A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory

Uncovering the functional relationship between temporal lobe amnesia and diencephalic amnesia depends on determining the role of the fornix, the major interlinking fiber tract. In this study relating fornix volume with memory, we made magnetic resonance imaging-based volume estimates of 13 brain structures in 38 individuals with surgically removed colloid cysts. Fornix status was assessed directly by overall volume and indirectly by mammillary body volume (which atrophies after fornix damage). Mammillary body volume significantly correlated with 13 out of 14 tests of episodic memory recall, but correlated poorly with recognition memory. Furthermore, as the volumes of the left fornix and the left mammillary bodies decreased, the difference between recall and recognition scores increased. No other structure was consistently associated with memory. These findings support models of diencephalic memory mechanisms that require hippocampal inputs for recall, but not for key elements of recognition.     

Reversion of age-related recognition memory impairment by iron chelation in rats

It is now generally accepted that iron accumulates in the brain during the ageing process. Increasing evidence demonstrate that iron accumulation in selective regions of the brain may generate free radicals, thereby possessing implications for the etiology of neurodegenerative disorders. In a previous study we have reported that aged rats present recognition memory deficits. The aim of the present study was to evaluate the effect of desferoxamine (DFO), an iron chelator agent, on age-induced memory impairment. Aged Wistar rats received intraperitoneal injections of saline or DFO (300mg/kg) for 2 weeks. The animals were submitted to a novel object recognition task 24h after the last injection. DFO-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that DFO is able to reverse age-induced recognition memory deficits. We also demonstrated that DFO reduced the oxidative damage to proteins in cortex and hippocampus. Thus, the present findings provide the first evidence that iron chelators might prevent age-related memory dysfunction.     

The functional cooperation of the hippocampus and anterior thalamus via the fimbria-fornix in spatial memory in rats

This study examined whether the cooperation of the hippocampus, and anterior thalamus via the fimbria-fornix is involved in the spatial memory. We compared the effect of contralateral lesions (Contra) with ipsilateral lesions (Ipsi) of the fimbria-fornix and anterior thalamus on the performance of an object exploration task and the Morris water maze task. If the hippocampus and anterior thalamus take part in a same functional system via fornix, the performance of Contra group will be more disruptive than that of Ipsi group. In the object exploration task, Contra and Ipsi groups did not differ from Control group in the performance of object recognition test. However, the performance of Contra group was significantly impaired in the spatial recognition test, compared with two other groups. In the Morris water maze task, only Contra group showed deficits in spatial learning but not the Ipsi group. These results indicate that contralateral, but not ipsilateral lesion caused deficits in spatial memory, supporting the notion that the functional cooperation of hippocampus and anterior thalamus via fornix is vital for spatial memory.     

Deep brain stimulation of fornix for memory improvement in Alzheimer’s disease: A critical review

Memory reflects the brain function in encoding, storage and retrieval of the data or information, which is a fundamental ability for any live organism. The development of approaches to improve memory attracts much attention due to the underlying mechanistic insight and therapeutic potential to treat neurodegenerative diseases with memory loss, such as Alzheimer’s disease (AD). Deep brain stimulation (DBS), a reversible, adjustable, and non-ablative therapy, has been shown to be safe and effective in many clinical trials for neurodegenerative and neuropsychiatric disorders. Among all potential regions with access to invasive electrodes, fornix is considered as it is the major afferent and efferent connection of the hippocampus known to be closely associated with learning and memory. Indeed, clinical trials have demonstrated that fornix DBS globally improved cognitive function in a subset of patients with AD, indicating fornix can serve as a potential target for neurosurgical intervention in treating memory impairment in AD. The present review aims to provide a better understanding of recent progresses in the application of fornix DBS for ameliorating memory impairments in AD patients.     

Frontal steady-state potential changes predict long-term recognition memory performance.

Converging evidence from event-related potential and functional brain imaging studies suggests that the brain activity at posterior regions of the frontal cortex can predict the strength of long-term memory traces. This study examined the relationship between posterior frontal steady-state visually evoked potential (SSVEP) latency changes and recognition memory after a delay of 7 days. Thirty-five female subjects viewed an 18-min television documentary program interspersed with 12 unfamiliar television advertisements while brain electrical activity was recorded from four pre-frontal, two posterior frontal and two occipital scalp sites. After 7 days, the recognition memory was tested for images coinciding with the 20 most prominent frontal SSVEP latency minima and maxima during the viewing of ten contiguous advertisements (advertisements 2-11). We found that images coinciding with posterior frontal latency minima were more likely to be recognized (58.7% recognition) than images coinciding with SSVEP latency maxima (45.3% recognition). Furthermore, the relationship between posterior frontal SSVEP latency and recognition performance after 7 days was only apparent at the left posterior frontal site. The correlation between the recognition performance and SSVEP latency evaluated at all eight sites reached significance only at the left posterior frontal site. These findings suggest that frontal SSVEP latency variations can be used to assess the strength of long-term memory encoding for naturalistic stimuli.     

Learning and retrieval of concurrently presented spatial discrimination tasks: role of the fornix

In macaque monkeys (Macaco mulatta), memory for scenes presented on touch screens is fornix dependent. However, scene learning is not a purely spatial task, and existing direct evidence for a fornix role in spatial memory comes exclusively from tasks involving learning about food-reward locations. Here the authors demonstrate that fornix transection impairs learning about spatial stimuli presented on touch screens. Using a new concurrent spatial discrimination learning task, they found that fornix transection did not impair recall of preoperatively learned problems. Relearning, on the other hand, was mildly impaired, and new learning was strongly impaired. New learning of smaller sets of harder problems was also markedly impaired, as was spatial configured learning. This pattern supports a functional specialization according to stimulus domain in the medial temporal lobe.     

Structure–function relationship of working memory activity with hippocampal and prefrontal cortex volumes

A rapidly increasing number of studies are quantifying the system-level network architecture of the human brain based on structural-to-structural and functional-to-functional relationships. However, a largely unexplored area is the nature and existence of “cross-modal” structural–functional relationships, in which, for example, the volume (or other morphological property) of one brain region is related to the functional response to a given task either in that same brain region, or another brain region. The present study investigated whether the gray matter volume of a selected group of structures (superior, middle, and inferior frontal gyri, thalamus, and hippocampus) was correlated with the fMRI response to a working memory task, within a mask of regions previously identified as involved with working memory. The subjects included individuals with schizophrenia, their siblings, and healthy controls (n = 154 total). Using rigorous permutation testing to define the null distribution, we found that the volume of the superior and middle frontal gyri was correlated with working memory activity within clusters in the intraparietal sulcus (i.e., dorsal parietal cortex) and that the volume of the hippocampus was correlated with working memory activity within clusters in the dorsal anterior cingulate cortex and left inferior frontal gyrus. However, we did not find evidence that the identified structure–function relationships differed between subject groups. These results show that long-distance structural–functional relationships exist within the human brain. The study of such cross-modal relationships represents an additional approach for studying systems-level interregional brain networks.     

The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance.     

Vaginocervical stimulation enhances social recognition memory in rats via oxytocin release in the olfactory bulb

The ability of vaginocervical stimulation (VCS) to promote olfactory social recognition memory at different stages of the ovarian cycle was investigated in female rats. A juvenile social recognition paradigm was used and memory retention tested at 30 and 300 min after an adult was exposed to a juvenile during three 4-min trials. Results showed that an intact social recognition memory was present at 30 min in animals with or without VCS and at all stages of the estrus cycle. However, whereas no animals in any stage of the estrus cycle showed retention of the specific recognition memory at 300 min, those in the proestrus/estrus phase that received VCS 10 min before the trial started did. In vivo microdialysis studies showed that there was a significant release of oxytocin after VCS in the olfactory bulb during proestrus. There was also increased oxytocin immunoreactivity within the olfactory bulb after VCS in proestrus animals compared with diestrus ones. Furthermore, when animals received an infusion of an oxytocin antagonist directly into the olfactory bulb, or a systemic administration of alpha or beta noradrenaline-antagonists, they failed to show evidence for maintenance of a selective olfactory recognition memory at 300 min. Animals with vagus or pelvic nerve section also showed no memory retention when tested after 300 min. These results suggest that VCS releases oxytocin in the olfactory bulb to enhance the social recognition memory and that this may be due to modulatory actions on noradrenaline release. The vagus and pelvic nerves are responsible for carrying the information from the pelvic area to the CNS.     

Visual recognition in monkeys: effects of separate vs. combined transection of fornix and amygdalofugal pathways

Summary Performance on an object recognition test was assessed in monkeys with transections of either the fornix, the amygdalofugal pathways, or both. Whereas separate transection of the two pathways produced only small and unreliable effects, their combined transection produced a severe deficit. Comparison with the results of a previous study (Mishkin 1978) indicates that combined disconnection of the amygdala and hippocampus from the diencephalon yields a memory impairment similar to that following combined damage to the two limbic structures themselves. The findings suggest that recognition memory in monkeys depends on two parallel limbo-diencephalic pathways.Portions of this material were presented at the Society for Neuroscience (Bachevalier et al. 1982)     

ERP correlates of true and false recognition after different retention delays: stimulus- and response-related processes

Performance and electrophysiological correlates of true and false recognition were examined after short (40 s) and long (80 s) delays. True recognition showed no significant decrease after a long delay, whereas false recognition increased. Early frontal and parietal ERP old/new effects, considered as correlates of familiarity and recollection, were observed across delay for true recognition. No frontal effect occurred in the long delay for false recognition. This absence may arise from weakened memory traces preventing familiarity discrimination for LUREs. Response-related analysis revealed an error-related negativity (ERN) for true and false recognition, assuming that the effect reflects at least partly an internal misrepresentation of the correct response. The larger and topographically different ERNs for false recognition suggest an additional contribution of increased task demands and conditions of high response uncertainty.     

Fornix transection impairs visuospatial memory acquisition more than retrieval

It has been hypothesized that some fornical fibres may instantiate a neuromodulatory reinforcement signal supporting memory acquisition in medial temporal cortical regions. This suggests that fornix transection should impair postoperative new learning more severely than the recall of preoperatively acquired information. Here, postoperative recall of 288 concurrent visuo-spatial discrimination problems acquired preoperatively was unaffected after fornix transection in the macaque, whereas new postoperative learning of 72 problems was impaired. This and other recent evidence supports the idea that the main function of the fornix in macaque monkeys is to support new learning about spatio-temporal context.     

Using Event-Related Potentials to Study Perinatal Nutrition and Brain Development in Infants of Diabetic Mothers

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birth weights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant.     

Using event-related potentials to study perinatal nutrition and brain development in infants of diabetic mothers

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birth weights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant.     

Intracranial topography of event-related potentials (N400/P600) elicited during a continuous recognition memory task

To isolate the anatomical locus of the neural activity most important for generating or modulating the scalp-recorded N400 and P600 components elicited during continuous recognition memory tasks, intracranial event-related potentials (ERPs) were recorded from medial and lateral aspects of the temporal, frontal, parietal, and occipital lobes in 25 patients undergoing stereoelectroencephalography for seizure localization. Large-amplitude and polarity-inverted ERPs were recorded from various temporal, frontal, and parietal structures, whereas the memory-related ERP modulation assessed by the ERP repetition effect was present only in those brain areas that play the most important role in memory processing. These data suggest that the scalp-recorded N400 and P600 components may represent the most readily observable aspect of synchronous activity occurring across widely distributed brain structures and neural systems underlying different cognitive mechanisms, which all contribute to some aspect of information processing during recognition memory.     

Developmental changes in attributes of memory in children

The present study investigated the developmental changes in dominance of memory attributes between second and sixth graders. Subjects studied a familiar word list followed by a recognition test; dominance was inferred from the types of false recognition error (semantic and acoustic) on the test. The results showed dominance of the semantic attribute for sixth graders, but no difference of dominance level between the semantic and the acoustic attribute for second graders. The evidence also indicated no effect of the stimulus mode on dominance of memory attributes for both graders.     

Mamillary-body lesions and visual recognition in monkeys

Summary Cynomolgus monkeys with complete bilateral destruction of the medial mamillary nucleus exhibited little, if any, deficit in object recognition, although they did show evidence of impairment in spatial memory. The pattern of effects thus resembled that found previously after either hippocampal ablations or transections of the fornix and suggests that, like such damage, mamillary-body damage alone is insufficient to produce the global amnesia attributed to it in clinical cases.     

Extensive immunolesions of basal forebrain cholinergic system impair offspring recognition in sheep

The involvement of the basal forebrain cholinergic system has been extensively investigated in instrumental learning but little is known of its participation in social memory, especially in the memorization of individual traits of a conspecific.The present study tested in sheep its contribution to both instrumental learning and individual offspring recognition. Six weeks before parturition, ewes received injections of a specific cholinergic immunotoxin (ME20.4 IgG-saporin) into the lateral ventricles (150 microg) and in some cases additional immunotoxin injections into the nucleus basalis (11 microg/side). After 3 weeks of recovery, ewes were trained on a classical instrumental visual discrimination task known to be sensitive to cholinergic deficits. The formation of memory of offspring was assessed through both olfactory and visual/auditory recognition tasks. Olfactory recognition was tested by presenting at suckling successively an alien and the familiar lamb at 2 and 4 h after parturition. Visual/auditory recognition of the lamb was performed using a non-olfactory discrimination test between the familiar and an alien lamb after 12 h of mother-young contact. The lesion extent was assessed by counting choline acetyltransferase-immunopositive neurons in the basal forebrain and measuring the density of acetylcholinesterase fibers in different target areas. Results showed that immunotoxic lesions delayed acquisition of the instrumental visual discrimination. Moreover, olfactory recognition of the lamb was severely impaired while visual/auditory lamb recognition was marginally altered. There was no evidence for sensorimotor or motivational deficits. Importantly, impairment was observed in animals for which loss of basal forebrain cholinergic neurons and their efferent fibers was higher than 75%, while striatal cholinergic neurons and Purkinje cells were unaffected.This study provides evidence that the basal forebrain cholinergic system contributes not only to instrumental but also to social learning. In addition, the cholinergic modulation seems of importance for processing visual and olfactory modalities. However, since only extensive lesions affect performance, this indicates that the basal forebrain cholinergic system possesses substantial reserve capacity to sustain cognitive functions.     

Age-related ERP differences at retrieval persist despite age-invariant performance and left-frontal negativity during encoding

Although it has been reported repeatedly that retrieval-related processes decline with aging, the influence of well-documented age-related encoding deficiencies on the observed changes at retrieval have not been ruled out as a contributing factor. Here, we disentangle this confound by using a serendipitous finding reported by Nessler et al. [D. Nessler, R. Johnson Jr., M. Bersick, D. Friedman, On why the elderly have normal semantic retrieval but deficient episodic encoding: a study of left inferior frontal ERP activity, Neuroimage 30 (2006) 299–312]. In that study, age-related differences in the magnitude of left inferior frontal brain activity at encoding and subsequent recognition memory performance were eliminated when a deeper level of semantic encoding in the older adults was compared with a shallow level in the young. Based on this earlier result, the present paper is concerned with the question of whether the matched recognition performance resulting from age-equivalent ERP encoding activity was also accompanied by age-invariant retrieval-related brain activity. The results in the young were consistent with dual-process models of recognition memory due to the presence of ERP activity linked previously to familiarity (frontal EM effect) and recollection (parietal EM effect). By contrast the older adults only showed evidence of familiarity-based processes. Thus, despite age-equivalent brain activity at encoding and subsequent recognition performance, older relative to young adults appeared to base their old–new decisions on a qualitatively different pattern of retrieval processes (i.e., more on familiarity and less on recollection). Consequently, these data suggest that the age-related changes in retrieval observed here are independent of, and likely occur in addition to, any age-related changes in encoding processes.     

大鼠纹状体边缘区与海马逃避性学习记忆功能的比较

为了比较纹状体边缘区 (Mr D)与海马在逃避性学习记忆方面的差别 ,藉以探讨 Mr D与海马两个不同脑区在大脑学习记忆功能上的区别和作用地位。应用 Y迷宫训练大鼠后 2 4h,化学损毁大鼠双侧 Mr D或切断双侧穹窿海马伞 (fornix/fimbria,FF ) ,手术 5 d后再观察大鼠在 Y迷宫中学习记忆的行为表现。结果表明 ,化学损毁 Mr D组大鼠在 Y迷宫中的记忆能力和对照组相比 ,明显降低 ,差别显著 (P<0 .0 1) ;而切断双侧穹窿海马伞组大鼠与对照组相比 ,无显著性差异 (P>0 .0 5 )。说明大鼠在 Y迷宫中的逃避性学习记忆行为主要和 Mr D有关 ,和海马无明显关系。提示 Mr D和海马两个脑区在参与大脑的学习记忆功能方面 ,并非处于相同的位置