The anterior cingulate cortex (ACC) is a complex and continually evolving brain region that remains a primary focus of research due to its multifaceted functions. Various studies and analyses have significantly advanced our understanding of how the ACC participates in a wide spectrum of memory and cognitive processes. However, despite its strong connections to brain areas associated with hippocampal and olfactory neurogenesis, the functions of the ACC in regulating postnatal and adult neurogenesis in these regions are still (...) insufficiently explored. Investigating the intricate involvement of the ACC in neurogenesis could enhance our comprehension of essential aspects of brain plasticity. This involvement stems from its complex circuitry with other relevant brain regions, thereby exerting both direct and indirect impacts on the neurogenesis process. This review sheds light on the promising significance of the ACC in orchestrating postnatal and adult neurogenesis in conditions related to memory, cognitive behavior, and associated disorders. (shrink)

Hippocampal neurogenesis has been implicated in the pathogenesis of and recovery from depression. However, most of the underlying studies were endpoint investigations in experimental animals yielding conflicting results, and it has been under debate to which extent these results could be transferred to human patients. Now, researchers have developed a powerful new tool to address these questions by a non‐invasive method in humans and animals in vivo, using magnetic resonance spectroscopy to detect a biomarker for proliferating progenitor cells (...) that give rise to new neurons.1 This makes it possible to study the role of neural progenitor cells in a wide variety of human brain disorders. BioEssays 30:806–810, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

As we move around in our environment, and interact with it, many of the most important problems we face involve the processing of spatial information. We have to be able to navigate by perceiving and remembering the locations and orientations of the objects around us relative to ourself; we have to sense and act upon these objects; and we need to move through space to position ourselves in favourable locations or to avoid dangerous ones. While this appears so simple that (...) we don't even think about it, the difficulty of solving these problems has been shown in the repeated failure of artificial systems to perform these kinds of tasks efficiently. In contrast, humans and other animals routinely overcome these problems every single day. This book examines some of the neural substrates and mechanisms that support these remarkable abilities. The hippocampus and the parietal cortex have been implicated in various core spatial behaviours, such as the ability to localise an object and navigate to it. Damage to these areas in humans and animals leads to impairment of these spatial functions. This collection of papers, written by internationally recognized experts in the field, reviews the evidence that each area is involved in spatial cognition, examines the mechanisms underlying the generation of spatial behaviours, and considers the relative roles of the parietal and hippocampal areas, including how each interacts with the other. The papers integrate a wide range of theoretical and experimental approaches, and touch on broader issues relating to memory and imagery. As such, this book represents the state of the art of current research into the neural basis of spatial cognition. It should be of interest to anyone - researchers or graduate students - working in the areas of cognitive neuroscience, neuroanatomy, neuropsychology, and cognition generally. (shrink)

What is the function of new neurons entering the olfactory bulb? Many insights regarding the molecular control of adult neurogenesis have been uncovered, but the purpose of new neurons entering the olfactory bulb has been difficult to ascertain. Here, studies investigating the role of adult neurogenesis in olfactory discrimination in mice are reviewed. Studies in which adult neurogenesis is affected are highlighted, with a focus on the role of environment enrichment and what happens during ageing. There is (...) evidence for a role of adult neurogenesis in fine discrimination tasks, as underscored by studies that enhance adult neurogenesis. This is also observed in ageing studies, where older mice with reduced levels of adult neurogenesis perform poorly in olfactory discrimination. Differences in methodology that could account for alternative conclusions, and the importance of specificity in methods being used to investigate the effect of adult neurogenesis in olfactory performance are emphasized. (shrink)

The transcription factor CREB has been implicated in signalling pathways relevant for pathogenesis and therapy of depression. CREB is upregulated and activated in the hippocampus by chronic antidepressant treatment, similarly as neurogenesis. Surprisingly, a recent study using CREB‐deficient mice also demonstrates an upregulation of neurogenesis correlating with an antidepressant behavioral phenotype.1 Interestingly, CREB‐deficient mice show a rapid behavioral response to antidepressants, while wild‐type mice do not. This minireview tries to reconcile these new findings with established concepts on CREB, (...) neurogenesis and depression. It also outlines some crucial experiments and lines of future research that could clarify some of the pending questions. BioEssays 29:957–961, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Adult neurogenesis is an exciting and rapidly advancing field of research. It addresses basic biological questions, such as the how and why of de novo neuronal production during adulthood, as well as medically relevant issues, including the potential link between adult neural stem cells and psychiatric disorders, or how stem cell manipulation might be used as a strategy for neuronal replacement. Current research mainly focuses on rodents, but we review here recent examination of non‐mammalian vertebrates, which demonstrates that bona (...) fide adult neural stem cells exist in these species. Importantly, especially in teleost fish, these cells can be abundant and located in various brain areas. Hence, non‐mammalian vertebrate species provide invaluable comparative material for extracting core mechanisms of adult neural stem cell maintenance and fate. BioEssays 29:745–757, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The discovery of neurogenesis and neural stem cells (NSC) in the adult CNS has overturned a long‐standing and deep‐routed “dogma” in neuroscience, established at the beginning of the 20th century. This dogma lasted for almost 90 years and died hard when NSC were finally isolated from the adult mouse brain. The scepticism in accepting adult neurogenesis has now turned into a rush to find applications to alleviate or cure the devastating diseases that affect the CNS. Here we highlight (...) a number of methodological, technical and conceptual drawbacks responsible for the historical denial of adult neurogenesis. Furthermore, we discuss old and new issues that need to be faced before NSC or endogenous neurogenesis can safely enter into the doctor's bag for therapies. BioEssays 30:135–145, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Elucidating distinct morphological atrophy patterns of Alzheimer’s disease and its prodromal stage, namely, mild cognitive impairment helps to improve early diagnosis and medical intervention of AD. On that account, we aimed to obtain distinct patterns of voxel-wise morphological atrophy and its further perturbation on structural covariance network in AD and MCI compared with healthy controls. T1-weighted anatomical images of matched AD, MCI, and HCs were included in this study. Gray matter volume was obtained using voxel-based morphometry and compared among three (...) groups. In addition, structural covariance network of identified brain regions exhibiting morphological difference was constructed and compared between pairs of three groups. Thus, patients with AD have a reduced hippocampal volume and an increased rate of atrophy compared with MCI and HCs. MCI exhibited a decreased trend in bilateral hippocampal volume compared with HCs and the accelerated right hippocampal atrophy rate than HCs. In AD, the hippocampus further exhibited increased structural covariance connected to reward related brain regions, including the anterior cingulate cortex, the putamen, the caudate, and the insula compared with HCs. In addition, the patients with AD exhibited increased structural covariance of left hippocampus with the bilateral insula, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum than MCI. These results reveal distinct patterns of morphological atrophy in AD and MCI, providing new insights into pathology of AD. (shrink)

Goal-directed spatial decision making video games combine spatial mapping, memory, and reward; all of which can involve hippocampal excitation through suppression of an inhibitory neurotransmitter, γ-aminobutyric acid. In this study, GABA was measured before and after 30 min of video game play within a voxel around the hippocampus. It was predicted that all participants would experience a decrease in GABA during gaming as a result of in-game rewards; and, those who were most competitive with the goal-directed spatial decision making (...) game would display lower hippocampal GABA concentrations after gaming. Those who were not competitive, because they were too skilled or not skilled enough, would demonstrate higher hippocampal GABA concentrations after gaming. While there were no significant differences in hippocampal GABA before and after gaming for gamers and non-gamers alike, there was a significant quadratic regression between performance on a spatial working memory task and post-gaming hippocampal GABA concentrations. (shrink)

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase II invasive monitoring for (...) intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject’s medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients. (shrink)

Continuing commentary raised several issues concerning our proposal that the hippocampus, parahippocampal region, and cortical association areas mediate different aspects of memory function. Recent relevant findings strengthen our argument that neocortical areas and the parahippocampal region maintain persistent encodings of specific single items and that the hippocampus mediates representations of the relations among these items. The reciprocally and closely interconnected structures that compose the hippocampal memory system work interactively to support flexible memory expression that is relevant to the natural (...) behavior of animals and to conscious recollection in humans. (shrink)

There is considerable evidence that the hippocampal system contributes both to (1) the temporary maintenance of memories and to (2) the processing of a particular type of memory representation. The findings on amnesia suggest that these two distinguishing features of hippocampal memory processing are orthogonal. Together with anatomical and physiological data, the neuropsychological findings support a model of cortico-hippocampal interactions in which the temporal and representational properties of hippocampal memory processing are mediated separately. We propose that (...) neocortical association areas maintain shortterm memories for specific items and events prior to hippocampal processing as well as providing the final repositories of long-term memory. The parahippocampal region supports intermediate-term storage of individual items, and the hippocampal formation itself mediates an organization of memories according to relevant relationships among items. Hippocampal-cortical interactions produce (i) strong and persistent memories for events, including their constituent elements and the relationships among them, and (ii) a capacity to express memories flexibly across a wide range of circumstances. (shrink)

Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli1–4. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse5. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its (...) expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution 18F-labelled deoxyglucose positron-emission tomography (FDG–PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression. Anxiety disorders are among the most common forms of psychopathology6, and frequently begin during childhood and adolescence. Although all children experience acute anxiety, children with AT display extreme behavioural and physiological reactivity to novel stimuli, and in the presence of strangers inhibit their locomotor activity and vocalizations3.. (shrink)