children who have sustained traumatic brain injury (TBI) (n = 28), as TBI typically disrupts the brain network that is important for long-term memory formation and recall. Healthy control children (n = 62) also participated. Contrary to the dominant conceptualization of ALF being a seizure-related phenomenon, children with TBI showed ALF. Sustaining a severe TBI and diffuse subcortical damage was related to ALF. Individually, 8 of the 13 children with severe TBI presented with ALF. ALF would remain undetected on standardized testing in six of these eight children. One child had the opposite pattern of dissociation, an impaired score on standardized testing, but an average long-term memory score. This is the first study, to our knowledge, to show ALF in patients with TBI, which has remained undiagnosed and untreated in this patient population. Our study also challenges the dominant hypothesis of ALF being a temporal lobe seizure-related phenomenon, and raises a possibility that short-term and long-term memory systems may be independent.

Effects of mobile phone radiation (900 MHz radiofrequency) on structure and functions of rat brain.

PubMed

Saikhedkar, Nidhi; Bhatnagar, Maheep; Jain, Ayushi; Sukhwal, Pooja; Sharma, Chhavi; Jaiswal, Neha

2014-12-01

The goals of this study were: (1) to obtain basic information about the effects of long-term use of mobile phones on cytological makeup of the hippocampus in rat brains (2) to evaluate the effects on antioxidant status, and (3) to evaluate the effects on cognitive behavior particularly on learning and memory. Rats (age 30 days, 120 ± 5 g) were exposed to 900 MHz radio waves by means of a mobile hand set for 4 hours per day for 15 days. Effects on anxiety, spatial learning, and memory were studied using the open field test, the elevated plus maze, the Morris water maze (MWM), and the classic maze test. Effects on brain antioxidant status were also studied. Cresyl violet staining was done to assess the neuronal damage. A significant change in behavior, i.e., more anxiety and poor learning was shown by test animals as compared to controls and sham group. A significant change in the level of antioxidant enzymes and non-enzymatic antioxidants, and an increase in lipid peroxidation were observed in the test rats. Histological examination showed neurodegenerative cells in hippocampal sub regions and the cerebral cortex. Thus our findings indicate extensive neurodegeneration on exposure to radio waves. Increased production of reactive oxygen species due to exhaustion of enzymatic and non-enzymatic antioxidants and increased lipid peroxidation indicate extensive neurodegeneration in selective areas of CA1, CA3, DG, and the cerebral cortex. This extensive neuronal damage results in alterations in behavior related to memory and learning.

The role of the basal ganglia in learning and memory: insight from Parkinson's disease.

PubMed

Foerde, Karin; Shohamy, Daphna

2011-11-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. Copyright © 2011 Elsevier Inc. All rights reserved.

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

PubMed

Maguire, Eleanor A; Frith, Christopher D; Rudge, Peter; Cipolotti, Lisa

2005-08-01

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

PubMed

Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

2016-01-01

Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice.

PubMed

Salehpour, Farzad; Farajdokht, Fereshteh; Erfani, Marjan; Sadigh-Eteghad, Saeed; Shotorbani, Siamak Sandoghchian; Hamblin, Michael R; Karimi, Pouran; Rasta, Seyed Hossein; Mahmoudi, Javad

2018-03-01

Sleep deprivation (SD) causes oxidative stress in the hippocampus and subsequent memory impairment. In this study, the effect of near-infrared (NIR) photobiomodulation (PBM) on learning and memory impairment induced by acute SD was investigated. The mice were subjected to an acute SD protocol for 72 h. Simultaneously, NIR PBM using a laser at 810 nm was delivered (once a day for 3 days) transcranially to the head to affect the entire brain of mice. The Barnes maze and the What-Where-Which task were used to assess spatial and episodic-like memories. The hippocampal levels of antioxidant enzymes and oxidative stress biomarkers were evaluated. The results showed that NIR PBM prevented cognitive impairment induced by SD. Moreover, NIR PBM therapy enhanced the antioxidant status and increased mitochondrial activity in the hippocampus of SD mice. Our findings revealed that hippocampus-related mitochondrial damage and extensive oxidative stress contribute to the occurrence of memory impairment. In contrast, NIR PBM reduced hippocampal oxidative damage, supporting the ability of 810 nm laser light to improve the antioxidant defense system and maintain mitochondrial survival. This confirms that non-invasive transcranial NIR PBM therapy ameliorates hippocampal dysfunction, which is reflected in enhanced memory function. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlation of neurocognitive function and brain parenchyma volumes in children surviving cancer

NASA Astrophysics Data System (ADS)

Reddick, Wilburn E.; White, Holly A.; Glass, John O.; Mulhern, Raymond K.

2002-04-01

This research builds on our hypothesis that white matter damage and associated neurocognitive symptoms, in children treated for cancer with cranial spinal irradiation, spans a continuum of severity that can be reliably probed using non-invasive MR technology. Quantitative volumetric assessments of MR imaging and psychological assessments were obtained in 40 long-term survivors of malignant brain tumors treated with cranial irradiation. Neurocognitive assessments included a test of intellect (Wechsler Intelligence Test for Children, Wechsler Adult Intelligence Scale), attention (Conner's Continuous Performance Test), and memory (California Verbal Learning Test). One-sample t-tests were conducted to evaluate test performance of survivors against age-adjusted scores from the test norms; these analyses revealed significant impairments in all apriori selected measures of intelligence, attention, and memory. Partial correlation analyses were performed to assess the relationships between brain tissues volumes (normal appearing white matter (NAWM), gray matter, and CSF) and neurocognitive function. Global intelligence (r = 0.32, p = 0.05) and global attentional (r = 0.49, p < 0.01) were significantly positively correlated with NAWM volumes, whereas global memory was significantly positively correlated with overall brain parenchyma (r = 0.38, p = 0.04). We conclude that quantitative assessment of MR examinations in survivors of childhood cancer treated with cranial irradiation reveal that loss of NAWM is associated with decreased intellectual and attentional deficits, whereas overall parenchyma loss, as reflected by increased CSF and decreased white matter, is associated with memory-related deficits.

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

PubMed

Cotman, Carl W; Head, Elizabeth; Muggenburg, Bruce A; Zicker, S; Milgram, Norton W

2002-01-01

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies. Copyright 2002 Elsevier Science Inc.

Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment

PubMed Central

Krynetskiy, Evgeny; Krynetskaia, Natalia; Rihawi, Diana; Wieczerzak, Katarzyna; Ciummo, Victoria; Walker, Ellen

2013-01-01

Aims Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al. 2008). Main methods Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24 h and weighed every 24 h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay). Key findings We detected significant differences (p<0.0001) for all DNA damage characteristics (DNA “comet” tail shape, migration pattern, tail moment and Olive moments) between control mice cohort and 5FU-treated mice cohort: tail length – 119 vs. 153; tail moment – 101 vs. 136; olive moment – 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r=0.52, p<0.05) and increased rate of errors (r=0.51, p<0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r=−0.75, p<0.02). Significance Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy. PMID:23567806

Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment.

PubMed

Krynetskiy, Evgeny; Krynetskaia, Natalia; Rihawi, Diana; Wieczerzak, Katarzyna; Ciummo, Victoria; Walker, Ellen

2013-10-17

Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al., 2008). Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24h and weighed every 24h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and the retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay). We detected significant differences (p<0.0001) for all DNA damage characteristics (DNA "comet" tail shape, migration pattern, tail moment and olive moments) between control mice cohort and 5FU-treated mice cohort: tail length - 119 vs. 153; tail moment - 101 vs. 136; olive moment - 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r=0.52, p<0.05) and increased rate of errors (r=0.51, p<0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r=-0.75, p<0.02). Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Modulation of Memory by Vestibular Lesions and Galvanic Vestibular Stimulation

PubMed Central

Smith, Paul F.; Geddes, Lisa H.; Baek, Jean-Ha; Darlington, Cynthia L.; Zheng, Yiwen

2010-01-01

For decades it has been speculated that there is a close association between the vestibular system and spatial memories constructed by areas of the brain such as the hippocampus. While many animal studies have been conducted which support this relationship, only in the last 10 years have detailed quantitative studies been carried out in patients with vestibular disorders. The majority of these studies suggest that complete bilateral vestibular loss results in spatial memory deficits that are not simply due to vestibular reflex dysfunction, while the effects of unilateral vestibular damage are more complex and subtle. Very recently, reports have emerged that sub-threshold, noisy galvanic vestibular stimulation can enhance memory in humans, although this has not been investigated for spatial memory as yet. These studies add to the increasing evidence that suggests a connection between vestibular sensory information and memory in humans. PMID:21173897

Hippocampal and diencephalic pathology in developmental amnesia.

PubMed

Dzieciol, Anna M; Bachevalier, Jocelyne; Saleem, Kadharbatcha S; Gadian, David G; Saunders, Richard; Chong, W K Kling; Banks, Tina; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2017-01-01

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

PubMed

Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

2010-08-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Chronic Lithium Treatment in a Rat Model of Basal Forebrain Cholinergic Depletion: Effects on Memory Impairment and Neurodegeneration.

PubMed

Gelfo, Francesca; Cutuli, Debora; Nobili, Annalisa; De Bartolo, Paola; D'Amelio, Marcello; Petrosini, Laura; Caltagirone, Carlo

2017-01-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term. On this basis, the aim of the present research was to evaluate the potential beneficial effects of a chronic lithium treatment in preventing the damage that a basal forebrain cholinergic neurodegeneration provokes, by investigating memory functions and neurodegeneration correlates. Adult male rats were lesioned by bilateral injections of the immunotoxin 192 IgG-Saporin into the basal forebrain. Starting 7 days before the surgery, the animals were exposed to a 30-day lithium treatment, consisting of a 0.24% Li2CO3 diet. Memory functions were investigated by the open field test with objects, the sociability and preference for social novelty test, and the Morris water maze. Hippocampal and neocortical choline acetyltransferase (ChAT) levels and caspase-3 activity were determined. Cholinergic depletion significantly impaired spatial and social recognition memory, decreased hippocampal and neocortical ChAT levels and increased caspase-3 activity. The chronic lithium treatment significantly rescued memory performances but did not modulate ChAT availability and caspase-3 activity. The present findings support the lithium protective effects against the cognitive impairment that characterizes the brain cholinergic depletion.

Comparisons of Korsakoff and Non-Korsakoff Alcoholics on Neuropsychological Tests of Prefrontal Brain Functioning

PubMed Central

Oscar-Berman, Marlene; Kirkley, Shalene M.; Gansler, David A.; Couture, Ashley

2014-01-01

Background Evidence suggests that alcoholics exhibit particular deficits in brain systems involving the prefrontal cortex, but few studies have directly compared patients with and without Korsakoff’s syndrome on measures of prefrontal integrity. Methods Neuropsychological tasks sensitive to dysfunction of frontal brain systems were administered, along with standard tests of memory, intelligence, and visuospatial abilities, to 50 healthy, abstinent, nonamnesic alcoholics, 6 patients with alcohol-induced persisting amnestic disorder (Korsakoff’s syndrome), 6 brain-damaged controls with right hemisphere lesions, and 82 healthy nonalcoholic controls. Results Korsakoff patients were impaired on tests of memory, fluency, cognitive flexibility, and perseveration. Non-Korsakoff alcoholics showed some frontal system deficits as well, but these were mild. Cognitive deficits in non-Korsakoff alcoholics were related to age, duration of abstinence (less than 5 years), duration of abuse (more than 20 years), and amount of alcohol intake. Conclusions Abnormalities of frontal system functioning are most apparent in alcoholics with Korsakoff’s syndrome. In non-Korsakoff alcoholics, factors contributing to cognitive performance are age, duration of abstinence, duration of alcoholism, and amount of alcohol consumed. PMID:15100620

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

PubMed

Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

2016-10-01

Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Achieving enlightenment: what do we know about the implicit learning system and its interaction with explicit knowledge?

PubMed

Vidoni, Eric D; Boyd, Lara A

2007-09-01

Two major memory and learning systems operate in the brain: one for facts and ideas (ie, the declarative or explicit system), one for habits and behaviors (ie, the procedural or implicit system). Broadly speaking these two memory systems can operate either in concert or entirely independently of one another during the performance and learning of skilled motor behaviors. This Special Issue article has two parts. In the first, we present a review of implicit motor skill learning that is largely centered on the interactions between declarative and procedural learning and memory. Because distinct neuroanatomical substrates support unique aspects of learning and memory and thus focal injury can cause impairments that are dependent on lesion location, we also broadly consider which brain regions mediate implicit and explicit learning and memory. In the second part of this article, the interactive nature of these two memory systems is illustrated by the presentation of new data that reveal that both learning implicitly and acquiring explicit knowledge through physical practice lead to motor sequence learning. In our new data, we discovered that for healthy individuals use of the implicit versus explicit memory system differently affected variability of performance during acquisition practice; variability was higher early in practice for the implicit group and later in practice for the acquired explicit group. Despite the difference in performance variability, by retention both groups demonstrated comparable change in tracking accuracy and thus, motor sequence learning. Clinicians should be aware of the potential effects of implicit and explicit interactions when designing rehabilitation interventions, particularly when delivering explicit instructions before task practice, working with individuals with focal brain damage, and/or adjusting therapeutic parameters based on acquisition performance variability.

Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

PubMed

Miotto, Eliane C; Balardin, Joana B; Vieira, Gilson; Sato, Joao R; Martin, Maria da Graça M; Scaff, Milberto; Teixeira, Manoel J; Junior, Edson Amaro

2014-01-01

Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilat, E.; Kadar, T.; Levy, A.

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsantmore » effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.« less

Personal relevance and the human right hemisphere.

PubMed

Van Lancker, D

1991-09-01

Brain damage can selectively disrupt or distort information and ability across the range of human behaviors. One domain that has not been considered as an independent attribute consists of acquisition and maintenance of personal relevant entities such as "familiar" faces, persons, voices, names, linguistic expressions, handwriting, topography, and so on. In experimental studies of normal mentation, personal relevance is revealed in studies of emotion, arousal, affect, preference and familiarity judgments, and memory. Following focal brain damage, deficits and distortions in the experience of personal relevance, as well as in recognizing formerly personally relevant phenomena, are well known to occur. A review and interpretation of these data lead to a proposal that the right hemisphere has a special role in establishing, maintaining, and processing personally relevant aspects of the individual's world.

Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

PubMed

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

Autobiographical memory and structural brain changes in chronic phase TBI.

PubMed

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical characteristics and brain PET findings in 3 cases of dissociative amnesia: disproportionate retrograde deficit and posterior middle temporal gyrus hypometabolism.

PubMed

Thomas-Antérion, C; Dubas, F; Decousus, M; Jeanguillaume, C; Guedj, E

2014-10-01

Precipitated by psychological stress, dissociative amnesia occurs in the absence of identifiable brain damage. Its clinical characteristics and functional neural basis are still a matter of controversy. In the present paper, we report 3 cases of retrograde autobiographical amnesia, characterized by an acute onset concomitant with emotional/neurological precipitants. We present 2 cases of dissociative amnesia with fugue (cases 1 and 2), and one case of focal dissociative amnesia after a minor head trauma (case 3). The individual case histories and neuropsychological characteristics are reported, as well as the whole-brain voxel-based 18FDG-PET metabolic findings obtained at group-level in comparison to 15 healthy subjects. All patients suffered from autobiographical memory loss, in the absence of structural lesion. They had no significant impairment of anterograde memory or of executive function. Impairment of autobiographical memory was complete for two of the three patients, with loss of personal identity (cases 1 and 2). A clinical recovery was found for the two patients in whom follow-up was available (cases 2 and 3). Voxel-based group analysis highlighted a metabolic impairment of the right posterior middle temporal gyrus. 18FDG-PET was repeated in case 3, and showed a complete functional brain recovery. The situation of dissociative amnesia with disproportionate retrograde amnesia is clinically heterogeneous between individuals. Our findings may suggest that impairment of high-level integration of visual and/or emotional information processing involving dysfunction of the right posterior middle temporal gyrus could reduce triggering of multi-modal visual memory traces, thus impeding reactivation of aversive memories. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Associative memory and its cerebral correlates in Alzheimer's disease: Evidence for distinct deficits of relational and conjunctive memory

PubMed Central

Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric; Lemaire, Christian; Collette, Fabienne; Genon, Sarah; Simon, Jessica; Guillaume, Bénédicte; Diana, Rachel A.; Yonelinas, Andrew P.; Salmon, Eric

2014-01-01

This study investigated the impact of Alzheimer's disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item-color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients' performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial least square analyses revealed that poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer's disease as a function of damage to the respective neural networks. PMID:25172390

ALE Meta-Analysis of Schizophrenics Performing the N-Back Task

NASA Astrophysics Data System (ADS)

Harrell, Zachary

2010-10-01

MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.

Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

PubMed Central

Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

2012-01-01

Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

[Impact of acquired brain injury towards the community integration: employment outcome, disability and dependence two years after injury].

PubMed

Luna-Lario, P; Ojeda, N; Tirapu-Ustarroz, J; Pena, J

2016-06-16

To analyze the impact of acquired brain injury towards the community integration (professional career, disability, and dependence) in a sample of people affected by vascular, traumatic and tumor etiology acquired brain damage, over a two year time period after the original injury, and also to examine what sociodemographic variables, premorbid and injury related clinical data can predict the level of the person's integration into the community. 106 adults sample suffering from acquired brain injury who were attended by the Neuropsychology and Neuropsychiatry Department at Hospital of Navarra (Spain) affected by memory deficit as their main sequel. Differences among groups have been analyzed by using t by Student, chi squared and U by Mann-Whitney tests. 19% and 29% of the participants who were actively working before the injury got back their previous status within one and two years time respectively. 45% of the total sample were recognized disabled and 17% dependant. No relationship between sociodemographic and clinical variables and functional parameters observed were found. Acquired brain damage presents a high intensity impact on affected person's life trajectory. Nevertheless, in Spain, its consequences at sociolaboral adjustment over the the two years following the damage through functional parameters analyzed with official governmental means over a vascular, traumatic and tumor etiology sample had never been studied before.

Strategies for preservation of memory function in patients with brain metastases.

PubMed

Dye, Nicholas B; Gondi, Vinai; Mehta, Minesh P

2015-06-01

Cognitive decline, particularly in memory, is a side effect seen in patients with brain metastases and when severe, can have a significant impact on their quality of life. It is most often the result of multiple intersecting etiologic factors, including the use of whole brain radiation therapy, effects of which, in part, are mediated by damage within the hippocampus. A variety of clinical factors and comorbidities may impact the likelihood and severity of this cognitive decline, and affected patients should be considered for evaluation in a comprehensive neuro-rehabilitation or "brain fitness" program. Avoiding WBRT is warranted for some patients with brain metastases; particularly those <50 years old. However, when WBRT is clinically indicated, hippocampal avoidance WBRT (HA-WBRT) has been shown to significantly reduce memory decline compared to historical controls without compromising treatment efficacy. Additionally, the NMDA receptor antagonist memantine and renin-angiotensin-aldosterone system (RAAS) blockers have shown promise as neuroprotective agents that could be used prophylactically with radiation. After the onset of neurocognitive decline the treatment is largely symptom-driven, however simply screening for and treating depression, fatigue, anxiety, cognitive slowing, and other processes may alleviate some impairment. Stimulants such as methylphenidate may be useful in treating symptoms of fatigue and cognitive slowing. Other treatments including donepezil and cognitive rehabilitation have been extensively tested in the population at risk for dementia, although they have not been adequately studied in patients following cranial radiotherapy. An innovative hypothetical approach is the use of intranasal metabolic stimulants such as low dose insulin, which could be valuable in improving cognition and memory, by reversing impaired brain metabolic activity. Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in those in whom avoidance cannot be utilized. Likewise treatment will require a personalized combination of strategies optimized to address the patient's symptoms.

Remembering preservation in hippocampal amnesia

PubMed Central

Clark, Ian A.; Maguire, Eleanor A.

2017-01-01

The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the last sixty years the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field’s focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus. PMID:26361051

A neural basis for category and modality specificity of semantic knowledge.

PubMed

Thompson-Schill, S L; Aguirre, G K; D'Esposito, M; Farah, M J

1999-06-01

Prevalent theories hold that semantic memory is organized by sensorimotor modality (e.g., visual knowledge, motor knowledge). While some neuroimaging studies support this idea, it cannot account for the category specific (e.g., living things) knowledge impairments seen in some brain damaged patients that cut across modalities. In this article we test an alternative model of how damage to interactive, modality-specific neural regions might give rise to these categorical impairments. Functional MRI was used to examine a cortical area with a known modality-specific function during the retrieval of visual and non-visual knowledge about living and non-living things. The specific predictions of our model regarding the signal observed in this area were confirmed, supporting the notion that semantic memory is functionally segregated into anatomically discrete, but highly interactive, modality-specific regions.

Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice

PubMed Central

Moon, Minho; Huh, Eugene; Song, Eun Ji; Hwang, Deok-Sang; Lee, Tae Hee; Oh, Myung Sook

2017-01-01

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology. PMID:28946610

Tiliacora triandra, an Anti-Intoxication Plant, Improves Memory Impairment, Neurodegeneration, Cholinergic Function, and Oxidative Stress in Hippocampus of Ethanol Dependence Rats.

PubMed

Phunchago, Nattaporn; Wattanathorn, Jintanaporn; Chaisiwamongkol, Kowit

2015-01-01

Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg(-1)BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

PubMed Central

Arya, Aditya; Gangwar, Anamika; Singh, Sushil Kumar; Roy, Manas; Das, Mainak; Sethy, Niroj Kumar; Bhargava, Kalpana

2016-01-01

Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs), also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs), we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5′-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein binding (AMPK-PKC-CBP) protein pathway. Our present study results suggest that nanoceria can be translated as promising therapeutic molecules for neurodegenerative diseases. PMID:27069362

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

PubMed

Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

2015-11-01

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. © The Author 2015. Published by Oxford University Press.

Developmental amnesia: effect of age at injury.

PubMed

Vargha-Khadem, F; Salmond, C H; Watkins, K E; Friston, K J; Gadian, D G; Mishkin, M

2003-08-19

Hypoxic-ischemic events sustained within the first year of life can result in developmental amnesia, a disorder characterized by markedly impaired episodic memory and relatively preserved semantic memory, in association with medial temporal pathology that appears to be restricted to the hippocampus. Here we compared children who had hypoxic-ischemic events before 1 year of age (early group, n = 6) with others who showed memory problems after suffering hypoxic-ischemic events between the ages of 6 and 14 years (late group, n = 5). Morphometric analyses of the whole brain revealed that, compared with age-matched controls, both groups had bilateral abnormalities in the hippocampus, putamen, and posterior thalamus, as well as in the right retrosplenial cortex. The two groups also showed similar reductions (approximately 40%) in hippocampal volumes. Neuropsychologically, the only significant differences between the two were on a few tests of immediate memory, where the early group surpassed the late group. The latter measures provided the only clear indication that very early injury can lead to greater functional sparing than injury acquired later in childhood, due perhaps to the greater plasticity of the infant brain. On measures of long-term memory, by contrast, the two groups had highly similar profiles, both showing roughly equivalent preservation of semantic memory combined with marked impairment in episodic memory. It thus appears that, if this selective memory disorder is a special syndrome related to the early occurrence of hypoxia-induced damage, then the effective age at injury for this syndrome extends from birth to puberty.

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

PubMed

Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

2017-03-01

Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

Evidence for regional hippocampal damage in patients with schizophrenia.

PubMed

Singh, Sadhana; Khushu, Subash; Kumar, Pawan; Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N

2018-02-01

Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ( 1 H MRS) procedures. 1 H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients.

The effect of acetyl-L-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease.

PubMed

Shenk, Justin C; Liu, Jiankang; Fischbach, Kathryn; Xu, Kui; Puchowicz, Michel; Obrenovich, Mark E; Gasimov, Eldar; Alvarez, Ludis Morales; Ames, Bruce N; Lamanna, Joseph C; Aliev, Gjumrakch

2009-08-15

We measured age-dependent effects of human ApoE4 on cerebral blood flow (CBF) using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice by use of [(14)C] iodoantipyrene autoradiography. ApoE4 associated factors reduce CBF gradually to create brain hypoperfusion when compared to WT, and the differences in CBF are greatest as animals age from 6-weeks to 12-months. Transmission electron microscopy with colloidal gold immunocytochemistry showed structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the cytoplasm of perivascular cells, perivascular nerve terminals and hippocampal neurons and glial cells. These abnormalities coexist with mitochondrial structural alteration and mitochondrial DNA overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed selective mitochondrial antioxidants acetyl-l-carnitine and R-alpha-lipoic acid. Our findings indicate that ApoE4 genotype-induced mitochondrial changes and associated structural damage may explain age-dependent pathology seen in AD, indicating potential for novel treatment strategies in the near future.

Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.

PubMed

Patterson, Susan L

2015-09-01

Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of electromagnetic radiation in the mobile phone range on the behaviour of the rat.

PubMed

Daniels, Willie M U; Pitout, Ianthe L; Afullo, Thomas J O; Mabandla, Musa V

2009-12-01

Electromagnetic radiation (EMR) is emitted from electromagnetic fields that surround power lines, household appliances and mobile phones. Research has shown that there are connections between EMR exposure and cancer and also that exposure to EMR may result in structural damage to neurons. In a study by Salford et al. (Environ Health Perspect 111:881-883, 2003) the authors demonstrated the presence of strongly stained areas in the brains of rats that were exposed to mobile phone EMR. These darker neurons were particularly prevalent in the hippocampal area of the brain. The aim of our study was to further investigate the effects of EMR. Since the hippocampus is involved in learning and memory and emotional states, we hypothesised that EMR will have a negative impact on the subject's mood and ability to learn. We subsequently performed behavioural, histological and biochemical tests on exposed and unexposed male and female rats to determine the effects of EMR on learning and memory, emotional states and corticosterone levels. We found no significant differences in the spatial memory test, and morphological assessment of the brain also yielded non-significant differences between the groups. However, in some exposed animals there were decreased locomotor activity, increased grooming and a tendency of increased basal corticosterone levels. These findings suggested that EMR exposure may lead to abnormal brain functioning.

Working memory training and semantic structuring improves remembering future events, not past events.

PubMed

Richter, Kim Merle; Mödden, Claudia; Eling, Paul; Hildebrandt, Helmut

2015-01-01

Objectives. Memory training in combination with practice in semantic structuring and word fluency has been shown to improve memory performance. This study investigated the efficacy of a working memory training combined with exercises in semantic structuring and word fluency and examined whether training effects generalize to other cognitive tasks. Methods. In this double-blind randomized control study, 36 patients with memory impairments following brain damage were allocated to either the experimental or the active control condition, with both groups receiving 9 hours of therapy. The experimental group received a computer-based working memory training and exercises in word fluency and semantic structuring. The control group received the standard memory therapy provided in the rehabilitation center. Patients were tested on a neuropsychological test battery before and after therapy, resulting in composite scores for working memory; immediate, delayed, and prospective memory; word fluency; and attention. Results. The experimental group improved significantly in working memory and word fluency. The training effects also generalized to prospective memory tasks. No specific effect on episodic memory could be demonstrated. Conclusion. Combined treatment of working memory training with exercises in semantic structuring is an effective method for cognitive rehabilitation of organic memory impairment. © The Author(s) 2014.

Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline.

PubMed

Charlton, R A; Schiavone, F; Barrick, T R; Morris, R G; Markus, H S

2010-01-01

Diffusion tensor imaging (DTI) is a sensitive method for detecting white matter damage, and in cross sectional studies DTI measures correlate with age related cognitive decline. However, there are few data on whether DTI can detect age related changes over short time periods and whether such change correlates with cognitive function. In a community sample of 84 middle-aged and elderly adults, MRI and cognitive testing were performed at baseline and after 2 years. Changes in DTI white matter histograms, white matter hyperintensity (WMH) volume and brain volume were determined. Change over time in performance on tests of executive function, working memory and information processing speed were also assessed. Significant change in all MRI measures was detected. For cognition, change was detected for working memory and this correlated with change in DTI only. In a stepwise regression, with change in working memory as the dependent variable, a DTI histogram measure explained 10.8% of the variance in working memory. Change in WMH or brain volume did not contribute to the model. DTI is sensitive to age related change in white matter ultrastructure and appears useful for monitoring age related white matter change even over short time periods.

[Organic brain damage in garage workers after long-term exposure to diesel exhaust fumes].

PubMed

Jensen, L K; Klausen, H; Elsnab, C

1989-09-04

Diesel motors are employed to an increasing extent for occupational transport and fumes from diesel driven vehicles constitute an increasing problem as regards atmospheric pollution but, in particular, they constitute a considerable risk to health for the workers exposed to diesel exhaust fumes in their daily work. In the clinic for occupational medicine, The University Hospital, Copenhagen, 14 garage workers were examined. Eleven of these had been exposed to great quantities of diesel exhaust fumes for 2 to 29 years. All 11 presented acute symptoms due to diesel exhaust fumes in the form of headache, vertigo, fatigue, irritation of mucous membranes, nausea, abdominal discomfort or diarrhoea. Seven persons had been employed for more than five years as garage workers. Six complained of failure of memory, difficulty in concentration, irritability, increased sleep requirement, psychological changes or reduced libido. Neuropsychological examination was undertaken in these six persons and in five of them organic brain damage, mainly of slight extent, was demonstrated. Diesel exhaust fumes contain many toxic substances: carbon monoxide, nitrous gases, sulphur oxides, aldehydes and hydrocarbons. It is not possible to indicate a single compound which is responsible for possible brain damage and a combination effect may well be concerned. This is a casuistic material. Only few investigations have previously been available which illustrated a possible connection between the neurotoxic effects and, in particular, brain damage. It is now considered important to emphasize that this may constitute a problem on exposure to diesel exhaust fumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive disorders after sporadic ecstasy use? A case report.

PubMed

Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke

2015-01-01

Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits.

Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model.

PubMed

Choi, Ji Yeon; Cho, Eun Ju; Lee, Hae Song; Lee, Jeong Min; Yoon, Young-Ho; Lee, Sanghyun

2013-03-01

Protective effects of Tartary buckwheat (TB) and common buckwheat (CB) on amyloid beta (Aβ)-induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer's disease (AD) and its associated progressive memory deficits, cognitive impairment, and personality changes. An in vivo mouse model of AD was created by injecting the brains of ICR mice with Aβ(25-35), a fragment of the full-length Aβ protein. Damage of mice recognition ability through following Aβ(25-35) brain injections was confirmed using the T-maze test, the object recognition test, and the Morris water maze test. Results of behavior tests in AD model showed that oral administration of the methanol (MeOH) extracts of TB and CB improved cognition and memory function following Aβ(25-35) injections. Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of Aβ(25-35), were also decrease. In particular, the MeOH extract of TB exerted a stronger protective activity than CB against Aβ(25-35)-induced memory and cognition impairment. The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with Aβ(25-35)-induced AD. Copyright © 2012 Elsevier Ltd. All rights reserved.

The remains of the day in dissociative amnesia.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J

2012-04-10

Memory is not a unity, but is divided along a content axis and a time axis, respectively. Along the content dimension, five long-term memory systems are described, according to their hierarchical ontogenetic and phylogenetic organization. These memory systems are assumed to be accompanied by different levels of consciousness. While encoding is based on a hierarchical arrangement of memory systems from procedural to episodic-autobiographical memory, retrieval allows independence in the sense that no matter how information is encoded, it can be retrieved in any memory system. Thus, we illustrate the relations between various long-term memory systems by reviewing the spectrum of abnormalities in mnemonic processing that may arise in the dissociative amnesia-a condition that is usually characterized by a retrieval blockade of episodic-autobiographical memories and occurs in the context of psychological trauma, without evidence of brain damage on conventional structural imaging. Furthermore, we comment on the functions of implicit memories in guiding and even adaptively molding the behavior of patients with dissociative amnesia and preserving, in the absence of autonoetic consciousness, the so-called "internal coherence of life".

The Remains of the Day in Dissociative Amnesia

PubMed Central

Staniloiu, Angelica; Markowitsch, Hans J.

2012-01-01

Memory is not a unity, but is divided along a content axis and a time axis, respectively. Along the content dimension, five long-term memory systems are described, according to their hierarchical ontogenetic and phylogenetic organization. These memory systems are assumed to be accompanied by different levels of consciousness. While encoding is based on a hierarchical arrangement of memory systems from procedural to episodic-autobiographical memory, retrieval allows independence in the sense that no matter how information is encoded, it can be retrieved in any memory system. Thus, we illustrate the relations between various long-term memory systems by reviewing the spectrum of abnormalities in mnemonic processing that may arise in the dissociative amnesia—a condition that is usually characterized by a retrieval blockade of episodic-autobiographical memories and occurs in the context of psychological trauma, without evidence of brain damage on conventional structural imaging. Furthermore, we comment on the functions of implicit memories in guiding and even adaptively molding the behavior of patients with dissociative amnesia and preserving, in the absence of autonoetic consciousness, the so-called “internal coherence of life”. PMID:24962768

Inferencing Processes After Right Hemisphere Brain Damage: Effects of Contextual Bias

PubMed Central

Blake, Margaret Lehman

2009-01-01

Purpose Comprehension deficits associated with right hemisphere brain damage (RHD) have been attributed to an inability to use context, but there is little direct evidence to support the claim. This study evaluated the effect of varying contextual bias on predictive inferencing by adults with RHD. Method Fourteen adults with no brain damage (NBD) and 14 with RHD read stories constructed with either high predictability or low predictability of a specific outcome. Reading time for a sentence that disconfirmed the target outcome was measured and compared with a control story context. Results Adults with RHD evidenced activation of predictive inferences only for highly predictive conditions, whereas NBD adults generated inferences in both high- and low-predictability stories. Adults with RHD were more likely than those with NBD to require additional time to integrate inferences in high-predictability conditions. The latter finding was related to working memory for the RHD group. Results are interpreted in light of previous findings obtained using the same stimuli. Conclusions RHD does not abolish the ability to use context. Evidence of predictive inferencing is influenced by task and strength of inference activation. Treatment considerations and cautions regarding interpreting results from one methodology are discussed. PMID:19252126

Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

PubMed

Le, Xoan Thi; Pham, Hang Thi Nguyet; Do, Phuong Thi; Fujiwara, Hironori; Tanaka, Ken; Li, Feng; Van Nguyen, Tai; Nguyen, Khoi Minh; Matsumoto, Kinzo

2013-10-01

This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

Cognitive Rehabilitation of Episodic Memory Disorders: From Theory to Practice

PubMed Central

Ptak, Radek; der Linden, Martial Van; Schnider, Armin

2010-01-01

Memory disorders are among the most frequent and most debilitating cognitive impairments following acquired brain damage. Cognitive remediation strategies attempt to restore lost memory capacity, provide compensatory techniques or teach the use of external memory aids. Memory rehabilitation has strongly been influenced by memory theory, and the interaction between both has stimulated the development of techniques such as spaced retrieval, vanishing cues or errorless learning. These techniques partly rely on implicit memory and therefore enable even patients with dense amnesia to acquire new information. However, knowledge acquired in this way is often strongly domain-specific and inflexible. In addition, individual patients with amnesia respond differently to distinct interventions. The factors underlying these differences have not yet been identified. Behavioral management of memory failures therefore often relies on a careful description of environmental factors and measurement of associated behavioral disorders such as unawareness of memory failures. The current evidence suggests that patients with less severe disorders benefit from self-management techniques and mnemonics whereas rehabilitation of severely amnesic patients should focus on behavior management, the transmission of domain-specific knowledge through implicit memory processes and the compensation for memory deficits with memory aids. PMID:20700383

Maternal intake of cashew nuts accelerates reflex maturation and facilitates memory in the offspring.

PubMed

de Melo, Marília Ferreira Frazão Tavares; Pereira, Diego Elias; Sousa, Morgana Moura; Medeiros, Dilian Maise Ferreira; Lemos, Leanderson Tulio Marques; Madruga, Marta Suely; Santos, Nayane Medeiros; de Oliveira, Maria Elieidy Gomes; de Menezes, Camila Carolina; Soares, Juliana Késsia Barbosa

2017-10-01

Essential fatty acids, being indispensable during the stages of pregnancy, lactation and infancy influence the transmission of nerve impulses and brain function, and cashew nuts are a good source of these fatty acids. The objective of this study was to evaluate the effects of cashew nut consumption on reflex development, memory and profile of fatty acids of rat offspring treated during pregnancy and lactation. The animals were divided into three groups: Control (CONT), treated with 7% lipid derived from soybean oil; Normolipidic (NL) treated with 7% lipids derived from cashew nuts; and Hyperlipidic (HL) treated with 20% lipids derived from cashew nuts. Reflex ontogeny, Open-field habituation test and the Object Recognition Test (ORT) were assessed. The profile of fatty acids in the brain was carried out when the animals were zero, 21 and 60days old. Accelerated reflex maturation was observed in animals treated with cashew nuts (p<0.05). NL presented better memory in the Open-field habituation test; the NL and HL showed improvement of short-term memory in the ORT, but long term damage in HL (p<0.05). The results of the lipid profile of the brain at the end of the experiment showed an increase in levels of saturated fatty acids and less Docosahexaenoic acid (DHA) in animals of the HL. The data showed that maternal consumption of cashew nuts can accelerate reflex maturation and facilitate memory in offspring when offered in adequate quantities. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

"The Memory of Beauty" Survives Alzheimer's Disease (but Cannot Help Memory).

PubMed

Silveri, Maria Caterina; Ferrante, Ilaria; Brita, Anna Clelia; Rossi, Paola; Liperoti, Rosa; Mammarella, Federica; Bernabei, Roberto; Marini Chiarelli, Maria Vittoria; De Luca, Martina

2015-01-01

The aesthetic experience, in particular the experience of beauty in the visual arts, should have neural correlates in the human brain. Neuroesthetics is principally implemented by functional studies in normal subjects, but the neuropsychology of the aesthetic experience, that is, the impact of brain damage on the appreciation of works of art, is a neglected field. Here, 16 mild to moderate Alzheimer's disease patients and 15 caregivers expressed their preference on 16 works of art (eight representational and eight abstract) during programmed visits to an art gallery. A week later, all subjects expressed a preference rate on reproductions of the same works presented in the gallery. Both patients and caregivers were consistent in assigning preference ratings, and in patients consistency was independent of the ability to recognize the works on which the preference rate had been given in an explicit memory task. Caregivers performed at ceiling in the memory task. Both patients and caregivers assigned higher preference ratings for representational than for abstract works and preference consistency was comparable in representational and abstract works. Furthermore, in the memory task, patients did not recognize better artworks they had assigned higher preference ratings to, suggesting that emotional stimuli (as presumably visual works of art are) cannot enhance declarative memory in this pathology. Our data, which were gathered in an ecological context and with real-world stimuli, confirm previous findings on the stability of aesthetic preference in patients with Alzheimer's disease and on the independence of aesthetic preference from cognitive abilities such as memory.

Postconditioning Effectively Prevents Trimethyltin Induced Neuronal Damage in the Rat Brain.

PubMed

Lalkovicova, Maria; Burda, Jozef; Nemethova, Miroslava; Burda, Rastislav; Danielisova, Viera

Trimethyltin (TMT) is a toxic substance formerly used as a catalyst in the production of organic substances, as well as in industry and agriculture. TMT poisoning has caused death or severe injury in many dozens of people. The toxicity of TMT is mediated by dose dependent selective damage to the limbic system in humans and other animals, specifically the degeneration of CA1 neurons in the hippocampus. The typical symptoms include memory loss and decreased learning ability. Using knowledge gained in previous studies of global ischaemia, we used delayed postconditioning after TMT intoxication (8 mg/kg i.p.), consisting of applying a stressor (BR, bradykinin 150 μg/kg i.p.) 24 or 48 hours after the injection of TMT. We found that BR had preventive effects on neurodegenerative changes as well as learning and memory deficits induced by TMT intoxication.

Two Dimensional Finite Element Analysis for the Effect of a Pressure Wave in the Human Brain

NASA Astrophysics Data System (ADS)

Ponce L., Ernesto; Ponce S., Daniel

2008-11-01

Brain injuries in people of all ages is a serious, world-wide health problem, with consequences as varied as attention or memory deficits, difficulties in problem-solving, aggressive social behavior, and neuro degenerative diseases such as Alzheimer's and Parkinson's. Brain injuries can be the result of a direct impact, but also pressure waves and direct impulses. The aim of this work is to develop a predictive method to calculate the stress generated in the human brain by pressure waves such as high power sounds. The finite element method is used, combined with elastic wave theory. The predictions of the generated stress levels are compared with the resistance of the arterioles that pervade the brain. The problem was focused to the Chilean mining where there are some accidents happen by detonations and high sound level. There are not formal medical investigation, however these pressure waves could produce human brain damage.

The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

PubMed

Fang, Shengyu; Wang, Yinyan; Jiang, Tao

2016-07-01

Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Associative memory and its cerebral correlates in Alzheimer׳s disease: evidence for distinct deficits of relational and conjunctive memory.

PubMed

Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric; Lemaire, Christian; Collette, Fabienne; Genon, Sarah; Simon, Jessica; Guillaume, Bénédicte; Diana, Rachel A; Yonelinas, Andrew P; Salmon, Eric

2014-10-01

This study investigated the impact of Alzheimer׳s disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item-color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients׳ performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial Least Square analyses revealed that poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer׳s disease as a function of damage to the respective neural networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model.

PubMed

Cerpa, W; Hancke, J L; Morazzoni, P; Bombardelli, E; Riva, Antonella; Marin, P P; Inestrosa, Nibaldo C

2010-03-01

The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (Abeta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of Abeta deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size Abeta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high Abeta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.

Neuropsychology of perpetrators of domestic violence: the role of traumatic brain injury and alcohol abuse and/or dependence.

PubMed

Romero-Martínez, Ángel; Moya-Albiol, Luis

2013-12-01

Neuropsychological impairments of the executive functions, memory, attention, intelligence quotient, and empathy have been found in perpetrators of domestic violence (intimate partner violence). These impairments could be partially explained by alcohol abuse, dependence, or traumatic brain injuries. This study reviews the neuropsychological deficits of perpetrators of intimate partner violence. At the same it seeks to integrate and relate these main points with their neuroanatomical correlates. We have also established the relationship between alcohol abuse, dependence, brain damage (including traumatic brain injuries) and those deficits. Scientific literature has been reviewed by means of Google Scholar, PsycINFO, PubMed, Medline and ISI Web of Knowledge. Perpetrators of domestic violence present high mental rigidity, as well as low levels of inhibition, processing speed, verbal and attention skills, and abstract reasoning. Additionally, perpetrators show working and long play memory impairments. Moreover, those deficits could be impaired by traumatic brain injuries and alcohol abuse and/or dependence. Nonetheless, these both variables are not enough to explain the deficits. Functional abnormalities on the prefrontal and occipital cortex, fusiform gyrus, posterior cingulate gyrus, hippocampus, thalamus and amygdala could be associated with these impairments. An analysis of these mechanisms may assist in the development of neuropsychological rehabilitation programmes that could help improve current therapies.

Effects of Long-Term Treatment on Brain Volume in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Kim, Hosung; Joo, Eun Yeon; Suh, Sooyeon; Kim, Jae-Hun; Kim, Sung Tae; Hong, Seung Bong

2015-01-01

We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of non-permanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA. PMID:26503297

Prism adaptation enhances activity of intact fronto-parietal areas in both hemispheres in neglect patients.

PubMed

Saj, Arnaud; Cojan, Yann; Vocat, Roland; Luauté, Jacques; Vuilleumier, Patrik

2013-01-01

Unilateral spatial neglect involves a failure to report or orient to stimuli in the contralesional (left) space due to right brain damage, with severe handicap in everyday activities and poor rehabilitation outcome. Because behavioral studies suggest that prism adaptation may reduce spatial neglect, we investigated the neural mechanisms underlying prism effects on visuo-spatial processing in neglect patients. We used functional magnetic resonance imaging (fMRI) to examine the effect of (right-deviating) prisms on seven patients with left neglect, by comparing brain activity while they performed three different spatial tasks on the same visual stimuli (bisection, search, and memory), before and after a single prism-adaptation session. Following prism adaptation, fMRI data showed increased activation in bilateral parietal, frontal, and occipital cortex during bisection and visual search, but not during the memory task. These increases were associated with significant behavioral improvement in the same two tasks. Changes in neural activity and behavior were seen only after prism adaptation, but not attributable to mere task repetition. These results show for the first time the neural substrates underlying the therapeutic benefits of prism adaptation, and demonstrate that visuo-motor adaptation induced by prism exposure can restore activation in bilateral brain networks controlling spatial attention and awareness. This bilateral recruitment of fronto-parietal networks may counteract the pathological biases produced by unilateral right hemisphere damage, consistent with recent proposals that neglect may reflect lateralized deficits induced by bilateral hemispheric dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

PubMed

Batista, Andre F; Forny-Germano, Leticia; Clarke, Julia R; Lyra E Silva, Natalia M; Brito-Moreira, Jordano; Boehnke, Susan E; Winterborn, Andrew; Coe, Brian C; Lablans, Ann; Vital, Juliana F; Marques, Suelen A; Martinez, Ana Mb; Gralle, Matthias; Holscher, Christian; Klein, William L; Houzel, Jean-Christophe; Ferreira, Sergio T; Munoz, Douglas P; De Felice, Fernanda G

2018-05-01

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Forgetting, Reminding, and Remembering: The Retrieval of Lost Spatial Memory

PubMed Central

Morris, Richard G. M

2004-01-01

Retrograde amnesia can occur after brain damage because this disrupts sites of storage, interrupts memory consolidation, or interferes with memory retrieval. While the retrieval failure account has been considered in several animal studies, recent work has focused mainly on memory consolidation, and the neural mechanisms responsible for reactivating memory from stored traces remain poorly understood. We now describe a new retrieval phenomenon in which rats' memory for a spatial location in a watermaze was first weakened by partial lesions of the hippocampus to a level at which it could not be detected. The animals were then reminded by the provision of incomplete and potentially misleading information—an escape platform in a novel location. Paradoxically, both incorrect and correct place information reactivated dormant memory traces equally, such that the previously trained spatial memory was now expressed. It was also established that the reminding procedure could not itself generate new learning in either the original environment, or in a new training situation. The key finding is the development of a protocol that definitively distinguishes reminding from new place learning and thereby reveals that a failure of memory during watermaze testing can arise, at least in part, from a disruption of memory retrieval. PMID:15314651

Disturbance of time orientation, attention, and verbal memory in amnesic patients with confabulation.

PubMed

Shingaki, Honoka; Park, Paeksoon; Ueda, Keita; Murai, Toshiya; Tsukiura, Takashi

2016-01-01

Confabulation is often observed in amnesic patients after brain damage. However, evidence regarding the relationship between confabulation and other neuropsychological functions is scarce. In addition, previous studies have proposed two possibilities of the relationship between confabulation and false memory, in which patients with confabulation are likely to retrieve false memories, or confabulations are relatively independent of false memories. The present study investigated how confabulation is related to various cognitive functions, including orientation, attention, frontal lobe function, memory, and mental status, and to false memories, as assessed by the Deese-Roediger-Mcdermott (DRM) paradigm. Patients with organic amnesia participated, and confabulations were evaluated using the Confabulation Battery. Amnestic patients were classified into two groups: confabulating (CP) and nonconfabulating patients (NCP). The CP group was significantly impaired in time orientation, attention, and verbal memory, compared to the NCP group and age-matched healthy controls (HC). Results of the DRM paradigm revealed no significant difference in false memory retrieval induced by critical lures across CP, NCP, and HC groups. Confabulating responses in organic amnesia could be in part induced by disturbance of time consciousness and attention control in severe impairment of verbal memories, and confabulation and false memory could be modulated by different cognitive systems.

Neuroprotective actions of perinatal choline nutrition

PubMed Central

Blusztajn, Jan Krzysztof; Mellott, Tiffany J.

2017-01-01

Choline is an essential nutrient for humans. Studies in rats and mice have shown that high choline intake during gestation or the perinatal period improves cognitive function in adulthood, prevents memory decline of old age, and protects the brain from damage and cognitive and neurological deterioration associated with epilepsy and hereditary conditions such as Down’s and Rett syndromes. These behavioral changes are accompanied by modified patterns of expression of hundreds of cortical and hippocampal genes including those encoding proteins central for learning and memory processing. The effects of choline correlate with cerebral cortical changes in DNA and histone methylation, thus suggesting an epigenomic mechanism of action of perinatal choline. PMID:23314544

[Korsakoff amnesia syndrome].

PubMed

Verstichel, P

2000-10-14

PATHOLOGY CORRELATIONS: The Korsakoff syndrome results from cerebral lesions due to thiamine depletion, usually of alcoholic etiology. Other nutritional, or genetic factors, could be implicated. Exceptionally, it results from thalamic disease or a tumor of the third ventricle floor. Anterograde and retrograde aspects of episodic memory are principally impaired, contrasting with the preservation of semantic and procedural memory. Opposition between explicit (impaired) and implicit (unimpaired) memory is one of the main cognitive features of this syndrome. Several cerebral structures, components of various memory systems, are simultaneously damaged. Critical lesion sites for anterograde amnesia involve the memillary bodies, the mamillotalamic tract and the anterior thalamus. Retrograde amnesia is dependent on function abnormalities of a circuit between the dorso-median thalamus and the prefrontal cortex. Impairment of retrieval and chronological disorganization of memories contribute to this extensive retrograde amnesia, probably because of frontal dysfunction. Confabulations and false recognitions are produced in the initial stage of the disease. They are, in the same way, interpreted as the consequence of frontal desafferentation due to dorso-median thalamus damage. The impact of diencephalic destruction on the frontal lobes is evidenced clinically by behavioral changes and dysexecutive syndrome. Neuroimaging studies of the brain show a decreased regional metabolic ration in the frontal areas. Korsakoff syndrome is a serious disorder, responsible for cognitive handicap. There is no curative treatment. Preventive measures, consisting in systematic prescription of thiamine in alcoholics, is the main effective measure.

[Long-term effects of early hyperbaric oxygen therapy on neonatal rats with hypoxic-ischemic brain damage].

PubMed

Liu, Mei-Na; Zhuang, Si-Qi; Zhang, Hong-Yu; Qin, Zhao-Yuan; Li, Xiao-Yu

2006-06-01

The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD. Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42. The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28 s; P < 0.05) and the probe time and probe length were shorter in the HIBD group (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P < 0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g; P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/- 27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75 +/- 5.57 respectively; P < 0.05) after HIBD. Early HBO treatment improved the abilities of spatial learning and alleviated the morphological and histological damage. The mean escape latency (39.17 +/- 21.20 s) was shortened, the probe time (36.84 +/- 4.36 s) and the probe length (686 +/- 76 cm) were longer, and the brain weight (0.768 +/- 0.85 g), the survival neurons (133 +/- 25/mm) and the AchE-positive unit (21.94 +/- 2.73%) increased significantly compared with those of the HIBD group (P < 0.05). Early HBO treatment resulted in a protective effect against HIBD-induced long-term brain morphological and histological deficits and spatial learning and memory disability.

Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined treatment with G-CSF.

PubMed

Griva, Myrsini; Lagoudaki, Rosa; Touloumi, Olga; Nousiopoulou, Evangelia; Karalis, Filippos; Georgiou, Thomas; Kokaraki, Georgia; Simeonidou, Constantina; Tata, Despina A; Spandou, Evangelia

2017-07-15

Increasing evidence shows that exposure to an enriched environment (EE) is neuroprotective in adult and neonatal animal models of brain ischemia. However, the mechanisms underlying this effect remain unclear. The aim of the current study was to investigate whether post-weaning EE would be effective in preventing functional deficits and brain damage by affecting markers of synaptic plasticity in a neonatal rat model of hypoxia-ischemia (HI). We also examined the possibility that granulocyte-colony stimulating factor (G-CSF), a growth factor with known neuroprotective effects in a variety of experimental brain injury models, combined with EE stimulation could enhance the potential beneficial effect of EE. Seven-day-old Wistar rats of either sex were subjected to permanent ligation of the left common carotid artery followed by 60min of hypoxia (8% O 2 ) and immediately after weaning (postnatal day 21) were housed in enriched conditions for 4weeks. A group of enriched-housed rats had been treated with G-CSF immediately after HI for 5 consecutive days (50μg/kg/day). Behavioral examination took place approximately at three months of age and included assessments of learning and memory (Morris water maze) as well as motor coordination (Rota-Rod). Infarct size and hippocampal area were estimated following behavioral assessment. Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in the dorsal hippocampus. EE resulted in recovery of post-HI motor deficits and partial improvement of memory impairments which was not accompanied by reduced brain damage. Increased synaptophysin expression was observed in the contralateral to carotid ligation hemisphere. Hypoxia-ischemia alone or followed by enriched conditions did not affect BDNF expression which was increased only in enriched-housed normal rats. The combined therapy of G-CSF and EE further enhanced cognitive function compared to EE provided as monotherapy and prevented HI-induced brain damage by altering synaptic plasticity as reflected by increased synaptophysin expression. The above findings demonstrate that combination of neuroprotective treatments may result in increased protection and it might be a more effective strategy for the treatment of neonatal hypoxic-ischemic brain injury. Copyright © 2017. Published by Elsevier B.V.

Remote semantic memory is impoverished in hippocampal amnesia

PubMed Central

Klooster, Nathaniel B.; Duff, Melissa C.

2015-01-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. PMID:26474741

Remote semantic memory is impoverished in hippocampal amnesia.

PubMed

Klooster, Nathaniel B; Duff, Melissa C

2015-12-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Semantic memory: a feature-based analysis and new norms for Italian.

PubMed

Montefinese, Maria; Ambrosini, Ettore; Fairfield, Beth; Mammarella, Nicola

2013-06-01

Semantic norms for properties produced by native speakers are valuable tools for researchers interested in the structure of semantic memory and in category-specific semantic deficits in individuals following brain damage. The aims of this study were threefold. First, we sought to extend existing semantic norms by adopting an empirical approach to category (Exp. 1) and concept (Exp. 2) selection, in order to obtain a more representative set of semantic memory features. Second, we extensively outlined a new set of semantic production norms collected from Italian native speakers for 120 artifactual and natural basic-level concepts, using numerous measures and statistics following a feature-listing task (Exp. 3b). Finally, we aimed to create a new publicly accessible database, since only a few existing databases are publicly available online.

Support for distinct subcomponents of spatial working memory: a double dissociation between spatial-simultaneous and spatial-sequential performance in unilateral neglect.

PubMed

Wansard, Murielle; Bartolomeo, Paolo; Bastin, Christine; Segovia, Fermín; Gillet, Sophie; Duret, Christophe; Meulemans, Thierry

2015-01-01

Over the last decade, many studies have demonstrated that visuospatial working memory (VSWM) can be divided into separate subsystems dedicated to the retention of visual patterns and their serial order. Impaired VSWM has been suggested to exacerbate left visual neglect in right-brain-damaged individuals. The aim of this study was to investigate the segregation between spatial-sequential and spatial-simultaneous working memory in individuals with neglect. We demonstrated that patterns of results on these VSWM tasks can be dissociated. Spatial-simultaneous and sequential aspects of VSWM can be selectively impaired in unilateral neglect. Our results support the hypothesis of multiple VSWM subsystems, which should be taken into account to better understand neglect-related deficits.

Stress and combined exposure to low doses of pyridostigmine bromide, DEET, and permethrin produce neurochemical and neuropathological alterations in cerebral cortex, hippocampus, and cerebellum.

PubMed

Abdel-Rahman, A; Abou-Donia, Suzanne; El-Masry, Eman; Shetty, Ashok; Abou-Donia, Mohamed

2004-01-23

Exposure to a combination of stress and low doses of the chemicals pyridostigmine bromide (PB), DEET, and permethrin in adult rats, a model of Gulf War exposure, produces blood-brain barrier (BBB) disruption and neuronal cell death in the cingulate cortex, dentate gyrus, thalamus, and hypothalamus. In this study, neuropathological alterations in other areas of the brain where no apparent BBB disruption was observed was studied following such exposure. Animals exposed to both stress and chemical exhibited decreased brain acetylcholinesterase (AChE) activity in the midbrain, brainstem, and cerebellum and decreased m2 muscarinic acetylcholine (ACh) receptor ligand binding in the midbrain and cerebellum. These alterations were associated with significant neuronal cell death, reduced microtubule-associated protein (MAP-2) expression, and increased glial fibrillary acidic protein (GFAP) expression in the cerebral cortex and the hippocampal subfields CA1 and CA3. In the cerebellum, the neurochemical alterations were associated with Purkinje cell loss and increased GFAP immunoreactivity in the white matter. However, animals subjected to either stress or chemicals alone did not show any of these changes in comparison to vehicle-treated controls. Collectively, these results suggest that prolonged exposure to a combination of stress and the chemicals PB, DEET, and permethrin can produce significant damage to the cerebral cortex, hippocampus, and cerebellum, even in the absence of apparent BBB damage. As these areas of the brain are respectively important for the maintenance of motor and sensory functions, learning and memory, and gait and coordination of movements, such alterations could lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype.

Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

PubMed Central

2016-01-01

The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms. PMID:26949445

(-)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats.

PubMed

Soung, Hung-Sheng; Wang, Mao-Hsien; Tseng, Hsiang-Chien; Fang, Hsu-Wei; Chang, Kuo-Chi

2015-08-18

Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bigger is better! Hippocampal volume and declarative memory performance in healthy young men.

PubMed

Pohlack, Sebastian T; Meyer, Patric; Cacciaglia, Raffaele; Liebscher, Claudia; Ridder, Stephanie; Flor, Herta

2014-01-01

The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail. For this purpose, 50 healthy young male participants performed the California Verbal Learning Test. Hippocampal volume was assessed by manual segmentation of high-resolution 3D magnetic resonance images. We found a significant positive correlation between putatively hippocampus-dependent memory measures like short-delay retention, long-delay retention and discriminability and percent hippocampal volume. No significant correlation with measures related to executive processes was found. In addition, percent amygdala volume was not related to any of these measures. Our data advance previous findings reported in studies of brain-damaged individuals in a large and homogeneous young healthy sample and are important for theories on the neural basis of episodic memory.

Nutrients, Microglia Aging, and Brain Aging.

PubMed

Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

2016-01-01

As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

Nutrients, Microglia Aging, and Brain Aging

PubMed Central

Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

2016-01-01

As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. PMID:26941889

Developmental amnesia associated with early hypoxic-ischaemic injury.

PubMed

Gadian, D G; Aicardi, J; Watkins, K E; Porter, D A; Mishkin, M; Vargha-Khadem, F

2000-03-01

We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.

Deficits of long-term memory in ecstasy users are related to cognitive complexity of the task.

PubMed

Brown, John; McKone, Elinor; Ward, Jeff

2010-03-01

Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use. The objective of this study is to evaluate ecstasy-related deficits in human verbal memory over a wide range of cognitive complexity using subjects drawn from a single geographical population. Ecstasy users were compared to non-drug using controls on verbal tasks with low cognitive complexity (stem completion), moderate cognitive complexity (stem-cued recall and word list learning) and high cognitive complexity (California Verbal Learning Test, Verbal Paired Associates and a novel Verbal Triplet Associates test). Where significant differences were found, both groups were also compared to cannabis users. More cognitively complex memory tasks were associated with clearer ecstasy-related deficits than low complexity tasks. In the most cognitively demanding task, ecstasy-related deficits remained even after multiple learning opportunities, whereas the performance of cannabis users approached that of non-drug using controls. Ecstasy users also had weaker deliberate strategy use than both non-drug and cannabis controls. Results were consistent with the proposal that ecstasy-related memory deficits are more reliable on tasks with greater cognitive complexity. This could arise either because such tasks require a greater contribution from the frontal lobe or because they require greater interaction between multiple brain regions.

Narratives of Focal Brain Injured Individuals: A Macro-Level Analysis

PubMed Central

Karaduman, Ayşenur; Göksun, Tilbe; Chatterjee, Anjan

2017-01-01

Focal brain injury can have detrimental effects on the pragmatics of communication. This study examined narrative production by unilateral brain damaged people (n= 36) and healthy controls and focused on the complexity (content and coherence) and the evaluative aspect of their narratives to test the general hypothesis that the left hemisphere is biased to process microlinguistic information and the right hemisphere is biased to process macrolinguistic information. We found that people with left hemisphere damage’s (LHD) narratives were less likely to maintain the overall theme of the story and produced fewer evaluative comments in their narratives. These deficits correlated with their performances on microlinguistic linguistic tasks. People with the right hemisphere damage (RHD) seemed to be preserved in expressing narrative complexity and evaluations as a group. Yet, single case analyses revealed that particular regions in the right hemisphere such as damage to the dorsolateral prefrontal cortex (DLPFC), the anterior and superior temporal gyrus, the middle temporal gyrus, and the supramarginal gyrus lead to problems in creating narratives. Our findings demonstrate that both hemispheres are necessary to produce competent narrative production. LHD people’s poor production is related to their microlinguistic language problems whereas RHD people’s impaired abilities can be associated with planning and working memory abilities required to relate events in a narrative. PMID:28347806

Injury of the developing cerebellum: a brief review of the effects of endotoxin and asphyxial challenges in the late gestation sheep fetus.

PubMed

Hutton, Lisa C; Yan, Edwin; Yawno, Tamara; Castillo-Melendez, Margie; Hirst, Jon J; Walker, David W

2014-12-01

The vulnerability of the fetal and newborn brain to events in utero or at birth that cause damage arising from perturbations of cerebral blood flow and metabolism, such as the accumulation of free radicals and excitatory transmitters to neurotoxic levels, has received considerable attention over the last few decades. Attention has usually been on the damage to cerebral structures, particularly, periventricular white matter. The rapid growth of the cerebellum in the latter half of fetal life in species with long gestations, such as the human and sheep, suggests that this may be a particularly important time for the development of cerebellar structure and function. In this short review, we summarize data from recent studies with fetal sheep showing that the developing cerebellum is particularly sensitive to infectious processes, chronic hypoxia and asphyxia. The data demonstrates that the cerebellum should be further studied in insults of this nature as it responds differently to the remainder of the brain. Damage to this region of the brain has implications not only for the development of motor control and posture, but also for higher cognitive processes and the subsequent development of complex behaviours, such as learning, memory and attention.

Natural distribution of environmental radon daughters in the different brain areas of an Alzheimer disease victim.

PubMed

Momcilović, Berislav; Lykken, Glenn I; Cooley, Marvin

2006-09-11

Radon is a ubiquitous noble gas in the environment and a primary source of harmful radiation exposure for humans; it decays in a cascade of daughters (RAD) by releasing the cell damaging high energy alpha particles. We studied natural distribution of RAD 210Po and 210Bi in the different parts of the postmortem brain of 86-year-old woman who had suffered from Alzheimer's disease (AD). A distinct brain map emerged, since RAD distribution was different among the analyzed brain areas. The highest RAD irradiation (mSv x year(-1)) occurred in the decreasing order of magnitude: amygdala (Amy) > hippocampus (Hip) > temporal lobe (Tem) approximately = frontal lobe (Fro) > occipital lobe (Occ) approximately = parietal lobe (Par) > substantia nigra (SN) > locus ceruleus (LC) approximately = nucleus basalis (NB); generally more RAD accumulated in the proteins than lipids of gray and white (gray > white) brain matter. Amy and Hip are particularly vulnerable brain structure targets to significant RAD internal radiation damage in AD (5.98 and 1.82 mSv x year(-1), respectively). Next, naturally occurring RAD radiation for Tem and Fro, then Occ and Par, and SN was an order of magnitude higher than that in LC and NB; the later was within RAD we observed previously in the healthy control brains. Naturally occurring environmental RAD exposure may dramatically enhance AD deterioration by selectively targeting brain areas of emotions (Amy) and memory (Hip).

Natural distribution of environmental radon daughters in the different brain areas of an Alzheimer Disease victim

PubMed Central

Momčilović, Berislav; Lykken, Glenn I; Cooley, Marvin

2006-01-01

Background Radon is a ubiquitous noble gas in the environment and a primary source of harmful radiation exposure for humans; it decays in a cascade of daughters (RAD) by releasing the cell damaging high energy alpha particles. Results We studied natural distribution of RAD 210Po and 210Bi in the different parts of the postmortem brain of 86-year-old woman who had suffered from Alzheimer's disease (AD). A distinct brain map emerged, since RAD distribution was different among the analyzed brain areas. The highest RAD irradiation (mSv·year-1) occurred in the decreasing order of magnitude: amygdale (Amy) >> hippocampus (Hip) > temporal lobe (Tem) ~ frontal lobe (Fro) > occipital lobe (Occ) ~ parietal lobe (Par) > substantia nigra (SN) >> locus ceruleus (LC) ~ nucleus basalis (NB); generally more RAD accumulated in the proteins than lipids of gray and white (gray > white) brain matter. Amy and Hip are particularly vulnerable brain structure targets to significant RAD internal radiation damage in AD (5.98 and 1.82 mSv·year-1, respectively). Next, naturally occurring RAD radiation for Tem and Fro, then Occ and Par, and SN was an order of magnitude higher than that in LC and NB; the later was within RAD we observed previously in the healthy control brains. Conclusion Naturally occurring environmental RAD exposure may dramatically enhance AD deterioration by selectively targeting brain areas of emotions (Amy) and memory (Hip). PMID:16965619

Lesion studies of human emotion and feeling.

PubMed

Feinstein, Justin S

2013-06-01

The lesion method provides unique insight into how the human brain generates emotion and feeling. Recent work has explored a number of interesting topics including the dissociation of emotional experience from memory in patients with amnesia, the reliability of specific emotional deficits following focal brain damage (including fear and the amygdala), and the investigation of compensatory neural mechanisms in lesion patients. Several detailed case studies have challenged the necessary role of the insular cortex in both awareness and feeling by showing that even in rare instances of complete bilateral insula destruction, the patient remains fully sentient and capable of expressing and feeling emotion. These findings highlight the distributed nature of emotion processing in the human brain and emphasize the importance of utilizing the lesion method for elucidating brain-behavior relationships. Copyright © 2012 Elsevier Ltd. All rights reserved.

Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-01-01

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

PubMed

Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

PubMed

Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2015-01-01

The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p < 0.001 for both right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

Phase Measurement of Cognitive Impairment Specific to Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania; Shera, David M.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29more » nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.« less

Fatal encephalopathy after an isolated overdose of cocaine

PubMed Central

Kondziella, D; Danielsen, E R; Arlien-Soeborg, P

2009-01-01

Cocaine induced brain damage can be divided into primary neurotoxic effects causing toxic encephalopathy, secondary effects of compromised cerebral blood flow in ischaemic and haemorrhagic stroke, cerebral vasculitis and vasospasm, and tertiary effects due to hypoxia as a result of cardiopulmonary collapse. Toxic leucoencephalopathy mainly affects white matter (WM) tracts serving higher cerebral function, thereby leading to altered personality, attention deficits and memory impairment in mild cases and to dementia, coma and brain death in severe cases. Here we describe the case of a 21-year-old man who committed suicide by injecting cocaine. The cocaine induced a toxic leucoencephalopathy, which was proven at autopsy. PMID:21731586

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PubMed

Huang, Ran-Ran; Jia, Bao-Hui; Xie, Lei; Ma, Shu-Hua; Yin, Jing-Jing; Sun, Zong-Bo; Le, Hong-Bo; Xu, Wen-Can; Huang, Jin-Zhuang; Luo, Dong-Xue

2016-01-01

To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction. © 2015 Wiley Periodicals, Inc.

Frontal lobe damage impairs process and content in semantic memory: evidence from category-specific effects in progressive non-fluent aphasia.

PubMed

Reilly, Jamie; Rodriguez, Amy D; Peelle, Jonathan E; Grossman, Murray

2011-06-01

Portions of left inferior frontal cortex have been linked to semantic memory both in terms of the content of conceptual representation (e.g., motor aspects in an embodied semantics framework) and the cognitive processes used to access these representations (e.g., response selection). Progressive non-fluent aphasia (PNFA) is a neurodegenerative condition characterized by progressive atrophy of left inferior frontal cortex. PNFA can, therefore, provide a lesion model for examining the impact of frontal lobe damage on semantic processing and content. In the current study we examined picture naming in a cohort of PNFA patients across a variety of semantic categories. An embodied approach to semantic memory holds that sensorimotor features such as self-initiated action may assume differential importance for the representation of manufactured artifacts (e.g., naming hand tools). Embodiment theories might therefore predict that patients with frontal damage would be differentially impaired on manufactured artifacts relative to natural kinds, and this prediction was borne out. We also examined patterns of naming errors across a wide range of semantic categories and found that naming error distributions were heterogeneous. Although PNFA patients performed worse overall on naming manufactured artifacts, there was no reliable relationship between anomia and manipulability across semantic categories. These results add to a growing body of research arguing against a purely sensorimotor account of semantic memory, suggesting instead a more nuanced balance of process and content in how the brain represents conceptual knowledge. Copyright © 2010 Elsevier Srl. All rights reserved.

Mesenchymal stem cells suppress neuronal apoptosis and decrease IL-10 release via the TLR2/NFκB pathway in rats with hypoxic-ischemic brain damage.

PubMed

Gu, Yan; Zhang, Yun; Bi, Yang; Liu, Jingjing; Tan, Bin; Gong, Min; Li, Tingyu; Chen, Jie

2015-10-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of infant mortality and neurological disability in children. Many studies have demonstrated that mesenchymal stem cell (MSC) transplantation facilitates the restoration of the biological function of injured tissue following HIBD via immunomodulation. This study aimed to elucidate the mechanisms by which MSCs mediate immunomodulation via the key effectors Toll-like receptor 2 (TLR2) and interleukin-10 (IL-10). We showed that TLR2 expression in the brain of HIBD rats was upregulated following HIBD and that MSC transplantation suppressed the expression of TLR2 and the release of IL-10, thereby alleviating the learning-memory deficits of HIBD rats. Following treatment with the specific TLR2 agonist Pam3CSK4 to activate TLR2, learning-memory function became further impaired, and the levels of nuclear factor kappa B (NFκB) and Bax expression and IL-10 release were significantly increased compared with those in HIBD rats that did not receive Pam3CSK4. In vitro, we found that MSC co-culture downregulated TLR2/NFκB signaling and repressed Bax expression and IL-10 secretion in oxygen and glucose deprivation (OGD)-injured adrenal pheochromocytoma (PC12) cells. Furthermore, NFκB and Bax expression and IL-10 release were enhanced following Pam3CSK4 treatment and were decreased following siTLR2 treatment in OGD-injured PC12 cells in the presence or absence of MSCs. Our data indicate that TLR2 is involved in HIBD and that MSCs decrease apoptosis and improve learning-memory function in HIBD rats by suppressing the TLR2/NFκB signaling pathway via a feedback mechanism that reduces IL-10 release. These findings strongly suggest that MSC transplantation improves HIBD via the inhibition of the TLR2/NFκB pathway.

The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

PubMed

Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

2016-04-01

Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury.

PubMed

Tao, Zhen-Yu; Gao, Peng; Yan, Yu-Hui; Li, Hong-Yan; Song, Jie; Yang, Jing-Xian

2017-01-01

Neuroendoscopy processes can cause severe traumatic brain injury. Existing therapeutic methods, such as neural stem cell transplantation and osthole have not been proven effective. Therefore, there is an emerging need on the development of new techniques for the treatment of brain injuries. In this study we propose to combine the above stem cell based methods and then evaluate the efficiency and accuracy of the new method. Mice were randomly divided into four groups: group 1 (brain injury alone); group 2 (osthole); group 3 (stem cell transplantation); and group 4 (osthole combined with stem cell transplantation). We carried out water maze task to exam spatial memory. Immunocytochemistry was used to test the inflammatory condition of each group, and the differentiation of stem cells. To evaluate the condition of the damaged blood brain barrier restore, we detect the Evans blue (EB) extravasation across the blood brain barrier. The result shows that osthole and stem cell transplantation combined therapeutic method has a potent effect on improving the spatial memory. This combined method was more effective on inhibiting inflammation and preventing neuronal degeneration than the single treated ones. In addition, there was a distinct decline of EB extravasation in the combined treatment groups, which was not observed in single treatment groups. Most importantly, the combined usage of osthole and stem cell transplantation provide a better treatment for the traumatic brain injury caused by neuroendoscopy. The collective evidence indicates osthole combined with neural stem cell transplantation is superior than either method alone for the treatment of traumatic brain injury caused by neuroendoscopy.

Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats.

PubMed

Tang, Jun; Zhang, Yuan; Yang, Liming; Chen, Qianwei; Tan, Liang; Zuo, Shilun; Feng, Hua; Chen, Zhi; Zhu, Gang

2015-03-19

With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900 MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia

PubMed Central

Kaewkaen, Pratchaya; Tong-un, Terdthai; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Kaewrueng, Wiroje; Wongcharoenwanakit, Sathaporn

2012-01-01

Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300–350 g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient. PMID:22952555

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

A combination cocktail improves spatial attention in a canine model of human aging and Alzheimer's disease.

PubMed

Head, Elizabeth; Murphey, Heather L; Dowling, Amy L S; McCarty, Katie L; Bethel, Samuel R; Nitz, Jonathan A; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R; Murphy, M Paul; Beckett, Tina L; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

2012-01-01

Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of amyloid-β (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t11 = 4.3, p = 0.001) and were more accurate across all distances (F(1,9) = 20.7, p = 0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and cerebrospinal fluid Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD.

Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats.

PubMed

Zhang, Juan; Tucker, Lorelei Donovan; DongYan; Lu, Yujiao; Yang, Luodan; Wu, Chongyun; Li, Yong; Zhang, Quanguang

2018-06-01

Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

NASA Astrophysics Data System (ADS)

Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

2016-05-01

The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

Parietal substrates for dimensional effects in visual search: evidence from lesion-symptom mapping

PubMed Central

Humphreys, Glyn W.; Chechlacz, Magdalena

2013-01-01

In visual search, the detection of pop-out targets is facilitated when the target-defining dimension remains the same compared with when it changes across trials. We tested the brain regions necessary for these dimensional carry-over effects using a voxel-based morphometry study with brain-lesioned patients. Participants had to search for targets defined by either their colour (red or blue) or orientation (right- or left-tilted), and the target dimension either stayed the same or changed on consecutive trials. Twenty-five patients were categorized according to whether they showed an effect of dimensional change on search or not. The two groups did not differ with regard to their performance on several working memory tasks, and the dimensional carry-over effects were not correlated with working memory performance. With spatial, sustained attention and working memory deficits as well as lesion volume controlled, damage within the right inferior parietal lobule (the angular and supramarginal gyri) extending into the intraparietal sulcus was associated with an absence of dimensional carry-over (P < 0.001, cluster-level corrected for multiple comparisons). The data suggest that these regions of parietal cortex are necessary to implement attention shifting in the context of visual dimensional change. PMID:23404335

White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults.

PubMed

Fernández-Cabello, Sara; Valls-Pedret, Cinta; Schurz, Matthias; Vidal-Piñeiro, Dídac; Sala-Llonch, Roser; Bargallo, Nuria; Ros, Emilio; Bartrés-Faz, David

2016-12-01

Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMHs) are a common age-associated finding that impacts cognition. In this study, we used functional magnetic resonance imaging to characterize the patterns of brain activation during a working memory task in older participants with high and low levels of education (as a proxy of CR) and high and low WMH volumes. Ninety older volunteers (aged 63-76 years) and 16 young adults (aged 21-27) completed the study. We found that older adults with higher education had better working memory performance than their less educated peers. Among the highly educated participants, those with WMH over-recruited areas engaged by young volunteers and showed activation in additional cortical and subcortical structures. However, those with low WMH differed little with respect to their younger counterparts. Our findings demonstrate that the functional mechanisms subtending the effects of education, as a proxy of CR, are modulated according to the WMH burden. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model

PubMed Central

Goldstein, Lee E.; Fisher, Andrew M.; Tagge, Chad A.; Zhang, Xiao-Lei; Velisek, Libor; Sullivan, John A.; Upreti, Chirag; Kracht, Jonathan M.; Ericsson, Maria; Wojnarowicz, Mark W.; Goletiani, Cezar J.; Maglakelidze, Giorgi M.; Casey, Noel; Moncaster, Juliet A.; Minaeva, Olga; Moir, Robert D.; Nowinski, Christopher J.; Stern, Robert A.; Cantu, Robert C.; Geiling, James; Blusztajn, Jan K.; Wolozin, Benjamin L.; Ikezu, Tsuneya; Stein, Thor D.; Budson, Andrew E.; Kowall, Neil W.; Chargin, David; Sharon, Andre; Saman, Sudad; Hall, Garth F.; Moss, William C.; Cleveland, Robin O.; Tanzi, Rudolph E.; Stanton, Patric K.; McKee, Ann C.

2013-01-01

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory. PMID:22593173

Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.

PubMed

Goldstein, Lee E; Fisher, Andrew M; Tagge, Chad A; Zhang, Xiao-Lei; Velisek, Libor; Sullivan, John A; Upreti, Chirag; Kracht, Jonathan M; Ericsson, Maria; Wojnarowicz, Mark W; Goletiani, Cezar J; Maglakelidze, Giorgi M; Casey, Noel; Moncaster, Juliet A; Minaeva, Olga; Moir, Robert D; Nowinski, Christopher J; Stern, Robert A; Cantu, Robert C; Geiling, James; Blusztajn, Jan K; Wolozin, Benjamin L; Ikezu, Tsuneya; Stein, Thor D; Budson, Andrew E; Kowall, Neil W; Chargin, David; Sharon, Andre; Saman, Sudad; Hall, Garth F; Moss, William C; Cleveland, Robin O; Tanzi, Rudolph E; Stanton, Patric K; McKee, Ann C

2012-05-16

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

Hemispatial neglect and serial order in verbal working memory.

PubMed

Antoine, Sophie; Ranzini, Mariagrazia; van Dijck, Jean-Philippe; Slama, Hichem; Bonato, Mario; Tousch, Ann; Dewulf, Myrtille; Bier, Jean-Christophe; Gevers, Wim

2018-01-09

Working memory refers to our ability to actively maintain and process a limited amount of information during a brief period of time. Often, not only the information itself but also its serial order is crucial for good task performance. It was recently proposed that serial order is grounded in spatial cognition. Here, we compared performance of a group of right hemisphere-damaged patients with hemispatial neglect to healthy controls in verbal working memory tasks. Participants memorized sequences of consonants at span level and had to judge whether a target consonant belonged to the memorized sequence (item task) or whether a pair of consonants were presented in the same order as in the memorized sequence (order task). In line with this idea that serial order is grounded in spatial cognition, we found that neglect patients made significantly more errors in the order task than in the item task compared to healthy controls. Furthermore, this deficit seemed functionally related to neglect severity and was more frequently observed following right posterior brain damage. Interestingly, this specific impairment for serial order in verbal working memory was not lateralized. We advance the hypotheses of a potential contribution to the deficit of serial order in neglect patients of either or both (1) reduced spatial working memory capacity that enables to keep track of the spatial codes that provide memorized items with a positional context, (2) a spatial compression of these codes in the intact representational space. © 2018 The British Psychological Society.

The Source for Learning & Memory Strategies.

ERIC Educational Resources Information Center

Richards, Regina G.

This book is a comprehensive guide to learning and memory strategies for all students and especially those with learning problems. Chapter 1, on memory and the brain, explains brain cells, the cortex, function of the cerebral lobes, and other brain structures. Chapter 2 examines the memory process and discusses sensory memory, short-term memory,…

ANOSOGNOSIA FOR MEMORY IMPAIRMENT IN ADDICTION: INSIGHTS FROM NEUROIMAGING AND NEUROPSYCHOLOGICAL ASSESSMENT OF METAMEMORY

PubMed Central

Le Berre, Anne-Pascale; Sullivan, Edith V.

2016-01-01

In addiction, notably, Alcohol Use Disorder (AUD), patients often have a tendency to fail to acknowledge the reality of the disease and to minimize the physical, psychological, and social difficulties attendant to chronic alcohol consumption. This lack of awareness can reduce the chances of initiating and maintaining sobriety. Presented here is a model focusing on compromised awareness in individuals with AUD of mild to moderate cognitive deficits, in particular, for episodic memory impairment—the ability to learn new information, such as recent personal experiences. Early in abstinence, alcoholics can be unaware of their memory deficits and overestimate their mnemonic capacities, which can be investigated with metamemory paradigms. Relevant neuropsychological and neuroimaging results considered suggest that the alcoholics’ impairment of awareness of their attenuated memory function can be a clinical manifestation explained mechanistically by neurobiological factors, including compromise of brain systems that result in a mild form of mnemonic anosognosia. Specifically, unawareness of memory impairment in AUD may result from a lack of personal knowledge updating attributable to damage in brain regions or connections supporting conscious recollection in episodic memory. Likely candidates are posterior parietal and medial frontal regions known to be integral part of the Default Mode Network (DMN) and the insula leading to an impaired switching mechanism between the DMN and the Central-Executive Control (i.e., Lateral Prefronto-Parietal) Network. The cognitive concepts and neural substrates noted for addictive disorders may also be relevant for problems in self-identification of functional impairment resulting from injury following war-related blast, sport-related concussion, and insidiously occurring dementia. PMID:27447979

Brain regions associated with anosognosia for memory disturbance in Alzheimer's disease: a magnetic resonance imaging study.

PubMed

Fujimoto, Hiroshi; Matsuoka, Teruyuki; Kato, Yuka; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

2017-01-01

Patients with Alzheimer's disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term "anosognosia" is used to indicate a general lack of awareness of one's disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD. The subjects were 49 patients with mild AD who participated in a retrospective cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance was assessed based on the discrepancy between questionnaire scores of patients and their caregivers. Structural MRI data were analyzed to explore the association between anosognosia and brain atrophy, using a voxel-based approach. Statistical parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates. The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus. The left superior frontal gyrus was involved in anosognosia for memory disturbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for anosognosia in mild AD.

AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation.

PubMed

Li, Xiao-Hong; Lv, Bing-Ling; Xie, Jia-Zhao; Liu, Jing; Zhou, Xin-Wen; Wang, Jian-Zhi

2012-07-01

Accumulation of β-amyloid and hyperphosphorylated tau with synapse damage and memory deterioration are hallmark lesions of Alzheimer disease (AD), but the upstream causative factors are elusive. The advanced glycation endproducts (AGEs) are elevated in AD brains and the AGEs can stimulate β-amyloid production. Whether and how AGEs may cause AD-like tau hyperphosphorylation and memory-related deficits is not known. Here we report that AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation (LTP) in rats. In SK-NS-H cells, upregulation of AGEs receptor (RAGE), inhibition of Akt, and activation of glycogen synthase kinase-3 (GSK-3), Erk1/2, and p38 were observed after treatment with AGEs. In rats, blockage of RAGE attenuated the AGE-induced GSK-3 activation, tau hyperphosphorylation, and memory deficit with restoration of synaptic functions, and simultaneous inhibition of GSK-3 also antagonized the AGE-induced impairments. Our data reveal that AGEs can induce tau hyperphosphorylation and impair synapse and memory through RAGE-mediated GSK-3 activation and targeting RAGE/GSK-3 pathway can efficiently improve the AD-like histopathological changes and memory deterioration. Copyright © 2012 Elsevier Inc. All rights reserved.

A stroke patient with impairment of auditory sensory (echoic) memory.

PubMed

Kojima, T; Karino, S; Yumoto, M; Funayama, M

2014-04-01

A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.

Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

PubMed

Mitchell, Gary F; van Buchem, Mark A; Sigurdsson, Sigurdur; Gotal, John D; Jonsdottir, Maria K; Kjartansson, Ólafur; Garcia, Melissa; Aspelund, Thor; Harris, Tamara B; Gudnason, Vilmundur; Launer, Lenore J

2011-11-01

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (-0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.

Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia.

PubMed

Gupta, Surbhi; Singh, Prabhat; Sharma, Brij Mohan; Sharma, Bhupesh

2015-01-01

Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.

Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

PubMed

Başar, Erol

2005-01-01

According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

[Ischemic brain injury and hepatocyte growth factor].

PubMed

Takeo, Satoshi; Takagi, Norio; Takagi, Keiko

2007-11-01

Cerebral ischemia causes an irreversible and neurodegenerative disorder that may lead to progressive dementia and global cognitive deterioration. Since the overall process of ischemic brain injuries is extremely complex, treatment with endogenous multifunctional factors would be better choices for preventing complicated ischemic brain injuries. Hepatocyte growth factor, HGF, is a multifunctional cytokine originally identified and purified as a potent mitogen for hepatocyte. The activation of the c-Met/HGF receptor evokes diverse cellular responses, including mitogenic, morphogenic, angiogenic and anti-apoptotic activities in various types of cell. Previous studies showed that HGF and c-Met were expressed in various brain regions under normal conditions and that HGF enhanced the survival of hippocampal and cortical neurons during the aging of cells in culture. The protective effects of HGF on in vivo ischemic brain injuries and their mechanisms have not fully understood. To elucidate therapeutic potencies of HGF for ischemic brain injuries, we examined effects of HGF on ischemia-induced learning and memory dysfunction, neuronal cell death and endothelial cell damage by using the 4-vessel occlusion model and the microsphere embolism model in rats. Our findings suggested that treatment with HGF was capable of protecting hippocampal neurons against ischemia-induced cell death through the prevention of apoptosis-inducing factor translocation to the nucleus. Furthermore, we demonstrated that HGF had the ability to prevent tissue degeneration and improved learning and memory function after cerebral embolism, possibly through prevention of cerebral vessel injuries. As HGF has a potent cerebroprotective effect, it could be a prospective agent for the therapy against complicated ischemic brain diseases.

Experience-near but not experience-far autobiographical facts depend on the medial temporal lobe for retrieval: Evidence from amnesia

PubMed Central

Grilli, Matthew D.; Verfaellie, Mieke

2015-01-01

This paper addresses the idea that there may be two types of autobiographical facts with distinct cognitive and neural mechanisms: “Experience-near” autobiographical facts, which contain spatiotemporal content derived from personal experience and thus depend on the medial temporal lobe (MTL) for retrieval, and “experience-far” autobiographical facts, which are abstract memories and thus rely on neocortical brain regions involved in retrieval of general semantic memory. To investigate this conceptual model of autobiographical fact knowledge, we analyzed the nature of autobiographical facts that were generated by 8 individuals with MTL amnesia and 12 control participants in a recent study of identity and memory [Grilli, M.D., & Verfaellie, M. (2015). Supporting the self-concept with memory: insight from amnesia. Social Cognitive and Affective Neuroscience, 10, 1684–1692]. Results revealed that MTL amnesic participants generated fewer experience-near autobiographical facts than controls. Experience-far autobiographical fact generation was not impaired in amnesic participants with damage restricted to the MTL, but there was preliminary evidence to suggest that it may be impaired in amnesic participants with damage to the MTL and anterior lateral temporal lobe. These results support a cognitive and neural distinction between experience-near and experience-far autobiographical facts and have implications for understanding the contribution of autobiographical fact knowledge to self-related cognition. PMID:26721761

Experience-near but not experience-far autobiographical facts depend on the medial temporal lobe for retrieval: Evidence from amnesia.

PubMed

Grilli, Matthew D; Verfaellie, Mieke

2016-01-29

This paper addresses the idea that there may be two types of autobiographical facts with distinct cognitive and neural mechanisms: "Experience-near" autobiographical facts, which contain spatiotemporal content derived from personal experience and thus depend on the medial temporal lobe (MTL) for retrieval, and "experience-far" autobiographical facts, which are abstract memories and thus rely on neocortical brain regions involved in retrieval of general semantic memory. To investigate this conceptual model of autobiographical fact knowledge, we analyzed the nature of autobiographical facts that were generated by 8 individuals with MTL amnesia and 12 control participants in a recent study of identity and memory [Grilli, M.D., & Verfaellie, M. (2015). Supporting the self-concept with memory: insight from amnesia. Social Cognitive and Affective Neuroscience, 10, 1684-1692]. Results revealed that MTL amnesic participants generated fewer experience-near autobiographical facts than controls. Experience-far autobiographical fact generation was not impaired in amnesic participants with damage restricted to the MTL, but there was preliminary evidence to suggest that it may be impaired in amnesic participants with damage to the MTL and anterior lateral temporal lobe. These results support a cognitive and neural distinction between experience-near and experience-far autobiographical facts and have implications for understanding the contribution of autobiographical fact knowledge to self-related cognition. Published by Elsevier Ltd.

Therapeutic Hypothermia and Hypoxia-Ischemia in the Term-equivalent Neonatal Rat: Characterization of a Translational Pre-clinical Model

PubMed Central

Patel, Shyama D.; Pierce, Leslie; Ciardiello, Amber; Hutton, Alexandra; Paskewitz, Samuel; Aronowitz, Eric; Voss, Henning U.; Moore, Holly; Vannucci, Susan J.

2015-01-01

Background Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32–36 week gestation infant, less relevant for these studies. We propose that HIE and TH in the term-equivalent P10 rat will be more translational. Methods P10–11 rat pups were subjected to unilateral hypoxia-ischemia (HI) and 4 hours recovery in normothermic (N) or hypothermic (TH) conditions. Brain damage was assessed longitudinally at 24 hours, 2 and 12 weeks. Motor function was assessed with the beam walk; recognition memory was measured by novel object recognition. Results Neuroprotection with TH was apparent at 2 and 12 weeks in both moderately and severely damaged animals. TH improved motor function in moderate, but not severe damage. Impaired object recognition occurred with severe damage with no evidence of protection of TH. Conclusion This adaptation of the immature rat model of HI provides a reproducible platform to further study HIE/TH in which individual animals are followed longitudinally to provide a useful translational preclinical model. PMID:25996893

Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice

PubMed Central

Kang, Jin Yong; Lee, Du Sang; Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Ha, Gi Jeong; Seo, Weon Taek

2017-01-01

The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H2O2-induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H2O2-induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis. PMID:29081819

Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice.

PubMed

Kang, Jin Yong; Lee, Du Sang; Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Ha, Gi Jeong; Seo, Weon Taek; Heo, Ho Jin

2017-01-01

The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H 2 O 2 -induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H 2 O 2 -induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis.

[Effects of quercetin on the learning and memory ability of neonatal rats with hypoxic-ischemic brain damage].

PubMed

Huang, Jing-Jing; Liu, Xuan; Wang, Xing-Qi; Yang, Li-Hua; Qi, Da-Shi; Yao, Rui-Qin

2012-06-01

To study the effects of quercetin, a flavonoid, on the learning and memory ability of 3-day-old neonatal rats with hypoxic-ischemic brain white matter damage (WMD). Sixty 3-day-old Sprague-Dawley rats were randomly divided into four groups: control, WMD model,and quercetin treatment groups (20 and 40 mg/kg). There were 15 rats in each group. Rats in the WMD model and the two quercetin treatment groups were subjected to right common carotid artery ligation followed by 2 hrs of exposure to 8% O2 to induce periventricular white matter injury. After the operation quercetin was administered daily in the two quercetin treatment groups for 6 weeks. Six weeks later, Morris water maze and open-field tests were carried out to test memory and learning ability as well as behavior and cognition. From the second day of training, escape latency in the Morris water maze test was more prolonged in the WMD model group than in the control group (P<0.01). The escape latency in the two quercetin treatment groups was shortened significantly compared with the WMD model group (P<0.05). The WMD model group crossed the original platform fewer times compared with the control and quercetin treatment groups (P<0.05). The open-field test indicated that the number of rearings increased and time spent in the centre was extended in the WMD model group compared with the control group. Compared with the WMD model group, the number of rearings was significantly reduced (P<0.05) and time spent in the centre was significantly shortened in the quercetin treatment groups (P<0.05). Quercetin treatment can improve memory and learning ability as well as cognitive ability in neonates with WMD, suggesting that quercetin protects against WMD resulting from hypoxia-ischemia.

Time-course of neurodegeneration and memory impairment following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

PubMed

Pereira, Francine Martins; Ferreira, Emilene Dias Fiuza; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

2012-04-15

The present work extends previous studies with the aim of developing the 4-vessel occlusion/internal carotid artery (4-VO/ICA) model of chronic cerebral hypoperfusion. The permanent occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) followed the sequence VA→ICA→ICA. The interstage interval (ISI, →), chronicity of 4-VO/ICA, and age of the animals may determine the success of the model with regard to neurohistological and behavioral outcomes. Using middle-aged rats, the present study evaluated (i) how brain damage evolves as the ISI is reduced and duration (i.e., "chronicity") of 4-VO/ICA is prolonged and (ii) how the duration of 4-VO/ICA affects retrograde memory performance. Male Wistar rats (12-15 months of age) were subjected to 4-VO/ICA with an ISI of 7, 5, 4, or 3 days, and hippocampal and cortical damage was examined 7, 30, and 90 days later. Using an ISI of 4 days, retrograde memory performance was assessed in the aversive radial maze after 4-VO/ICA with a duration of 7, 30, and 90 days. The severity of brain neurodegeneration and rate of mortality progressively increased as the ISI length decreased from 7 to 3 days, an effect that was not significantly altered by the chronicity of 4-VO/ICA. Permanent 4-VO/ICA effectively caused retrograde amnesia, an effect that worsened as the chronicity of 4-VO/ICA was prolonged. The findings confirm and expand the notion that permanent, 3-stage 4-VO/ICA effectively produces extensive neurodegeneration and persistent learning/memory impairment in middle-aged rats and that the ISI length, more than the chronicity of 4-VO/ICA, determines the final results. Copyright © 2012 Elsevier B.V. All rights reserved.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

Neuroprotective Effects of Sevoflurane against Electromagnetic Pulse-Induced Brain Injury through Inhibition of Neuronal Oxidative Stress and Apoptosis

PubMed Central

Wang, Jin; Han, Li-Chun; Li, Li-Ya; Wu, Guang-Li; Hou, Yan-Ning; Guo, Guo-Zhen; Wang, Qiang; Sang, Han-Fei; Xu, Li-Xian

2014-01-01

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis. PMID:24614080

Neuroprotective effects of sevoflurane against electromagnetic pulse-induced brain injury through inhibition of neuronal oxidative stress and apoptosis.

PubMed

Deng, Bin; Xu, Hao; Zhang, Jin; Wang, Jin; Han, Li-Chun; Li, Li-Ya; Wu, Guang-Li; Hou, Yan-Ning; Guo, Guo-Zhen; Wang, Qiang; Sang, Han-Fei; Xu, Li-Xian

2014-01-01

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis.

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.

PubMed

Sheen, Jiunn-Ming; Huang, Li-Tung; Hsieh, Chih-Sung; Chen, Chih-Cheng; Wang, Jia-Yi; Tain, You-Lin

2010-08-01

Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations. Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4). The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels. Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats. Copyright 2010 Elsevier Inc. All rights reserved.

Anthocyanins from Black Chokeberry (Aroniamelanocarpa Elliot) Delayed Aging-Related Degenerative Changes of Brain.

PubMed

Wei, Jie; Zhang, Guokun; Zhang, Xiao; Xu, Dexin; Gao, Jun; Fan, Jungang; Zhou, Zhiquan

2017-07-26

Aging is the greatest risk factor for most neurodegenerative diseases, which is associated with decreasing cognitive function and significantly affecting life quality in the elderly. Computational analysis suggested that 4 anthocyanins from chokeberry fruit increased Klotho (aging-suppressor) structural stability, so we hypothesized that chokeberry anthocyanins could antiaging. To explore the effects of anthocyanins treatment on brain aging, mice treated with 15 or 30 mg/kg anthocyanins by gavage and injected D-galactose accelerated aging per day. After 8 weeks, cognitive and noncognitive components of behavior were determined. Our studies showed that anthocyanins blocked age-associated cognitive decline and response capacity in senescence accelerated mice. Furthermore, mice treated with anthocyanins-supplemented showed better balance of redox systems (SOD, GSH-PX, and MDA) in all age tests. Three major monoamines were norepinephrine, dopamine, and 5-hydroxytryptamine, and their levels were significantly increased; the levels of inflammatory cytokines (COX2, TGF-β1, and IL-1) transcription and DNA damage were decreased significantly in brains of anthocyanins treated mice compared to aged models. The DNA damage signaling pathway was also regulated with anthocyanins. Our results suggested that anthocyanins was a potential approach for maintaining thinking and memory in aging mice, possibly by regulating the balance of redox system and reducing inflammation accumulation, and the most important factor was inhibiting DNA damage.

Alcohol-related amnesia and dementia: Animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

PubMed Central

Vetreno, Ryan P.; Hall, Joseph M.; Savage, Lisa M.

2011-01-01

Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models—from repeated and chronic ethanol exposure to thiamine deficiency—is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone. PMID:21256970

Middle-aged, but not young, rats develop cognitive impairment and cortical neurodegeneration following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion.

PubMed

Ferreira, Emilene D Fiuza; Romanini, Cássia V; Mori, Marco A; de Oliveira, Rúbia M Weffort; Milani, Humberto

2011-10-01

Permanent, stepwise occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) following the sequence VA→ICA→ICA, with an interstage interval (ISI, →) of 7 days, has been investigated as a four-vessel occlusion (4-VO)/ICA model of chronic cerebral hypoperfusion. This model has the advantage of not causing retinal damage. In young rats, however, 4-VO/ICA with an ISI of 7 days fails to cause behavioral sequelae. We hypothesized that such a long ISI would allow the brain to efficiently compensate for cerebral hypoperfusion, preventing the occurrence of cognitive impairment and neurodegeneration. The present study evaluated whether brain neurodegeneration and learning/memory deficits can be expressed by reducing the length of the ISI and whether aging influences the outcome. Young, male Wistar rats were subjected to 4-VO/ICA with different ISIs (5, 4, 3 or 2 days). An ISI of 4 days was used in middle-aged rats. Ninety days after 4-VO/ICA, the rats were tested for learning/memory impairment in a modified radial maze and then examined for neurodegeneration of the hippocampus and cerebral cortex. Regardless of the ISI, young rats were not cognitively impaired, although hippocampal damage was evident. Learning/memory deficits and hippocampal and cortical neurodegeneration occurred in middle-aged rats. The data indicate that 4-VO/ICA has no impact on the capacity of young rats to learn the radial maze task, despite 51% hippocampal cell death. Such resistance is lost in middle-aged animals, for which the most extensive neurodegeneration observed in both the hippocampus and cerebral cortex may be responsible. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment.

PubMed

Tapia-Rojas, Cheril; Carvajal, Francisco J; Mira, Rodrigo G; Arce, Camila; Lerma-Cabrera, José Manuel; Orellana, Juan A; Cerpa, Waldo; Quintanilla, Rodrigo A

2018-05-01

In the young population, binge drinking is a pattern of problematic alcohol consumption, characterized by a short period of heavy drinking followed by abstinence which is frequently repeated over time. This drinking pattern is associated with mental problems, use of other drugs, and an increased risk of excessive alcohol intake during adulthood. However, little is known about the effects of binge drinking on brain function in adolescents and its neurobiological impact during the adulthood. In the present study, we evaluated the effects of alcohol on hippocampal memory, synaptic plasticity, and mitochondrial function in adolescent rats after a binge drinking episode in vivo. These effects were analyzed at 1, 3, or 7 weeks post alcohol exposure. Our results showed that binge-like ethanol pre-treated (BEP) rats exhibited early alterations in learning and memory tests accompanied by an impairment of synaptic plasticity that was total and partially compensated, respectively. These changes could be attributed to a rapid increase in oxidative damage and a late inflammatory response induced by post ethanol exposure. Additionally, BEP alters the regulation of mitochondrial dynamics and modifies the expression of mitochondrial permeability transition pore (mPTP) components, such as cyclophilin D (Cyp-D) and the voltage-dependent anion channel (VDAC). These mitochondrial structural changes result in the impairment of mitochondrial bioenergetics, decreasing ATP production progressively until adulthood. These results strongly suggest that teenage alcohol binge drinking impairs the function of the adult hippocampus including memory and synaptic plasticity as a consequence of the mitochondrial damage induced by alcohol and that the recovery of hippocampal function could implicate the activation of alternative pathways that fail to reestablish mitochondrial function.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

PubMed

Tseng, Hsiang-Chien; Wang, Mao-Hsien; Soung, Hung-Sheng; Chang, Yi; Chang, Kuo-Chi

2015-12-01

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

PubMed Central

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

Molecular bases of methamphetamine-induced neurodegeneration.

PubMed

Cadet, Jean Lud; Krasnova, Irina N

2009-01-01

Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. The addiction to METH is a major public concern because its chronic abuse is associated with serious health complications including deficits in attention, memory, and executive functions in humans. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. Thus, the purpose of the present paper is to review cellular and molecular mechanisms that might be responsible for METH neurotoxicity. These include oxidative stress, activation of transcription factors, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation, and various apoptotic pathways. Several approaches that allow protection against METH-induced neurotoxic effects are also discussed. Better understanding of the cellular and molecular mechanisms involved in METH toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of psychostimulant use disorders in humans.

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

PubMed

Lin, Cai-Hou; Liu, Gui-Fen; Chen, Jing; Chen, Yan; Lin, Ru-Hui; He, Hong-Xing; Chen, Jian-Ping

2017-11-20

Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

PubMed

Bavarsad, Kowsar; Hadjzadeh, Mousa-Al-Reza; Hosseini, Mahmoud; Pakdel, Roghayeh; Beheshti, Farimah; Bafadam, Soleyman; Ashaari, Zeinab

2018-06-21

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

PubMed

Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

2011-08-01

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

True memory, false memory, and subjective recollection deficits after focal parietal lobe lesions.

PubMed

Drowos, David B; Berryhill, Marian; André, Jessica M; Olson, Ingrid R

2010-07-01

There is mounting evidence that the posterior parietal cortex (PPC) plays an important role in episodic memory. We previously found that patients with PPC damage exhibit retrieval-related episodic memory deficits. Here we assess whether parietal lobe damage affects episodic memory on a different task: the Deese-Roediger-McDermott (DRM) false-memory paradigm. Two patients with bilateral PPC damage and a group of matched controls were tested. In Experiment 1, the task was to remember words; in Experiment 2 the task was to remember pictures of common objects. Prior studies have shown that normal participants have high levels of false memory to words, low levels to pictures. The patients exhibited significantly lower levels of false memory to words. One patient showed significantly elevated levels of false memory to pictures. The patients' false memories were accompanied by reduced levels of recollection, as tested by a Remember/Know procedure. PPC damage causes decreased levels of false memories and an abnormal Remember/Know profile. Their false memory rate is similar to the rate exhibited by patients with medial temporal lobe damage. These results support the view that portions of the PPC play a critical role in objective and subjective aspects of recollection.

Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

PubMed

Keerativittayayut, Ruedeerat; Aoki, Ryuta; Sarabi, Mitra Taghizadeh; Jimura, Koji; Nakahara, Kiyoshi

2018-06-18

Although activation/deactivation of specific brain regions have been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here we investigated time-varying functional connectivity patterns across the human brain in periods of 30-40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding. © 2018, Keerativittayayut et al.

Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

PubMed

da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

2014-02-01

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

The impact of neurotechnology on rehabilitation.

PubMed

Berger, Theodore W; Gerhardt, Greg; Liker, Mark A; Soussou, Walid

2008-01-01

This paper present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease) and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of the multi-laboratory effort include: (1) experimental study of neuron and neural network function--how does the hippocampus encode information? (2) formulation of biologically realistic models of neural system dynamics--can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event? (3) microchip implementation of neural system models--can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization? and (4) creation of hybrid neuron-silicon interfaces-can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed and is replaced by a microchip model of CA3 nonlinear dynamics--the "hybrid" hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.

Binge ethanol effects on prefrontal cortex neurons, spatial working memory and task-induced neuronal activation in male and female rats.

PubMed

West, Rebecca K; Maynard, Mark E; Leasure, J Leigh

2018-05-01

Excessive alcohol intake is associated with a multitude of health risks, especially for women. Recent studies in animal models indicate that the female brain is more negatively affected by alcohol, compared to the male brain. Among other regions, excessive alcohol consumption damages the frontal cortex, an area important for many functions and decision making of daily life. The objective of the present study was to determine whether the medial prefrontal cortex (mPFC) in female rats is selectively vulnerable to alcohol-induced damage. In humans, loss of prefrontal grey matter resulting from heavy alcohol consumption has been documented, however this volume loss is not necessarily due to a decrease in the number of neurons. We therefore quantified both number and nuclear volume of mPFC neurons following binge alcohol, as well as performance and neuronal activation during a prefrontal-dependent behavioral task. Adult male and female Long-Evans rats were assigned to binge or control groups and exposed to ethanol using a well-established 4-day model of alcohol-induced neurodegeneration. Both males and females had significantly smaller average neuronal nuclei volumes than their respective control groups immediately following alcohol binge, but neither sex showed a decrease in neuron number. Binged rats of both sexes initially showed spatial working memory deficits. Although they eventually achieved control performance, binged rats of both sexes showed increased c-Fos labeling in the mPFC during rewarded alternation, suggesting decreased neural efficiency. Overall, our results substantiate prior evidence indicating that the frontal cortex is vulnerable to alcohol, but also indicate that sex-specific vulnerability to alcohol may be brain region-dependent. Copyright © 2018 Elsevier Inc. All rights reserved.

Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism

PubMed Central

2018-01-01

Our previous research revealed that Cordyceps militaris can improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by which Cordyceps militaris improves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects of Cordyceps polypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes Pik3r5, Il-1β, and Slc18a2 were involved in the effects of Cordyceps polypeptide on the nervous system of these mice. Our findings suggest that Cordyceps polypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system. PMID:29736181

Alcohol-related dementia: an update of the evidence

PubMed Central

2013-01-01

The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome, or WKS) are reviewed. Neuropathological and imaging studies suggest that excessive and prolonged use of alcohol may lead to structural and functional damage that is permanent in nature; however, there is debate about the relative contributions of the direct toxic effect of alcohol (neurotoxicity hypothesis), and the impact of thiamine deficiency, to lasting damage. Investigation of alcohol-related cognitive impairment has been further complicated by differing definitions of patterns of alcohol use and associated lifestyle factors related to the abuse of alcohol. Present diagnostic systems identify two main syndromes of alcohol-related cognitive impairment: ARD and WKS. However, 'alcohol-related brain damage' is increasingly used as an umbrella term to encompass the heterogeneity of these disorders. It is unclear what level of drinking may pose a risk for the development of brain damage or, in fact, whether lower levels of alcohol may protect against other forms of dementia. Epidemiological studies suggest that individuals with ARD typically have a younger age of onset than those with other forms of dementia, are more likely to be male, and often are socially isolated. The cognitive profile of ARD appears to involve both cortical and subcortical pathology, and deficits are most frequently observed on tasks of visuospatial function as well as memory and higher-order (executive) tasks. The WKS appears more heterogeneous in nature than originally documented, and deficits on executive tasks commonly are reported in conjunction with characteristic memory deficits. Individuals with alcohol-related disorders have the potential to at least partially recover - both structurally and functionally - if abstinence is maintained. In this review, considerations in a clinical setting and recommendations for diagnosis and management are discussed. PMID:23347747

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats.

PubMed

Gordon, Rita; Podolski, Igor; Makarova, Ekaterina; Deev, Alexander; Mugantseva, Ekaterina; Khutsyan, Sergey; Sengpiel, Frank; Murashev, Arkady; Vorobyov, Vasily

2017-01-01

Primary memory impairments associated with increased level of amyloid-β (Aβ) in the brain have been shown to be linked, partially, with early pathological changes in the entorhinal cortex (EC) which spread on the whole limbic system. While the hippocampus is known to play a key role in learning and memory mechanisms, it is as yet unclear how its structures are involved in the EC pathology. In this study, changes in memory and neuronal morphology in male Wistar rats intrahippocampally injected with Aβ25-35 were correlated on days 14 and 45 after the injection to reveal specific cognitive-structural associations. The main focus was on the dentate gyrus (DG) and hippocampal areas of CA1 and CA3 because of their involvement in afferent flows from EC to the hippocampus through tri-synaptic (EC → DG → CA3 → CA1) and/or mono-synaptic (EC → CA1) pathways. Evident memory impairments were observed at both time points after Aβ25-35 injection. However, on day 14, populations of morphological intact neurons were decreased in CA3 and, drastically, in CA1, and the DG supramedial bundle was significantly damaged. On day 45, this bundle largely and CA1 neurons partially recovered, whereas CA3 neurons remained damaged. We suggest that Aβ25-35 primarily affects the tri-synaptic pathway, destroying the granular cells in the DG supramedial area and neurons in CA3 and, through the Schaffer collaterals, in CA1. Intrahippocampal pretreatment with hydrated fullerene C60 allows the neurons and their connections to survive the amyloidosis, thus supporting the memory mechanisms.

Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Changlian; Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University; Gao, Jianfeng

2011-01-07

Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI),more » could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.« less

Bilateral Parietal Cortex Damage Does Not Impair Associative Memory for Paired Stimuli

PubMed Central

Berryhill, Marian E.; Drowos, David B.; Olson, Ingrid R.

2010-01-01

Recent neuroimaging and neuropsychological findings indicate that the posterior parietal cortex (PPC) plays an important, albeit undefined, role in episodic memory. Here we ask whether this region is specifically involved in associative aspects of episodic memory. Experiment 1 tested whether PPC damage affects the ability to learn and retrieve novel word-pair associations. Experiment 2 tested whether PPC damage affects the retrieval of object-location associations, in a spatial fan task. In both experiments, patients showed normal levels of associative memory. These findings demonstrated that PPC damage did not prevent association memory for verbal items. Finally Experiment 3 tested whether PPC damage affects memory for non-verbal audio-visual pairs. The patients performed with normal accuracy, but with significantly reduced confidence. These findings indicate that the PPC does not have a central role in association formation per se and instead, indicate that the PPC is involved in other aspects of episodic memory. PMID:20104378

Following the crowd: Brain Substrates of Long-Term Memory Conformity

PubMed Central

Edelson, Micah; Sharot, Tali; Dolan, Raymond J; Dudai, Yadin

2012-01-01

Human memory is strikingly susceptible to social influences, yet we know little about the underlying mechanisms. We examined how socially induced memory errors are generated in the brain by studying the memory of individuals exposed to recollections of others. Participants exhibited a strong tendency to conform to erroneous recollections of the group, producing both long-lasting and temporary errors, even when their initial memory was strong and accurate. Functional brain imaging revealed that social influence modified the neuronal representation of memory. Specifically, a particular brain signature of enhanced amygdala activity and enhanced amygdala-hippocampus connectivity predicted long-lasting, but not temporary memory alterations. Our findings reveal how social manipulation can alter memory and extend the known functions of the amygdala to encompass socially-mediated memory distortions. PMID:21719681

Evaluation of the Effect of Moringa peregrina Extract on Learning and Memory: Role of Oxidative Stress.

PubMed

Alzoubi, Karem H; Rawashdeh, Nasab Q; Khabour, Omar F; El-Elimat, Tamam; Albataineh, Hanan; Al-Zghool, Hamzeh M; Alali, Feras Q

2017-12-01

Oxidative stress interferes with the functional roles of the hippocampus and results in cognitive decline. Antioxidant supplementation has a cognitive enhancing activity through protecting hippocampus brain cells from the damaging effects of the reactive oxygen species. The dried methanolic extract of the aboveground parts of Moringa peregrina (Forssk.) Fiori (Moringaceae) was hypothesized to have memory-enhancing activity via its antioxidative properties. HPLC and LC-MS methods were used for qualitative analysis of the marker compounds. Six major compounds of the methanolic extract of M. peregrina were identified, namely, rutin, myricetin, α-amyrin, β-amyrin, lupeol acetate, and β-sitosterol. Male Wistar rats were administered via oral gavage three dose levels (50, 100, and 500 mg/kg) of M. peregrina methanolic extract for 2 months. The radial arm water maze (RAWM) was used to test spatial learning and memory. In addition, ELISA was used to analyze the levels of brain-derived neurotrophic factor (BDNF) and to assess the level of some oxidative stress markers. M. peregrina (150 mg/kg) resulted in short- and long-term memory enhancement (P < 0.05). Moreover, M. peregrina administration elevated BDNF levels in the hippocampus (P < 0.05) and caused favorable changes in oxidative stress biomarkers. In particular, an increase in glutathione (GSH), a decrease in oxidized glutathione (GSSG), and an increase in the antioxidant enzyme glutathione peroxidase (GPx) levels in the hippocampus were elicited after treatment with M. peregrina. Taken together, our data show that oral administration of M. peregrina enhances both short- and long-term memory functions via combating oxidative stress and increasing BDNF levels in the hippocampus. Consuming this safe plant may thus help promote spatial learning and improve memory.

Preliminary associations between brain derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI

PubMed Central

Failla, Michelle D.; Juengst, Shannon B.; Arenth, Patricia; Wagner, Amy K.

2015-01-01

Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, impacting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective Evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n=113) were evaluated for PTD (Patient Health Questionnaire-9), cognitive impairment (cognitive composite score) and functional cognition (Functional Independence Measure–Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid (CSF) and serum 0–6 days post-injury and in serum at 6 and 12 months post-injury. Results Serum BDNF was reduced after TBI versus controls at all time-points. Acute serum BDNF positively correlated with Memory composites (6 months: r=0.43, p=0.019, n=30; 12 months: r=0.53, p=0.005, n=26) and FIM-Memory scores (6 months: r=0.35, p=0.019, n=45; 12 months: r=0.38, p=0.018, n=38). Acute serum BDNF negatively correlated with 12 month PHQ-9 scores (r=−0.38, p=0.044, n=29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (p=0.07) and correlated with PHQ-9 scores (r=−0.41, p=0.019, n=32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI. PMID:26276123

Right medial thalamic lesion causes isolated retrograde amnesia.

PubMed

Miller, L A; Caine, D; Harding, A; Thompson, E J; Large, M; Watson, J D

2001-01-01

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

PubMed

Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

2010-07-01

Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

Is functional integration of resting state brain networks an unspecific biomarker for working memory performance?

PubMed

Alavash, Mohsen; Doebler, Philipp; Holling, Heinz; Thiel, Christiane M; Gießing, Carsten

2015-03-01

Is there one optimal topology of functional brain networks at rest from which our cognitive performance would profit? Previous studies suggest that functional integration of resting state brain networks is an important biomarker for cognitive performance. However, it is still unknown whether higher network integration is an unspecific predictor for good cognitive performance or, alternatively, whether specific network organization during rest predicts only specific cognitive abilities. Here, we investigated the relationship between network integration at rest and cognitive performance using two tasks that measured different aspects of working memory; one task assessed visual-spatial and the other numerical working memory. Network clustering, modularity and efficiency were computed to capture network integration on different levels of network organization, and to statistically compare their correlations with the performance in each working memory test. The results revealed that each working memory aspect profits from a different resting state topology, and the tests showed significantly different correlations with each of the measures of network integration. While higher global network integration and modularity predicted significantly better performance in visual-spatial working memory, both measures showed no significant correlation with numerical working memory performance. In contrast, numerical working memory was superior in subjects with highly clustered brain networks, predominantly in the intraparietal sulcus, a core brain region of the working memory network. Our findings suggest that a specific balance between local and global functional integration of resting state brain networks facilitates special aspects of cognitive performance. In the context of working memory, while visual-spatial performance is facilitated by globally integrated functional resting state brain networks, numerical working memory profits from increased capacities for local processing, especially in brain regions involved in working memory performance. Copyright © 2014 Elsevier Inc. All rights reserved.

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

PubMed

Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

Significance of the Feuerstein approach in neurocognitive rehabilitation.

PubMed

Lebeer, Jo

2016-06-18

The theory of Structural Cognitive Modifiability and Mediated Learning Experience of Reuven Feuerstein states that individuals with brain impairment, because of congenital or acquired origin, may substantially and structurally improve their cognitive functioning, by a systematic intervention based on a specific, criteria-based type of interaction ("mediated learning"). Three application systems are based on it: a dynamic-interactive assessment of learning capacity and processes of learning, the LPAD (Learning Propensity Assessment Device); a cognitive intervention program called "Instrumental Enrichment Program", which trains cognitive, metacognitive and executive functions; and a program, which is oriented at working in context, Shaping Modifying Environments. These programs have been applied in widely different target groups: from children and young adults with learning and developmental disabilities, at risk of school failure, or having failed at school, because of socio-economic disadvantage or congenital neurological impairment; disadvantaged youngsters and adults in vocational training, to elderly people at the beginning of a dementia process. Experience with cognitive rehabilitation of children and adults with acquired brain damage, has been relatively recent, first in the Feuerstein Institute's Brain Injury Unit in Jerusalem, later in other centers in different parts of the world; therefore scientific data are scarce. The purpose of this paper is to examine how the Feuerstein-approach fits into the goals and proposed approaches of cognitive rehabilitation, and to explore its relevance for assessment and intervention in individuals with congenital or acquired brain damage. The methodology of the Feuerstein approach consists of four pillars: dynamic assessment, cognitive activation, mediated learning and shaping a modifying environment. The criteria of mediated learning experience are explained with specific reference to people with acquired brain injury. The procedure of learning propensity assessment device uses visuo-spatial and verbal tasks known from neuropsychological assessment (such as Rey's complex figure drawing), as well as a in a pre-test - brief intervention - post-test format. Cognitive activation is done in various ways: a paper-and-pencil relatively content-free program called "instrumental enrichment", with transfer of learned principles into daily life situations, followed by metacognitive feedback. Four case histories of acquired brain damage are analyzed: a 19 year old man with extensive post-astrocytoma frontotemporal brain lesions; a 19 year old man with bilateral frontal and right temporal and parieto-occipital parenchymatous destruction after a traumatic brain injury; a 24 year old man with hemispherectomy for intractable epilepsy because of Sturge-Weber syndrome; and a 30-year old man with left porencephalic cyst after cerebral hemorrhage. Structural cognitive improvement could be demonstrated in positive change scores in visuo-spatial memory, associative and verbal memory, abstract thinking, and organizing tasks, even more than 10 years post-TBI. In some cases a rise in IQ has been documented. Improvement in daily life functioning and academic skills (re)learning has also been seen. Though impossible to claim scientific evidence, the case histories nevertheless suggest the importance of interactive assessment in designing intervention programs which have sufficient intensity, frequency, duration and consistency of mediation; furthermore, an essential ingredient is the ecological approach which requires working with the patient and the whole network around; a firm "belief system" or that modifiability is possible even with severe brain damage and many years after the injury; a cognitive, metacognitive and executive approach, and a quality of interaction according to criteria of mediated learning. They suggest that Feuerstein approach may offer interesting perspectives to cognitive rehabilitation. More extensive research is needed to provide a broader scientific evidence base.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Temporally graded semantic memory loss in amnesia and semantic dementia: Further evidence for opposite gradients.

PubMed

Estmacott, Robyn W; Moscovitch, Morris

2002-03-01

The consolidation theory of long-term memory (e.g., Squire, 1992) predicts that damage to the medial temporal lobes will result in temporally graded retrograde memory loss, with a disproportionate impairment of recent relative to remote knowledge; in contrast, severe atrophy of the temporal neocortex is predicted to result in the reverse temporally graded pattern, with a selective sparing of recent memory (K.S. Graham & Hodges, 1997). Previously, we reported evidence that autobiographical episodic memory does not follow this temporal pattern (Westmacott, Leach, Freedman, & Moscovitch, 2001). In the present study, we found evidence suggesting that semantic memory loss does follow the predicted temporal pattern. We used a set of tasks that tap implicit and explicit memory for famous names and English vocabulary terms from across the 20th century. KC, a person with medial temporal amnesia, consistently demonstrated across tasks a selective deficit for famous names and vocabulary terms from the 5-year period just prior to injury; this deficit was particularly profound for elaborated semantic knowledge (e.g., word definitions, occupation of famous person). However, when asked to guess on unfamiliar items, KC's performance for names and words from this 5-year time period increased substantially, suggesting that he retains some of this knowledge at an implicit or rudimentary level. Conversely, EL, a semantic dementia patient with temporal neocortical atrophy and relative sparing of the medial temporal lobe, demonstrated a selective sparing of names and words from the most recent time period. However, this selective sparing of recent semantic memory was demonstrated in the implicit tasks only; performance on explicit tasks suggested an equally severe impairment of semantics across all time periods. Unlike the data from our previous study of autobiographical episodic memory, these findings are consistent with the predictions both of consolidation theory (Hodges & Graham, 1998; Squire, 1992) and multiple trace theory (Nadel & Moscovitch, 1999) that the hippocampus plays a timelimited role in the acquisition and representation of long-term semantic memories. Moreover, our findings suggest that tasks requiring minimal verbal production and explicit recall may provide a more sensitive and comprehensive assessment of intact memory capacity in brain-damaged individuals.

Identification and Manipulation of Memory Engram Cells.

PubMed

Liu, Xu; Ramirez, Steve; Redondo, Roger L; Tonegawa, Susumu

2014-01-01

How memories are formed and stored in the brain remains a fascinating question in neuroscience. Here we discuss the memory engram theory, our recent attempt to identify and manipulate memory engram cells in the brain with optogenetics, and how these methods are used to address questions such as how false memory is formed and how the valence of a memory can be changed in the brain. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Trachyspermum ammi Seeds Supplementation Helps Reverse Scopolamine, Alprazolam and Electroshock Induced Amnesia.

PubMed

Soni, Kapil; Parle, Milind

2017-05-01

The present study was designed to explore the beneficial effects of successive 10 days administration of Trachyspermum ammi seed's powder (TASP) along with diet (at the dose of 0.5%, 1.0% and 2.0% w/w) on learning and memory of mice. A total of 306 mice divided in 51 equal groups were employed in the study. Passive avoidance paradigm (PAP) and Object recognition Task (ORT) were employed as exteroceptive models. The brain acetylcholinesterase activity (AChE), serum cholesterol, brain monoaldehyde (MDA), brain reduced glutathione (GSH) and brain nitrite were estimated and Alprazolam, Scopolamine and Electroshock induced amnesia was employed to describe the actions. Treatment of TASP significantly increased step down latency of PAA and significantly increased discrimination index of ORT in groups with or without amnesia when compared to respective control groups. Furthermore, TASP administration resulted in significant fall in brain AChE activity, brain MDA level and brain nitrite level with simultaneous rise in brain GSH level, thereby decreased oxidative damage. A significant decrease in serum cholesterol was also observed. Ajowan supplementation may prove a remedy for the management of cognitive disorders owing to have pro-cholinergic, antioxidant and hypo-lipidemic activities.

The iconic memory skills of brain injury survivors and non-brain injured controls after visual scanning training.

PubMed

McClure, J T; Browning, R T; Vantrease, C M; Bittle, S T

1994-01-01

Previous research suggests that traumatic brain injury (TBI) results in impairment of iconic memory abilities.We would like to acknowledge the contribution of Jeffrey D. Vantrease, who wrote the software program for the Iconic Memory procedure and measurement. This raises serious implications for brain injury rehabilitation. Most cognitive rehabilitation programs do not include iconic memory training. Instead it is common for cognitive rehabilitation programs to focus on attention and concentration skills, memory skills, and visual scanning skills.This study compared the iconic memory skills of brain-injury survivors and control subjects who all reached criterion levels of visual scanning skills. This involved previous training for the brain-injury survivors using popular visual scanning programs that allowed them to visually scan with response time and accuracy within normal limits. Control subjects required only minimal training to reach normal limits criteria. This comparison allows for the dissociation of visual scanning skills and iconic memory skills.The results are discussed in terms of their implications for cognitive rehabilitation and the relationship between visual scanning training and iconic memory skills.

The path to memory is guided by strategy: distinct networks are engaged in associative encoding under visual and verbal strategy and influence memory performance in healthy and impaired individuals

PubMed Central

Hales, J. B.; Brewer, J. B.

2018-01-01

Given the diversity of stimuli encountered in daily life, a variety of strategies must be used for learning new information. Relating and encoding visual and verbal stimuli into memory has been probed using various tasks and stimulus-types. Engagement of specific subsequent memory and cortical processing regions depends on the stimulus modality of studied material; however, it remains unclear whether different encoding strategies similarly influence regional activity when stimulus-type is held constant. In this study, subjects encoded object pairs using a visual or verbal associative strategy during functional magnetic resonance imaging (fMRI), and subsequent memory was assessed for pairs encoded under each strategy. Each strategy elicited distinct regional processing and subsequent memory effects: middle / superior frontal, lateral parietal, and lateral occipital for visually-associated pairs and inferior frontal, medial frontal, and medial occipital for verbally-associated pairs. This regional selectivity mimics the effects of stimulus modality, suggesting that cortical involvement in associative encoding is driven by strategy, and not simply by stimulus-type. The clinical relevance of these findings, probed in two patients with recent aphasic strokes, suggest that training with strategies utilizing unaffected cortical regions might improve memory ability in patients with brain damage. PMID:22390467

[Activation of autophagy pathway in hippocampus and deterioration of learning and memory ability by intermittent hypoxia in rats after cerebral ischemia].

PubMed

Guo, Xiangfei; Zhao, Yaning; Li, Jianmin; Liu, Wenqian; Chen, Changxiang

2016-09-01

Objective To investigate the effects of different duration of intermittent hypoxia on the autophagy pathway in the hippocampus and the learning and memory ability after cerebral ischemia in rats. Methods 100 male Wistar rats were randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R) group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7-I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion (IH14-I/R) group, intermittent hypoxia for 21 days combined with ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R group, IH14-I/R group and IH21-I/R group were respectively subjected to intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells in the hippocampus of rat brain were detected by HE staining; the levels of mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were determined by quantitative real-time PCR; the distribution of mTOR and beclin 1 in the hippocampus was observed by immunohistochemistry; the learning and memory ability of rats was assessed by the Morris water maze test. Results Compared with the SO group, the never cell morphology was damaged, the number of survival neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in the hippocampus were strengthened, and the learning and memory ability declined in the I/R group. Compared with the I/R group, the never cell morphology was damaged seriously, the number of survival neurons in the hippocampus decreased, the expressions of mTOR and beclin 1 in the hippocampus increased, and the learning and memory ability dropped in the intermittent hypoxia groups. What's more, the above changes were dependent on the duration of intermittent hypoxia. Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory after cerebral ischemia and the damages increase with time passing, which are related to mTOR-beclin 1 activation and increasing neuronal cell death.

Multiple systems of category learning.

PubMed

Smith, Edward E; Grossman, Murray

2008-01-01

We review neuropsychological and neuroimaging evidence for the existence of three qualitatively different categorization systems. These categorization systems are themselves based on three distinct memory systems: working memory (WM), explicit long-term memory (explicit LTM), and implicit long-term memory (implicit LTM). We first contrast categorization based on WM with that based on explicit LTM, where the former typically involves applying rules to a test item and the latter involves determining the similarity between stored exemplars or prototypes and a test item. Neuroimaging studies show differences between brain activity in normal participants as a function of whether they are instructed to categorize novel test items by rule or by similarity to known category members. Rule instructions typically lead to more activation in frontal or parietal areas, associated with WM and selective attention, whereas similarity instructions may activate parietal areas associated with the integration of perceptual features. Studies with neurological patients in the same paradigms provide converging evidence, e.g., patients with Alzheimer's disease, who have damage in prefrontal regions, are more impaired with rule than similarity instructions. Our second contrast is between categorization based on explicit LTM with that based on implicit LTM. Neuropsychological studies with patients with medial-temporal lobe damage show that patients are impaired on tasks requiring explicit LTM, but perform relatively normally on an implicit categorization task. Neuroimaging studies provide converging evidence: whereas explicit categorization is mediated by activation in numerous frontal and parietal areas, implicit categorization is mediated by a deactivation in posterior cortex.

Lead-induced changes of cytoskeletal protein is involved in the pathological basis in mice brain.

PubMed

Ge, Yaming; Chen, Lingli; Sun, Xianghe; Yin, Zhihong; Song, Xiaochao; Li, Chong; Liu, Junwei; An, Zhixing; Yang, Xuefeng; Ning, Hongmei

2018-04-01

Lead poisoning is a geochemical disease. On the other hand, lead is highly carcinogenic and exhibits liver and kidney toxicity. This element can also cross the blood-brain barrier, reduce learning and memory ability and damage the structure of the cerebral cortex and hippocampus. To further investigate the mechanism of lead neurotoxicity, 4-week-old Kunming mice were used to explore the effects of different concentrations of Pb 2+ (0, 2.4, 4.8 and 9.6 mM) for 9 days. In this study, pathological and ultrastructural changes in brain cells of the treated group were related to damages to mitochondria, chromatin and the nucleus. Lead content in blood was tested by atomic absorption spectroscopy, which showed high lead concentrations in the blood with increasing doses of lead. Distribution of lead in nerve cells was analysed by transmission electron microscopy with energy dispersive spectroscopy. Data showed the presence of lead in nucleopores, chromatin and nuclear membrane of nerve cells in the treatment groups, whereas lead content increased with increasing doses of lead acetate. Finally, microtubule-associated protein 2 (MAP2) mRNA and protein expression levels were detected by real-time PCR and Western blotting, which showed a reduction in MAP2 expression with increasing lead doses in the mouse brain. These findings suggest that acute lead poisoning can cause significant dose-dependent toxic effects on mouse brain function and can contribute to better understanding of lead-induced toxicity.

Methods of Making and Using Shape Memory Polymer Composite Patches

NASA Technical Reports Server (NTRS)

Hood, Patrick J.

2011-01-01

A method of repairing a composite component having a damaged area including: laying a composite patch over the damaged area: activating the shape memory polymer resin to easily and quickly mold said patch to said damaged area; deactivating said shape memory polymer so that said composite patch retains the molded shape; and bonding said composite patch to said damaged part.

The importance of providing scaffolding to support patient narratives when brain damage impairs storytelling ability.

PubMed

Hydén, Lars C

2011-01-01

Boundaries connected to illness are defined and redefined through new ways of interacting with other people and especially by storytelling and listening to the stories of others. Diseases or traumas that affect the brain can result in memory loss, impaired cognition, and difficulties in expressing oneself clearly, hence making it difficult to present and negotiate identities. In such situations, others often try to remedy the communicative problems by taking over those narrative functions that are lost or impaired and thereby scaffolding the injured person's storytelling capacity. This narrative scaffolding is directed at keeping interpersonal relationships functional and makes it possible for persons with communicative disabilities to continue to be participants in a shared life.

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment ofmore » learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential in As induced VaD.« less

Computational Cognitive Neuroscience of Early Memory Development

ERIC Educational Resources Information Center

Munakata, Yuko

2004-01-01

Numerous brain areas work in concert to subserve memory, with distinct memory functions relying differentially on distinct brain areas. For example, semantic memory relies heavily on posterior cortical regions, episodic memory on hippocampal regions, and working memory on prefrontal cortical regions. This article reviews relevant findings from…

Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear.

PubMed

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-09-19

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or retrieval. To investigate this possibility, we systematically imaged the brain activity patterns in the lateral amygdala, MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene zif268 after recent and remote memory retrieval of auditory conditioned fear. Consistent with the critical role of the amygdala in fear memory, the zif268 activity in the lateral amygdala was significantly increased after both recent and remote memory retrieval. Interesting, however, the density of zif268 (+) neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was increased only after remote but not recent fear memory retrieval compared to control groups. Further analysis of zif268 signals in AuV/TeA revealed that conditioned tone induced stronger zif268 induction compared to familiar tone in each individual zif268 (+) neuron after recent memory retrieval. Taken together, our results support that the lateral amygdala is a key brain site for permanent fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for remote memory storage or retrieval of auditory conditioned fear, or, alternatively, that these auditory brain regions might have a different way of processing for familiar or conditioned tone information at recent and remote time phases.

Non-spatial neglect for the mental number line.

PubMed

van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Doricchi, Fabrizio; Fias, Wim

2011-07-01

Several psychophysical investigations, expanding the classical introspective observations by Galton, have suggested that the mental representation of numbers takes the form of a number line along which magnitude is positioned in ascending order according to reading habits, i.e. from left to right in Western cultures. In keeping with the evidence, pathological rightward deviations in the bisection of number intervals due to right brain damage are generally interpreted as originating from a purely spatial-attentional deficit in the processing of the left side of number intervals. However, consistent double dissociations between defective processing of the left side of physical and mental number space have called into question the universality of this interpretation. Recent evidence suggests a link between rightward deviations in number space and defective memory for both spatial and non-spatial sequences of items. Here we describe the case of a left brain-damaged patient exhibiting right-sided neglect for extrapersonal and representational space, and left-sided neglect on the mental number line. Accurate neuropsychological examination revealed that the apparent left-sided neglect in the bisection of number intervals had a purely non-spatial origin and was based on mnemonic difficulties for the initial items of verbal sequences presented visually at an identical spatial position. These findings show that effective position-based verbal working memory might be crucial for numerical tasks that are usually considered to involve purely spatial representation of numerical magnitudes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural correlates of subjective and objective memory performance in multiple sclerosis.

PubMed

Pardini, Matteo; Bergamino, Maurizio; Bommarito, Giulia; Bonzano, Laura; Luigi Mancardi, Gian; Roccatagliata, Luca

2014-04-01

Subjective and objective memory deficits represent a frequent and ill-understood aspect of multiple sclerosis (MS), and a significant cause of disability and quality of life reduction. The aim of the study is to verify the role of hippocampal and temporal associative fibers' damage in MS-related memory complaints. To reach this aim, 25 patients with low disability relapsing-remitting MS and 19 healthy controls were included in the study. All subjects underwent 3D T1 structural imaging and Diffusion Tensor Imaging. Additionally, MS patients underwent neuropsychological evaluation of objective (Selective Reminding Test and Spatial Recall Test) and of subjective (Perceived Deficit Questionnaire, Retrospective and Prospective Memory Subscales) memory deficits. Normalized hippocampal volume (NHV) and mean Fractional Anisotropy (FA) for the uncinate fasciculus (UF) and for the ventral division of the cingulum bundle (VCB) were calculated for all subjects. We showed that, compared to controls, MS subjects presented with reduced right NHV and with reduced mean FA bilaterally in the UF and the VCB. In the MS group, verbal memory scores correlated with left NHV, spatial memory scores correlated with right NHV, while perceived retrospective and prospective memory deficits correlated with left VCB and left UF mean FA respectively. Our data confirm an early involvement of memory-related brain structures in MS patients. Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS. Copyright © 2013 Wiley Periodicals, Inc.

Bidirectional Modulation of Recognition Memory

PubMed Central

Ho, Jonathan W.; Poeta, Devon L.; Jacobson, Tara K.; Zolnik, Timothy A.; Neske, Garrett T.; Connors, Barry W.

2015-01-01

Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30–40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30–40 Hz was not effective in increasing exploration of novel images. Stimulation at 10–15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally. SIGNIFICANCE STATEMENT Recognition of novelty and familiarity are important for learning, memory, and decision making. Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects, but how novelty and familiarity are encoded and transmitted in the brain is not known. Perirhinal neurons respond to novelty and familiarity by changing firing rates, but recent work suggests that brain oscillations may also be important for recognition. In this study, we showed that stimulation of the PER could increase or decrease exploration of novel and familiar images depending on the frequency of stimulation. Our findings suggest that optical stimulation of PER at specific frequencies can predictably alter recognition memory. PMID:26424881

Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

PubMed

Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

2018-02-01

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

Tuna Oil Alleviates d-Galactose Induced Aging in Mice Accompanied by Modulating Gut Microbiota and Brain Protein Expression.

PubMed

Zhang, Dijun; Han, Jiaojiao; Li, Yanyan; Yuan, Bei; Zhou, Jun; Cheong, Lingzhi; Li, Ye; Lu, Chenyang; Su, Xiurong

2018-06-06

To discern whether tuna oil modulates the expression of brain proteins and the gut microbiota structure during aging induced by d-galactose, we generated an aging mouse model with d-galactose treatment, and the mice showed aging and memory deterioration symptoms according to physiological and biochemical indices. Treatment with different doses of tuna oil alleviated the symptoms; the high dose showed a better effect. Subsequently, brain proteomic analysis showed the differentially expressed proteins were involved in damaged synaptic system repairment and signal transduction system enhancement. In addition, tuna oil treatment restored the diversity of gut microbiota, 27 key operational taxonomic units, which were identified using a redundancy analysis and were significantly correlated with at least one physiological index and three proteins or genes. These findings suggest that the combination of proteomics and gut microbiota is an effective strategy to gain novel insights regarding the effect of tuna oil treatment on the microbiota-gut-brain axis.

A symbolic/subsymbolic interface protocol for cognitive modeling

PubMed Central

Simen, Patrick; Polk, Thad

2009-01-01

Researchers studying complex cognition have grown increasingly interested in mapping symbolic cognitive architectures onto subsymbolic brain models. Such a mapping seems essential for understanding cognition under all but the most extreme viewpoints (namely, that cognition consists exclusively of digitally implemented rules; or instead, involves no rules whatsoever). Making this mapping reduces to specifying an interface between symbolic and subsymbolic descriptions of brain activity. To that end, we propose parameterization techniques for building cognitive models as programmable, structured, recurrent neural networks. Feedback strength in these models determines whether their components implement classically subsymbolic neural network functions (e.g., pattern recognition), or instead, logical rules and digital memory. These techniques support the implementation of limited production systems. Though inherently sequential and symbolic, these neural production systems can exploit principles of parallel, analog processing from decision-making models in psychology and neuroscience to explain the effects of brain damage on problem solving behavior. PMID:20711520

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anthocyanins control neuroinflammation and consequent memory dysfunction in mice exposed to lipopolysaccharide.

PubMed

Carvalho, Fabiano B; Gutierres, Jessié M; Bueno, Andressa; Agostinho, Paula; Zago, Adriana M; Vieira, Juliano; Frühauf, Pâmela; Cechella, José L; Nogueira, Cristina Wayne; Oliveira, Sara M; Rizzi, Caroline; Spanevello, Roselia M; Duarte, Marta M F; Duarte, Thiago; Dellagostin, Odir A; Andrade, Cinthia M

2017-07-01

Peripheral inflammatory stimuli may activate a brain neuroinflammatory processes with consequences in brain function. The present study investigated if anthocyanins (ANT) consumption was able to prevent the memory loss, the neuronal damage, and the neuroinflammatory processes triggered by the intraperitoneal lipopolysaccharide (LPS) administration. C57BL6 male mice were treated with ANT (30-100 mg/kg by gavage). With a single dose or during 10 days, before be challenged with LPS (250 μg/kg intraperitoneally single administration), a classical inductor of inflammation. The data obtained showed that ANT was able to confer protection against the memory impairment after 10 days of ANT treatment (100 mg/kg). This phytonutrient also prevented the hypothermia episode induced by LPS. Moreover, ANT prevented the increase in protein carbonyl, NOx, and MDA levels in the hippocampus and cerebral cortex (4 and 24 h) in animal challenged with LPS. ANT showed a protective effect on the increase in the pro-inflammatory cytokines content, especially Interleukin (IL)-1β, tumoral necrosis factor-α and on the reduction of IL-10 induced by LPS. ANT 100 mg/kg prevented the infiltration of peripheral immune cells in the hippocampus at 24 h post-LPS administration. In parallel, LPS increased the activity of myeloperoxidase in cortex and hippocampus, and ANT prevented this effect, also reducing microglia (Iba-1) and astrocyte (GFAP) immunoreactivity. Thus, our data support that ANT are a promising therapeutic component against brain disorders associated with process of neuroinflammation. Graphical Abstract ᅟ.

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

Insights from child development on the relationship between episodic and semantic memory.

PubMed

Robertson, Erin K; Köhler, Stefan

2007-11-05

The present study was motivated by a recent controversy in the neuropsychological literature on semantic dementia as to whether episodic encoding requires semantic processing or whether it can proceed solely based on perceptual processing. We addressed this issue by examining the effect of age-related limitations in semantic competency on episodic memory in 4-6-year-old children (n=67). We administered three different forced-choice recognition memory tests for pictures previously encountered in a single study episode. The tests varied in the degree to which access to semantically encoded information was required at retrieval. Semantic competency predicted recognition performance regardless of whether access to semantic information was required. A direct relation between picture naming at encoding and subsequent recognition was also found for all tests. Our findings emphasize the importance of semantic encoding processes even in retrieval situations that purportedly do not require access to semantic information. They also highlight the importance of testing neuropsychological models of memory in different populations, healthy and brain damaged, at both ends of the developmental continuum.

Lack of color integration in visual short-term memory binding.

PubMed

Parra, Mario A; Cubelli, Roberto; Della Sala, Sergio

2011-10-01

Bicolored objects are retained in visual short-term memory (VSTM) less efficiently than unicolored objects. This is unlike shape-color combinations, whose retention in VSTM does not differ from that observed for shapes only. It is debated whether this is due to a lack of color integration and whether this may reflect the function of separate memory mechanisms. Participants judged whether the colors of bicolored objects (each with an external and an internalcolor) were the same or different across two consecutive screens. Colors had to be remembered either individually or in combination. In Experiment 1, external colors in the combined colors condition were remembered better than the internal colors, and performance for both was worse than that in the individual colors condition. The lack of color integration observed in Experiment 1 was further supported by a reduced capacity of VSTM to retain color combinations, relative to individual colors (Experiment 2). An additional account was found in Experiment 3, which showed spared color-color binding in the presence of impaired shape-color binding in a brain-damaged patient, thus suggesting that these two memory mechanisms are different.

Sex-specific effects of cytotoxic chemotherapy agents cyclophospha-mide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus – an aging connection

PubMed Central

Kovalchuk, Anna; Rodriguez-Juarez, Rocio; Ilnytskyy, Yaroslav; Byeon, Boseon; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis. PMID:27032448

Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity

PubMed Central

Zeidman, Peter; Mullally, Sinéad L.; Maguire, Eleanor A.

2015-01-01

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes. PMID:25405941

Revisiting the continuum hypothesis: toward an in-depth exploration of executive functions in korsakoff syndrome.

PubMed

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS.

Revisiting the Continuum Hypothesis: Toward an In-Depth Exploration of Executive Functions in Korsakoff Syndrome

PubMed Central

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS. PMID:25071526

BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1.

PubMed

Yang, Jenq-Lin; Lin, Yu-Ting; Chuang, Pei-Chin; Bohr, Vilhelm A; Mattson, Mark P

2014-03-01

Brain-derived neurotrophic factor (BDNF) promotes the survival and growth of neurons during brain development and mediates activity-dependent synaptic plasticity and associated learning and memory in the adult. BDNF levels are reduced in brain regions affected in Alzheimer's, Parkinson's, and Huntington's diseases, and elevation of BDNF levels can ameliorate neuronal dysfunction and degeneration in experimental models of these diseases. Because neurons accumulate oxidative lesions in their DNA during normal activity and in neurodegenerative disorders, we determined whether and how BDNF affects the ability of neurons to cope with oxidative DNA damage. We found that BDNF protects cerebral cortical neurons against oxidative DNA damage-induced death by a mechanism involving enhanced DNA repair. BDNF stimulates DNA repair by activating cyclic AMP response element-binding protein (CREB), which, in turn, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference abolishes the ability of BDNF to protect neurons against oxidized DNA damage-induced death. The ability of BDNF to activate CREB and upregulate APE1 expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3 kinase, and Akt kinase. Voluntary running wheel exercise significantly increases levels of BDNF, activates CREB, and upregulates APE1 in the cerebral cortex and hippocampus of mice, suggesting a novel mechanism whereby exercise may protect neurons from oxidative DNA damage. Our findings reveal a previously unknown ability of BDNF to enhance DNA repair by inducing the expression of the DNA repair enzyme APE1.

Episodic Memory Impairments in Primary Brain Tumor Patients.

PubMed

Durand, Thomas; Berzero, Giulia; Bompaire, Flavie; Hoffmann, Sabine; Léger, Isabelle; Jego, Virginie; Baruteau, Marie; Delgadillo, Daniel; Taillia, Hervé; Psimaras, Dimitri; Ricard, Damien

2018-01-04

Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.)

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

ABSTRACT Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe), whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC) in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect. PMID:29330349

Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington's disease in rats.

PubMed

Shivasharan, B D; Nagakannan, Pandian; Thippeswamy, Boreddy Shivanandappa; Veerapur, Veeresh Prabakar; Bansal, Punit; Unnikrishnan, Mazhuvancherry K

2013-10-01

Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

PubMed

McCormick, Cornelia; Quraan, Maher; Cohn, Melanie; Valiante, Taufik A; McAndrews, Mary Pat

2013-05-01

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Neuroanatomical and Cognitive Mediators of Age-Related Differences in Episodic Memory

PubMed Central

Head, Denise; Rodrigue, Karen M.; Kennedy, Kristen M.; Raz, Naftali

2009-01-01

Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. PMID:18590361

Differences in Brain Activity during a Verbal Associative Memory Encoding Task in High- and Low-fit Adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2013-01-01

Aerobic fitness is associated with better memory performance as well as larger volumes in memory-related brain regions in children, adolescents, and elderly. It is unclear if aerobic exercise also influences learning and memory functional neural circuitry. Here, we examine brain activity in 17 high-fit (HF) and 17 low-fit (LF) adolescents during a subsequent memory encoding paradigm using fMRI. Despite similar memory performance, HF and LF youth displayed a number of differences in memory-related and default mode (DMN) brain regions during encoding later remembered versus forgotten word pairs. Specifically, HF youth displayed robust deactivation in DMN areas, including the ventral medial PFC and posterior cingulate cortex, whereas LF youth did not show this pattern. Furthermore, LF youth showed greater bilateral hippocampal and right superior frontal gyrus activation during encoding of later remembered versus forgotten word pairs. Follow-up task-dependent functional correlational analyses showed differences in hippocampus and DMN activity coupling during successful encoding between the groups, suggesting aerobic fitness during adolescents may impact functional connectivity of the hippocampus and DMN during memory encoding. To our knowledge, this study is the first to examine the influence of aerobic fitness on hippocampal function and memory-related neural circuitry using fMRI. Taken together with previous research, these findings suggest aerobic fitness can influence not only memory-related brain structure, but also brain function. PMID:23249350

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis.

PubMed

Sumowski, James F; Wylie, Glenn R; Chiaravalloti, Nancy; DeLuca, John

2010-06-15

Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis.

Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

PubMed

Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

2016-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.

PubMed

Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

2018-05-05

Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic markers, inflammatory chemokines, and cytokines, but on the other hand, it upregulated M2 phenotypic markers and anti-inflammatory cytokines. Neuronal viability and synaptic plasticity markers were also modulated significantly by this strategy. Behavioral study revealed significant downregulation in the number of working memory errors at a time-dependent manner after silencing the Mac-1 gene during continuous hypoxic exposure. The novel findings of this study for the very first time, unmasked the role of Mac-1 receptor in neurodegenerative disease progression under hypoxic condition and at the same time indicated the potential therapeutic value of this non-invasive siRNA delivery approach for treating working memory loss. Copyright © 2018 Elsevier Ltd. All rights reserved.

The MNESIS model: Memory systems and processes, identity and future thinking.

PubMed

Eustache, Francis; Viard, Armelle; Desgranges, Béatrice

2016-07-01

The Memory NEo-Structural Inter-Systemic model (MNESIS; Eustache and Desgranges, Neuropsychology Review, 2008) is a macromodel based on neuropsychological data which presents an interactive construction of memory systems and processes. Largely inspired by Tulving's SPI model, MNESIS puts the emphasis on the existence of different memory systems in humans and their reciprocal relations, adding new aspects, such as the episodic buffer proposed by Baddeley. The more integrative comprehension of brain dynamics offered by neuroimaging has contributed to rethinking the existence of memory systems. In the present article, we will argue that understanding the concept of memory by dividing it into systems at the functional level is still valid, but needs to be considered in the light of brain imaging. Here, we reinstate the importance of this division in different memory systems and illustrate, with neuroimaging findings, the links that operate between memory systems in response to task demands that constrain the brain dynamics. During a cognitive task, these memory systems interact transiently to rapidly assemble representations and mobilize functions to propose a flexible and adaptative response. We will concentrate on two memory systems, episodic and semantic memory, and their links with autobiographical memory. More precisely, we will focus on interactions between episodic and semantic memory systems in support of 1) self-identity in healthy aging and in brain pathologies and 2) the concept of the prospective brain during future projection. In conclusion, this MNESIS global framework may help to get a general representation of human memory and its brain implementation with its specific components which are in constant interaction during cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Memory for the perceptual and semantic attributes of information in pure amnesic and severe closed-head injured patients.

PubMed

Carlesimo, Giovanni A; Bonanni, Rita; Caltagirone, Carlo

2003-05-01

This study investigated the hypothesis that brain damaged patients with memory disorder are poorer at remembering the semantic than the perceptual attributes of information. Eight patients with memory impairment of different etiology and 24 patients with chronic consequences of severe closed-head injury were compared to similarly sized age- and literacy-matched normal control groups on recognition tests for the physical aspect and the semantic identity of words and pictures lists. In order to avoid interpretative problems deriving from different absolute levels of performance, study conditions were manipulated across subjects to obtain comparable accuracy on the perceptual recognition tests in the memory disordered and control groups. The results of the Picture Recognition test were consistent with the hypothesis. Indeed, having more time for the stimulus encoding, the two memory disordered groups performed at the same level as the normal subjects on the perceptual test but significantly lower on the semantic test. Instead, on the Word Recognition test, following study condition manipulation, patients and controls performed similarly on both the perceptual and the semantic tests. These data only partially support the hypothesis of the study; rather they suggest that in memory disordered patients there is a reduction of the advantage, exhibited by normal controls, of retrieving pictures over words (picture superiority effect).

Permanent global amnesia: case report.

PubMed

Bertolucci, Paulo H F; Siviero, Marilena O; Bueno, Orlando F A; Okamoto, Ivan H; Camargo, Candida H P; Santos, Ruth F

2004-04-01

To present a case of permanent global amnesia related to hippocampal damage. Permanent global amnesia is a very rare condition of unknown etiology; lesions restricted to the hippocampus are uncommon, which hinders investigations of this pattern of memory loss. This case is unusually well documented, as the patient underwent extensive neuropsychological evaluations. A cheerful right-handed, 83-year-old retired electrician was first evaluated in 1990 for progressive difficulty in learning new information and in recalling events over the preceding 3-4 years. Tests over the next 5 years showed that the impairment was confined to episodic declarative memory. New verbal information could be stored only in episodic memory in a restricted manner, limited by short-term memory capacity. A relatively mild retrograde amnesia was detected. Semantic and implicit memory was spared, as were other functions evaluated. The patient's language and executive function were strikingly efficient. Magnetic resonance imaging of the brain showed bilateral atrophy of the hippocampi and amygdalae, ruling out conditions such as tumour growth. A diagnosis of permanent global amnesia was made. In the ensuing years, the retrograde amnesia worsened, but no new deficits were identified. This case, the first with a detailed cognitive examination, is evidence of a relatively pure hippocampal pattern for memory loss in permanent global amnesia.

Episodic and working memory deficits in alcoholic Korsakoff patients: the continuity theory revisited.

PubMed

Pitel, Anne Lise; Beaunieux, Hélène; Witkowski, Thomas; Vabret, François; de la Sayette, Vincent; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

2008-07-01

The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Tough times call for bigger brains

PubMed Central

Pravosudov, Vladimir V

2009-01-01

Memory is crucial for survival in many animals. Spatial memory in particular is important for food-caching species and may be influenced by selective pressures such as climate. The influence of climate on memory may be facilitated through the hippocampus (Hp), the part of the brain responsible in part for spatial memory. In a recent paper, we conducted the first large-scale test of the relationship between memory, the climate and the brain in a single food-caching species, the black-capped chickadee (Poecile atricapillus). We found that birds from more harsh northern climates had significantly larger hippocampal volumes and more neurons than those from more mild southern latitudes. This work suggests that environmental pressures are capable of influencing specific brain regions, which may result in enhanced memory, and hence survival, in harsh climates. This work gives us a better understanding of how the brain responds to different environments and how animals can adapt to their environment in general. PMID:19641741

Human Genomic Signatures of Brain Oscillations During Memory Encoding.

PubMed

Berto, Stefano; Wang, Guang-Zhong; Germi, James; Lega, Bradley C; Konopka, Genevieve

2018-05-01

Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

[Neuropsychological evaluation of children in low conciseness state after a severe traumatic brain injury].

PubMed

Fufaeva, E V; Mikadze, Yu V; Lukyanov, V I

2017-01-01

To follow up patterns of cognitive recovery in children (6-17 years of age) at the first four months after a severe traumatic brain injury (TBI). Seventeen children with TBI (GCS ≤8) were evaluated with the Coma Recovery Scale-R (CRS). Children were stratified into three groups according to their consciousness recovery. Seven children regained their consciousness completely and were assessed by the Luria Neuropsychological Battery test. Six children remained in the minimally conscious state (MCS) and were tested by the adapted procedure of neuropsychological assessment during the first four months. Four children with low level of consciousness were evaluated with CRS. The most destroying functions at the early recovery period were the processing speed (neurodynamics of mental activity), executive functions and memory. Children with the anterior cortex damage had the slowest dynamics of recovery. The slower dynamics of consciousness recovery was combined with severe primary damages of visual gnosis, speech and executive functions according to neuropsychological examination. The positive dynamics of consciousness recovery was combined with early behavioral changes and the greater rate of behavioral changes.

AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

PubMed

Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

2011-03-09

Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

Neurobiology of the aging dog.

PubMed

Head, Elizabeth

2011-09-01

Aged canines naturally accumulate several types of neuropathology that may have links to cognitive decline. On a gross level, significant cortical atrophy occurs with age along with an increase in ventricular volume based on magnetic resonance imaging studies. Microscopically, there is evidence of select neuron loss and reduced neurogenesis in the hippocampus of aged dogs, an area critical for intact learning and memory. The cause of neuronal loss and dysfunction may be related to the progressive accumulation of toxic proteins, oxidative damage, cerebrovascular pathology, and changes in gene expression. For example, aged dogs naturally accumulate human-type beta-amyloid peptide, a protein critically involved with the development of Alzheimer's disease in humans. Further, oxidative damage to proteins, DNA/RNA and lipids occurs with age in dogs. Although less well explored in the aged canine brain, neuron loss, and cerebrovascular pathology observed with age are similar to human brain aging and may also be linked to cognitive decline. Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age.

Protection against brain tissues oxidative damage as a possible mechanism for the beneficial effects of Rosa damascena hydroalcoholic extract on scopolamine induced memory impairment in rats.

PubMed

Mohammadpour, Toktam; Hosseini, Mahmoud; Naderi, Asieh; Karami, Reza; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Vafaee, Farzaneh

2015-10-01

Hypnotic, analgesic, anticonvulsant, and antioxidant effects of Rosa damascena have been reported. This study, investigated the effect of R. damascena hydroalcoholic extract on memory performance in a scopolamine-induced memory impairment model. The rats were divided into control group received just saline; scopolamine group was treated by saline for 2 weeks, but was injected by scopolamine 30 minutes before each trial in Morris water maze test; treatment groups (scopolamine + extract 50; Sco + Ext 50) and (scopolamine + extract 250; Sco + Ext 250) were daily treated by 50 and 250 mg/kg of R. damascena extract (2 weeks) and were finally injected by scopolamine before each trial in Morris water maze. The brains were removed for biochemical measurements. Time latency and path length in the scopolamine group were higher than control (P < 0.01 to <0.001). Both treatment groups showed shorter traveled distance and time latency compared with scopolamine group (P < 0.05 to <0.001). Time spent in target quadrant by scopolamine group was lower than control (P < 0.05), while Sco + Ext 250 group spent longer time in target quadrant than scopolamine group (P < 0.05). Malondialdehyde concentrations in hippocampal and cortical tissues of scopolamine group were higher, while thiol concentrations were lower than control ones (P < 0.001). Treatment by both doses of the extract decreased the malondialdehyde concentration, while increased the thiol concentration (P < 0.05 to <0.001). The results of this study showed that the hydroalcoholic extract of R. damascena prevents scopolamine-induced memory deficits. This finding suggests that memory improvement may be in part due to the antioxidant effects.

Lentivirus-mediated klotho up-regulation improves aging-related memory deficits and oxidative stress in senescence-accelerated mouse prone-8 mice.

PubMed

Zhou, Hong-Jing; Zeng, Chen-Ye; Yang, Ting-Ting; Long, Fang-Yi; Kuang, Xi; Du, Jun-Rong

2018-05-01

Oxidative stress caused by aging aggravates neuropathological changes and cognitive deficits. Klotho, an anti-aging protein, shows an anti-oxidative effect. The aims of the present study were to determine the potential therapeutic effect of klotho in aging-related neuropathological changes and memory impairments in senescence-accelerated mouse prone-8 (SAMP8) mice, and identify the potential mechanism of these neuroprotective effects. A lentivirus was used to deliver and sustain the expression of klotho. The lentiviral vectors were injected into the bilateral lateral ventricles of 7-month-old SAMP8 mice or age-matched SAMR1 mice. Three months later, the Y-maze alternation task and passive avoidance task were used to assess the memory deficits of the mice. In situ hybridization, immunohistochemistry, immunofluorescence, Nissl staining, quantitative real-time PCR and Western blot assays were applied in the following research. Our results showed that 3 months after injection of the lentiviral vectors encoding the full-length klotho gene, the expression of klotho in the brain was significantly increased in 10-month-old SAMP8 mice. This treatment reduced memory deficits, neuronal loss, synaptic damage and 4-HNE levels but increased mitochondrial manganese-superoxide dismutase (Mn-SOD) and catalase (CAT) expression. Moreover, the up-regulation of klotho expression decreased Akt and Forkhead box class O1 (FoxO1) phosphorylation. The present study provides a novel approach for klotho gene therapy and demonstrates that direct up-regulation of klotho in the brain might improve aging-related memory impairments and decrease oxidative stress. The underlying mechanism of this effect likely involves the inhibition of the Akt/FoxO1 pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

PubMed

Squire, L R

1992-01-01

Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

Memory and functional brain differences in a national sample of U.S. veterans with Gulf War Illness.

PubMed

Cooper, Crystal M; Briggs, Richard W; Farris, Emily A; Bartlett, James; Haley, Robert W; Odegard, Timothy N

2016-04-30

Roughly 26-32% of U. S. veterans who served in the 1991 Persian Gulf War report suffering from chronic health problems. Memory complaints are regularly reported by ill Gulf War veterans (GWV), but limited data verify their complaints. This study investigated episodic memory and brain function in a nationally representative sample of GWV, using a face-name memory task and functional magnetic resonance imaging during encoding. A syndrome classification system was used to subdivide ill GWV into the three major Gulf War Illness syndrome types, "impaired cognition" (GWV-1), "confusion ataxia" (GWV-2), and "central pain" (GWV-3). Memory and brain function of ill GWV were contrasted to deployed and nondeployed well GWV controls (GWV-C). Ill GWV exhibited impaired memory function relative to GWV-C but the patterns of functional brain differences varied. Brain activation differentiated the GWV-C from the ill GWV. The different syndrome types also differed from one another in several brain regions. Additionally, the current study was the first to observe differences in brain function between deployed and nondeployed GWV-C. These results provide (1) evidence of memory impairment in ill GWV and differentiate the syndrome types at a functional neurobiological level, and (2) the role of deployment in the war on brain function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

PubMed

Kanayama, Gen; Rogowska, Jadwiga; Pope, Harrison G; Gruber, Staci A; Yurgelun-Todd, Deborah A

2004-11-01

Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. We assessed brain function among recent heavy cannabis users while they performed a working memory task. Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6-36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques. Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings remained essentially unchanged when re-analyzed using subjects' ages as a covariate. Brain activation showed little or no significant correlation with subjects' years of education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning. Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

A biased competition account of attention and memory in Alzheimer's disease

PubMed Central

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-01-01

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD. PMID:24018724

A biased competition account of attention and memory in Alzheimer's disease.

PubMed

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-10-19

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application.

PubMed

Zahodne, Laura B; Manly, Jennifer J; Brickman, Adam M; Narkhede, Atul; Griffith, Erica Y; Guzman, Vanessa A; Schupf, Nicole; Stern, Yaakov

2015-10-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. Copyright © 2015. Published by Elsevier Ltd.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application

PubMed Central

Zahodne, Laura B.; Manly, Jennifer J.; Brickman, Adam M.; Narkhede, Atul; Griffith, Erica Y.; Guzman, Vanessa A.; Schupf, Nicole; Stern, Yaakov

2016-01-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. PMID:26348002

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis

PubMed Central

Sumowski, James F.; Wylie, Glenn R.; Chiaravalloti, Nancy; DeLuca, John

2010-01-01

Objective: Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Methods: Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Results: Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. Conclusion: These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis. GLOSSARY AD = Alzheimer disease; ANOVA = analysis of variance; MPRAGE = magnetization-prepared rapid gradient echo; MS = multiple sclerosis; SRT = Selective Reminding Test; TVW = third ventricle width; WASI = Wechsler Abbreviated Scale of Intelligence. PMID:20548040

Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure.

PubMed

Zhou, Xue; da Li, Wen-; Yuan, Bao-Long; Niu, Li-Jun; Yang, Xiao-Yu; Zhou, Zhi-Bin; Chen, Xiao-Hui; Feng, Xia

2016-08-01

We aimed to observe the therapeutic effects of lithium on inhalational anesthetic sevoflurane-induced apoptosis in immature brain hippocampus. From postnatal day 5 (P5) to P28, male Sprague-Dawley pups were intraperitoneally injected with lithium chloride or 0.9 % sodium chloride. On P7 after the injection, pups were exposed to 2.3 % sevoflurane or air for 6 h. Brain tissues were harvested 12 h and 3 weeks after exposure. Cleaved caspase-3, nNOS protein, GSK-3β,p-GSK-3β were assessed by Western blot, and histopathological changes were assessed using Nissl stain and TUNEL stain. From P28, we used the eight-arm radial maze test and step-through test to evaluate the influence of sevoflurane exposure on the learning and memory of juvenile rats. The results showed that neonatal sevoflurane exposure induced caspase-3 activation and histopathological changes in hippocampus can be attenuated by lithium chloride. Sevoflurane increased GSK-3β activity while pretreatment of lithium decreased GSK-3β activity. Moreover, sevoflurane showed possibly slight but temporal influence on the spatial learning and the memory of juvenile rats, and chronic use of lithium chloride might have the therapeutic effect. Our current study suggests that lithium attenuates sevoflurane induced neonatal hippocampual damage by GSK-3β pathway and might improve learning and memory deficits in rats after neonatal exposure.

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

PubMed Central

Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

2011-01-01

Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8 −/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8 −/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma. PMID:21957448

GABA function may be related to the impairment of learning and memory caused by systemic prenatal hypoxia-ischemia.

PubMed

Cunha-Rodrigues, Marta Cristina; Balduci, Cassiana Thayara do Nascimento; Tenório, Frank; Barradas, Penha Cristina

2018-03-01

Intrauterine adverse conditions may be responsible for long-lasting damages which impact health even during adult phase. Hypoxic-ischemic (HI) events are a relevant cause of newborn mortality and the principal factor leading to permanent brain lesions. Using a model in which the ovarian and uterine flux of a pregnant rat is obstructed for 45 min we have described oligodendrocyte death, astrogliosis and neuronal loss. In this work we investigated hippocampal neuronal population and performed a functional evaluation of memory and learning of young rats that had been affected by prenatal HI. Anesthetized Wistar rats on the 18th gestation day had the uterine horns exposed and the ovarian and uterine arteries clamped for 45 min (HI group). Sham-operated rats (SH group) had the horns exposed but no arteries were clamped. We measured the levels of different proteins related to excitatory/inhibitory transmission in the hippocampi of young pups (P45). Histological evaluation was also performed in order to characterize hippocampal neuronal population. Rats from both groups were tested through Novel Object Recognition Test (NORT) using two inter-trial intervals: 5 min and 8 h. Here we show a loss in the total number of hippocampal neurons although the immunostaining of parvalbumin and levels of GAD enzyme were increased in HI group. Functional assessment indicated a marked difference concerning HI learning and memory abilities. Our results reflect permanent damages concerning GABA function which may disturb neurotransmitter homeostasis leading to the observed deficits in learning and memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuropsychological alterations and neuroradiological findings in patients with post-traumatic concussion: Results of a pilot study.

PubMed

Rădoi, A; Poca, M A; Cañas, V; Cevallos, J M; Membrado, L; Saavedra, M C; Vidal, M; Martínez-Ricarte, F; Sahuquillo, J

2016-12-19

Mild traumatic brain injury (mTBI) has traditionally been considered to cause no significant brain damage since symptoms spontaneously remit after a few days. However, this idea is facing increasing scrutiny. The purpose of this study is to demonstrate the presence of early cognitive alterations in a series of patients with mTBI and to link these findings to different markers of brain damage. We conducted a prospective study of a consecutive series of patients with mTBI who were evaluated over a 12-month period. Forty-one (3.7%) of the 1144 included patients had experienced a concussion. Patients underwent a routine clinical evaluation and a brain computed tomography (CT) scan, and were also administered a standardised test for post-concussion symptoms within the first 24hours of mTBI and also 1 to 2 weeks later. The second assessment also included a neuropsychological test battery. The results of these studies were compared to those of a control group of 28 healthy volunteers with similar characteristics. Twenty patients underwent an MRI scan. Verbal memory and learning were the cognitive functions most affected by mTBI. Seven out of the 20 patients with normal CT findings displayed structural alterations on MR images, which were compatible with diffuse axonal injury in 2 cases. Results from this pilot study suggest that early cognitive alterations and structural brain lesions affect a considerable percentage of patients with post-concussion syndrome following mTBI. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

PubMed

Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

2013-08-01

This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women.

PubMed

Dumas, Julie A; Filippi, Christopher G; Newhouse, Paul A; Naylor, Magdalena R

2017-02-01

The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior.

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

PubMed Central

Chanraud, Sandra; Leroy, Claire; Martelli, Catherine; Kostogianni, Nikoleta; Delain, Françoise; Aubin, Henri-Jean; Reynaud, Michel; Martinot, Jean-Luc

2009-01-01

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics. Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software. In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant. These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence. PMID:19707568

Impact of the Educational Boost Your Brain and Memory Program Among Senior Living Residents.

PubMed

Nicholson, Roscoe; O'Brien, Catherine

2017-12-01

This random assignment waitlist control intervention study examined an implementation of the educational Boost Your Brain and Memory cognitive fitness intervention in 12 senior living organizations. Older adult participants ( n = 166) completed measures of brain health knowledge, use of memory techniques, physical and intellectual activity, and mindfulness, at baseline and after the intervention group's completion of the course. Changes in knowledge scores and in self-reported physical and intellectual activity increased significantly more for intervention participants than for waitlist controls at the conclusion of the course. There were no significant changes between the groups in mindfulness or use of memory techniques. This suggests that in senior living settings Boost Your Brain and Memory is effective in educating participants about brain healthy behaviors and in motivating behavioral change in the areas of physical and intellectual activity.

[Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration].

PubMed

Narberhaus, A; Segarra-Castells, M D; Verger-Maestre, K; Serra-Grabulosa, J M; Salgado-Pineda, P; Bartomeus-Jené, F; Mercader-Sobrequés, J M

Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

From Hippocampus to Whole-Brain: The Role of Integrative Processing in Episodic Memory Retrieval

PubMed Central

Geib, Benjamin R.; Stanley, Matthew L.; Dennis, Nancy A.; Woldorff, Marty G.; Cabeza, Roberto

2017-01-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. PMID:28112460

Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease.

PubMed

Parra, Mario A; Mikulan, Ezequiel; Trujillo, Natalia; Sala, Sergio Della; Lopera, Francisco; Manes, Facundo; Starr, John; Ibanez, Agustin

2017-01-01

Alzheimer's disease (AD) as a disconnection syndrome which disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions share pathophysiological mechanisms remains unknown. To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the Visual Short-Term Memory binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence-Based Practice for the Use of Internal Strategies as a Memory Compensation Technique After Brain Injury: A Systematic Review.

PubMed

OʼNeil-Pirozzi, Therese M; Kennedy, Mary R T; Sohlberg, McKay M

2016-01-01

To complete a systematic review of internal memory strategy use with people who have brain injury and provide practitioners with information that will impact their clinical work. A systematic literature search to identify published intervention studies that evaluated an internal memory strategy or technique to improve memory function of individuals with brain injury. Relevant data from reviewed articles were coded using 4 clinical questions targeting participants, interventions, research methods, and outcomes. A comprehensive search identified 130 study citations and abstracts. Forty-six met inclusion/exclusion criteria and were systematically reviewed. Visual imagery was most frequently studied, in isolation or in combination with other internal strategies. Despite significant variability in research methods and outcomes across studies, the evidence provides impetus for use of internal memory strategies with individuals following brain injury. Individuals with traumatic brain injury may benefit from internal memory strategy use, and clinicians should consider internal memory strategy instruction as part of intervention plans. Further research needs to better delineate influences on intervention candidacy and outcomes.

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

PubMed

Geib, Benjamin R; Stanley, Matthew L; Dennis, Nancy A; Woldorff, Marty G; Cabeza, Roberto

2017-04-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

PubMed Central

2016-01-01

The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems operate independently and in parallel when rats learn one type of task at a time, but interact cooperatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex. PMID:27307234

Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience.

PubMed

Ferbinteanu, Janina

2016-06-15

The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue-response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel "other" task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue-response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems operate independently and in parallel when rats learn one type of task at a time, but interact cooperatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex. Copyright © 2016 the authors 0270-6474/16/366459-12$15.00/0.

Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease.

PubMed

Lacor, Pascale N; Buniel, Maria C; Furlow, Paul W; Clemente, Antonio Sanz; Velasco, Pauline T; Wood, Margaret; Viola, Kirsten L; Klein, William L

2007-01-24

The basis for memory loss in early Alzheimer's disease (AD) seems likely to involve synaptic damage caused by soluble Abeta-derived oligomers (ADDLs). ADDLs have been shown to build up in the brain and CSF of AD patients and are known to interfere with mechanisms of synaptic plasticity, acting as gain-of-function ligands that attach to synapses. Because of the correlation between AD dementia and synaptic degeneration, we investigated here the ability of ADDLs to affect synapse composition, structure, and abundance. Using highly differentiated cultures of hippocampal neurons, a preferred model for studies of synapse cell biology, we found that ADDLs bound to neurons with specificity, attaching to presumed excitatory pyramidal neurons but not GABAergic neurons. Fractionation of ADDLs bound to forebrain synaptosomes showed association with postsynaptic density complexes containing NMDA receptors, consistent with observed attachment of ADDLs to dendritic spines. During binding to hippocampal neurons, ADDLs promoted a rapid decrease in membrane expression of memory-related receptors (NMDA and EphB2). Continued exposure resulted in abnormal spine morphology, with induction of long thin spines reminiscent of the morphology found in mental retardation, deafferentation, and prionoses. Ultimately, ADDLs caused a significant decrease in spine density. Synaptic deterioration, which was accompanied by decreased levels of the spine cytoskeletal protein drebrin, was blocked by the Alzheimer's therapeutic drug Namenda. The observed disruption of dendritic spines links ADDLs to a major facet of AD pathology, providing strong evidence that ADDLs in AD brain cause neuropil damage believed to underlie dementia.

[Short-and long-term effects of cannabinoids on memory, cognition and mental illness].

PubMed

Sagie, Shira; Eliasi, Yehuda; Livneh, Ido; Bart, Yosi; Monovich, Einat

2013-12-01

Marijuana is considered the most commonly used drug in the world, with estimated millions of users. There is dissent in the medical world about the positive and negative effects of marijuana, and recently, a large research effort has been directed to that domain. The main influencing drug ingredient is THC, which acts on the cannabinoid system and binds to the CB1 receptor. The discovery of the receptor led to the finding of an endogenous ligand, anandamide, and another receptor-CB2. The researchers also discovered that cannabinoids have extensive biological activity, and its short and long-term effects may cause cognitive and emotional deficiencies. Findings show that the short-term effects, such as shortterm memory and verbal Learning, are reversible. However, despite the accumulation of evidence about long-term cognitive damage due to cannabis use, it is difficult to find unequivocal results, arising from the existence of many variables such as large differences between cannabis users, frequency of use, dosage and endogenous brain compensation. Apart from cognitive damage, current studies investigate how marijuana affects mental illness: a high correlation between cannabis use and schizophrenia was found and a high risk to undergo a psychotic attack. Furthermore, patients with schizophrenia who used cannabis showed a selective neuro-psychological disruption, and similar cognitive deficiencies and brain morphological changes were found among healthy cannabis users and schizophrenia patients. In contrast to the negative effects of marijuana including addiction, there are the medical uses: reducing pain, anxiety and nausea, increasing appetite and an anti-inflammatory activity. Medicalization of marijuana encourages frequent use, which may elevate depression.

Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

PubMed

Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

2015-01-01

Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

Tracking the fear engram: the lateral amygdala is an essential locus of fear memory storage.

PubMed

Schafe, Glenn E; Doyère, Valérie; LeDoux, Joseph E

2005-10-26

Although it is believed that different types of memories are localized in discreet regions of the brain, concrete experimental evidence of the existence of such engrams is often elusive. Despite being one of the best characterized memory systems of the brain, the question of where fear memories are localized in the brain remains a hotly debated issue. Here, we combine site-specific behavioral pharmacology with multisite electrophysiological recording techniques to show that the lateral nucleus of the amygdala, long thought to be critical for the acquisition of fear memories, is also an essential locus of fear memory storage.

Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus.

PubMed

Aguilar-Arredondo, Andrea; Zepeda, Angélica

2018-07-01

The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

Beneficial effects of enriched environment following status epilepticus in immature rats.

PubMed

Faverjon, S; Silveira, D C; Fu, D D; Cha, B H; Akman, C; Hu, Y; Holmes, G L

2002-11-12

There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.

Cognitive reserve as a predictor of two year neuropsychological performance in early onset first-episode schizophrenia.

PubMed

de la Serna, Elena; Andrés-Perpiñá, Susana; Puig, Olga; Baeza, Inmaculada; Bombin, Igor; Bartrés-Faz, David; Arango, Celso; Gonzalez-Pinto, Ana; Parellada, Mara; Mayoral, María; Graell, Montserrat; Otero, Soraya; Guardia, Joan; Castro-Fornieles, Josefina

2013-01-01

The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks. Copyright © 2012 Elsevier B.V. All rights reserved.

Gross morphology and morphometric sequelae in the hippocampus, fornix, and corpus callosum of patients with severe non-missile traumatic brain injury without macroscopically detectable lesions: a T1 weighted MRI study

PubMed Central

Tomaiuolo, F; Carlesimo, G; Di, P; Petrides, M; Fera, F; Bonanni, R; Formisano, R; Pasqualetti, P; Caltagirone, C

2004-01-01

Objective: The gross morphology and morphometry of the hippocampus, fornix, and corpus callosum in patients with severe non-missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions was examined and the volumes of these structures were correlated with performance on memory tests. In addition, the predictability of the length of coma from the selected anatomical volumes was examined. Method: High spatial resolution T1 weighted MRI scans of the brain (1 mm3) and neuropsychological evaluations with standardised tests were performed at least 3 months after trauma in 19 patients. Results: In comparison with control subjects matched in terms of gender and age, volume reduction in the hippocampus, fornix, and corpus callosum of the nmTBI patients was quantitatively significant. The length of coma correlated with the volume reduction in the corpus callosum. Immediate free recall of word lists correlated with the volume of the fornix and the corpus callosum. Delayed recall of word lists and immediate recall of the Rey figure both correlated with the volume of the fornix. Delayed recall of the Rey figure correlated with the volume of the fornix and the right hippocampus. Conclusion: These findings demonstrate that in severe nmTBI without obvious neuroradiological lesions there is a clear hippocampal, fornix, and callosal volume reduction. The length of coma predicts the callosal volume reduction, which could be considered a marker of the severity of axonal loss. A few memory test scores correlated with the volumes of the selected anatomical structures. This relationship with memory performance may reflect the diffuse nature of the damage, leading to the disruption of neural circuits at multiple levels and the progressive neural degeneration occurring in TBI. PMID:15314123

Epigenetic memory: the Lamarckian brain

PubMed Central

Fischer, Andre

2014-01-01

Recent data support the view that epigenetic processes play a role in memory consolidation and help to transmit acquired memories even across generations in a Lamarckian manner. Drugs that target the epigenetic machinery were found to enhance memory function in rodents and ameliorate disease phenotypes in models for brain diseases such as Alzheimer's disease, Chorea Huntington, Depression or Schizophrenia. In this review, I will give an overview on the current knowledge of epigenetic processes in memory function and brain disease with a focus on Morbus Alzheimer as the most common neurodegenerative disease. I will address the question whether an epigenetic therapy could indeed be a suitable therapeutic avenue to treat brain diseases and discuss the necessary steps that should help to take neuroepigenetic research to the next level. PMID:24719207

[Memory engram of brain circuit].

PubMed

Kojima, Hiroto; Sakaguchi, Tetsuya; Ikegaya, Yuji

2015-05-01

How are memories stored in the brain and retrieved on demand? This is a frequently asked question. Indeed, we acquire new memories daily and remember old ones. However, how we can memorize one-time experiences is yet to be investigated. Here, we review possible mechanisms by which memories are maintained in neural networks.

Role of Copper and Cholesterol Association in the Neurodegenerative Process

PubMed Central

Morel, Gustavo R.; de Alaniz, María J. T.; Castillo, Omar; Marra, Carlos A.

2013-01-01

Age is one of the main factors involved in the development of neurological illnesses, in particular, Alzheimer, and it is widely held that the rapid aging of the world population is accompanied by a rise in the prevalence and incidence of Alzheimer disease. However, evidence from recent decades indicates that Cu and Cho overload are emerging causative factors in neurodegeneration, a hypothesis that has been partially investigated in experimental models. The link between these two variables and the onset of Alzheimer disease has opened up interesting new possibilities requiring more in-depth analysis. The aim of the present study was therefore to investigate the effect of the association of Cu + Cho (CuCho) as a possible synergistic factor in the development of an Alzheimer-like pathology in Wistar rats. We measured total- and nonceruloplasmin-bound Cu and Cho (free and sterified) contents in plasma and brain zones (cortex and hippocampus), markers of oxidative stress damage, inflammation, and programmed cell death (caspase-3 and calpain isoforms). The ratio beta-amyloid (1-42)/(1-40) was determined in plasma and brain as neurodegenerative biomarker. An evaluation of visuospatial memory (Barnes maze test) was also performed. The results demonstrate the establishment of a prooxidative and proinflammatory environment after CuCho treatment, hallmarked by increased TBARS, protein carbonyls, and nitrite plus nitrate levels in plasma and brain zones (cortex and hippocampus) with a consequent increase in the activity of calpains and no significant changes in caspase-3. A simultaneous increase in the plasma Aβ1-42/Aβ1-40 ratio was found. Furthermore, a slight but noticeable change in visuospatial memory was observed in rats treated with CuCho. We conclude that our model could reflect an initial stage of neurodegeneration in which Cu and Cho interact with one another to exacerbate neurological damage. PMID:24288650

A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

PubMed

Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

2014-09-01

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.

The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery.

PubMed

Helmstaedter, C; Brosch, T; Kurthen, M; Elger, C E

2004-07-01

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language dominance-dependent late, i.e. adult age, plasticity for verbal memory when epilepsy surgery is performed in these patients. Pre- and 1-year postoperative memory performance was evaluated in 169 patients (94 males and 75 females) who underwent left temporal lobe surgery and who had WADA testing of hemispheric language dominance prior to surgery. Verbal memory and figural memory were assessed by list-learning paradigms. According to the Bonn intracarotid amobarbital test (IAT) protocol, patients were categorized into left dominant or atypically dominant (right, incomplete left or right, and bilateral dominant) groups. Results were controlled for the hypothesized sex differences. Thirty-four percent of men and 47% of women displayed patterns of atypical language dominance. Atypical dominance was related to an early onset of epilepsy. Men showed a larger time window for development of atypical dominance but, differently from women, the pattern of atypical dominance was more strictly determined by the age at onset of epilepsy. Atypically dominant women showed better verbal memory than typically dominant women or men. After surgery, right dominant patients had better verbal memory outcome than patients with bilateral or left language dominance who showed significant memory loss. No effect of sex on verbal memory change was found. Figural memory deteriorated in men and improved in women, when they were not left dominant. Seizure outcome had no effect on performance changes. It was concluded that better preserved verbal memory in atypically dominant women before surgery indicates greater benefit from atypical dominance in women than men with regard to the initial damage associated with left hemisphere epilepsy. Later in life, when epilepsy surgery causes additional damage, no such sex difference is observed, indicating that the women's advantage over men is fixed to an early time window in life. Postoperative changes in figural memory suggest dynamics in crowding and suppression patterns. Whether this reflects late plasticity and compensation needs further demonstration. For clinical practice, it is important to note that incomplete right hemisphere and bilateral language dominance do not protect against verbal memory loss after left-sided temporal lobe surgery. Copyright 2004 Guarantors of Brain

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

PubMed

Wright, P; Rogers, N; Hall, C; Wilson, B; Evans, J; Emslie, H

2001-12-01

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

Memory Impairment in Multiple Sclerosis is Due to a Core Deficit in Initial Learning

PubMed Central

DeLuca, John; Leavitt, Victoria M.; Chiaravalloti, Nancy; Wylie, Glenn

2013-01-01

Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < .01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > .05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS. PMID:23832311

Compound mechanism hypothesis on +Gz induced brain injury and dysfunction of learning and memory

NASA Astrophysics Data System (ADS)

Sun, Xi-Qing; Li, Jin-Sheng; Cao, Xin-Sheng; Wu, Xing-Yu

2005-08-01

We systematically studied the effect of high- sustained +Gz on the brain and its mechanism in past ten years by animal centrifuge experiments. On the basis of the facts we observed and the more recent advances in acceleration physiology, we put forward a compound mechanism hypothesis to offer a possible explanation for +Gz-induced brain injury and dysfunction of learning and memory. It states that, ischemia during high G exposure might be the main factor accounting for +Gz-induced brain injury and dysfunction of learning and memory, including transient depression of brain energy metabolism, disturbance of ion homeostasis, increased blood-brain barrier permeability, increased brain nitric oxide synthase expression, and the protective effect of heat shock protein 70. In addition, the large rapid change of intracranial pressure and increased stress during +Gz exposure, and the hemorrheologic change after +Gz exposure might be one of the important factors accounting for +Gz-induced brain injury and dysfunction of learning and memory.

Memory retrieval along the proximodistal axis of CA1.

PubMed

Nakazawa, Yuki; Pevzner, Aleksandr; Tanaka, Kazumasa Z; Wiltgen, Brian J

2016-09-01

The proximal and distal segments of CA1 are thought to perform distinct computations. Neurons in proximal CA1 are reciprocally connected with the medial entorhinal cortex (MEC) and exhibit precise spatial firing. In contrast, cells in distal CA1 communicate with the lateral entorhinal cortex (LEC), exhibit more diffuse spatial firing and are affected by the presence of objects in the environment. To determine if these segments make unique contributions to memory retrieval, we examined cellular activity along the proximodistal axis of CA1 using transgenic reporter mice. Neurons tagged during context learning in proximal CA1 were more likely to be reactivated during testing than those in distal CA1. This was true following context fear conditioning and after exposure to a novel environment. Reactivation was also higher in brain regions connected to proximal CA1 (MEC, distal CA3) than those connected to the distal segment (LEC, proximal CA3). To examine contributions to memory retrieval, we performed neurotoxic lesions of proximal or distal CA1 after training. Lesions of the proximal segment significantly impaired memory retrieval while damage to distal CA1 had no effect. These data suggest that context memories are retrieved by a hippocampal microcircuit that involves the proximal but not distal segment of CA1. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of SenseCam on memory, identity and mood in Korsakoff's syndrome: a single case experimental design study.

PubMed

Svanberg, Jenny; Evans, Jonathan J

2014-01-01

This study aimed to investigate the impact of SenseCam, a wearable, automatic camera, on subjective mood and identity in a patient with severe memory impairment due to Korsakoff's syndrome. It was hypothesised that SenseCam would improve Ms A's mood and identity through enhancing recall of autobiographical memories of recent events, therefore supporting a coherent sense of self; the lack of which was contributing to Ms A's mood deterioration. An ABA single case experimental design investigated whether using SenseCam to record regular activities impacted on Ms A's mood and identity. Ms A experienced improved recall for events recorded using SenseCam, and showed improvement on subjective ratings of identity. However, a corresponding improvement in mood was not seen, and the study was ended early at Ms A's request. Qualitative information was gathered to explore Ms A's experience of the study, and investigate psychosocial factors that may have impacted on the use of SenseCam. SenseCam may be of significant use as a compensatory memory aid for people with Korsakoff's syndrome and other types of alcohol-related brain damage (ARBD), but acceptance of memory impairment and consistent support may be among the factors required to support the use of such assistive technologies in a community setting.

Molecular mechanism of brain impairment caused by drinking-acquired fluorosis and selenium intervention.

PubMed

Zheng, Xiangren; Sun, Yan; Ke, Lulu; Ouyang, Wei; Zhang, Zigui

2016-04-01

This study investigated the molecular mechanism of brain impairment induced by drinking fluoridated water and selenium intervention. Results showed that the learning and memory of rats in NaF group significantly decreased. Moreover, the number of apoptotic cells, the expression levels of Cytc mRNA and protein, and the expression levels of Caspase-9 and Caspase-3 mRNA significantly increased; by contrast, Caspase-9 and Caspase-3 protein levels significantly decreased. Compared with the NaF group, the mRNA levels of Cytc and Caspase-9, as well as the protein levels of Cytc in NaF+Se group, significantly decreased. Conversely, the protein levels of Caspase-3 and Caspase-9, as well as the mRNA levels of Caspase-3, significantly increased. Thus, the mitochondrial CytC-Caspase-9-Caspase-3 apoptosis pathway in the hippocampus was one of the mechanisms leading to fluorosis-induced brain damage. Furthermore, the Cytc signaling molecules were possibly the key target molecules in fluorosis-induced apoptosis, and selenium could alleviate fluorosis-induced brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

[Inflammation and oxidation: predictive and/or causative factors].

PubMed

Fernández-Viadero, Carlos; Jiménez-Sanz, Magdalena; Fernández-Pérez, Anzu; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

2016-06-01

Brain ageing leads to a series of changes that reduce the processes of adaptation and response. These transformations can end in cognitive impairment and/or dementia. Although the cause of these changes is diverse, inflammation and oxidative stress explain some of the pathophysiological mechanisms of these anomalies of brain functioning. Neuroinflammation triggers neuronal injury through the presence of inflammatory cytokines and the activation of microglia through membrane receptors and nuclear activation factors. This neuroinflammatory phenomenon also affects neuron plasticity, altering the genesis and maintenance of long-term potentiation, leading to impairment of hippocampus-dependent memory. Oxidative stress and the production of free oxygen radicals also cause toxic effects in aged brains, largely due to lipid peroxidation and DNA damage. The identification of the molecular mechanisms involved in the pathogenesis of these events could shed new light on possible therapeutic targets and offer strategies for the prevention of diseases related to brain ageing, cognitive impairment and dementia. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

Medial PFC Damage Abolishes the Self-reference Effect

PubMed Central

Philippi, Carissa L.; Duff, Melissa C.; Denburg, Natalie L.; Tranel, Daniel; Rudrauf, David

2012-01-01

Functional neuroimaging studies suggest that the medial PFC (mPFC) is a key component of a large-scale neural system supporting a variety of self-related processes. However, it remains unknown whether the mPFC is critical for such processes. In this study, we used a human lesion approach to examine this question. We administered a standard trait judgment paradigm [Kelley, W. M., Macrae, C. N., Wyland, C. L., Caglar, S., Inati, S., & Heatherton, T. F. Finding the self? An event-related fMRI study. Journal of Cognitive Neuroscience, 14, 785–794, 2002] to patients with focal brain damage to the mPFC. The self-reference effect (SRE), a memory advantage conferred by self-related processing, served as a measure of intact self-processing ability. We found that damage to the mPFC abolished the SRE. The results demonstrate that the mPFC is necessary for the SRE and suggest that this structure is important for self-referential processing and the neural representation of self. PMID:21942762

Dopaminergic contributions to working memory-related brain activation in postmenopausal women

PubMed Central

Dumas, Julie A.; Filippi, Christopher G.; Newhouse, Paul A.; Naylor, Magdalena R.

2016-01-01

Objective The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Method Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed an fMRI visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. Results We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared to dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Conclusions Patterns of increased BOLD signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women in order to determine the effects of the increased brain activation on cognition and behavior. PMID:27676634

Is there a positive bias in false recognition? Evidence from confabulating amnesia patients.

PubMed

Alkathiri, Nura H; Morris, Robin G; Kopelman, Michael D

2015-10-01

Although there is some evidence for a positive emotional bias in the content of confabulations in brain damaged patients, findings have been inconsistent. The present study used the semantic-associates procedure to induce false recall and false recognition in order to examine whether a positive bias would be found in confabulating amnesic patients, relative to non-confabulating amnesic patients and healthy controls. Lists of positive, negative and neutral words were presented in order to induce false recall or false recognition of non-presented (but semantically associated) words. The latter were termed 'critical intrusions'. Thirteen confabulating amnesic patients, 13 non-confabulating amnesic patients and 13 healthy controls were investigated. Confabulating patients falsely recognised a higher proportion of positive (but unrelated) words, compared with non-confabulating patients and healthy controls. No differences were found for recall memory. Signal detection analysis, however, indicated that the positive bias for false recognition memory might reflect weaker memory in the confabulating amnesic group. This suggested that amnesia patients with weaker memory are more likely to confabulate and the content of these confabulations are more likely to be positive. Copyright © 2015 Elsevier Ltd. All rights reserved.

Memory-guided saccade processing in visual form agnosia (patient DF).

PubMed

Rossit, Stéphanie; Szymanek, Larissa; Butler, Stephen H; Harvey, Monika

2010-01-01

According to Milner and Goodale's model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and oV-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF's saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.

Amygdala in action: relaying biological and social significance to autobiographical memory.

PubMed

Markowitsch, Hans J; Staniloiu, Angelica

2011-03-01

The human amygdala is strongly embedded in numerous other structures of the limbic system, but is also a hub for a multitude of other brain regions it is connected with. Its major involvement in various kinds of integrative sensory and emotional functions makes it a cornerstone for self-relevant biological and social appraisals of the environment and consequently also for the processing of autobiographical events. Given its contribution to the integration of emotion, perception and cognition (including memory for past autobiographical events) the amygdala also forges the establishment and maintenance of an integrated self. Damage or disturbances of amygdalar connectivity may therefore lead to disconnection syndromes, in which the synchronous processing of affective and cognitive aspects of memory is impaired. We will provide support for this thesis by reviewing data from patients with a rare experiment of nature - Urbach-Wiethe disease - as well as other conditions associated with amygdala abnormalities. With respect to memory processing, we propose that the amygdala's role is to charge cues so that mnemonic events of a specific emotional significance can be successfully searched within the appropriate neural nets and re-activated. Copyright © 2010 Elsevier Ltd. All rights reserved.

Magnetization Transfer Ratio Relates to Cognitive Impairment in Normal Elderly

PubMed Central

Seiler, Stephan; Pirpamer, Lukas; Hofer, Edith; Duering, Marco; Jouvent, Eric; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2014-01-01

Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38–86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia. PMID:25309438

Fibrin deposited in the Alzheimer’s disease brain promotes neuronal degeneration

PubMed Central

Cortes-Canteli, Marta; Mattei, Larissa; Richards, Allison T.; Norris, Erin H.; Strickland, Sidney

2014-01-01

Alzheimer’s disease (AD) is the most common form of dementia and has no effective treatment. Besides the well-known pathological characteristics, this disease also has a vascular component, and substantial evidence shows increased thrombosis as well as a critical role for fibrin(ogen) in AD. This molecule has been implicated in neuroinflammation, neurovascular damage, blood brain barrier permeability, vascular amyloid deposition, and memory deficits that are observed in AD. Here we present evidence demonstrating that fibrin deposition increases in the AD brain and correlates with the degree of pathology. Moreover, we show that fibrin(ogen) is present in areas of dystrophic neurites and that a modest decrease in fibrinogen levels improves neuronal health and ameliorates amyloid pathology in the subiculum of AD mice. Our results further characterize the important role of fibrin(ogen) in this disease and support the design of therapeutic strategies aimed at blocking the interaction between fibrinogen and Aβ and/or normalizing the increased thrombosis present in AD. PMID:25475538

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Emotion regulation modulates anticipatory brain activity that predicts emotional memory encoding in women.

PubMed

Galli, Giulia; Griffiths, Victoria A; Otten, Leun J

2014-03-01

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.

Functional brain microstate predicts the outcome in a visuospatial working memory task.

PubMed

Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

2016-11-01

Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Ephs and Ephrins in Memory Formation

PubMed Central

Dines, Monica

2016-01-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer’s disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID:26371183

Optimization of immunolabeling and clearing techniques for indelibly-labeled memory traces.

PubMed

Pavlova, Ina P; Shipley, Shannon C; Lanio, Marcos; Hen, René; Denny, Christine A

2018-04-16

Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e. engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert-Butanol, circumvented these harmful effects, but still did not permit whole-brain immunolabeling. CUBIC and CUBIC with Reagent 1A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole-brain memory trace visualization. Modification of CUBIC with Reagent-1A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm-thick tissue sections. In summary, our data show that CUBIC with Reagent-1A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm-thick tissue sections from ArcCreER T2 mice. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Binge drinking and declarative memory in university students.

PubMed

Parada, María; Corral, Montserrat; Caamaño-Isorna, Francisco; Mota, Nayara; Crego, Alberto; Holguín, Socorro Rodríguez; Cadaveira, Fernando

2011-08-01

Binge drinking (BD), which is characterized by sporadic consumption of large quantities of alcohol in short periods, is prevalent among university students. Animal studies have shown that BD is associated with damage to the hippocampus, a region of the brain that plays a key role in learning and memory. The temporal cortex undergoes structural and functional changes during adolescence. The aim of the present study was to examine the association between BD and declarative memory in male and female university students. The participants were 122 students (between 18 and 20 years of age): 62 BD (30 women) and 60 non-BD (29 women). The neuropsychological assessment included the Rey Auditory Verbal Learning Test (RAVLT) and Weschler Memory Scale-3rd ed. (WMS-III) Logical Memory subtest, to evaluate verbal declarative memory, and the WMS-III Family Pictures subtest, to measure visual declarative memory. The BD students remembered fewer words in the interference list and displayed greater proactive interference in the RAVLT; they performed worse in the Logical Memory subtest, both on immediate and delayed recall. There were no differences between the groups in performance of the Family Pictures subtest. No significant interactions were observed between BD and sex. Binge drinking is associated with poorer verbal declarative memory, regardless of sex. The findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. Longitudinal studies will help determine the nature of this relationship, the neurodevelopmental trajectories for each sex, and the repercussions on academic performance. Copyright © 2011 by the Research Society on Alcoholism.

Comprehension of Idioms in Turkish Aphasic Participants.

PubMed

Aydin, Burcu; Barin, Muzaffer; Yagiz, Oktay

2017-12-01

Brain damaged participants offer an opportunity to evaluate the cognitive and linguistic processes and make assumptions about how the brain works. Cognitive linguists have been investigating the underlying mechanisms of idiom comprehension to unravel the ongoing debate on hemispheric specialization in figurative language comprehension. The aim of this study is to evaluate and compare the comprehension of idiomatic expressions in left brain damaged (LBD) aphasic, right brain damaged (RBD) and healthy control participants. Idiom comprehension in eleven LBD aphasic participants, ten RBD participants and eleven healthy control participants were assessed with three tasks: String to Picture Matching Task, Literal Sentence Comprehension Task and Oral Idiom Definition Task. The results of the tasks showed that in overall idiom comprehension category, the left brain-damaged aphasic participants interpret idioms more literally compared to right brain-damaged participants. What is more, there is a significant difference in opaque idiom comprehension implying that left brain-damaged aphasic participants perform worse compared to right brain-damaged participants. On the other hand, there is no statistically significant difference in scores of transparent idiom comprehension between the left brain-damaged aphasic and right brain-damaged participants. This result also contribute to the idea that while figurative processing system is damaged in LBD aphasics, the literal comprehension mechanism is spared to some extent. The results of this study support the view that idiom comprehension sites are mainly left lateralized. Furthermore, the results of this study are in consistence with the Giora's Graded Salience Hypothesis.

Eye-Target Synchrony and Attention

NASA Astrophysics Data System (ADS)

Contreras, R.; Kolster, R.; Basu, S.; Voss, H. U.; Ghajar, J.; Suh, M.; Bahar, S.

2007-03-01

Eye-target synchrony is critical during smooth pursuit. We apply stochastic phase synchronization to human pursuit of a moving target, in both normal and mild traumatic brain injured (TBI) subjects. Smooth pursuit utilizes the same neural networks used by attention. To test whether smooth pursuit is modulated by attention, subjects tracked a target while loaded with tasks involving working memory. Preliminary results suggest that additional cognitive load increases normal subjects' performance, while the effect is reversed in TBI patients. We correlate these results with eye-target synchrony. Additionally, we correlate eye-target synchrony with frequency of target motion, and discuss how the range of frequencies for optimal synchrony depends on the shift from attentional to automatic-response time scales. Synchrony deficits in TBI patients can be correlated with specific regions of brain damage imaged with diffusion tensor imaging (DTI).

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease.

PubMed

Hirni, Daniela I; Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

2013-04-01

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes.

PubMed

Yau, Po Lai; Javier, David; Tsui, Wai; Sweat, Victoria; Bruehl, Hannah; Borod, Joan C; Convit, Antonio

2009-12-30

Declarative memory impairment is frequently reported among adults with type 2 diabetes mellitus (T2DM), who also demonstrate hippocampal volume reduction. Our goals were to ascertain whether emotional memory, which is mediated by neural circuits overlapping those of declarative memory, is also affected. In addition we wanted to characterize cerebral white matter (WM) involvement in T2DM. We studied 24 middle-aged and elderly patients with T2DM who were free of obvious vascular pathology or a psychiatric disorder, and 17 age- and education-matched healthy individuals with no evidence of insulin resistance. We examined emotional and neutral memory and performed a whole-brain voxelwise WM assessment utilizing diffusion tensor imaging (DTI). We found clear evidence of impairment in declarative memory among diabetic subjects and in addition found some preliminary support to suggest a possible blunting of the memory facilitation by emotional material among female but not male diabetics. This report is also the first DTI assessment among individuals with T2DM, which after accounting for overt WM damage, revealed diffuse but predominantly frontal and temporal WM microstructural abnormalities, with extensive involvement of the temporal stem. Hierarchical regression analyses demonstrated that immediate, but not delayed, emotional memory performance was explained by temporal stem FA, independent of age, poor metabolic regulation, and systolic blood pressure. Given that the temporal lobe memory networks appear to be particularly vulnerable to the deleterious effects of T2DM, this may help explain the observed memory impairments among diabetics. Future efforts should better clarify, with a larger sample, whether emotional memory is affected in adults with T2DM and whether there are clear gender effects.

Aβ Damages Learning and Memory in Alzheimer's Disease Rats with Kidney-Yang Deficiency

PubMed Central

Qi, Dongmei; Qiao, Yongfa; Zhang, Xin; Yu, Huijuan; Cheng, Bin; Qiao, Haifa

2012-01-01

Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal Aβ 40 and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synaptic plasticity is involved in the learning and memory impairment of Kidney-yang deficiency rats. We determined that the learning and memory damage in Kidney-yang deficiency due to synaptic plasticity impairment and increases of Aβ 40 and 42 was not caused via NMDA receptor internalization induced by Aβ increase. β-Adrenergic receptor agonist can rescue the impaired long-term potential (LTP) in Kidney-yang rats. Taken together, our results suggest that spatial learning and memory inhibited in Kidney-yang deficiency might be induced by Aβ increase and the decrease of β 2 receptor function in glia. PMID:22645624

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging.

PubMed

Sun, Felicia W; Stepanovic, Michael R; Andreano, Joseph; Barrett, Lisa Feldman; Touroutoglou, Alexandra; Dickerson, Bradford C

2016-09-14

Decline in cognitive skills, especially in memory, is often viewed as part of "normal" aging. Yet some individuals "age better" than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20-30 years younger (i.e., "superagers"), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60-80 years old) based on their performance compared to young adults (18-32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults. Copyright © 2016 Sun, Stepanovic et al.

Statistical and perceptual updating: correlated impairments in right brain injury.

PubMed

Stöttinger, Elisabeth; Filipowicz, Alex; Marandi, Elahe; Quehl, Nadine; Danckert, James; Anderson, Britt

2014-06-01

It has been hypothesized that many of the cognitive impairments commonly seen after right brain damage (RBD) can be characterized as a failure to build or update mental models. We (Danckert et al. in Neglect as a disorder of representational updating. NOVA Open Access, New York, 2012a; Cereb Cortex 22:2745-2760, 2012b) were the first to directly assess the association between RBD and updating and found that RBD patients were unable to exploit a strongly biased play strategy in their opponent in the children's game rock, paper, scissors. Given that this game required many other cognitive capacities (i.e., working memory, sustained attention, reward processing), RBD patients could have failed this task for various reasons other than a failure to update. To assess the generality of updating deficits after RBD, we had RBD, left brain-damaged (LBD) patients and healthy controls (HCs) describe line drawings that evolved gradually from one figure (e.g., rabbit) to another (e.g., duck) in addition to the RPS updating task. RBD patients took significantly longer to alter their perceptual report from the initial object to the final object than did LBD patients and HCs. Although both patient groups performed poorly on the RPS task, only the RBD patients showed a significant correlation between the two, very different, updating tasks. We suggest these data indicate a general deficiency in the ability to update mental representations following RBD.

On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-10-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

On Initial Brain Activity Mapping of Associative Memory Code in the Hippocampus

PubMed Central

Tsien, Joe Z.; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Lei Wang, Phillip; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-01-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. PMID:23838072

The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

2016-01-01

Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs.

How Does the Sparse Memory “Engram” Neurons Encode the Memory of a Spatial–Temporal Event?

PubMed Central

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns. PMID:27601979

How Does the Sparse Memory "Engram" Neurons Encode the Memory of a Spatial-Temporal Event?

PubMed

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns.

The importance of mammillary body efferents for recency memory: towards a better understanding of diencephalic amnesia.

PubMed

Nelson, Andrew J D; Vann, Seralynne D

2017-07-01

Despite being historically one of the first brain regions linked to memory loss, there remains controversy over the core features of diencephalic amnesia as well as the critical site for amnesia to occur. The mammillary bodies and thalamus appear to be the primary locus of pathology in the cases of diencephalic amnesia, but the picture is complicated by the lack of patients with circumscribed damage. Impaired temporal memory is a consistent neuropsychological finding in Korsakoff syndrome patients, but again, it is unclear whether this deficit is attributable to pathology within the diencephalon or concomitant frontal lobe dysfunction. To address these issues, we used an animal model of diencephalic amnesia and examined the effect of mammillothalamic tract lesions on tests of recency memory. The mammillothalamic tract lesions severely disrupted recency judgements involving multiple items but left intact both recency and familiarity judgements for single items. Subsequently, we used disconnection procedures to assess whether this deficit reflects the indirect involvement of the prefrontal cortex. Crossed-lesion rats, with unilateral lesions of the mammillothalamic tract and medial prefrontal cortex in contralateral hemispheres, were unimpaired on the same recency tests. These results provide the first evidence for the selective importance of mammillary body efferents for recency memory. Moreover, this contribution to recency memory is independent of the prefrontal cortex. More broadly, these findings identify how specific diencephalic structures are vital for key elements of event memory.

Neuropsychological deficits in temporal lobe epilepsy: A comprehensive review

PubMed Central

Zhao, Fengqing; Kang, Hai; You, LIbo; Rastogi, Priyanka; Venkatesh, D.; Chandra, Mina

2014-01-01

Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders. PMID:25506156

Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

PubMed

Geva, Sharon; Cooper, Janine M; Gadian, David G; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2016-08-01

One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain-behavior relationships in source memory: Effects of age and memory ability.

PubMed

Meusel, Liesel-Ann; Grady, Cheryl L; Ebert, Patricia E; Anderson, Nicole D

2017-06-01

There is considerable evidence for age-related decrements in source memory retrieval, but the literature on the neural correlates of these impairments is mixed. In this study, we used functional magnetic resonance imaging to examine source memory retrieval-related brain activity, and the monotonic relationship between retrieval-related brain activity and source memory accuracy, as a function of both healthy aging (younger vs older) and memory ability within the older adult group (Hi-Old vs Lo-Old). Participants studied lists of word pairs, half visually, half aurally; these were re-presented visually in a scanned test phase and participants indicated if the pair was 'seen' or 'heard' in the study phase. The Lo-Old, but not the Hi-Old, showed source memory performance decrements compared to the Young. During retrieval of source memories, younger and older adults engaged lateral and medial prefrontal cortex (PFC) and medial posterior parietal (and occipital) cortices. The groups differed in how brain activity related to source memory accuracy in dorsal anterior cingulate cortex, precuneus/cuneus, and the inferior parietal cortex; in each of these areas, greater activity was associated with poorer accuracy in the Young, but with higher accuracy in the Hi-Old (anterior cingulate and precuneus/cuneus) and Lo-Old (inferior parietal lobe). Follow-up pairwise group interaction analyses revealed that greater activity in right parahippocampal gyrus was associated with better source memory in the Hi-Old, but not in the Lo-Old. We conclude that older adults recruit additional brain regions to compensate for age-related decline in source memory, but the specific regions involved differ depending on their episodic memory ability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Memory-related brain lateralisation in birds and humans.

PubMed

Moorman, Sanne; Nicol, Alister U

2015-03-01

Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

Multifunctional liposomes delay phenotype progression and prevent memory impairment in a presymptomatic stage mouse model of Alzheimer disease.

PubMed

Mancini, Simona; Balducci, Claudia; Micotti, Edoardo; Tolomeo, Daniele; Forloni, Gianluigi; Masserini, Massimo; Re, Francesca

2017-07-28

The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes were administered once a week to Tg mice for 7months, starting at the age of 5months and up to the age of 12 when they display AD-like cognitive and brain biochemical/anatomical features. The treatment prevented the onset of the long-term memory impairment and slowed down the deposition of brain Aβ; at anatomical level, prevented both ventricle enlargement and entorhinal cortex thickness reduction, otherwise occurring in untreated mice. Strikingly, these effects were maintained 3months after treatment discontinuation. An increase of Aβ levels in the liver was detected at the end of the treatment, then followed also by reduction of brain Amyloid Precursor Protein and increase of Aβ-degrading enzymes. These results suggest that the treatment promotes brain Aβ clearance by a peripheral 'sink' effect and ultimately affects Aβ turnover in the brain. Worth of note, the treatment was apparently not toxic for all the organs analyzed, in particular for brain, as suggested by the lower brain TNF-α and MDA levels, and by higher level of SOD activity in treated mice. Together, these findings promote a very early treatment with multi-functional liposomes as a well-tolerated nanomedicine-based approach, potentially suitable for a disease-modifying therapy of AD, able to delay or prevent relevant features of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players.

PubMed

Gasiorowski, Kazimierz; Brokos, Barbara; Leszek, Jerzy; Tarasov, Vadim V; Ashraf, Ghulam Md; Aliev, Gjumrakch

2017-01-01

Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g. ceramide and products of advanced glycation) and ROS-modified cellular components, together with the activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

PubMed

García-Moreno, Luis M; Cimadevilla, Jose M

2012-12-01

Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. Copyright © 2012 Elsevier Inc. All rights reserved.

[The pharmacology of memory (results and prospects)].

PubMed

Borodkin, Iu S; Zaĭtsev, Iu V

1984-07-01

Principal possibilities and limits of using the pharmacological approach for control of memory in studies of neurophysiological and neurochemical mechanisms of learning and memory in humans and animals are reviewed as well as its place in experimental and clinical therapy of memory disorders. Using an unspecific connector aethimizol as a pharmacological probe aided to assess changes accompanying the formation and consolidation of memory traces. The significance of fast and slow bioelectrical brain activity in the memory processing, the role of enzymes involved in transcription and template chromatine activity of the neurons under the effect of drugs on memory and learning, the correlation between time-depending learning and the pattern of RNA synthesis in brain cells, as well as possibilities and pathways of utilization of drugs in the correction of the long-term memory matrix formed by a stable pathological state of the brain, are discussed.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

PubMed

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

Variability in memory performance in aged healthy individuals: an fMRI study.

PubMed

Grön, Georg; Bittner, Daniel; Schmitz, Bernd; Wunderlich, Arthur P; Tomczak, Reinhard; Riepe, Matthias W

2003-01-01

Episodic memory performance varies in older subjects but underlying biological correlates remain as yet ambiguous. We investigated episodic memory in healthy older individuals (n=24; mean age: 64.4+/-6.7 years) without subjective memory complaints or objective cognitive impairment. Episodic memory was assessed with repetitive learning and recall of abstract geometric patterns during fMRI. Group analysis of brain activity during initial learning and maximum recall revealed hippocampal activation. Correlation analysis of brain activation and task performance demonstrated significant hippocampal activity during initial learning and maximum recall in a success-dependent manner. Neither age nor gray matter densities correlated with hippocampal activation. Functional imaging of episodic memory thus permits to detect objectively variability in hippocampal recruitment in healthy aged individuals without subjective memory complaints. Correlation analysis of brain activation and performance during an episodic memory task may be used to determine and follow-up hippocampal malfunction in a very sensitive manner.

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welzel, Grit; Fleckenstein, Katharina; Department of Radiation Oncology, Duke University Medical Center, Durham, NC

2008-12-01

Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy,more » prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.« less

A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

PubMed

Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

2015-09-01

A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders. © 2015 Wiley Periodicals, Inc.

Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: a correlation with neuropsychological performance.

PubMed

Ichise, M; Chung, D G; Wang, P; Wortzman, G; Gray, B G; Franks, W

1994-02-01

The purposes of this study were: (1) to compare 99mTc-hexamethylpropyleneamineoxime (HMPAO) SPECT with CT and MRI in chronic traumatic brain injury (TBI) patients and (2) to correlate both functional and structural neuroimaging measurements of brain damage with neuropsychological (NP) performance. Twenty-nine patients (minor TBI, n = 15 and major TBI, n = 14) and 17 normal controls (NC) underwent HMPAO SPECT, CT, MRI and NP testing. Imaging data were analyzed both visually and quantitatively. Nineteen (66%) patients showed 42 abnormalities on SPECT images, whereas 13 (45%) and 10 (34%) patients showed 29 abnormalities on MRI and 24 abnormalities on CT. SPECT detected relatively more abnormalities than CT or MRI in the minor TBI subgroup. The TBI group showed impairment on 11 tests for memory, attention and executive function. Of these, the anterior-posterior ratio (APR) correlated with six tests, whereas the ventricle-to-brain ratio (VBR), a known structural index of a poor NP outcome, correlated with only two tests. In evaluating chronic TBI patients, HMPAO SPECT, as a complement to CT or MRI, may play a useful role by demonstrating brain dysfunction in morphologically intact brain regions and providing objective evidence for some of the impaired NP performance.

Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria.

PubMed

Miwa, Satomi; Czapiewski, Rafal; Wan, Tengfei; Bell, Amy; Hill, Kirsten N; von Zglinicki, Thomas; Saretzki, Gabriele

2016-10-22

Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.

Effects of aluminum and extremely low frequency electromagnetic radiation on oxidative stress and memory in brain of mice.

PubMed

Deng, Yuanxin; Zhang, Yanwen; Jia, Shujie; Liu, Junkang; Liu, Yanxia; Xu, Weiwei; Liu, Lei

2013-12-01

This study was aimed to investigate the effect of aluminum and extremely low-frequency magnetic fields (ELF-MF) on oxidative stress and memory of SPF Kunming mice. Sixty male SPF Kunming mice were divided randomly into four groups: control group, ELF-MF group (2 mT, 4 h/day), load aluminum group (200 mg aluminum/kg, 0.1 ml/10 g), and ELF-MF + aluminum group (2 mT, 4 h/day, 200 mg aluminum/kg). After 8 weeks of treatment, the mice of three experiment groups (ELF-MF group, load aluminum group, and ELF-MF + aluminum group) exhibited firstly the learning memory impairment, appearing that the escaping latency to the platform was prolonged and percentage in the platform quadrant was reduced in the Morris water maze (MWM) task. Secondly are the pathologic abnormalities including neuronal cell loss and overexpression of phosphorylated tau protein in the hippocampus and cerebral cortex. On the other hand, the markers of oxidative stress were determined in mice brain and serum. The results showed a statistically significant decrease in superoxide dismutase activity and increase in the levels of malondialdehyde in the ELF-MF group (P < 0.05 or P < 0.01), load aluminum group (P < 0.01), and ELF-MF + aluminum group (P < 0.01). However, the treatment with ELF-MF + aluminum induced no more damage than ELF-MF and aluminum did, respectively. In conclusion, both aluminum and ELF-MF could impact on learning memory and pro-oxidative function in Kunming mice. However, there was no evidence of any association between ELF-MF exposure with aluminum loading.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

PubMed

Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

2009-03-31

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2014-01-01

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

PubMed Central

Smith, Amanda L.; Hill, Courtney A.; Alexander, Michelle; Szalkowski, Caitlin E.; Chrobak, James J.; Rosenkrantz, Ted S.; Fitch, R. Holly

2014-01-01

Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36–38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI. PMID:24961760

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

PubMed

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

PubMed Central

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

Objective It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID:26139105

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes

PubMed Central

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A.

2015-01-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

Rutin hydrate ameliorates cadmium chloride-induced spatial memory loss and neural apoptosis in rats by enhancing levels of acetylcholine, inhibiting JNK and ERK1/2 activation and activating mTOR signalling.

PubMed

Abdel-Aleem, Ghada A; Khaleel, Eman F

2017-12-07

This study aimed at studying the potential neuroprotective effect of Rutin hydrate (RH) alone or in conjugation with α-tocopherol against cadmium chloride (CdCl 2 )-induced neurotoxicity and cognitive impairment in rats and to investigate the mechanisms of action. Rats intoxicated with CdCl 2 were treated with the vehicle, RH, α-tocopherol or combined treatment were examined, and compared to control rats received vehicle or individual doses of either drug. Data confirmed that RH improves spatial memory function by increasing acetylcholine availability, boosting endogenous antioxidant potential, activating cell survival and inhibiting apoptotic pathways, an effect that is more effective when RH was conjugated with α-tocopherol. Mechanism of RH action includes activation of PP2A mediated inhibiting of ERK1/2 and JNK apoptotic pathways and inhibition of PTEN mediated activation of mTOR survival pathway. In conclusion, RH affords a potent neuroprotection against CdCl 2 -induced brain damage and memory dysfunction and co-administration of α-tocopherol enhances its activity.

Thalidomide attenuates learning and memory deficits induced by intracerebroventricular administration of streptozotocin in rats.

PubMed

Elçioğlu, Hk; Kabasakal, L; Alan, S; Salva, E; Tufan, F; Karan, Ma

2013-05-01

Neuroinflammatory responses caused by amyloid β (Aβ) peptide deposits are involved in the pathogenesis of Alzheimer's disease (AD). Thalidomide has a significant anti-inflammatory effect by inhibiting TNF-α, which plays role in Aβ neurotoxicity. We investigated the effect of thalidomide on AD-like cognitive deficits caused by intracerebroventricular injection of streptozotocin (STZ). Intraperitoneal thalidomide was administered 1 h before the first dose of STZ and continued for 21 days. Learning and memory behavior was evaluated on days 17, 18 and 19, and the rats were sacrificed on day 21 to examine histopathological changes. STZ injection caused a significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in Morris water maze tests. Histopathological changes were examined using hematoxylin-eosin and Bielschowsky staining. Brain sections of STZ treated rats showed increased neurodegeneration and disturbed linear arrangement of cells in the cortical area compared to controls. Thalidomide treatment attenuated significantly STZ induced cognitive impairment and histopathological changes. Thalidomide appears to provide neuroprotection from the memory deficits and neuronal damage induced by STZ.

Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

ERIC Educational Resources Information Center

Ravizza, Susan M.; Mccormick, Cristin A.; Schlerf, John E.; Justus, Timothy; Ivry, Richard B.; Fiez, Julie A.

2006-01-01

The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The…

Committing to Memory: Memory Prosthetics Show Promise in Helping Those with Neurodegenerative Disorders.

PubMed

Solis, Michele

2017-01-01

Cell phone chimes, sticky notes, even the proverbial string around a finger-these timehonored external cues help guard against our inevitable memory lapses. But some internal help to the brain itself may be on the way in the form of what's being called memory prosthetics. Once considered to be on the fringes of neuroscience, the idea of adding hardware to the brain to help with memory has gathered steam. In 2014, the U.S. Defense Advanced Research Projects Agency (DARPA) made a US$30 million investment in memory prosthetic research as part of the Obama administration's Brain Research through Advancing Innovative Neurotechnologies initiative. In August 2016, Kernel, a startup based in Los Angeles, California, announced its goal to develop a clinical memory device for those debilitated by neurodegenerative disorders such as Alzheimer's disease.

Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia.

PubMed

Li, Xiaobo; Thermenos, Heidi W; Wu, Ziyan; Momura, Yoko; Wu, Kai; Keshavan, Matcheri; Seidman, Lawrence; DeLisi, Lynn E

2016-10-01

Working memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal- and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. Functional MRI data acquired during a verbal- vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A-B), 4) spatial higher than verbal (B-A), 5) conjunction of brain regions that were activated during both A and B (A∧B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. Compared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A-B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. Our findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies.

PubMed

Zimmermann, Kathrin; Eschen, Anne

2017-04-01

Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.

Professionals' views on the use of smartphone technology to support children and adolescents with memory impairment due to acquired brain injury.

PubMed

Plackett, Ruth; Thomas, Sophie; Thomas, Shirley

2017-04-01

Purpose To identify from a health-care professionals' perspective whether smartphones are used by children and adolescents with acquired brain injury as memory aids; what factors predict smartphone use and what barriers prevent the use of smartphones as memory aids by children and adolescents. Method A cross-sectional online survey was undertaken with 88 health-care professionals working with children and adolescents with brain injury. Results Children and adolescents with brain injury were reported to use smartphones as memory aids by 75% of professionals. However, only 42% of professionals helped their clients to use smartphones. The only factor that significantly predicted reported smartphone use was the professionals' positive attitudes toward assistive technology. Several barriers to using smartphones as memory aids were identified, including the poor accessibility of devices and cost of devices. Conclusion Many children and adolescents with brain injury are already using smartphones as memory aids but this is often not facilitated by professionals. Improving the attitudes of professionals toward using smartphones as assistive technology could help to increase smartphone use in rehabilitation. Implications for Rehabilitation Smartphones could be incorporated into rehabilitation programs for young people with brain injury as socially acceptable compensatory aids. Further training and support for professionals on smartphones as compensatory aids could increase professionals' confidence and attitudes in facilitating the use of smartphones as memory aids. Accessibility could be enhanced by the development of a smartphone application specifically designed to be used by young people with brain injury.

Through the Immune Looking Glass: A Model for Brain Memory Strategies

PubMed Central

Sánchez-Ramón, Silvia; Faure, Florence

2016-01-01

The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust’s madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model’s approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID:26869886

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

PubMed

Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

2016-03-01

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Brain plasticity, memory, and aging: a discussion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, E.L.; Rosenzweig, M.R.

1977-12-01

It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing formore » the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.« less

Associations Between White Matter Microstructure and Infants’ Working Memory

PubMed Central

Short, Sarah J.; Elison, Jed T.; Goldman, Barbara Davis; Styner, Martin; Gu, Hongbin; Connelly, Mark; Maltbie, Eric; Woolson, Sandra; Lin, Weili; Gerig, Guido; Reznick, J. Steven; Gilmore, John H.

2013-01-01

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants’ visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants’ gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity. PMID:22989623

Brain networks in posterior cortical atrophy: a single case tractography study and literature review.

PubMed

Migliaccio, Raffaella; Agosta, Federica; Toba, Monica N; Samri, Dalila; Corlier, Fabian; de Souza, Leonardo C; Chupin, Marie; Sharman, Michael; Gorno-Tempini, Maria L; Dubois, Bruno; Filippi, Massimo; Bartolomeo, Paolo

2012-01-01

Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways. Copyright © 2011 Elsevier Srl. All rights reserved.

Hemispheric processing of vocal emblem sounds.

PubMed

Neumann-Werth, Yael; Levy, Erika S; Obler, Loraine K

2013-01-01

Vocal emblems, such as shh and brr, are speech sounds that have linguistic and nonlinguistic features; thus, it is unclear how they are processed in the brain. Five adult dextral individuals with left-brain damage and moderate-severe Wernicke's aphasia, five adult dextral individuals with right-brain damage, and five Controls participated in two tasks: (1) matching vocal emblems to photographs ('picture task') and (2) matching vocal emblems to verbal translations ('phrase task'). Cross-group statistical analyses on items on which the Controls performed at ceiling revealed lower accuracy by the group with left-brain damage (than by Controls) on both tasks, and lower accuracy by the group with right-brain damage (than by Controls) on the picture task. Additionally, the group with left-brain damage performed significantly less accurately than the group with right-brain damage on the phrase task only. Findings suggest that comprehension of vocal emblems recruits more left- than right-hemisphere processing.

Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals.

PubMed

Doi, Kunio

2011-01-01

It is not widely known how the developing brain responds to extrinsic damage, although the developing brain is considered to be sensitive to diverse environmental factors including DNA-damaging agents. This paper reviews the mechanisms of neurotoxicity induced in the developing brain of mice and rats by six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide), which cause DNA damage in different ways, especially from the viewpoints of apoptosis and cell cycle arrest in neural progenitor cells. In addition, this paper also reviews the repair process following damage in the developing brain.

The Role of Ephs and Ephrins in Memory Formation.

PubMed

Dines, Monica; Lamprecht, Raphael

2016-04-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Ability to solve riddles in patients with speech and language impairments after stroke.

PubMed

Savić, Goran

2016-01-01

Successful riddle solving requires recognition of the meaning of words, attention, concentration, memory, connectivity and analysis of riddle content, and sufficiently developed associative thinking. The aim of the study was to determine the ability to solve riddles in stroke patients who do or do not have speech and language disorders (SLDs), to determine the presence of SLDs in relation to the lesion localization, as well as to define the relationship between riddle-solving and functional impairment of a body side. The sample consisted of 88 patients. The data used included age, sex, educational level, time of stroke onset, presence of an SLD, lesion localization, and functional damage of the body side. The patients were presented with a task of solving 10 riddles. A significant SLD was present in 38.60% of the patients. Brain lesions were found distributed at 46 different brain sites. Patients with different lesion localization had different success in solving riddles. Patients with perisylvian cortex brain lesions, or patients with Wernicke and global aphasia, had the poorest results. The group with SLDs had an average success of solved riddles of 26.76% (p = 0.000). The group with right-sided functional impairments had average success of 37.14%, and the group with functional impairments of the left side of the body 56.88% (p = 0.002). Most patients with SLDs had a low ability of solving riddles. Most of the patients with left brain lesions and perisylvian cortex damage demonstrated lower ability in solving riddles in relation to patients with right hemisphere lesions.

Repeated mild traumatic brain injury can cause acute neurologic impairment without overt structural damage in juvenile rats.

PubMed

Meconi, Alicia; Wortman, Ryan C; Wright, David K; Neale, Katie J; Clarkson, Melissa; Shultz, Sandy R; Christie, Brian R

2018-01-01

Repeated concussion is becoming increasingly recognized as a serious public health concern around the world. Moreover, there is a greater awareness amongst health professionals of the potential for repeated pediatric concussions to detrimentally alter the structure and function of the developing brain. To better study this issue, we developed an awake closed head injury (ACHI) model that enabled repeated concussions to be performed reliably and reproducibly in juvenile rats. A neurological assessment protocol (NAP) score was generated immediately after each ACHI to help quantify the cumulative effects of repeated injury on level of consciousness, and basic motor and reflexive capacity. Here we show that we can produce a repeated ACHI (4 impacts in two days) in both male and female juvenile rats without significant mortality or pain. We show that both single and repeated injuries produce acute neurological deficits resembling clinical concussion symptoms that can be quantified using the NAP score. Behavioural analyses indicate repeated ACHI acutely impaired spatial memory in the Barnes maze, and an interesting sex effect was revealed as memory impairment correlated moderately with poorer NAP score performance in a subset of females. These cognitive impairments occurred in the absence of motor impairments on the Rotarod, or emotional changes in the open field and elevated plus mazes. Cresyl violet histology and structural magnetic resonance imaging (MRI) indicated that repeated ACHI did not produce significant structural damage. MRI also confirmed there was no volumetric loss in the cortex, hippocampus, or corpus callosum of animals at 1 or 7 days post-ACHI. Together these data indicate that the ACHI model can provide a reliable, high throughput means to study the effects of concussions in juvenile rats.

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

A History and Overview of the Behavioral Neuroscience of Learning and Memory.

PubMed

Clark, Robert E

2018-01-01

Here, I provide a basic history of important milestones in the development of theories for how the brain accomplishes the phenomenon of learning and memory. Included are the ideas of Plato, René Descartes, Théodule Ribot, William James, Ivan Pavlov, John Watson, Karl Lashley, and others. The modern era of learning and memory research begins with the description of H.M. by Brenda Milner and the gradual discovery that the brain contains multiple learning and memory systems that are supported by anatomically discrete brain structures. Finally, a brief overview is provided for the chapters that are included in current topics in Behavioral Neuroscience-Learning and Memory.

A History and Overview of the Behavioral Neuroscience of Learning and Memory.

PubMed

Clark, Robert E

2018-01-05

Here, I provide a basic history of important milestones in the development of theories for how the brain accomplishes the phenomenon of learning and memory. Included are the ideas of Plato, René Descartes, Théodule Ribot, William James, Ivan Pavlov, John Watson, Karl Lashley, and others. The modern era of learning and memory research begins with the description of H.M. by Brenda Milner and the gradual discovery that the brain contains multiple learning and memory systems that are supported by anatomically discrete brain structures. Finally, a brief overview is provided for the chapters that are included in current topics in Behavioral Neuroscience-Learning and Memory.

Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

PubMed Central

Wahl, Devin; Coogan, Sean CP; Solon-Biet, Samantha M; de Cabo, Rafael; Haran, James B; Raubenheimer, David; Cogger, Victoria C; Mattson, Mark P; Simpson, Stephen J; Le Couteur, David G

2017-01-01

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. PMID:28932108

Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise.

PubMed

Mehdizadeh, Hajar; Pourahmad, Jalal; Taghizadeh, Ghorban; Vousooghi, Nasim; Yoonessi, Ali; Naserzadeh, Parvaneh; Behzadfar, Ladan; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2017-10-03

Despite the worldwide use of tramadol, few studies have been conducted about its effects on memory and mitochondrial function, and controversial results have been reported. Recently, there has been an increasing interest in physical exercise as a protective approach to neuronal and cognitive impairments. Therefore, the aim of this study was to investigate the effects of physical exercise on spatial learning and memory and brain mitochondrial function in tramadol-treated rats. After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day) intraperitoneally for 30days. Then spatial learning and memory was assessed by Morris water maze test (MWM). Moreover, brain mitochondrial function was evaluated by determination of mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release from mitochondria. Chronic administration of tramadol impaired spatial learning and memory as well as brain mitochondrial function as indicated by increased ROS level, MMP collapse, increased mitochondrial swelling and cytochrome c release from mitochondria. Conversely, treadmill exercise significantly attenuated the impairments of spatial learning and memory and brain mitochondrial dysfunction induced by tramadol. The results revealed that chronic tramadol treatment caused memory impairments through induction of brain mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise markedly mitigated these impairments through its positive effects on brain mitochondrial function. Copyright © 2017. Published by Elsevier Inc.

Memory for Items and Relationships among Items Embedded in Realistic Scenes: Disproportionate Relational Memory Impairments in Amnesia

PubMed Central

Hannula, Deborah E.; Tranel, Daniel; Allen, John S.; Kirchhoff, Brenda A.; Nickel, Allison E.; Cohen, Neal J.

2014-01-01

Objective The objective of this study was to examine the dependence of item memory and relational memory on medial temporal lobe (MTL) structures. Patients with amnesia, who either had extensive MTL damage or damage that was relatively restricted to the hippocampus, were tested, as was a matched comparison group. Disproportionate relational memory impairments were predicted for both patient groups, and those with extensive MTL damage were also expected to have impaired item memory. Method Participants studied scenes, and were tested with interleaved two-alternative forced-choice probe trials. Probe trials were either presented immediately after the corresponding study trial (lag 1), five trials later (lag 5), or nine trials later (lag 9) and consisted of the studied scene along with a manipulated version of that scene in which one item was replaced with a different exemplar (item memory test) or was moved to a new location (relational memory test). Participants were to identify the exact match of the studied scene. Results As predicted, patients were disproportionately impaired on the test of relational memory. Item memory performance was marginally poorer among patients with extensive MTL damage, but both groups were impaired relative to matched comparison participants. Impaired performance was evident at all lags, including the shortest possible lag (lag 1). Conclusions The results are consistent with the proposed role of the hippocampus in relational memory binding and representation, even at short delays, and suggest that the hippocampus may also contribute to successful item memory when items are embedded in complex scenes. PMID:25068665

Brain STAT5 signaling modulates learning and memory formation.

PubMed

Furigo, Isadora C; Melo, Helen M; Lyra E Silva, Natalia M; Ramos-Lobo, Angela M; Teixeira, Pryscila D S; Buonfiglio, Daniella C; Wasinski, Frederick; Lima, Eliana R; Higuti, Eliza; Peroni, Cibele N; Bartolini, Paolo; Soares, Carlos R J; Metzger, Martin; de Felice, Fernanda G; Donato, Jose

2018-06-01

The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.

A novel synthetic phosphodiesterase 5 inhibitor, KJH-1002, ameliorates scopolamine-induced cognitive impairments in mice by activating the cGMP/CREB signaling pathway and attenuating oxidative damage.

PubMed

Zhang, Lijun; Seo, Jae Hong; Li, Huan; Nam, Ghilsoo; Yang, Hyun Ok

2018-05-30

Inhibition of PDE5 has been demonstrated to improve synaptic plasticity and memory via enhancing of cGMP expression, thus activating the cGMP/CREB signaling pathway. This study aimed to investigate the ameliorating effect of PDE5 inhibitor on scopolamine-induced cognitive dysfunction using memory-related behavioral tests and biochemical assays. After the mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine administration. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using western blot and spectrophotometry, respectively. KJH-1002, a novel inhibitor of phosphodiesterase 5 (PDE5), was synthesized (IC 50 of 0.059 ±0.04 nmol·L -1 ), and it markedly improved the memory performance impaired by scopolamine in the behavioral tests, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased the cGMP level in the cortex, the scopolamine-reduced expression of phosphorylated cAMP response element binding protein (CREB), extracellular-regulated kinase 1/2 (ERK 1/2), protein kinase B (Akt) and brain-derived neurotrophic factor (BDNF) in the cortex and hippocampus were reversed by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), and decreased the level of malondialdehyde (MDA). KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signaling pathway and attenuating oxidative stress. The beneficial effect of KJH-1002 on cognition suggests its potential as a therapeutic candidate for Alzheimer's disease. This article is protected by copyright. All rights reserved.

Brain Oscillations during Semantic Evaluation of Speech

ERIC Educational Resources Information Center

Shahin, Antoine J.; Picton, Terence W.; Miller, Lee M.

2009-01-01

Changes in oscillatory brain activity have been related to perceptual and cognitive processes such as selective attention and memory matching. Here we examined brain oscillations, measured with electroencephalography (EEG), during a semantic speech processing task that required both lexically mediated memory matching and selective attention.…

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

PubMed

Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

2014-10-01

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Pioglitazone Improves Cognitive Function via Increasing Insulin Sensitivity and Strengthening Antioxidant Defense System in Fructose-Drinking Insulin Resistance Rats

PubMed Central

Yin, Qing-Qing; Pei, Jin-Jing; Xu, Song; Luo, Ding-Zhen; Dong, Si-Qing; Sun, Meng-Han; You, Li; Sun, Zhi-Jian; Liu, Xue-Ping

2013-01-01

Insulin resistance (IR) links Alzheimer’s disease (AD) with oxidative damage, cholinergic deficit, and cognitive impairment. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone previously used to treat type 2 diabetes mellitus (T2DM) has also been demonstrated to be effective in anti-inflammatory reaction and anti-oxidative stress in the animal models of AD and other neuroinflammatory diseases. Here, we investigated the effect of pioglitazone on learning and memory impairment and the molecular events that may cause it in fructose-drinking insulin resistance rats. We found that long-term fructose-drinking causes insulin resistance, oxidative stress, down-regulated activity of cholinergic system, and cognitive deficit, which could be ameliorated by pioglitazone administration. The results from the present study provide experimental evidence for using pioglitazone in the treatment of brain damage caused by insulin resistance. PMID:23527159

Nutraceuticals, aging, and cognitive dysfunction.

PubMed

Head, Elizabeth; Zicker, Steven C

2004-01-01

Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

Behavioral and Functional Neuroanatomical Correlates of Anterograde Autobiographical Memory in Isolated Retrograde Amnesic Patient M. L.

ERIC Educational Resources Information Center

Levine, Brian; Svoboda, Eva; Turner, Gary R.; Mandic, Marina; Mackey, Allison

2009-01-01

Patient M. L. [Levine, B., Black, S. E., Cabeza, R., Sinden, M., Mcintosh, A. R., Toth, J. P., et al. (1998). "Episodic memory and the self in a case of isolated retrograde amnesia." "Brain", "121", 1951-1973], lost memory for events occurring before his severe traumatic brain injury, yet his anterograde (post-injury) learning and memory appeared…

Contralateral Cortical Organisation of Information in Visual Short-Term Memory: Evidence from Lateralized Brain Activity during Retrieval

ERIC Educational Resources Information Center

Fortier-Gauthier, Ulysse; Moffat, Nicolas; Dell'Acqua, Robert; McDonald, John J.; Jolicoeur, Pierre

2012-01-01

We studied brain activity during retention and retrieval phases of two visual short-term memory (VSTM) experiments. Experiment 1 used a balanced memory array, with one color stimulus in each hemifield, followed by a retention interval and a central probe, at the fixation point that designated the target stimulus in memory about which to make a…

Preterm Infant Hippocampal Volumes Correlate with Later Working Memory Deficits

ERIC Educational Resources Information Center

Beauchamp, Miriam H.; Thompson, Deanne K.; Howard, Kelly; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.; Anderson, Peter J.

2008-01-01

Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal…

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Shielding cognition from nociception with working memory.

PubMed

Legrain, Valéry; Crombez, Geert; Plaghki, Léon; Mouraux, André

2013-01-01

Because pain often signals the occurrence of potential tissue damage, nociceptive stimuli have the capacity to capture attention and interfere with ongoing cognitive activities. Working memory is known to guide the orientation of attention by maintaining goal priorities active during the achievement of a task. This study investigated whether the cortical processing of nociceptive stimuli and their ability to capture attention are under the control of working memory. Event-related brain potentials (ERPs) were recorded while participants performed primary tasks on visual targets that required or did not require rehearsal in working memory (1-back vs 0-back conditions). The visual targets were shortly preceded by task-irrelevant tactile stimuli. Occasionally, in order to distract the participants, the tactile stimuli were replaced by novel nociceptive stimuli. In the 0-back conditions, task performance was disrupted by the occurrence of the nociceptive distracters, as reflected by the increased reaction times in trials with novel nociceptive distracters as compared to trials with standard tactile distracters. In the 1-back conditions, such a difference disappeared suggesting that attentional capture and task disruption induced by nociceptive distracters were suppressed by working memory, regardless of task demands. Most importantly, in the conditions involving working memory, the magnitude of nociceptive ERPs, including ERP components at early latency, were significantly reduced. This indicates that working memory is able to modulate the cortical processing of nociceptive input already at its earliest stages, and could explain why working memory reduces consequently ability of nociceptive stimuli to capture attention and disrupt performance of the primary task. It is concluded that protecting cognitive processing against pain interference is best guaranteed by keeping out of working memory pain-related information. Copyright © 2012 Elsevier Ltd. All rights reserved.

The medial prefrontal cortex is involved in spatial memory retrieval under partial-cue conditions.

PubMed

Jo, Yong Sang; Park, Eun Hye; Kim, Il Hwan; Park, Soon Kwon; Kim, Hyun; Kim, Hyun Taek; Choi, June-Seek

2007-12-05

Brain circuits involved in pattern completion, or retrieval of memory from fragmented cues, were investigated. Using different versions of the Morris water maze, we explored the roles of the CA3 subregion of the hippocampus and the medial prefrontal cortex (mPFC) in spatial memory retrieval under various conditions. In a hidden platform task, both CA3 and mPFC lesions disrupted memory retrieval under partial-cue, but not under full-cue, conditions. For a delayed matching-to-place task, CA3 lesions produced a deficit in both forming and recalling spatial working memory regardless of extramaze cue conditions. In contrast, damage to mPFC impaired memory retrieval only when a fraction of cues was available. To corroborate the lesion study, we examined the expression of the immediate early gene c-fos in mPFC and the hippocampus. After training of spatial reference memory in full-cue conditions for 6 d, the same training procedure in the absence of all cues except one increased the number of Fos-immunoreactive cells in mPFC and CA3. Furthermore, mPFC inactivation with muscimol, a GABA agonist, blocked memory retrieval in the degraded-cue environment. However, mPFC-lesioned animals initially trained in a single-cue environment had no difficulty in retrieving spatial memory when the number of cues was increased, demonstrating that contextual change per se did not impair the behavioral performance of the mPFC-lesioned animals. Together, these findings strongly suggest that pattern completion requires interactions between mPFC and the hippocampus, in which mPFC plays significant roles in retrieving spatial information maintained in the hippocampus for efficient navigation.

The savant syndrome and autistic disorder.

PubMed

Treffert, D A

1999-12-01

Savant syndrome, characterized by remarkable islands of mental ability in otherwise mentally handicapped persons, may occur in autistic as well as nonautistic individuals. Overall, approximately 10% of autistic persons exhibit savant abilities; roughly 50% of those with savant syndrome have autism, and the remaining 50% have other forms of developmental disability. Most commonly, savant syndrome takes the form of extraordinary musical abilities, but may also include calendar-calculation, artistic, mathematical, spatial, mechanical, and memory skills. While savant syndrome was first described more than a century ago, only recently have researchers begun to employ a more uniform nomenclature and more standardized testing in an effort to compare the abilities of savants with those of normal persons. Males show signs of savant syndrome approximately four times more often than females. Along with imaging study findings, this fact suggests the presence of a developmental disorder involving left-brain damage with right-brain compensation.

Lokomat training in vascular dementia: motor improvement and beyond!

PubMed

Calabrò, Rocco Salvatore; De Luca, Rosaria; Leo, Antonino; Balletta, Tina; Marra, Angela; Bramanti, Placido

2015-12-01

Vascular dementia (VaD) is a general term describing problems with reasoning, planning, judgment, memory, and other thought processes caused by brain damage from impaired blood flow to the brain. Cognitive rehabilitation and physical therapy are the mainstays of dementia treatment, although often ineffective because of the scarce collaboration of the patients. However, emerging data suggest that physical activity may reduce the risk of cognitive impairment, mainly VaD, in older people living independently. Herein, we describe a 72-year-old male affected by VaD, in which traditional cognitive training in addition to intensive gait robotic rehabilitation (by using Lokomat device) led to a significant improvement in the motor and cognitive function. This promising finding may be related either to the intensive and repetitive aerobic exercises or to the task-oriented training with computerized visual feedback, which can be considered as a relevant tool to increase patients' motor output, involvement, and motivation during robotic training.

Memantine and Kynurenic Acid: Current Neuropharmacological Aspects

PubMed Central

Majláth, Zsófia; Török, Nóra; Toldi, József; Vécsei, László

2016-01-01

Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive activation of N-methyl- D-aspartate (NMDA) receptors may result in excitotoxic neuronal damage; this process has been implicated in the pathomechanism of different neurodegenerative disorders, such as Alzheimer’s disease (AD). Memantine is an uncompetitive antagonist of NMDA receptors with a favorable pharmacokinetic profile, and is therefore clinically well tolerated. Memantine is approved for the treatment of AD, but may additionally be beneficial for other dementia forms and pain conditions. Kynurenic acid (KYNA) is an endogenous antagonist of NMDA receptors which has been demonstrated under experimental conditions to be neuroprotective. The development of a well-tolerated NMDA antagonist may offer a novel therapeutic option for the treatment of neurodegenerative disease and pain syndromes. KYNA may be a valuable candidate for future drug development. PMID:26564141

Brain training game boosts executive functions, working memory and processing speed in the young adults: a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. UMIN Clinical Trial Registry 000005618.

Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial Registration UMIN Clinical Trial Registry 000005618. PMID:23405164

First steps in using machine learning on fMRI data to predict intrusive memories of traumatic film footage

PubMed Central

Clark, Ian A.; Niehaus, Katherine E.; Duff, Eugene P.; Di Simplicio, Martina C.; Clifford, Gari D.; Smith, Stephen M.; Mackay, Clare E.; Woolrich, Mark W.; Holmes, Emily A.

2014-01-01

After psychological trauma, why do some only some parts of the traumatic event return as intrusive memories while others do not? Intrusive memories are key to cognitive behavioural treatment for post-traumatic stress disorder, and an aetiological understanding is warranted. We present here analyses using multivariate pattern analysis (MVPA) and a machine learning classifier to investigate whether peri-traumatic brain activation was able to predict later intrusive memories (i.e. before they had happened). To provide a methodological basis for understanding the context of the current results, we first show how functional magnetic resonance imaging (fMRI) during an experimental analogue of trauma (a trauma film) via a prospective event-related design was able to capture an individual's later intrusive memories. Results showed widespread increases in brain activation at encoding when viewing a scene in the scanner that would later return as an intrusive memory in the real world. These fMRI results were replicated in a second study. While traditional mass univariate regression analysis highlighted an association between brain processing and symptomatology, this is not the same as prediction. Using MVPA and a machine learning classifier, it was possible to predict later intrusive memories across participants with 68% accuracy, and within a participant with 97% accuracy; i.e. the classifier could identify out of multiple scenes those that would later return as an intrusive memory. We also report here brain networks key in intrusive memory prediction. MVPA opens the possibility of decoding brain activity to reconstruct idiosyncratic cognitive events with relevance to understanding and predicting mental health symptoms. PMID:25151915

Differential associations between types of verbal memory and prefrontal brain structure in healthy aging and late life depression.

PubMed

Lamar, Melissa; Charlton, Rebecca; Zhang, Aifeng; Kumar, Anand

2012-07-01

Verbal memory deficits attributed to late life depression (LLD) may result from executive dysfunction that is more detrimental to list-learning than story-based recall when compared to healthy aging. Despite these behavioral dissociations, little work has been done investigating related neuroanatomical dissociations across types of verbal memory performance in LLD. We compared list-learning to story-based memory performance in 24 non-demented individuals with LLD (age ~ 66.1 ± 7.8) and 41 non-demented/non-depressed healthy controls (HC; age ~ 67.6 ± 5.3). We correlated significant results of between-group analyses across memory performance variables with brain volumes of frontal, temporal and parietal regions known to be involved with verbal learning and memory. When compared to the HC group, the LLD group showed significantly lower verbal memory performance for spontaneous recall after repeated exposure and after a long-delay but only for the list-learning task; groups did not differ on story-based memory performance. Despite equivalent brain volumes across regions, only the LLD group showed brain associations with verbal memory performance and only for the list-learning task. Specifically, frontal volumes important for subjective organization and response monitoring correlated with list-learning performance in the LLD group. This study is the first to demonstrate neuroanatomical dissociations across types of verbal memory performance in individuals with LLD. Results provide structural evidence for the behavioral dissociations between list-learning and story-based recall in LLD when compared to healthy aging. More specifically, it points toward a network of predominantly anterior brain regions that may underlie the executive contribution to list-learning in older adults with depression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.

PubMed

Jager, Gerry; Kahn, Rene S; Van Den Brink, Wim; Van Ree, Jan M; Ramsey, Nick F

2006-04-01

Excessive use of cannabis may have long-term effects on cognitive abilities. Mild impairments have been found in several cognitive domains, particularly in memory and attention. It is not clear, however, whether these effects also occur with moderate, recreational use of cannabis. Furthermore, little is known about underlying brain correlates. The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex. No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

PubMed

Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

2017-05-01

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

Galantamine

MedlinePlus

... AD; a brain disease that slowly destroys the memory and the ability to think, learn, communicate and ... substance in the brain that is needed for memory and thought. Galantamine may improve the ability to ...

Individual Differences in Working Memory, Nonverbal IQ, and Mathematics Achievement and Brain Mechanisms Associated with Symbolic and Nonsymbolic Number Processing

ERIC Educational Resources Information Center

Gullick, Margaret M.; Sprute, Lisa A.; Temple, Elise

2011-01-01

Individual differences in mathematics performance may stem from domain-general factors like working memory and intelligence. Parietal and frontal brain areas have been implicated in number processing, but the influence of such cognitive factors on brain activity during mathematics processing is not known. The relationship between brain mechanisms…

Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal

PubMed Central

Namazi, Hamidreza; Kulish, Vladimir V.

2016-01-01

One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory. PMID:27528219

Memory and Self–Neuroscientific Landscapes

PubMed Central

Markowitsch, Hans J.

2013-01-01

Relations between memory and the self are framed from a number of perspectives—developmental aspects, forms of memory, interrelations between memory and the brain, and interactions between the environment and memory. The self is seen as dividable into more rudimentary and more advanced aspects. Special emphasis is laid on memory systems and within them on episodic autobiographical memory which is seen as a pure human form of memory that is dependent on a proper ontogenetic development and shaped by the social environment, including culture. Self and episodic autobiographical memory are seen as interlocked in their development and later manifestation. Aside from content-based aspects of memory, time-based aspects are seen along two lines—the division between short-term and long-term memory and anterograde—future-oriented—and retrograde—past-oriented memory. The state dependency of episodic autobiographical is stressed and implications of it—for example, with respect to the occurrence of false memories and forensic aspects—are outlined. For the brain level, structural networks for encoding, consolidation, storage, and retrieval are discussed both by referring to patient data and to data obtained in normal participants with functional brain imaging methods. It is elaborated why descriptions from patients with functional or dissociative amnesia are particularly apt to demonstrate the facets in which memory, self, and personal temporality are interwoven. PMID:24967303

Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal.

PubMed

Namazi, Hamidreza; Khosrowabadi, Reza; Hussaini, Jamal; Habibi, Shaghayegh; Farid, Ali Akhavan; Kulish, Vladimir V

2016-08-30

One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory.

Retrieval Search and Strength Evoke Dissociable Brain Activity during Episodic Memory Recall

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Neuroimaging studies of episodic memory retrieval have revealed activations in the human frontal, parietal, and medial-temporal lobes that are associated with memory strength. However, it remains unclear whether these brain responses are veritable signals of memory strength or are instead regulated by concomitant subcomponents of retrieval such as retrieval effort or mental search. This study used event-related fMRI during cued recall of previously memorized word-pair associates to dissociate brain responses modulated by memory search from those modulated by the strength of a recalled memory. Search-related deactivations, dissociated from activity due to memory strength, were observed in regions of the default network, whereas distinctly strength-dependent activations were present in superior and inferior parietal and dorsolateral PFC. Both search and strength regulated activity in dorsal anterior cingulate and anterior insula. These findings suggest that, although highly correlated and partially subserved by overlapping cognitive control mechanisms, search and memory strength engage dissociable regions of frontoparietal attention and default networks. PMID:23190328

Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

PubMed Central

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

Mnemonic training reshapes brain networks to support superior memory

PubMed Central

Dresler, Martin; Shirer, William R.; Konrad, Boris N.; Müller, Nils C.J.; Wagner, Isabella C.; Fernández, Guillén; Czisch, Michael; Greicius, Michael D.

2017-01-01

Summary Memory skills strongly differ across the general population, however little is known about the brain characteristics supporting superior memory performance. Here, we assess functional brain network organization of 23 of the world’s most successful memory athletes and matched controls by fMRI during both task-free resting state baseline and active memory encoding. We demonstrate that in a group of naïve controls, functional connectivity changes induced by six weeks of mnemonic training were correlated with the network organization that distinguishes athletes from controls. During rest, this effect was mainly driven by connections between rather than within the visual, medial temporal lobe and default mode networks, whereas during task it was driven by connectivity within these networks. Similarity with memory athlete connectivity patterns predicted memory improvements up to 4 months after training. In conclusion, mnemonic training drives distributed rather than regional changes, reorganizing the brain’s functional network organization to enable superior memory performance. PMID:28279356

The role of the hippocampus in recognition memory.

PubMed

Bird, Chris M

2017-08-01

Many theories of declarative memory propose that it is supported by partially separable processes underpinned by different brain structures. The hippocampus plays a critical role in binding together item and contextual information together and processing the relationships between individual items. By contrast, the processing of individual items and their later recognition can be supported by extrahippocampal regions of the medial temporal lobes (MTL), particularly when recognition is based on feelings of familiarity without the retrieval of any associated information. These theories are domain-general in that "items" might be words, faces, objects, scenes, etc. However, there is mixed evidence that item recognition does not require the hippocampus, or that familiarity-based recognition can be supported by extrahippocampal regions. By contrast, there is compelling evidence that in humans, hippocampal damage does not affect recognition memory for unfamiliar faces, whilst recognition memory for several other stimulus classes is impaired. I propose that regions outside of the hippocampus can support recognition of unfamiliar faces because they are perceived as discrete items and have no prior conceptual associations. Conversely, extrahippocampal processes are inadequate for recognition of items which (a) have been previously experienced, (b) are conceptually meaningful, or (c) are perceived as being comprised of individual elements. This account reconciles findings from primate and human studies of recognition memory. Furthermore, it suggests that while the hippocampus is critical for binding and relational processing, these processes are required for item recognition memory in most situations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Semantic and episodic memory of music are subserved by distinct neural networks.

PubMed

Platel, Hervé; Baron, Jean-Claude; Desgranges, Béatrice; Bernard, Frédéric; Eustache, Francis

2003-09-01

Numerous functional imaging studies have shown that retrieval from semantic and episodic memory is subserved by distinct neural networks. However, these results were essentially obtained with verbal and visuospatial material. The aim of this work was to determine the neural substrates underlying the semantic and episodic components of music using familiar and nonfamiliar melodic tunes. To study musical semantic memory, we designed a task in which the instruction was to judge whether or not the musical extract was felt as "familiar." To study musical episodic memory, we constructed two delayed recognition tasks, one containing only familiar and the other only nonfamiliar items. For each recognition task, half of the extracts (targets) were presented in the prior semantic task. The episodic and semantic tasks were to be contrasted by a comparison to two perceptive control tasks and to one another. Cerebral blood flow was assessed by means of the oxygen-15-labeled water injection method, using high-resolution PET. Distinct patterns of activations were found. First, regarding the episodic memory condition, bilateral activations of the middle and superior frontal gyri and precuneus (more prominent on the right side) were observed. Second, the semantic memory condition disclosed extensive activations in the medial and orbital frontal cortex bilaterally, the left angular gyrus, and predominantly the left anterior part of the middle temporal gyri. The findings from this study are discussed in light of the available neuropsychological data obtained in brain-damaged subjects and functional neuroimaging studies.

Relational and conjunctive binding functions dissociate in short-term memory.

PubMed

Parra, Mario A; Fabi, Katia; Luzzi, Simona; Cubelli, Roberto; Hernandez Valdez, Maria; Della Sala, Sergio

2015-02-01

Remembering complex events requires binding features within unified objects (conjunctions) and holding associations between objects (relations). Recent studies suggest that the two functions dissociate in long-term memory (LTM). Less is known about their functional organization in short-term memory (STM). The present study investigated this issue in patient AE affected by a stroke which caused damage to brain regions known to be relevant for relational functions both in LTM and in STM (i.e., the hippocampus). The assessment involved a battery of standard neuropsychological tasks and STM binding tasks. One STM binding task (Experiment 1) presented common objects and common colors forming either pairs (relations) or integrated objects (conjunctions). Free recall of relations or conjunctions was assessed. A second STM binding task used random polygons and non-primary colors instead (Experiment 2). Memory was assessed by selecting the features that made up the relations or the conjunctions from a set of single polygons and a set of single colors. The neuropsychological assessment revealed impaired delayed memory in AE. AE's pronounced relational STM binding deficits contrasted with his completely preserved conjunctive binding functions in both Experiments 1 and 2. Only 2.35% and 1.14% of the population were expected to have a discrepancy more extreme than that presented by AE in Experiments 1 and 2, respectively. Processing relations and conjunctions of very elementary nonspatial features in STM led to dissociating performances in AE. These findings may inform current theories of memory decline such as those linked to cognitive aging.

Effect of perinatal asphyxia on tuberomammillary nucleus neuronal density and object recognition memory: A possible role for histamine?

PubMed

Flores-Balter, Gabriela; Cordova-Jadue, Héctor; Chiti-Morales, Alessandra; Lespay, Carolyne; Espina-Marchant, Pablo; Falcon, Romina; Grinspun, Noemi; Sanchez, Jessica; Bustamante, Diego; Morales, Paola; Herrera-Marschitz, Mario; Valdés, José L

2016-10-15

Perinatal asphyxia (PA) is associated with long-term neuronal damage and cognitive deficits in adulthood, such as learning and memory disabilities. After PA, specific brain regions are compromised, including neocortex, hippocampus, basal ganglia, and ascending neuromodulatory pathways, such as dopamine system, explaining some of the cognitive disabilities. We hypothesize that other neuromodulatory systems, such as histamine system from the tuberomammillary nucleus (TMN), which widely project to telencephalon, shown to be relevant for learning and memory, may be compromised by PA. We investigated here the effect of PA on (i) Density and neuronal activity of TMN neurons by double immunoreactivity for adenosine deaminase (ADA) and c-Fos, as marker for histaminergic neurons and neuronal activity respectively. (ii) Expression of the histamine-synthesizing enzyme, histidine decarboxylase (HDC) by western blot and (iii) thioperamide an H3 histamine receptor antagonist, on an object recognition memory task. Asphyxia-exposed rats showed a decrease of ADA density and c-Fos activity in TMN, and decrease of HDC expression in hypothalamus. Asphyxia-exposed rats also showed a low performance in object recognition memory compared to caesarean-delivered controls, which was reverted in a dose-dependent manner by the H3 antagonist thioperamide (5-10mg/kg, i.p.). The present results show that the histaminergic neuronal system of the TMN is involved in the long-term effects induced by PA, affecting learning and memory. Copyright © 2016 Elsevier B.V. All rights reserved.

An uncommon case of random fire-setting behavior associated with Todd paralysis: a case report.

PubMed

Kanehisa, Masayuki; Morinaga, Katsuhiko; Kohno, Hisae; Maruyama, Yoshihiro; Ninomiya, Taiga; Ishitobi, Yoshinobu; Tanaka, Yoshihiro; Tsuru, Jusen; Hanada, Hiroaki; Yoshikawa, Tomoya; Akiyoshi, Jotaro

2012-08-31

The association between fire-setting behavior and psychiatric or medical disorders remains poorly understood. Although a link between fire-setting behavior and various organic brain disorders has been established, associations between fire setting and focal brain lesions have not yet been reported. Here, we describe the case of a 24-year-old first time arsonist who suffered Todd's paralysis prior to the onset of a bizarre and random fire-setting behavior. A case of a 24-year-old man with a sudden onset of a bizarre and random fire-setting behavior is reported. The man, who had been arrested on felony arson charges, complained of difficulties concentrating and of recent memory disturbances with leg weakness. A video-EEG recording demonstrated a close relationship between the focal motor impairment and a clear-cut epileptic ictal discharge involving the bilateral motor cortical areas. The SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). eZIS revealed hypoperfusion in cingulate cortex, basal ganglia and hyperperfusion in frontal cortex,. A neuropsychological test battery revealed lower than normal scores for executive function, attention, and memory, consistent with frontal lobe dysfunction. The fire-setting behavior and Todd's paralysis, together with an unremarkable performance on tests measuring executive function fifteen months prior, suggested a causal relationship between this organic brain lesion and the fire-setting behavior. The case describes a rare and as yet unreported association between random, impulse-driven fire-setting behavior and damage to the brain and suggests a disconnection of frontal lobe structures as a possible pathogenic mechanism.

Iconic memory and parietofrontal network: fMRI study using temporal integration.

PubMed

Saneyoshi, Ayako; Niimi, Ryosuke; Suetsugu, Tomoko; Kaminaga, Tatsuro; Yokosawa, Kazuhiko

2011-08-03

We investigated the neural basis of iconic memory using functional magnetic resonance imaging. The parietofrontal network of selective attention is reportedly relevant to readout from iconic memory. We adopted a temporal integration task that requires iconic memory but not selective attention. The results showed that the task activated the parietofrontal network, confirming that the network is involved in readout from iconic memory. We further tested a condition in which temporal integration was performed by visual short-term memory but not by iconic memory. However, no brain region revealed higher activation for temporal integration by iconic memory than for temporal integration by visual short-term memory. This result suggested that there is no localized brain region specialized for iconic memory per se.