Narcolepsy: pathophysiology and neuropsychological changes

Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.     

Ovarian steroids and cognitive function

The ovarian steroids, estrogen and progesterone, not only govern reproductive events in mammalian females but also influence an array of other processes. Of particular clinical interest is the potential of ovarian steroids to facilitate storage of new memories and to protect neurons from various threats. Research during the past decade confirms that estrogen and progesterone influence the biochemical, electrical, and structural properties of neurons in brain regions that subserve learning and memory. These mechanisms form the biological foundations for the complex effects of ovarian steroids on cognitive functions in various species, including humans. Despite significant progress in our understanding of the roles of hormonal factors in cognitive function and neuronal survival, the value of hormone replacement as a treatment and deterrent for cognitive impairments associated with age, disease, and injury remains uncertain as we enter the new century.     

17beta-estradiol: effect on CA1 hippocampal synaptic plasticity.

An understanding of synaptic plasticity in the mammalian brain has been one of R. F. Thompson's major pursuits throughout his illustrious career. A current series of experiments of significant interest to R. F. Thompson is an examination of the interactions between sex hormones, synaptic plasticity, aging, and stress. This research is contained within a broader project whose aim is to investigate animal models that evaluate estrogen interactions with Alzheimer's disease. This paper reviews the recent results that have led to a better understanding of how the sex hormone estrogen influences synaptic plasticity in an important structure within the mammalian brain responsible for learning and memory: the hippocampus. In this review, a number of experiments have been highlighted that investigate the molecular mechanisms that underlie estrogen's effect on two specific forms of synaptic plasticity commonly studied in neurophysiology and the behavioral neurosciences: long-term potentiation and long-term depression.     

17β-Estradiol: Effect on CA1 Hippocampal Synaptic Plasticity

An understanding of synaptic plasticity in the mammalian brain has been one of R. F. Thompson's major pursuits throughout his illustrious career. A current series of experiments of significant interest to R. F. Thompson is an examination of the interactions between sex hormones, synaptic plasticity, aging, and stress. This research is contained within a broader project whose aim is to investigate animal models that evaluate estrogen interactions with Alzheimer's disease. This paper reviews the recent results that have led to a better understanding of how the sex hormone estrogen influences synaptic plasticity in an important structure within the mammalian brain responsible for learning and memory: the hippocampus. In this review, a number of experiments have been highlighted that investigate the molecular mechanisms that underlie estrogen's effect on two specific forms of synaptic plasticity commonly studied in neurophysiology and the behavioral neurosciences: long-term potentiation and long-term depression.     

The path to epigenetic treatment of memory disorders

A new line of neuroscience research suggests that epigenetics may be the site of nature and nurture integration by providing the environment with a mechanism to directly influence the read-out of our genome. Epigenetic mechanisms in the brain are a series of post-translational chromatin and DNA modifications driven by external input. Given the critical hub that epigenetics appears to be, neuroscientists have come to suspect its fundamental influence on how our minds change in response to our unique environment and, in turn, how these changes can then impact our future interactions with the environment. The field of learning and memory is becoming particularly interested in understanding the cognitive influence of epigenetics. With the majority of us working with an eye toward therapeutics, the question naturally arises: "Has neuroepigenetics gotten us closer to treating memory disorders and if so, where do we go from here?" This review will begin with a brief exploration of recent advances in our understanding of how epigenetic mechanisms contribute to learning and memory processes that are susceptible to failure. Next the implications for disorders of cognition, such as Alzheimer's disease, will be discussed. Finally, we will use parallels from the field of cancer to speculate on where we should consider heading from here in the pursuit of therapeutics.     

Cholinergic modulation of learning and memory in the human brain as detected with functional neuroimaging

The advent of neuroimaging methods such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has provided investigators with a tool to study neuronal processes involved in cognitive functions in humans. Recent years have seen an increasing amount of studies which mapped higher cognitive functions to specific brain regions. These studies have had a great impact on our understanding of neuroanatomical correlates of learning and memory in the living human brain. Recently, advances were made to go beyond the use of fMRI as a pure cognitive brain mapping device. One of these advances includes the use of psychopharmacological approaches in conjunction with neuroimaging. The paper will introduce the combination of neuroimaging and psychopharmacology as a tool to study neurochemical modulation of human brain function. A review of imaging studies using cholinergic challenges in the context of explicit and implicit learning and memory paradigms is provided which show that cholinergic neurotransmission modulates task-related activity in sensory and frontal cortical brain areas.     

Role of estrogen in balancing contributions from multiple memory systems

In addition to modulating memory per se, estrogen alters the learning strategy used to solve a task, thereby regulating the quality of information processed by the brain. This review discusses estrogen's actions on cognition within a memory systems framework, highlighting our work with a variety of paradigms showing that learning strategy is sensitive to estrogen even when learning rate is not. Specifically, high levels of gonadal steroids, in particular, elevations in estrogen, bias female rats toward using hippocampal-sensitive approaches while low levels of gonadal steroids promote the use of non-hippocampal sensitive strategies. In light of findings from a variety of approaches involving the hippocampus in allocentric and the striatum in egocentric response patterns, it is likely that estrogen alters the relative participation of these, and most undoubtedly other, neural systems during cognition. Changes in neuromodulators such as acetylcholine that regulate other processes such as inhibitory tone and excitability reflect one mechanism by which estrogen may orchestrate learning and memory.     

Amnesia and criminal law: A clinical overview

The use of amnesia as a legal defense raises complex issues for both psychology and jurisprudence. Our review of the legal literature suggests that recent advances in the understanding of clinical disorders of memory have not yet found their way into the courtroom. In this paper, we address the assumptions that amnesia means simply having a very bad memory and that amnesia is a unitary syndrome. We then review recent neuropsychological research on amnesia and its implications for the judicial process. Emphasis is placed on describing the amnesic disorders that most often arise in criminal proceedings. It is concluded that both psychologists and legal professionals should ensure that research findings from the clinic and the laboratory are applied appropriately in cases of defendants claiming amnesia.     

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

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.     

人类记忆再巩固研究现状及临床应用

巩固的记忆被提取后,进入不稳定状态,再重新稳定下来,这个过程称为记忆再巩固。本文首先阐述人类记忆再巩固主要研究方法和经典范式,梳理记忆再巩固在人类恐惧记忆和情景记忆两个方面的相关研究,并从认知神经科学角度整理记忆再巩固的加工机制。然后总结记忆再巩固应用于创伤性应激障碍和药物成瘾等心理障碍临床治疗的相关文献。最后本文提出未来研究的方向和建议,希冀对人类记忆再巩固的理论研究和临床应用提供新思路。     

Neural correlates of establishing, maintaining, and switching brain states

Although the study of brain states is an old one in neuroscience, there has been growing interest in brain state specification owing to MRI studies tracing brain connectivity at rest. In this review, we summarize recent research on three relatively well-described brain states: the resting, alert, and meditation states. We explore the neural correlates of maintaining a state or switching between states, and argue that the anterior cingulate cortex and striatum play a critical role in state maintenance, whereas the insula has a major role in switching between states. Brain state may serve as a predictor of performance in a variety of perceptual, memory, and problem solving tasks. Thus, understanding brain states is critical for understanding human performance.     

Brain Networks in Schizophrenia

Schizophrenia—a severe psychiatric condition characterized by hallucinations, delusions, loss of initiative and cognitive function—is hypothesized to result from abnormal anatomical neural connectivity and a consequent decoupling of the brain’s integrative thought processes. The rise of in vivo neuroimaging techniques has refueled the formulation of dysconnectivity hypotheses, linking schizophrenia to abnormal structural and functional connectivity in the brain at both microscopic and macroscopic levels. Over the past few years, advances in high-field structural and functional neuroimaging techniques have made it increasingly feasible to reconstruct comprehensive maps of the macroscopic neural wiring system of the human brain, know as the connectome. In parallel, advances in network science and graph theory have improved our ability to study the spatial and topological organizational layout of such neural connectivity maps in detail. Combined, the field of neural connectomics has created a novel platform that provides a deeper understanding of the overall organization of brain wiring, its relation to healthy brain function and human cognition, and conversely, how brain disorders such as schizophrenia arise from abnormal brain network wiring and dynamics. In this review we discuss recent findings of connectomic studies in schizophrenia that examine how the disorder relates to disruptions of brain connectivity.     

Neural evidence supports a novel framework for spatial navigation

The spatial knowledge used for human navigation has traditionally been separated into three categories: landmark, route, and survey knowledge. While behavioral research has retained this framework, it has become increasingly clear from recent neuroimaging studies that such a classification system is not adequate for understanding the brain. This review proposes a new framework, with a taxonomy based on the cognitive processes and subprocesses involved in spatial navigation. The neural correlates of spatial memory can inform our understanding of the cognitive processes involved in human navigation, and conversely, the specific task demands of an experiment can inform the interpretation of neuroimaging results. This review examines the neural correlates of each cognitive process separately, to provide a closer inspection of each component of spatial navigation. While landmark, route, and survey knowledge are still important components of human navigation, the neural correlates are not neatly ascribed to these three categories. The present findings provide motivation for a more detailed examination of the cognitive processes engaged during wayfinding.     

Learning to remember: Social-communicative exchanges and the development of children’s memory skills

For more than three decades, the question “What is memory development the development of?” has guided research on children’s memory. As theories and methodologies have evolved, so too has our knowledge of the mnemonic competencies of young children, and of age-related differences in memory performance. Unfortunately, however, current understanding of the development of memory is seriously limited, largely because the bulk of the literature is based on cross-sectional experiments. From our perspective, in order to increase our understanding of the development of children’s skills for remembering, it is necessary to conduct longitudinal studies that illuminate mechanisms underlying developmental change. In addition, experimental methods must be used to explore further the operation of these potential mediators of change. In this article, we review our own recent longitudinal and experimental research to illustrate how we are addressing a new call—to study both memory development and the development of memory.     

Effects of Hormone Replacement Therapy and Aging on Cognition: Evidence for Executive Dysfunction

ABSTRACT

The present study was designed to explore whether the frontal lobe hypothesis of cognitive aging may be extended to describe the cognitive effects associated with estrogen use in postmenopausal women. Postmenopausal estrogen-only users, estrogen + progesterone users, and non-users (60–80 years old), as well as young, regularly cycling women (18–30 years old) completed an item and source memory task. Since source memory is thought to rely more on executive processes than item memory, we hypothesized that aging and estrogen effects would be greater for source memory than for item memory. Neuropsychological tests explored whether the effects of aging and estrogen use were revealed on other tests of frontal lobe function. Results from the experimental task revealed greater aging and estrogen effects for source memory than for item memory, and neuropsychological results revealed aging and estrogen effects on a subset of tests of executive function. Women on estrogen + progesterone therapy did not outperform non-users, suggesting that the addition of progesterone to hormone therapy may mitigate the benefits induced by estrogen use alone. Overall, findings support the hypothesis that estrogen use may temper age-related cognitive decline by helping to maintain functions subserved by the frontal lobes.     

Effects of hormone replacement therapy and aging on cognition: evidence for executive dysfunction

The present study was designed to explore whether the frontal lobe hypothesis of cognitive aging may be extended to describe the cognitive effects associated with estrogen use in postmenopausal women. Postmenopausal estrogen-only users, estrogen + progesterone users, and non-users (60-80 years old), as well as young, regularly cycling women (18-30 years old) completed an item and source memory task. Since source memory is thought to rely more on executive processes than item memory, we hypothesized that aging and estrogen effects would be greater for source memory than for item memory. Neuropsychological tests explored whether the effects of aging and estrogen use were revealed on other tests of frontal lobe function. Results from the experimental task revealed greater aging and estrogen effects for source memory than for item memory, and neuropsychological results revealed aging and estrogen effects on a subset of tests of executive function. Women on estrogen + progesterone therapy did not outperform non-users, suggesting that the addition of progesterone to hormone therapy may mitigate the benefits induced by estrogen use alone. Overall, findings support the hypothesis that estrogen use may temper age-related cognitive decline by helping to maintain functions subserved by the frontal lobes.     

Frontal-Lobe Involvement in Spatial Memory: Evidence from PET,fMRI, and Lesion Studies

Many studies have identified the prefrontal cortex as the brain area that is critical for spatial memory, both in humans and in other primates. Other studies, however, have failed to establish this relation. Therefore, the aim of this paper was to review the literature regarding the role of the human prefrontal lobe in spatial memory. This was done by examining the evidence obtained from neuropsychological patients and from studies using brain-imaging techniques (PET and fMRI). Evidence supporting the notion that the prefrontal cortex is extensively involved in spatial working memory was found. The majority of these studies, however, suggests that frontal-lobe involvement is not related to the type of material that is being processed (e.g., spatial vs. nonspatial), but to process-specific functions, such as encoding and retrieval. Theoretically, these functions could be linked to the central executive within Baddeley's working-memory model, or to recent theories that emphasize the various processes that play a role in working memory. Also, methodological issues were discussed. Further research is needed to enhance our understanding of the precise interaction of domain-specific and general processes.     

The neuroanatomy and neuroendocrinology of fragile X syndrome

Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical features that are unique to this syndrome. In this article, we summarize studies focused on the neuroanatomy and neuroendocrinology of FXS. A review of structural imaging studies of individuals with the full mutation shows that several brain regions are enlarged, including the hippocampus, amygdala, caudate nucleus, and thalamus, even after controlling for overall brain volume. These regions mediate several cognitive and behavioral functions known to be aberrant in FXS such as memory and learning, information and sensory processing, and social and emotional behavior. Two regions, the cerebellar vermis, important for a variety of cognitive tasks and regulation of motor behavior, and the superior temporal gyrus, involved in processing complex auditory stimuli, are reported to be reduced in size relative to controls. Functional imaging, typically limited to females, has emphasized that individuals with FXS do not adequately recruit brain regions that are normally utilized by unaffected individuals to carry out various cognitive tasks, such as arithmetic processing or visual memory tasks. Finally, we review a number of neuroendocrine studies implicating hypothalamic dysfunction in FXS, including abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. These studies may help to explain the abnormal stress responses, sleep abnormalities, and physical growth patterns commonly seen in affected individuals. In the future, innovative longitudinal studies to investigate development of neurobiologic and behavioral features over time, and ultimately empirical testing of pharmacological, behavioral, and even molecular genetic interventions using MRI are likely to yield significant positive changes in the lives of persons with FXS, as well as increase our understanding of the development of psychiatric and learning problems in the general population.     

Mechanisms and the current state of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is unique among the current brain stimulation techniques because it is relatively non-invasive. TMS markedly differs from vagus nerve stimulation, deep brain stimulation and magnetic seizure therapy, all of which require either an implanted prosthesis or general anesthesia, or both. Since its rebirth in its modern form in 1985, TMS has already shown potential usefulness in at least three important domains-as a basic neuroscience research instrument, as a potential clinical diagnostic tool, and as a therapy for several different neuropsychiatric conditions. The TMS scientific literature has now expanded beyond what a single summary article can adequately cover. This review highlights several new developments in combining TMS with functional brain imaging, using TMS as a psychiatric therapy, potentially using TMS to enhance performance, and finally recent advances in the core technology of TMS. TMS' ability to non-invasively and focally stimulate the brain of an awake human is proving to be a most important development for neuroscience in general, and neuropsychiatry in particular.