Memory fMRI Research Articles

Tai Chi Chuan and Baduanjin Mind-Body Training Changes Resting-State Low-Frequency Fluctuations in the Frontal Lobe of Older Adults: A Resting-State fMRI Study.

Age-related cognitive decline is a significant public health concern. Recently, non-pharmacological methods, such as physical activity and mental training practices, have emerged as promising low-cost methods to slow the progression of age-related memory decline. In this study, we investigated if Tai Chi Chuan (TCC) and Baduanjin modulated the fractional amplitude of low-frequency fluctuations (fALFF) in different frequency bands (low-frequency: 0.01–0.08 Hz; slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz) and improved memory function. Older adults were recruited for the randomized study. Participants in the TCC and Baduanjin groups received 12 weeks of training (1 h/day for 5 days/week). Participants in the control group received basic health education. Each subject participated in memory tests and fMRI scans at the beginning and end of the experiment. We found that compared to the control group: (1) TCC and Baduanjin groups demonstrated significant improvements in memory function; (2) TCC increased fALFF in the dorsolateral prefrontal cortex (DLPFC) in the slow-5 and low-frequency bands; and (3) Baduanjin increased fALFF in the medial PFC in the slow-5 and low-frequency bands. This increase was positively associated with memory function improvement in the slow-5 and low-frequency bands across the TCC and Baduanjin groups. Our results suggest that TCC and Baduanjin may work through different brain mechanisms to prevent memory decline due to aging.

Verbal working memory and functional large-scale networks in schizophrenia

The aim of this study was to test whether bilinear and nonlinear effective connectivity (EC) measures of working memory fMRI data can differentiate between patients with schizophrenia (SZ) and healthy controls (HC). We applied bilinear and nonlinear Dynamic Causal Modeling (DCM) for the analysis of verbal working memory in 16 SZ and 21 HC. The connection strengths with nonlinear modulation between the dorsolateral prefrontal cortex (DLPFC) and the ventral tegmental area/substantia nigra (VTA/SN) were evaluated. We used Bayesian Model Selection at the group and family levels to compare the optimal bilinear and nonlinear models. Bayesian Model Averaging was used to assess the connection strengths with nonlinear modulation. The DCM analyses revealed that SZ and HC used different bilinear networks despite comparable behavioral performance. In addition, the connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area showed differences between SZ and HC. The adoption of different functional networks in SZ and HC indicated neurobiological alterations underlying working memory performance, including different connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area. These novel findings may increase our understanding of connectivity in working memory in schizophrenia.

Author response: Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. Methods: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with Results and recommendations: The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

Characterization of a Factual Knowledge-Associated Brain Memory Area by Functional Magnetic Resonance Imaging and Implementation in Tumor and Epilepsy Brain Surgery.

The role of the dominant hippocampus in verbal and episodic memory recall has been extensively investigated. However, there are categories of memory estimated independent of hippocampal function. In particular, factual knowledge is solely constituted from written or spoken input independent on undertaken experience, but the temporal structures involved are not well defined. In this retrospective study, we mapped the activity of factual knowledge recall using functional magnetic resonance imaging (fMRI) in 60 patients scheduled for tumor or epilepsy surgery and in 18 patients resected within or close to the left mesial temporal lobe. Memory tests were performed preoperatively and postoperatively to investigate deficit symptoms in factual knowledge retrieval. We found a highly reproducible localized brain area within the parahippocampal gyrus, in the depth of the dorsal collateral sulcus, which was constantly involved in factual knowledge retrieval during fMRI tasks in 93% of patients (56/60) during recall of capital cities or multiplication tasks, in two thirds of the patients mainly on the dominant side. In addition, all 18 patients after surgery within this area showed postoperative factual knowledge deficits (56% permanent, 44% transitory), memory prognosis significantly correlating with the first day's factual knowledge retrieval task results. Using fMRI, we visualized a circumscribed brain area within the parahippocampal gyrus during factual knowledge retrieval, the lesioning of which led to factual knowledge deficits. Thus, impairment of factual knowledge retrieval may occur if resection is extended into the parahippocampal gyrus. Preoperative fMRI memory maps may contribute to avoiding such deficits.

The Effects Of An Eight Week Exercise Intervention On Brain Activity In Depressed And Non Depressed Individuals

PURPOSE: Memory deficits is the most frequently reported cognitive symptom in people suffering with Major Depressive Disorder (MDD). Supporting clinical findings, neuroimaging studies investigating memory impairment in people with MDD have identified brain areas such as the prefrontal cortex and medial temporal lobe to be dysregulated during both memory encoding and retrieval. Exercise for brain health has been a common research theme for the past several years. Research has found that exercise protects against the development of neurodegenerative diseases, reverses brain volume loss in the elderly, upregulates neurogenesis in rodents and improves learning and memory. The aim of this study is to investigate the effects of an eight week exercise program on brain function during a memory task in people suffering with MDD and young healthy individuals. METHODS: Eight medicated patients with a clinical diagnosis of MDD based on DSM-IV criteria and eight healthy controls completed an eight week supervised exercise intervention. Participants performed an associative memory fMRI task matching names to faces pre and post the exercise intervention. Region of interest (ROI; anterior hippocampus) and whole-brain analyses were conducted to examine changes in brain function pre and post the exercise intervention. RESULTS: Following the eight weeks of exercise our ROI analyses revealed no group x time interaction, no main effect of group and a marginal main effect of time that did not reach significance. When examining the whole sample, collapsing across groups, increases in activity were present following the intervention in several regions, such as the basal ganglia, medial frontal and parietal lobe, and posterior cingulate. A regression analysis was conducted to determine if the change in activity pre/post was related to improvement in depression scores. We found those who showed the greatest improvement in depression scores had a reduction in activity in the left occipital and right motor regions. This finding suggests an improvement in sensory and motor processing. CONCLUSIONS: Our study shows that exercise can modulate brain activity during memory encoding in both healthy controls and those suffering from depression, which may be related to the reduction in symptoms shown in patients.

A Functional MRI-Based Model for Individual Memory Assessment in Patients Eligible for Anterior Temporal Lobe Resection.

Title:A functional (f) MRI-based model for individual memory assessment in patients eligible for temporal lobe resection.Aim:To investigate if pre-operative fMRI memory paradigms, add predictive information with regard to post-surgical memory deficits.Methods:Fourteen pharmacoresistant Temporal Lobe Epilepsy (TLE) patients accepted for Anterior Temporal Lobe Resection (ATLR) were included. A clinical risk assessment score (RAS 0-3) was constructed from structural MRI, neuropsychological testing and hemisphere dominance. fMRI lateralization indices (LIs) over frontal language and medial temporal regions were calculated. Predictive value from clinical risk scoring and added value from fMRI LIs were correlated to post-surgical memory change scores (significant decline -1 SD). Verbal memory outcome was classified either as expected (RAS 2-3 and post-operative decline; RAS 0-1 and intact post-operative verbal memory) or as unexpected (RAS 2-3 and intact post-operative verbal memory post-surgery; RAS 0-1 and post-operative decline).Results:RAS for verbal memory decline exhibited a specificity of 67% and a sensitivity of 75%. Significant correlations were found between frontal language LIs and post-operative verbal memory (r = -0.802; p = 0.017) for left (L) TLE and between medial temporal lobe LIs and visuospatial memory (r = 0.829; p = 0.021), as well as verbal memory (r = 0.714; p = 0.055) for right (R) TLE. Ten patients had expected outcome and four patients had an unexpected outcome. In two MRI-negative RTLE patients that suffered significant verbal memory decline post-operatively, fMRI identified bilateral language and right lateralized medial temporal verbal encoding. In two LTLE patients with MRI pathology and verbal memory dysfunction, neither RAS nor fMRI identified the risk for aggravated verbal memory decline following ATLR.Conclusion:fMRI visualization of temporal-frontal network activation may add value to the pre-surgical work-up in epilepsy patients eligible for ATLR. Frontal language patterns are important for prediction in both L and RTLE. Strong left lateralized language in LTLE, as well as bilateral language combined with right lateralized encoding in RTLE, seems to indicate an increased risk for post-operative verbal memory decline.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

ObjectivesDiminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI).MethodMCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus.ResultsWe found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors.ConclusionsOur results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI.Key Points• PCC functioning during episodic memory relates to hippocampal functioning in MCI.• PCC functioning during episodic memory does not relate to hippocampal structure in MCI.• Functional network changes are an important predictor of PCC functioning in MCI.

6.4 Structural and Functional Brain Abnormalities Associated With Distinct Dimensions of Subthreshold Psychosis in Youth

Abstract Background: Neuroimaging in population-based studies of youth can help identify neurodevelopmental abnormalities associated with psychosis-spectrum symptoms and risk. To date, little work has examined specific dimensions of psychosis spectrum symptoms in this population, a gap we sought to address here in the large Philadelphia Neurodevelopmental Cohort (PNC). Methods: In the PNC, ~20% of youth were categorized as psychosis spectrum (PS) based on elevations in positive or negative/disorganized symptoms. Baseline multimodal imaging data were acquired from 1601 youth from the PNC, aged 8–23 years, 452 of whom were identified as PS. Dimensional subclinical positive and negative/disorganized were derived from factor analysis of a structured clinical interview; cognition was measured with the Penn Computerized Neurocognitive Battery. Results: Subthreshold positive and negative symptom severity was moderately correlated (r = .37); reduced cognitive performance was modestly associated with both positive (r = −.14) and negative (r = −.17) domains. These 3 domains showed distinctive associations with functional and structural imaging. In the working memory fMRI task, PS showed reduced activation in executive control circuitry, which correlated with cognitive deficits (r = .32) but not positive or negative symptoms. During emotion identification fMRI, PS demonstrated elevated amygdala responses to threatening facial expressions, which correlated selectively with positive symptom severity (r = .16). Structural imaging revealed gray matter volume reductions in hippocampus associated with positive symptom severity (r = −.15). In contrast, unmodulated gray matter density was selectively reduced in the bilateral nucleus accumbens in association with negative symptom severity (r = −.16). Conclusion: These findings extend support for the continuum view of psychosis by demonstrating that specific circuit–symptom correlations found in schizophrenia are also evident in youth with subthreshold symptoms. Complementing the more common categorical focus, dimensional examination of specific illness domains may identify neurodevelopmental abnormalities within key brain circuits. This in turn can help parse clinically-relevant heterogeneity within the at-risk population and facilitate the development of early diagnostic and prognostic tests and novel treatments designed to target-specific symptom domains.

Tai Chi Chuan and Baduanjin practice modulates functional connectivity of the cognitive control network in older adults

Cognitive impairment is one of the most common problem saffecting older adults. In this study, we investigated whether Tai Chi Chuan and Baduanjin practice can modulate mental control functionand the resting state functional connectivity (rsFC) of the cognitive control network in older adults. Participants in the two exercise groups practiced either Tai Chi Chuan or Baduanjin for 12 weeks, and those in the control group received basic health education. Memory tests and fMRI scans were conducted at baseline and at the end of the study. Seed-based (bilateral dorsolateral prefrontal cortex, DLPFC) rsFC analysis was performed. We found that compared to the controls, 1) both Tai Chi Chuan and Baduanjin groups demonstrated significant improvements in mental control function; 2) the Tai Chi Chuan group showed a significant decrease in rsFC between the DLPFC and the left superior frontal gyrus (SFG) and anterior cingulate cortex; and 3) the Baduanjin group showed a significant decrease in rsFC between the DLPFC and the left putamen and insula. Mental control improvement was negatively associated with rsFC DLPFC-putamen changes across all subjects. These findings demonstrate the potential of Tai Chi Chuan and Baduanjin exercises in preventing cognitive decline.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy

To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls

Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.

A family of locally constrained CCA models for detecting activation patterns in fMRI

Canonical correlation analysis (CCA) has been used in Functional Magnetic Resonance Imaging (fMRI) for improved detection of activation by incorporating time series from multiple voxels in a local neighborhood. To improve the specificity of local CCA methods, spatial constraints were previously proposed. In this study, constraints are generalized by introducing a family model of spatial constraints for CCA to further increase both sensitivity and specificity in fMRI activation detection.The proposed locally-constrained CCA (cCCA) model is formulated in terms of a multivariate constrained optimization problem and solved efficiently with numerical optimization techniques. To evaluate the performance of this cCCA model, simulated data are generated with a Signal-To-Noise Ratio of 0.25, which is realistic to the noise level contained in episodic memory fMRI data. Receiver operating characteristic (ROC) methods are used to compare the performance of different models. The cCCA model with optimum parameters (called optimum-cCCA) obtains the largest area under the ROC curve. Furthermore, a novel validation method is proposed to validate the selected optimum-cCCA parameters based on ROC from simulated data and real fMRI data. Results for optimum-cCCA are then compared with conventional fMRI analysis methods using data from an episodic memory task. Wavelet-resampled resting-state data are used to obtain the null distribution of activation.For simulated data, accuracy in detecting activation increases for the optimum-cCCA model by about 43% as compared to the single voxel analysis with comparable Gaussian smoothing. Results from the real fMRI data set indicate a significant increase in activation detection, particularly in hippocampus, para-hippocampal area and nearby medial temporal lobe regions with the proposed method.

The Primacy Effect in Amnestic Mild Cognitive Impairment: Associations with Hippocampal Functional Connectivity.

Background: The “primacy effect,” i.e., increased memory recall for the first items of a series compared to the following items, is reduced in amnestic mild cognitive impairment (aMCI). Memory task-fMRI studies demonstrated that primacy recall is associated with higher activation of the hippocampus and temporo-parietal and frontal cortical regions in healthy subjects. Functional magnetic resonance imaging (fMRI) at resting state revealed that hippocampus functional connectivity (FC) with neocortical brain areas, including regions of the default mode network (DMN), is altered in aMCI. The present study aimed to investigate whether resting state fMRI FC between the hippocampus and cortical brain regions, especially the DMN, is associated with primacy recall performance in aMCI.Methods: A number of 87 aMCI patients underwent resting state fMRI and verbal episodic memory assessment. FC between the left or right hippocampus, respectively, and all other voxels in gray matter was mapped voxel-wise and used in whole-brain regression analyses, testing whether FC values predicted delayed primacy recall score. The delayed primacy score was defined as the number of the first four words recalled on the California Verbal Learning Test. Additionally, a partial least squares (PLS) analysis was performed, using DMN regions as seeds to identify the association of their functional interactions with delayed primacy recall.Results: Voxel-based analyses indicated that delayed primacy recall was mainly (positively) associated with higher FC between the left and right hippocampus. Additionally, significant associations were found for higher FC between the left hippocampus and bilateral temporal cortex, frontal cortical regions, and for higher FC between the right hippocampus and right temporal cortex, right frontal cortical regions, left medial frontal cortex and right amygdala (p < 0.01, uncorr.). PLS analysis revealed positive associations of delayed primacy recall with FC between regions of the DMN, including the left and right hippocampus, as well as middle cingulate cortex and thalamus (p < 0.04). In conclusion, in the light of decreased hippocampus function in aMCI, inter-hemispheric hippocampus FC and hippocampal FC with brain regions predominantly included in the DMN may contribute to residual primacy recall in aMCI.

Distinct Neural Suppression and Encoding Effects for Conceptual Novelty and Familiarity.

Like yin and yang, novelty and familiarity are typically described as separate-yet-complementary aspects of an experience, two ends of a single continuum. However, novelty and familiarity are also multifaceted. For instance, novelty can sometimes result in enhanced mnemonic performance, whereas at other times familiarity is better remembered. As previous investigations focused primarily on the experimental aspect of novelty, the mechanisms supporting conceptual novelty (the novel combination of two previously unrelated existing concepts) remain unclear. Importantly, conceptual novelty can be recognized as such only when compared with preexperimental familiar knowledge, regardless of experimental status. Here we applied a combined repetition suppression/subsequent memory fMRI paradigm, focusing on the conceptual aspect of novelty and familiarity as the subject matter. Conceptual novelty was characterized by sustained neural activity; familiarity, on the other hand, exhibited repetition effects in multiple cortical regions, a subset of which was modulated by successful encoding. Subsequent memory of novelty was associated only with activation differences in a distinct set of regions, including the hippocampus and medial cortical regions. These results suggest that conceptual novelty (a) does not (easily) trigger the repetition suppression phenomenon but requires sustained neural recruitment and (b) activates dedicated encoding mechanisms. Conceptual familiarity, in contrast, allows rapid neural processing that depends upon existing neural representations. Overall, these findings challenge the definition of novelty as a unitary concept. Furthermore, they bear important implications for research into the neural bases of knowledge representation and recognition memory.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients’ relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.

Spatial Memory Activity Distributions Indicate the Hippocampus Operates in a Continuous Manner.

There is a long-standing debate as to whether recollection is a continuous/graded process or a threshold/all-or-none process. In the current spatial memory functional magnetic resonance imaging (fMRI) study, we examined the hippocampal activity distributions—the magnitude of activity as a function of memory strength—to determine the nature of processing in this region. During encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, old shapes were presented at fixation and participants classified each shape as previously in the “left” or “right” visual field followed by an “unsure”–“sure”–“very sure” confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus. The hippocampal activity distributions for left shapes and right shapes were completely overlapping. Critically, the magnitude of activity associated with right-miss-very sure responses was significantly greater than zero. These results support the continuous model of recollection, which predicts overlapping activity distributions, and contradict the threshold model of recollection, which predicts a threshold above which only one distribution exists. Receiver operating characteristic analysis did not distinguish between models. The present results demonstrate that the hippocampus operates in a continuous manner during recollection and highlight the utility of analyzing activity distributions to determine the nature of neural processing.

Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes.

Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network’s hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions.

Antiepileptic drugs as a new therapeutic concept for the prevention of cognitive impairment and Alzheimer’s disease. Recent advances

SummaryIntroduction.Excessive accumulation of amyloid-beta (Aβ) peptides in the brain results initially in mild cognitive impairment (MCI) and finally in Alzheimer’s disease (AD). Evidences from experimental and clinical studies show that pathological hyperexcitability of hippocampal neurons is a very early functional impairment observed in progressive memory dysfunctions. Therefore, antiepileptic drugs (AEDs) whose mechanism of action is aimed at inhibition of such neuronal hyperexcitability, seems to be an rationale choice for MCI and AD treatment.Aim.To provide data from experimental and clinical studies on: 1. The unfavorable impact of neuronal hyperexcitability, mainly within the hippocampus, on cognitive processes. 2. Efficacy of AEDs against such abnormally elevated neuronal activity for the prevention of progressive cognitive impairment.Methods.A literature review of publications published within the last fifteen years, was conducted using the PubMed database.Review.The authors describe Aβ-induced hyperexcitability of hippocampal nerve cells as the cause of cognitive deficits, the connection of such activity with an increased risk of seizures and epilepsy in patients with MCI/AD, and finally the efficacy of AEDs: valproic acid (VPA), phenytoin (PHT), topiramate (TPM), lamotrigine (LTG), ethosuximide (ESM) and levetiracetam (LEV) in the prevention of cognitive impairment in experimental models and patients with MCI/AD.Conclusions.The majority of the studied AEDs improve cognitive dysfunction in various experimental models of Aβ-induced brain pathology with accompanied neuronal hyperexcitability. The promising results achieved for LEV in animal models of cognitive impairment were also confirmed in patients with MCI/AD. LEV was well-tolerated and it’s beneficial antidementive effect was confirmed by memory tests and fMRI examination. In conclusion, the use of AEDs could be a novel therapeutic concept for preventing cognitive impairment in patients with Aβ-associated brain pathology.

Neural correlates of successful memory retrieval in aging: Do executive functioning and task difficulty matter?

The current experiment aimed to explore age differences in brain activity associated with successful memory retrieval in older adults with different levels of executive functioning, at different levels of task demand. Memory performance and fMRI activity during a recognition task were compared between a young group and two older groups characterized by a low (old-low group) vs. high (old-high group) level of executive functioning. Participants first encoded pictures, presented once (Hard condition) or twice (Easy condition), and then completed a recognition memory task. Old-low adults had poorer memory performance than the two other groups, which did not differ, in both levels of task demands. In the Easy condition, even though older adults demonstrated reduced activity compared to young adults in several regions, they also showed additional activations in the right superior frontal gyrus and right parietal lobule (positively correlated to memory accuracy) for the old-high group and in the right precuneus (negatively correlated to memory accuracy), right anterior cingulate gyrus and right supramarginal gyrus for the old-low group. In the Hard condition, some regions were also more activated in the young group than in the older groups. Vice versa, old-high participants demonstrated more activity than either the young or the old-low group in the right frontal gyrus, associated with more accurate memory performance, and in the left frontal gyrus. In sum, the present study clearly showed that age differences in the neural correlates of retrieval success were modulated by task difficulty, as suggested by the CRUNCH model, but also by interindividual variability, in particular regarding executive functioning.

Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20–24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20–24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.