Neural correlates of incidental memory in mild cognitive impairment: an fMRI study

Behaviour and fMRI brain activation patterns were compared during encoding and recognition tasks in mild cognitive impairment (MCI) (n=14) and normal controls (NC) (n=14). Deep (natural vs. man-made) and shallow (color vs. black and white) decisions were made at encoding and pictures from each condition were presented for yes/no recognition 20 min later. MCI showed less inferior frontal activation during deep (left only) and superficial encoding (bilaterally) and in both medial temporal lobes (MTL). When performance was equivalent (recognition of words encoded superficially), MTL activation was similar for the two groups, but during recognition testing of deeply encoded items NC showed more activation in both prefrontal and left MTL region. In a region of interest analysis, the extent of activation during deep encoding in the parahippocampi bilaterally and in left hippocampus correlated with subsequent recognition accuracy for those items in controls but not in MCI, which may reflect the heterogeneity of activation responses in conjunction with different degrees of pathology burden and progression status in the MCI group.     

Using developmental cognitive neuroscience to study behavioral and attentional control

Adult cognitive neuroscience employs a wide variety of techniques to investigate a broad range of behavioral and cognitive functions. One prominent area of study is that of executive control, complemented by a smaller but growing literature exploring the developmental cognitive neuroscience of executive control. To date this approach has often compared children with specific developmental disorders, such as ADHD and ASD, with typically developing controls. Whilst these comparisons have done much to advance our understanding of the neural markers that underpin behavioral difficulties at specific time-points in development, we contend that they should leave developmental cognitive neuroscientists wanting. Studying the neural correlates of typical changes in executive control in their own right can reveal how different neural mechanisms characteristic of the adult end-state emerge, and it can therefore inform the adult cognitive neuroscience of executive control itself. The current review addresses the extent to which developmentalists and adult cognitive neuroscientists have tapped this common ground. Some very elegant investigations illustrate how seemingly common processes in adulthood present as separable in childhood, on the basis of their distinctive developmental trajectories. These demonstrations have implications not only for an understanding of changing behavior from infancy through childhood and adolescence into adulthood, but, moreover, for our grasp of the adult end-state per se. We contend that, if used appropriately, developmental cognitive neuroscience could enable us to construct a more mechanistic account of executive control.     

Neural correlates of actual and predicted memory formation

We aimed to discover the neural correlates of subjective judgments of learning-whereby participants judge whether current experiences will be subsequently remembered or forgotten-and to compare these correlates to the neural correlates of actual memory formation. During event-related functional magnetic resonance imaging, participants viewed 350 scenes and predicted whether they would remember each scene in a later recognition-memory test. Activations in the medial temporal lobe were associated with actual encoding success (greater activation for objectively remembered than forgotten scenes), but not with predicted encoding success (activations did not differ for scenes predicted to be remembered versus forgotten). Conversely, activations in the ventromedial prefrontal cortex were associated with predicted but not actual encoding success, and correlated with individual differences in the accuracy of judgments of learning. Activations in the lateral and dorsomedial prefrontal cortex were associated with both actual and predicted encoding success. These findings indicate specific dissociations and associations between the neural systems that mediate actual and predicted memory formation.     

The roles of functional neuroimaging and cognitive neuropsychology in the development of cognitive theory: A reply to Coltheart

This is a rejoinder in response to the book review by Max Coltheart on the book The Organization of Mind, edited by Tim Shallice and Richard P. Cooper, Oxford: Oxford University Press, 2011, pp. 608. ISBN 978-0-19-957924-2.     

Using developmental, cognitive, and neuroscience approaches to understand executive control in young children

The 7 articles in this special issue address the nature of executive control in young children. Executive control is framed in a developmental context, where the unique aspects of cognition in this age range are considered. The set of articles demonstrates the multidisciplinary approaches to study cognition in young children that includes application of cognitive, neuroscience, and developmental paradigms in typically developing youngsters, as well as those affected by clinical conditions, such as traumatic brain injury, exposure to low levels of lead in the environment, and prematurity. Although much work remains to be done, these study results are illustrative of the dynamic work in this exciting developmental period.     

Dissociation of behavioral and neural correlates of early associative learning

Wistar rat pups were trained in an olfactory associative conditioning task on postnatal Day 6, 12, or 20. The training consisted of 20 pairings of a novel odor (peppermint) with footshock (1.5 mA, 1 s) with an intertrial interval of 3 min. Additional pups were trained in either unpaired or naive control conditions. On the day following training, pups were either tested for their behavioral response to the conditioned odor in a two-odor choice test, or injected with ¹⁴C-2-deoxyglucose and exposed to the odor for examination of olfactory bulb neural responses to the odor. The results demonstrate that, although pups at all ages learned to avoid the odor, only pups trained during the first postnatal week had a modified olfactory-bulb glomerular-layer response to the odor. These results suggest that although olfactory memory is correlated with modification of olfactory bulb glomerular layer function in newborns, these changes are not required for normal memory in older pups. © 1995 John Wiley & Sons, Inc.     

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.     

Sleep pressure correlates of cognitive and behavioral morbidity in snoring children

STUDY OBJECTIVES: Sleep architecture is not preserved in children with sleep-disordered breathing but, rather, undergoes dynamic changes that exhibit significant correlation with severity of sleep-disordered breathing. A sleep pressure score (SPS) with a cutoff value of 0.25 was derived from analysis of a large cohort of snoring and control children. Neurocognitive batteries were applied to examine the potential effect of SPS. DESIGN: Prospective study. PARTICIPANTS: 199 children who underwent a battery of neurobehavioral tests following an overnight sleep study were assigned to SPSHigh (> or = 0.25) or SPSLow (< 0.25) groups, and their neurocognitive performances were compared. RESULTS: Children in the SPSHigh group were significantly more likely to have deficits in memory, language abilities, verbal abilities, and some visuospatial functions than were children in the SPSLow group. These effects remained highly significant after adjusting for confounding variables and exhibited small to moderate effect sizes. CONCLUSIONS: We conclude that a sleep-pressure numerical factor derived from the overnight polysomnogram in snoring children is associated with deficits in neurobehavioral daytime functions that is independent of respiratory disturbance and hypoxemia and suggests a significant role for disturbed sleep homeostasis in pediatric sleep-disordered breathing.     

Brain mapping in cognitive disorders: a multidisciplinary approach to learning the tools and applications of functional neuroimaging

Background  

With rapid advances in functional imaging methods, human studies that feature functional neuroimaging techniques are increasing exponentially and have opened a vast arena of new possibilities for understanding brain function and improving the care of patients with cognitive disorders in the clinical setting. There is a growing need for medical centers to offer clinically relevant functional neuroimaging courses that emphasize the multifaceted and multidisciplinary nature of this field. In this paper, we describe the implementation of a functional neuroimaging course focusing on cognitive disorders that might serve as a model for other medical centers. We identify key components of an active learning course design that impact student learning gains in methods and issues pertaining to functional neuroimaging that deserve consideration when optimizing the medical neuroimaging curriculum.     

Neural correlates of delayed episodic memory in patients with mild cognitive impairment—A FDG PET study

Mild cognitive impairment (MCI) is characterized by cognitive deficits which do not yet reach the threshold of dementia but represent a putative preclinical state of Alzheimer's disease (AD). Little is known about the neural correlates of delayed episodic memory which is among the earliest signs of cognitive decline in patients at risk of developing AD. We performed resting state positron emission tomography (PET) with ¹⁸Fluorodeoxyglucose (FDG) in patients with MCI, and hypothesized a correlation between delayed episodic memory performance and frontal glucose metabolism since the latter is relatively spared in the preclinical phase of the disease. 43 patients (age: 69.7 ± 7.9 years; 24 male, 19 female) with MCI were investigated by FDG PET. Significant positive correlations with delayed episodic memory performance were calculated by statistical parametric mapping. To our knowledge the present study is the first to demonstrate by FDG PET the neural correlates of delayed episodic memory in patients with MCI. Our study revealed a pattern of cerebral glucose metabolism including bifrontal regions which may contribute to the delayed episodic memory performance of patients with MCI. Since not all patients with MCI will further deteriorate, AD specific mechanism may not be concluded from the present study but warrant longitudinal investigations.     

Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures

The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.     

Neural correlates of encoding and expression in implicit sequence learning

It has been shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a lasting increase in corticospinal excitability. Here we recorded motor evoked potentials (MEPs) from the right first dorsal interosseus muscle to investigate how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At an intensity of 90% of active motor threshold, rTMS produced no effect on MEP amplitude at rest. Increasing the intensity to 90% of resting motor threshold (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect gradually built up during the course of rTMS, reaching significance after the administration of 900 stimuli. In a second experiment, MEPs were elicited during tonic contraction using weak anodal electrical or magnetic test stimuli. 1500 (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli were given at 90% of RMT to the M1-HAND. Using two well-established conditioning-test paradigms, we found a decrease in short-latency intracortical inhibition (SICI), and a facilitation of the first peak of facilitatory I-waves interaction (SICF). There was no correlation between the relative changes in SICI and SICF. These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes in specific neuronal subpopulations in the human corticospinal motor system, depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at 90% of RMT can selectively shape the excitability of distinct intracortical circuits, whereas prolonged 5 Hz rTMS (900 stimuli) provokes an overall increase in excitability of the corticospinal output system, including spinal motoneurones.     

Neural correlates of sensory and decision processes in auditory object identification

Physiological studies of auditory perception have not yet clearly distinguished sensory from decision processes. In this experiment, human participants identified speech sounds masked by varying levels of noise while blood oxygenation signals in the brain were recorded with functional magnetic resonance imaging (fMRI). Accuracy and response time were used to characterize the behavior of sensory and decision components of this perceptual system. Oxygenation signals in a cortical subregion just anterior and lateral to primary auditory cortex predicted accuracy of sound identification, whereas signals in an inferior frontal region predicted response time. Our findings provide neurophysiological evidence for a functional distinction between sensory and decision mechanisms underlying auditory object identification. The present results also indicate a link between inferior frontal lobe activation and response-selection processes during auditory perception tasks.     

Neural correlates of second-language word learning: minimal instruction produces rapid change

Adult second-language (L2) learning is often claimed to be slow and laborious compared to native language (L1) acquisition, but little is known about the rate of L2 word learning. Here we report that adult second-language learners' brain activity, as measured by event-related potentials (ERPs), discriminated between L2 words and L2 'pseudowords' (word-like letter strings) after just 14 h of classroom instruction. This occurred even while the learners performed at chance levels when making overt L2 word-nonword judgments, indicating that the early acquisition of some aspects of a new language may be overlooked by current behavioral assessments.     

The use of null mutant mice to study complex learning and memory processes

A number of neural substrates have been proposed to mediate complex learning and memory processes in mammalian organisms. One strategy for testing the involvement of a particular gene in learning and memory is to create a mouse line with a null mutation in that gene. Recently, embryonic stem cell-based gene-targeted homologous recombination techniques have been employed to create a number of such mutant mouse lines that do not express interesting candidate genes. These animals have been examined for impairments in several complex learning paradigms which are known to depend on the integrity of the hippocampus. In this review several complex learning and memory paradigms are described, the techniques to create null mutants are reviewed, and the results of recent studies with null mutants are described. Finally, the limitations for interpretation of behavioral data using null mutants are discussed.     

Biophysical and behavioral correlates of memory storage, degradation, and reactivation.

Neural correlates of associative memory and "forgetting" were observed 1, 6, and 14 days after acquisition of a conditioned response (CR) in the marine snail Hermissenda. Behavioral expression of a light-rotation association, as indexed by contraction of the animal's foot in response to light, dissipated throughout the 14-day interval such that a CR was observed 1 and 6 days after conditioning but was absent 14 days later. In relation to naive or pseudoconditioned animals, membrane resistance (inversely related to neuronal membrane conductance and directly related to excitability) of the isolated Type B photoreceptor (B cell) was elevated in conditioned animals on Days 1 and 6, whereas no elevation was detectable on Day 14. However, both the behavioral response and the elevated membrane resistance in conditioned animals were hypersensitive to light-rotation pairings (i.e., exhibited "savings") on Day 14, which is indicative of a latent memory trace. In a second experiment, a current-induced depolarization of the B cell after 14 retention days resulted in an increase in input resistance of the B cell membrane in previously conditioned animals but a weaker, transient rise in resistance in B cells from animals exposed to the nonassociative control procedure 14 days earlier. This effect was Ca(2+)-dependent because no rise in resistance was observed if Ca2+ was removed from the extracellular bath. These results indicate that modification of membrane conductance (i.e., elevated resistance), although apparently critical for the behavioral expression of the memory, is not essential for the maintenance of the latent memory trace, whereas Ca2+ hypersensitivity may be a principal contributor to the storage of a latent memory trace and memory reactivation.     

Effect of an afternoon confectionery snack on cognitive processes critical to learning

Two experiments examined how an afternoon confectionery snack affects a variety of cognitive processes critical to learning. For Experiment 1, thirty-eight male undergraduates completed a dual learning task where the primary task involved learning either a map or stories and the secondary task required monitoring a radio broadcast for a specific word category. Results showed that for map learning, participants who consumed the confectionery snack performed better on the primary task. They correctly placed more country names and left fewer blanks on a map during long-term recall. However, on the secondary attention task, participants who consumed the confectionery snack had a lower hit rate. The confectionary snack did not affect story memory performance. In Experiment 2, 38 boys, aged 9-11 years, participated in a similar, age appropriate task. Results showed that boys who had consumed the confectionery snack correctly placed more names and left fewer blanks on a map in both short-term and long-term recall. In contrast with Experiment 1, performance on the secondary task was better after confectionary consumption. However, when tested on a separate vigilance attention task, children who consumed the placebo performed better. Overall results indicate that a confectionery snack, ingested in the afternoon, generally improves spatial memory, but has a mixed effect on attention performance.