Compromised Behavior and Gamma Power During Working Memory in Cognitively Healthy Individuals With Abnormal CSF Amyloid/Tau

Abstract Cortical gamma oscillations are believed to be involved in mental processes which are disturbed in schizophrenia. For example, the magnitudes of sensory-evoked oscillations, as measured by auditory steady-state responses (ASSRs) at 40 Hz, are robustly diminished, whereas the baseline gamma power is enhanced in schizophrenia. Such dual gamma oscillation abnormalities are also present in a mouse model of N-methyl-D-aspartate receptor hypofunction (Ppp1r2cre/Grin1 knockout mice). However, it is unclear whether the abnormal gamma oscillations are associated with dysfunction in schizophrenia. We found that glycogen synthase kinase-3 (GSK3) is overactivated in corticolimbic parvalbumin-positive GABAergic interneurons in Grin1 mutant mice. Here we addressed whether GSK3β inhibition reverses both abnormal gamma oscillations and behavioral deficits with high correlation by pharmacological and genetic approach. We demonstrated that the paralog selective-GSK3β inhibitor, but not GSK3α inhibitor, normalizes the diminished ASSRs, excessive baseline gamma power, and deficits in spatial working memory and prepulse inhibition (PPI) of acoustic startle in Grin1 mutant mice. Cell-type specific GSK3B knockdown, but not GSK3A knockdown, also reversed abnormal gamma oscillations and behavioral deficits. Moreover, GSK3B knockdown, but not GSK3A knockdown, reverses the mutants’ in vivo spike synchrony deficits. Finally, ex vivo patch-clamp recording from pairs of neighboring cortical pyramidal neurons showed a reduction of synchronous spontaneous inhibitory-postsynaptic-current events in mutants, which was reversed by GSK3β inhibition genetically and pharmacologically. Together, GSK3β inhibition in corticolimbic interneurons ameliorates the deficits in spatial working memory and PPI, presumably by restoration of synchronous GABA release, synchronous spike firing, and evoked-gamma power increase with lowered baseline power.

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A putative high risk diplotype of the G72 gene is in healthy individuals associated with better performance in working memory functions and altered brain activity in the medial temporal lobe

NeuroImage ◽

10.1016/j.neuroimage.2008.12.054 ◽

2009 ◽

Vol 45 (3) ◽

pp. 1002-1008 ◽

Cited By ~ 29

Author(s):

Andreas Jansen ◽

Sören Krach ◽

Axel Krug ◽

Valentin Markov ◽

Thomas Eggermann ◽

...

Keyword(s):

Working Memory ◽

High Risk ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Brain Activity ◽

Healthy Individuals ◽

Memory Functions

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Evidence of Neuroplasticity Due to Acupuncture: An fNIRS Study

10.21203/rs.3.rs-70733/v1 ◽

2020 ◽

Author(s):

M. N. Afzal Khan ◽

Usman Ghafoor ◽

Ho-Ryong Yoo ◽

Keum-Shik Hong

Keyword(s):

Working Memory ◽

Near Infrared ◽

Information Service ◽

Image Feature ◽

Healthy Individuals ◽

Brain Response ◽

Functional Near Infrared Spectroscopy ◽

Aging Society ◽

Temporal Features ◽

Healthy Control

Abstract Background: Mild cognitive impairment (MCI) is a precursor to the critical disease known as Alzheimer’s. It is imperative to develop a proper treatment for this neurological disease in the aging society. This study investigates the effects of acupuncture therapy (AT) on MCI patients.Methods: Eleven healthy individuals and eleven MCI patients were recruited for this study. Oxy- and deoxy-hemoglobin signals in the prefrontal cortex during working-memory tasks were monitored using functional near-infrared spectroscopy. Before the AT, working-memory experiments were conducted for healthy control (HC) and MCI groups (MCI-0), followed by 24 sessions of AT for the MCI group. The AT sessions were initially carried out for six weeks (two sessions per week), after which experiments were performed again on the MCI group (MCI-1). This was followed by another set of AT sessions that also lasted for six weeks, after which the experiments were repeated again on the MCI group (MCI-2). Statistical analyses of the signals and classifications based on activation maps as well as temporal features were performed.Results: The highest classification accuracies obtained using binary connectivity maps were 85.7% HC vs. MCI-0, 69.5% HC vs. MCI-1, and 61.69% HC vs. MCI-2. The classification accuracies using the temporal features mean (i.e., mean(5:28 s)) and maximum (i.e., max(5:28 s)) values were 60.6% HC vs. MCI-0, 56.9% HC vs. MCI-1, and 56.4% HC vs. MCI-2. Conclusions: The results reveal that there was a change in the temporal characteristics of the hemodynamic response of MCI patients due to acupuncture. This was reflected by a reduction in the classification accuracy after the therapy, indicating that the patients’ brain response improved and became comparable to those of healthy subjects. Similar trend was reflected in the classification using image feature. These results indicate that acupuncture can be used for the treatment of MCI patients.Trial registration: Clinical research and information service (CRIS), KCT 0002451, Registered 05 September 2017, https://cris.nih.go.kr/cris/en/

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P3-077: CEREBRO-CARDIOVASCULAR RELATIONSHIPS DURING WORKING MEMORY TESTING ARE DIFFERENT IN COGNITIVELY HEALTHY INDIVIDUALS WITH ABNORMAL CSF AMYLOID/TAU

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3104 ◽

2019 ◽

Vol 15 ◽

pp. P955-P955

Author(s):

Rebecca Johnson ◽

Dylan Kwang ◽

Robert Kloner ◽

Alfred N. Fonteh ◽

Michael T. Kleinman ◽

...

Keyword(s):

Working Memory ◽

Memory Testing ◽

Healthy Individuals

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Prefrontal gamma power and LFP tuning in working memory decrease during monkey adolescent development

Journal of Vision ◽

10.1167/jov.21.9.2795 ◽

2021 ◽

Vol 21 (9) ◽

pp. 2795

Author(s):

Zhengyang Wang ◽

Balbir Singh ◽

Xuelian Qi ◽

Xin Zhou ◽

Christos Constantinidis

Keyword(s):

Working Memory ◽

Adolescent Development ◽

Gamma Power

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Strong gamma frequency oscillations in the adolescent prefrontal cortex

10.1101/2021.08.20.455686 ◽

2021 ◽

Author(s):

Zhengyang Wang ◽

Balbir Singh ◽

Xin Zhou ◽

Christos Constantinidis

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Adolescent Development ◽

Adult Stage ◽

Delay Period ◽

Local Network ◽

Frequency Range ◽

Gamma Frequency ◽

Power Increase ◽

Gamma Power

AbstractWorking memory ability continues to mature into adulthood in both humans and non-human primates. At the single neuron level, adolescent development is characterized by increased prefrontal firing rate in the delay period, but less is known about how coordinated activity between neurons is altered. Local field potentials (LFP) provide a window into the computation carried out by the local network. To address the effects of adolescent development on LFP activity, three male rhesus monkeys were trained to perform an oculomotor delayed response task and tested at both the adolescent and adult stage. Simultaneous single-unit and LFP signals were recorded from areas 8a and 46 of the dorsolateral prefrontal cortex (dlPFC). In both the cue and delay period, power relative to baseline increased in the gamma frequency range (32 - 128 Hz). In the adult stage, high-firing neurons were also more likely to reside at sites with strong gamma power increase from baseline. For both stages, the gamma power increase in the delay was selective for sites with neuron encoding stimulus information in their spiking. Gamma power and neuronal firing did not show stronger temporal correlations. Our results establish gamma power decrease to be a feature of prefrontal cortical maturation.Significance StatementGamma-frequency oscillations in extracellular field recordings (such as LFP or EEG) are a marker of normal interactions between excitatory and inhibitory neurons in neural circuits. Abnormally low gamma power during working memory is seen in conditions such as schizophrenia. We sought to examine whether the immature prefrontal cortex similarly exhibits lower power in the gamma frequency range during working memory, in a non-human primate model of adolescence. Contrary to this expectation, the adolescent PFC exhibited stronger gamma power during the maintenance of working memory. Our findings reveal an unknown developmental maturation trajectory of gamma band oscillations and raise the possibility that schizophrenia represent an excessive state of prefrontal maturation.

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Common default mode network dysfunction across psychopathologies: A neuroimaging meta-analysis of the n-back working memory paradigm

10.1101/2020.01.30.927210 ◽

2020 ◽

Author(s):

Michael C Farruggia ◽

Angela R Laird ◽

Aaron T Mattfeld

Keyword(s):

Bipolar Disorder ◽

Working Memory ◽

Memory Performance ◽

Meta Analysis ◽

Healthy Individuals ◽

Research Domain Criteria ◽

Default Mode ◽

Within Subjects ◽

The Brain ◽

Research Domain

ABSTRACTThe National Institute of Mental Health’s (NIMH) Research Domain Criteria (RDoC) classifies disorders based on shared aspects of behavioral and neurobiological dysfunction. One common behavioral deficit observed in various psychopathologies, namely ADHD, addiction, bipolar disorder, depression, and schizophrenia, is a deficit in working memory performance. However, it is not known to what extent, if any, these disorders share common neurobiological abnormalities that contribute to decrements in performance. The goal of the present study was to examine convergence and divergence of working memory networks across psychopathologies. We used the Activation Likelihood Estimate (ALE) meta-analytic technique to collapse prior data obtained from published studies using the n-back working memory paradigm in individuals with a DSM-criteria diagnosis of the aforementioned disorders. These studies examined areas in the brain that showed increases in activity as a function of working memory-related load compared to a baseline condition, both within subjects and between healthy individuals and those with psychiatric disorder. A meta-analysis of 281 foci covering 81 experiments and 2,629 participants found significant convergence of hyperactivity in medial prefrontal cortex (mPFC) for DSM-diagnosed individuals compared to healthy controls. Foci from ADHD, addiction, bipolar disorder, schizophrenia, and major depression studies contributed to the formation of this cluster. These results provide evidence that default-mode intrusion may constitute a shared seed of dysregulation across multiple psychopathologies, ultimately resulting in poorer working memory performance.

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The Preliminary Investigation of Multi-Level Working Memory in Predicting Anxiety/Depressive Symptomatology in Childhood/Adolescence

10.31234/osf.io/qvedc ◽

2019 ◽

Author(s):

Brian Kavanaugh ◽

Alexa Fryc ◽

Simona Temereanca Ibanescu ◽

Eric Tirrell ◽

Lindsay Oberman ◽

...

Keyword(s):

Working Memory ◽

Depressive Symptomatology ◽

Preliminary Investigation ◽

Gamma Oscillations ◽

Composite Score ◽

Clinical Markers ◽

Measurement Variability ◽

Parent Questionnaire ◽

Gamma Power ◽

Multi Level

Prior research in working memory (WM) has been hampered by measurement variability and a lack of integration of neural and clinical markers. This study sought to examine whether a multi-level composite of WM with neural, cognitive, and behavioral levels could predict childhood affective symptomatology in seventeen children and adolescents receiving outpatient mental health services. WM-related theta/gamma oscillations at the F3 electrode were measured via electroencephalography (EEG) recording during a spatial WM task. Other measures included a neuropsychological measure of WM, parent questionnaire assessing WM, and self-reported affective symptoms. Gamma power and theta-gamma coupling, but not theta power, predicted high WM demands performance (i.e., 16-19% of variance). Two composite scores were created consisting of gamma power or theta-gamma coupling, clinical WM measure performance, and parent-reported WM symptoms. These multi-level composite score predicted self-reported depressive (22-32% of variance) symptoms, while only the gamma-version of the composite predicted anxious symptoms (39% of variance compared to 12% of variance). A WM composite score consisting of neural, cognitive, and behavioral levels predicted the severity of childhood affective symptomatology. WM, like other EFs, is highly complex and may be most appropriately measured in clinical and research settings with a combination of neural, cognitive, and behavioral measures.

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