Quantifying the Variability of Neural Activation in Working Memory: A Functional Probabilistic Atlas

AbstractObjectives: Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients. Methods: Patients treated for craniopharyngioma [N=104, 10.0±4.6 years, 48% male] participated in fitness, cognitive and fMRI (n=51) assessments following surgery but before proton radiation therapy. Results: Patients demonstrated impaired aerobic fitness [peak oxygen uptake (PKVO2)=23.9±7.1, 41% impaired (i.e., 1.5 SD<normative mean)], motor proficiency [Bruininks-Oseretsky (BOT2)=38.6±9.0, 28% impaired], and executive functions (e.g., WISC-IV Working Memory Index (WMI)=96.0±15.3, 11% impaired). PKVO2 correlated with better executive functions (e.g., WISC-IV WMI r=.27, p=.02) and academic performance (WJ-III Calculation r=.24, p=.04). BOT2 correlated with better attention (e.g., CPT-II omissions r=.26, p=.04) and executive functions (e.g., WISC-IV WMI r=.32, p=.01). Areas of robust neural activation during an n-back task included superior parietal lobule, dorsolateral prefrontal cortex, and middle and superior frontal gyri (p<.05, corrected). Higher network activation was associated with better working memory task performance and better BOT2 (p<.001). Conclusions: Before adjuvant therapy, children with craniopharyngioma demonstrate significantly reduced aerobic fitness, motor proficiency, and working memory. Better aerobic fitness and motor proficiency are associated with better attention and executive functions, as well as greater activation of a well-established working memory network. These findings may help explain differential risk/resiliency with respect to acute cognitive changes that may portend cognitive late effects. (JINS, 2019, 25, 413–425)

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Aberrant modulation of brain activity underlies impaired working memory following traumatic brain injury

10.1101/2021.03.23.436708 ◽

2021 ◽

Author(s):

Abbie S. Taing ◽

Matthew E. Mundy ◽

Jennie L. Ponsford ◽

Gershon Spitz

Keyword(s):

Traumatic Brain Injury ◽

Working Memory ◽

Brain Injury ◽

Cognitive Load ◽

Brain Activity ◽

Memory Task ◽

Task Demands ◽

Neural Activation ◽

Neural Processing ◽

Specific Working

AbstractImpaired working memory capacity is a common and disabling consequence of traumatic brain injury (TBI) that is caused by aberrant neural processing. However, due to high heterogeneity in results across studies, it is challenging to conclude whether impaired working memory in this population is driven by neural hypo- or hyper-activation, and the extent to which deficits are perpetuated by specific working memory subprocesses. Using a combined functional magnetic resonance imaging and working memory paradigm, we tested the hypothesis that the pattern of neural activation subserving working memory following TBI would interact with both task demands and specific working memory subcomponents: encoding, maintenance, and retrieval. Behaviourally, we found that working memory deficits were confined to the high cognitive load trials. Our results confirmed our key prediction. Overall, TBI participants showed reduced brain activity while performing the working memory task. However, interrogation of the subcomponents of working memory revealed a more nuanced pattern of activation. When we simply averaged across all task trials, regardless of cognitive load or subcomponent, TBI participants showed reduced neural activation. When examined more closely, patterns of brain activity following TBI were found to interact with both task demands and working memory subcomponent. Participants with TBI demonstrated an inability to appropriately modulate brain activity between low and high demand conditions necessary during encoding and maintenance stages. Therefore, we demonstrate that conclusions about aberrant neural processing are dependent upon the level of analysis and the extent to which general cognitive domains can be parcellated into its constituent parts.

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Decoding the neural dynamics of free choice in humans

10.1101/788091 ◽

2019 ◽

Author(s):

Thomas Thiery ◽

Anne-Lise Saive ◽

Etienne Combrisson ◽

Arthur Dehgan ◽

Julien Bastin ◽

...

Keyword(s):

Decision Making ◽

Working Memory ◽

Free Choice ◽

Temporal Dynamics ◽

Motor Planning ◽

Decision Task ◽

Neural Activation ◽

List Type ◽

High Gamma ◽

Eeg Recordings

SummaryHow do we choose a particular action among equally valid alternatives? Non-human primate findings have shown that decision-making implicates modulations in unit firing rates and local field potentials (LFPs) across frontal and parietal cortices. Yet the electrophysiological brain mechanisms that underlie free choice in humans remain ill defined. Here, we address this question using rare intracerebral EEG recordings in surgical epilepsy patients performing a delayed oculomotor decision task. We find that the temporal dynamics of high gamma (HG, 60-140 Hz) neural activity in distinct frontal and parietal brain areas robustly discriminate free choice from instructed saccade planning at the level of single trials. Classification analysis was applied to the LFP signals to isolate decision-related activity from sensory and motor planning processes. Compared to instructed saccades, free choice trials exhibited delayed and longer-lasting HG activity. The temporal dynamics of these sustained decision-related responses distinguished deliberation-related from working memory processes. Taken together, these findings provide the first direct electrophysiological evidence in humans for the role of sustained high-frequency neural activation in fronto-parietal cortex in mediating the intrinsically driven process of freely choosing among competing behavioral alternatives.HighlightsFirst intracerebral recordings in humans performing an oculomotor decision-making taskMachine learning analytics unravel underlying spectral and temporal brain dynamicsFree choice trials exhibit sustained fronto-parietal high gamma (HG) activity during the delayMaking a decision and maintaining it in working memory are associated with distinct sustained HG dynamics

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The PICO Study: Impact of Phenylalanine on Cognitive, Cerebral and Neurometabolic Parameters in Adult Patients with Phenylketonuria – a Randomized, Placebo-Controlled, Crossover, Non-inferiority Trial

10.21203/rs.2.9834/v1 ◽

2019 ◽

Author(s):

Roman Trepp ◽

Raphaela Muri ◽

Lenka Bosanska ◽

Stephanie Abgottspon ◽

Michel Hochuli ◽

...

Keyword(s):

Working Memory ◽

Memory Task ◽

Brain Regions ◽

Primary Objective ◽

Adult Patients ◽

Target Range ◽

Neural Activation ◽

Level Of Evidence ◽

Double Blind ◽

The Brain

Abstract Background The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood Phe levels in adults outside pregnancy is discussed controversially. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional and neurometabolic parameters of the brain. Methods The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week phenylalanine (Phe) load on cognition and cerebral parameters in 30 adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, non-inferiority trial. The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance in adults with early-treated PKU. As secondary objective, the PICO Study will elucidate cerebral and neurometabolic mechanisms, which accompany changes in Phe concentration using advanced neuroimaging methods. In addition to the intervention study, cognition, structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls, who will be comparable with regard to age, gender and education level. Advanced MR-techniques will be used to investigate intensity of neural activation during the working memory task (fMRI), strength of functional connectivity between brain regions related to performance in working memory (rsfMRI), white matter integrity (DTI), cerebral blood flow (ASL) and brain Phe concentrations (MRS). Discussion Using a combination of neuropsychological and neuroimaging data, the PICO study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed.

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Prefrontal hypoactivation during working memory in bipolar II depression

Psychological Medicine ◽

10.1017/s0033291714002852 ◽

2015 ◽

Vol 45 (8) ◽

pp. 1731-1740 ◽

Cited By ~ 13

Author(s):

J. O. Brooks ◽

N. Vizueta ◽

C. Penfold ◽

J. D. Townsend ◽

S. Y. Bookheimer ◽

...

Keyword(s):

Working Memory ◽

Memory Load ◽

Memory Task ◽

Anterior Cingulate ◽

Middle Temporal Gyrus ◽

Magnetic Resonance Imaging Scan ◽

Neural Activation ◽

Significant Group ◽

Differential Activation ◽

Bipolar Ii

Background.Patterns of abnormal neural activation have been observed during working memory tasks in bipolar I depression, yet the neural changes associated with bipolar II depression have yet to be explored.Method.An n-back working memory task was administered during a 3T functional magnetic resonance imaging scan in age- and gender-matched groups of 19 unmedicated, bipolar II depressed subjects and 19 healthy comparison subjects. Whole-brain and region-of-interest analyses were performed to determine regions of differential activation across memory-load conditions (0-, 1- and 2-back).Results.Accuracy for all subjects decreased with higher memory load, but there was no significant group × memory load interaction. Random-effects analyses of memory load indicated that subjects with bipolar II depression exhibited significantly less activation than healthy subjects in left hemispheric regions of the middle frontal gyrus [Brodmann area (BA) 11], superior frontal gyrus (BA 10), inferior parietal lobule (BA 40), middle temporal gyrus (BA 39) and bilateral occipital regions. There was no evidence of differential activation related to increasing memory load in the dorsolateral prefrontal or anterior cingulate cortex.Conclusions.Bipolar II depression is associated with hypoactivation of the left medio-frontal and parietal cortex during working memory performance. Our findings suggest that bipolar II depression is associated with disruption of the fronto-parietal circuit that is engaged in working memory tasks, which is a finding reported across bipolar subtypes and mood states.

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Independent Components of Neural Activation Associated with 100 Days of Cognitive Training

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01396 ◽

2019 ◽

Vol 31 (6) ◽

pp. 808-820 ◽

Cited By ~ 1

Author(s):

Molly Simmonite ◽

Thad A. Polk

Keyword(s):

Working Memory ◽

Cognitive Training ◽

Memory Performance ◽

Working Memory Training ◽

Memory Training ◽

Neural Activation ◽

Perceptual Decision Making ◽

Training Effects ◽

Data Set ◽

Motor Network

Some cognitive training studies have reported working memory benefits that generalize beyond the trained tasks, whereas others have only found task-specific training effects. What brain networks are associated with general training effects, rather than task-specific effects? We investigated this question in the context of working memory training using the COGITO data set, a longitudinal project including behavioral assessments before and after 100 days of cognitive training in 101 younger (20–31 years) and 103 older (65–80 years) adults. Pre- and postassessments included verbal, numerical, and spatial measures of working memory. It was therefore possible to assess training effects on working memory at a general latent ability level. Previous analyses of these data found training-related improvements on this latent working memory factor in both young and old participants. fMRI data were collected from a subsample of participants (24 young and 15 old) during pre- and post-training sessions. We used independent component analysis to identify networks involved in a perceptual decision-making task performed in the scanner. We identified five task-positive components that were task-related: two frontal networks, a ventral visual network, a motor network, and a cerebellar network. Pre-training activity of the motor network predicted latent working memory performance before training. Additionally, activity in the motor network predicted training-related changes in working memory ability. These findings suggest activity in the motor network plays a role in task-independent working memory improvements and have implications for our understanding of working memory training and for the design and implementation of future training interventions.

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Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome

PLoS ONE ◽

10.1371/journal.pone.0056279 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56279 ◽

Cited By ~ 14

Author(s):

Patrick Vigren ◽

Anders Tisell ◽

Maria Engström ◽

Thomas Karlsson ◽

Olof Leinhard Dahlqvist ◽

...

Keyword(s):

Working Memory ◽

Neural Activation

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Holding On to the Past: Older Adults Show Lingering Neural Activation of No-Longer-Relevant Items in Working Memory

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01596 ◽

2020 ◽

Vol 32 (10) ◽

pp. 1946-1962 ◽

Cited By ~ 1

Author(s):

Jennifer C. Weeks ◽

Cheryl L. Grady ◽

Lynn Hasher ◽

Bradley R. Buchsbaum

Keyword(s):

Older Adults ◽

Working Memory ◽

Delay Interval ◽

Medial Temporal Lobe ◽

Memory Task ◽

Relevant Information ◽

Specific Pattern ◽

Long Term Memory ◽

Neural Activation ◽

Task Goals

Goal-relevant information can be maintained in working memory over a brief delay interval to guide an upcoming decision. There is also evidence suggesting the existence of a complementary process: namely, the ability to suppress information that is no longer relevant to ongoing task goals. Moreover, this ability to suppress or inhibit irrelevant information appears to decline with age. In this study, we compared younger and older adults undergoing fMRI on a working memory task designed to address whether the modulation of neural representations of relevant and no-longer-relevant items during a delay interval is related to age and overall task performance. Following from the theoretical predictions of the inhibitory deficit hypothesis of aging, we hypothesized that older adults would show higher activation of no-longer-relevant items during a retention delay compared to young adults and that higher activation of these no-longer-relevant items would predict worse recognition memory accuracy for relevant items. Our results support this prediction and more generally demonstrate the importance of goal-driven modulation of neural activity in successful working memory maintenance. Furthermore, we showed that the largest age differences in the regulation of category-specific pattern activity during working memory maintenance were seen throughout the medial temporal lobe and prominently in the hippocampus, further establishing the importance of “long-term memory” retrieval mechanisms in the context of high-load working memory tasks that place large demands on attentional selection mechanisms.

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Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

PLoS ONE ◽

10.1371/journal.pone.0189287 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0189287 ◽

Cited By ~ 4

Author(s):

Yosefu Arime ◽

Kazufumi Akiyama

Keyword(s):

Working Memory ◽

Memory Impairment ◽

Neural Activation ◽

Activation Patterns

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