An Early Stage Researcher's Primer on Systems Medicine Terminology.

Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of applications, and lists of relevant references. Results: This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic.

Association of the use of hearing aids with the conversion from mild cognitive impairment to dementia and progression of dementia: A longitudinal retrospective study.

INTRODUCTION: Hearing aid usage has been linked to improvements in cognition, communication, and socialization, but the extent to which it can affect the incidence and progression of dementia is unknown. Such research is vital given the high prevalence of dementia and hearing impairment in older adults, and the fact that both conditions often coexist. In this study, we examined for the first time the effect of the use of hearing aids on the conversion from mild cognitive impairment (MCI) to dementia and progression of dementia. METHODS: We used a large referral-based cohort of 2114 hearing-impaired patients obtained from the National Alzheimer's Coordinating Center. Survival analyses using multivariable Cox proportional hazards regression model and weighted Cox regression model with censored data were performed to assess the effect of hearing aid use on the risk of conversion from MCI to dementia and risk of death in hearing-impaired participants. Disease progression was assessed with Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Three types of sensitivity analyses were performed to validate the robustness of the results. RESULTS: MCI participants that used hearing aids were at significantly lower risk of developing all-cause dementia compared to those not using hearing aids (hazard ratio [HR] 0.73, 95% confidence interval [CI], 0.61 to 0.89; false discovery rate [FDR] P = 0.004). The mean annual rate of change (standard deviation) in CDR-SB scores for hearing aid users with MCI was 1.3 (1.45) points and significantly lower than for individuals not wearing hearing aids with a 1.7 (1.95) point increase in CDR-SB per year (P = 0.02). No association between hearing aid use and risk of death was observed. Our findings were robust subject to sensitivity analyses. DISCUSSION: Among hearing-impaired adults, hearing aid use was independently associated with reduced dementia risk. The causality between hearing aid use and incident dementia should be further tested.

Metastable neural dynamics underlies cognitive performance across multiple behavioural paradigms.

Despite resting state networks being associated with a variety of cognitive abilities, it remains unclear how these local areas act in concert to express particular cognitive operations. Theoretical and empirical accounts indicate that large-scale resting state networks reconcile dual tendencies towards integration and segregation by operating in a metastable regime of their coordination dynamics. Metastability may confer important behavioural qualities by binding distributed local areas into large-scale neurocognitive networks. We tested this hypothesis by analysing fMRI data in a large cohort of healthy individuals (N = 566) and comparing the metastability of the brain's large-scale resting network architecture at rest and during the performance of several tasks. Metastability was estimated using a well-defined collective variable capturing the level of 'phase-locking' between large-scale networks over time. Task-based reasoning was principally characterised by high metastability in cognitive control networks and low metastability in sensory processing areas. Although metastability between resting state networks increased during task performance, cognitive ability was more closely linked to spontaneous activity. High metastability in the intrinsic connectivity of cognitive control networks was linked to novel problem solving or fluid intelligence, but was less important in tasks relying on previous experience or crystallised intelligence. Crucially, subjects with resting architectures similar or 'pre-configured' to a task-general arrangement demonstrated superior cognitive performance. Taken together, our findings support a key linkage between the spontaneous metastability of large-scale networks in the cerebral cortex and cognition.

Speed of Rapid Serial Visual Presentation of Pictures, Numbers and Words Affects Event-Related Potential-Based Detection Accuracy.

Rapid serial visual presentation (RSVP) based brain-computer interfaces (BCIs) can detect target images among a continuous stream of rapidly presented images, by classifying a viewer's event related potentials (ERPs) associated with the target and non-targets images. Whilst the majority of RSVP-BCI studies to date have concentrated on the identification of a single type of image, namely pictures, here we study the capability of RSVP-BCI to detect three different target image types: pictures, numbers and words. The impact of presentation duration (speed) i.e., 100-200ms (5-10Hz), 200-300ms (3.3-5Hz) or 300-400ms (2.5-3.3Hz), is also investigated. 2-way repeated measure ANOVA on accuracies of detecting targets from non-target stimuli (ratio 1:9) measured via area under the receiver operator characteristics curve (AUC) for N=15 subjects revealed a significant effect of factor Stimulus-Type (pictures, numbers, words) (F (2,28) = 7.243, p = 0.003 ) and for Stimulus-Duration (F (2,28) = 5.591, p = 0.011). Furthermore, there is an interaction between stimulus type and duration: F (4,56) = 4.419, p = 0.004 ). The results indicate that when designing RSVP-BCI paradigms, the content of the images and the rate at which images are presented impact on the accuracy of detection and hence these parameters are key experimental variables in protocol design and applications, which apply RSVP for multimodal image datasets.

A review of learning in biologically plausible spiking neural networks.

Artificial neural networks have been used as a powerful processing tool in various areas such as pattern recognition, control, robotics, and bioinformatics. Their wide applicability has encouraged researchers to improve artificial neural networks by investigating the biological brain. Neurological research has significantly progressed in recent years and continues to reveal new characteristics of biological neurons. New technologies can now capture temporal changes in the internal activity of the brain in more detail and help clarify the relationship between brain activity and the perception of a given stimulus. This new knowledge has led to a new type of artificial neural network, the Spiking Neural Network (SNN), that draws more faithfully on biological properties to provide higher processing abilities. A review of recent developments in learning of spiking neurons is presented in this paper. First the biological background of SNN learning algorithms is reviewed. The important elements of a learning algorithm such as the neuron model, synaptic plasticity, information encoding and SNN topologies are then presented. Then, a critical review of the state-of-the-art learning algorithms for SNNs using single and multiple spikes is presented. Additionally, deep spiking neural networks are reviewed, and challenges and opportunities in the SNN field are discussed.

A practical computerized decision support system for predicting the severity of Alzheimer's disease of an individual.

Computerized clinical decision support systems can help to provide objective, standardized, and timely dementia diagnosis. However, current computerized systems are mainly based on group analysis, discrete classification of disease stages, or expensive and not readily accessible biomarkers, while current clinical practice relies relatively heavily on cognitive and functional assessments (CFA). In this study, we developed a computational framework using a suite of machine learning tools for identifying key markers in predicting the severity of Alzheimer's disease (AD) from a large set of biological and clinical measures. Six machine learning approaches, namely Kernel Ridge Regression (KRR), Support Vector Regression, and k-Nearest Neighbor for regression and Support Vector Machine (SVM), Random Forest, and k-Nearest Neighbor for classification, were used for the development of predictive models. We demonstrated high predictive power of CFA. Predictive performance of models incorporating CFA was shown to consistently have higher accuracy than those based solely on biomarker modalities. We found that KRR and SVM were the best performing regression and classification methods respectively. The optimal SVM performance was observed for a set of four CFA test scores (FAQ, ADAS13, MoCA, MMSE) with multi-class classification accuracy of 83.0%, 95%CI = (72.1%, 93.8%) while the best performance of the KRR model was reported with combined CFA and MRI neuroimaging data, i.e., R 2 = 0.874, 95%CI = (0.827, 0.922). Given the high predictive power of CFA and their widespread use in clinical practice, we then designed a data-driven and self-adaptive computerized clinical decision support system (CDSS) prototype for evaluating the severity of AD of an individual on a continuous spectrum. The system implemented an automated computational approach for data pre-processing, modelling, and validation and used exclusively the scores of selected cognitive measures as data entries. Taken together, we have developed an objective and practical CDSS to aid AD diagnosis.

Primary care use of laboratory tests in Northern Ireland's Western Health and Social Care Trust: a cross-sectional study.

OBJECTIVES: To describe the laboratory test ordering patterns by general practitioners (GPs) in Northern Ireland Western Health and Social Care Trust (WHSCT) and explore demographic and socioeconomic associations with test requesting. DESIGN: Cross-sectional study. SETTING: WHSCT, Northern Ireland. : Particip ANTS: 55 WHSCT primary care medical practices that remained open throughout the study period 1 April 2011-31 March 2016. OUTCOMES: To identify the temporal patterns of laboratory test ordering behaviour for eight commonly requested clinical biochemistry tests/test groups in WHSCT. To analyse the extent of variations in laboratory test requests by GPs and to explore whether these variations can be accounted for by clinical outcomes or geographical, demographic and socioeconomic characteristics. RESULTS: The median number of adjusted test request rates over 5 consecutive years of the study period decreased by 45.7% for urine albumin/creatinine ratio (p<0.000001) and 19.4% for lipid profiles (p<0.000001) while a 60.6%, 36.6% and 29.5% increase was observed for HbA1c (p<0.000001), immunoglobulins (p=0.000007) and prostate-specific antigen (PSA) (p=0.0003), respectively. The between-practice variation in test ordering rates increased by 272% for immunoglobulins (p=0.008) and 500% for HbA1c (p=0.0001). No statistically significant relationship between ordering activity and either demographic (age and gender) and socioeconomic factors (deprivation) or Quality and Outcome Framework scores was observed. We found the rural-urban differences in between-practice variability in ordering rates for lipid profiles, thyroid profiles, PSA and immunoglobulins to be statistically significant at the Bonferroni-adjusted significance level p<0.01. CONCLUSIONS: We explored potential factors of the interpractice variability in the use of laboratory tests and found that differences in requesting activity appear unrelated to either demographic and socioeconomic characteristics of GP practices or clinical outcome indicators.

Metastable neural dynamics in Alzheimer's disease are disrupted by lesions to the structural connectome.

Current theory suggests brain regions interact to reconcile the competing demands of integration and segregation by leveraging metastable dynamics. An emerging consensus recognises the importance of metastability in healthy neural dynamics where the transition between network states over time is dependent upon the structural connectivity between brain regions. In Alzheimer's disease (AD) - the most common form of dementia - these couplings are progressively weakened, metastability of neural dynamics are reduced and cognitive ability is impaired. Accordingly, we use a joint empirical and computational approach to reveal how behaviourally relevant changes in neural metastability are contingent on the structural integrity of the anatomical connectome. We estimate the metastability of fMRI BOLD signal in subjects from across the AD spectrum and in healthy controls and demonstrate the dissociable effects of structural disconnection on synchrony versus metastability. In addition, we reveal the critical role of metastability in general cognition by demonstrating the link between an individuals cognitive performance and their metastable neural dynamic. Finally, using whole-brain computer modelling, we demonstrate how a healthy neural dynamic is conditioned upon the topological integrity of the structural connectome. Overall, the results of our joint computational and empirical analysis suggest an important causal relationship between metastable neural dynamics, cognition, and the structural efficiency of the anatomical connectome.

A Supervised Learning Algorithm for Learning Precise Timing of Multiple Spikes in Multilayer Spiking Neural Networks.

There is a biological evidence to prove information is coded through precise timing of spikes in the brain. However, training a population of spiking neurons in a multilayer network to fire at multiple precise times remains a challenging task. Delay learning and the effect of a delay on weight learning in a spiking neural network (SNN) have not been investigated thoroughly. This paper proposes a novel biologically plausible supervised learning algorithm for learning precisely timed multiple spikes in a multilayer SNNs. Based on the spike-timing-dependent plasticity learning rule, the proposed learning method trains an SNN through the synergy between weight and delay learning. The weights of the hidden and output neurons are adjusted in parallel. The proposed learning method captures the contribution of synaptic delays to the learning of synaptic weights. Interaction between different layers of the network is realized through biofeedback signals sent by the output neurons. The trained SNN is used for the classification of spatiotemporal input patterns. The proposed learning method also trains the spiking network not to fire spikes at undesired times which contribute to misclassification. Experimental evaluation on benchmark data sets from the UCI machine learning repository shows that the proposed method has comparable results with classical rate-based methods such as deep belief network and the autoencoder models. Moreover, the proposed method can achieve higher classification accuracies than single layer and a similar multilayer SNN.

A hybrid computational approach for efficient Alzheimer's disease classification based on heterogeneous data.

There is currently a lack of an efficient, objective and systemic approach towards the classification of Alzheimer's disease (AD), due to its complex etiology and pathogenesis. As AD is inherently dynamic, it is also not clear how the relationships among AD indicators vary over time. To address these issues, we propose a hybrid computational approach for AD classification and evaluate it on the heterogeneous longitudinal AIBL dataset. Specifically, using clinical dementia rating as an index of AD severity, the most important indicators (mini-mental state examination, logical memory recall, grey matter and cerebrospinal volumes from MRI and active voxels from PiB-PET brain scans, ApoE, and age) can be automatically identified from parallel data mining algorithms. In this work, Bayesian network modelling across different time points is used to identify and visualize time-varying relationships among the significant features, and importantly, in an efficient way using only coarse-grained data. Crucially, our approach suggests key data features and their appropriate combinations that are relevant for AD severity classification with high accuracy. Overall, our study provides insights into AD developments and demonstrates the potential of our approach in supporting efficient AD diagnosis.

SPANNER: A Self-Repairing Spiking Neural Network Hardware Architecture.

Recent research has shown that a glial cell of astrocyte underpins a self-repair mechanism in the human brain, where spiking neurons provide direct and indirect feedbacks to presynaptic terminals. These feedbacks modulate the synaptic transmission probability of release (PR). When synaptic faults occur, the neuron becomes silent or near silent due to the low PR of synapses; whereby the PRs of remaining healthy synapses are then increased by the indirect feedback from the astrocyte cell. In this paper, a novel hardware architecture of Self-rePAiring spiking Neural NEtwoRk (SPANNER) is proposed, which mimics this self-repairing capability in the human brain. This paper demonstrates that the hardware can self-detect and self-repair synaptic faults without the conventional components for the fault detection and fault repairing. Experimental results show that SPANNER can maintain the system performance with fault densities of up to 40%, and more importantly SPANNER has only a 20% performance degradation when the self-repairing architecture is significantly damaged at a fault density of 80%.

Quantitative analysis of breast cancer diagnosis using a probabilistic modelling approach.

BACKGROUND: Breast cancer is the most prevalent cancer in women in most countries of the world. Many computer-aided diagnostic methods have been proposed, but there are few studies on quantitative discovery of probabilistic dependencies among breast cancer data features and identification of the contribution of each feature to breast cancer diagnosis. METHODS: This study aims to fill this void by utilizing a Bayesian network (BN) modelling approach. A K2 learning algorithm and statistical computation methods are used to construct BN structure and assess the obtained BN model. The data used in this study were collected from a clinical ultrasound dataset derived from a Chinese local hospital and a fine-needle aspiration cytology (FNAC) dataset from UCI machine learning repository. RESULTS: Our study suggested that, in terms of ultrasound data, cell shape is the most significant feature for breast cancer diagnosis, and the resistance index presents a strong probabilistic dependency on blood signals. With respect to FNAC data, bare nuclei are the most important discriminating feature of malignant and benign breast tumours, and uniformity of both cell size and cell shape are tightly interdependent. CONTRIBUTIONS: The BN modelling approach can support clinicians in making diagnostic decisions based on the significant features identified by the model, especially when some other features are missing for specific patients. The approach is also applicable to other healthcare data analytics and data modelling for disease diagnosis.

A review of rapid serial visual presentation-based brain-computer interfaces.

Rapid serial visual presentation (RSVP) combined with the detection of event-related brain responses facilitates the selection of relevant information contained in a stream of images presented rapidly to a human. Event related potentials (ERPs) measured non-invasively with electroencephalography (EEG) can be associated with infrequent targets amongst a stream of images. Human-machine symbiosis may be augmented by enabling human interaction with a computer, without overt movement, and/or enable optimization of image/information sorting processes involving humans. Features of the human visual system impact on the success of the RSVP paradigm, but pre-attentive processing supports the identification of target information post presentation of the information by assessing the co-occurrence or time-locked EEG potentials. This paper presents a comprehensive review and evaluation of the limited, but significant, literature on research in RSVP-based brain-computer interfaces (BCIs). Applications that use RSVP-based BCIs are categorized based on display mode and protocol design, whilst a range of factors influencing ERP evocation and detection are analyzed. Guidelines for using the RSVP-based BCI paradigms are recommended, with a view to further standardizing methods and enhancing the inter-relatability of experimental design to support future research and the use of RSVP-based BCIs in practice.

Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment.

Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adults with aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impaired thalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.

Corrigendum: Multi-Kernel Learning with Dartel Improves Combined MRI-PET Classification of Alzheimer's Disease in AIBL Data: Group and Individual Analyses.

[This corrects the article on p. 380 in vol. 11, PMID: 28790908.].

Multi-Kernel Learning with Dartel Improves Combined MRI-PET Classification of Alzheimer's Disease in AIBL Data: Group and Individual Analyses.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) are neuroimaging modalities typically used for evaluating brain changes in Alzheimer's disease (AD). Due to their complementary nature, their combination can provide more accurate AD diagnosis or prognosis. In this work, we apply a multi-modal imaging machine-learning framework to enhance AD classification and prediction of diagnosis of subject-matched gray matter MRI and Pittsburgh compound B (PiB)-PET data related to 58 AD, 108 mild cognitive impairment (MCI) and 120 healthy elderly (HE) subjects from the Australian imaging, biomarkers and lifestyle (AIBL) dataset. Specifically, we combined a Dartel algorithm to enhance anatomical registration with multi-kernel learning (MKL) technique, yielding an average of >95% accuracy for three binary classification problems: AD-vs.-HE, MCI-vs.-HE and AD-vs.-MCI, a considerable improvement from individual modality approach. Consistent with t-contrasts, the MKL weight maps revealed known brain regions associated with AD, i.e., (para)hippocampus, posterior cingulate cortex and bilateral temporal gyrus. Importantly, MKL regression analysis provided excellent predictions of diagnosis of individuals by r2 = 0.86. In addition, we found significant correlations between the MKL classification and delayed memory recall scores with r2 = 0.62 (p < 0.01). Interestingly, outliers in the regression model for diagnosis were mainly converter samples with a higher likelihood of converting to the inclined diagnostic category. Overall, our work demonstrates the successful application of MKL with Dartel on combined neuromarkers from different neuroimaging modalities in the AIBL data. This lends further support in favor of machine learning approach in improving the diagnosis and risk prediction of AD.

SpikeTemp: An Enhanced Rank-Order-Based Learning Approach for Spiking Neural Networks With Adaptive Structure.

This paper presents an enhanced rank-order-based learning algorithm, called SpikeTemp, for spiking neural networks (SNNs) with a dynamically adaptive structure. The trained feed-forward SNN consists of two layers of spiking neurons: 1) an encoding layer which temporally encodes real-valued features into spatio-temporal spike patterns and 2) an output layer of dynamically grown neurons which perform spatio-temporal classification. Both Gaussian receptive fields and square cosine population encoding schemes are employed to encode real-valued features into spatio-temporal spike patterns. Unlike the rank-order-based learning approach, SpikeTemp uses the precise times of the incoming spikes for adjusting the synaptic weights such that early spikes result in a large weight change and late spikes lead to a smaller weight change. This removes the need to rank all the incoming spikes and, thus, reduces the computational cost of SpikeTemp. The proposed SpikeTemp algorithm is demonstrated on several benchmark data sets and on an image recognition task. The results show that SpikeTemp can achieve better classification performance and is much faster than the existing rank-order-based learning approach. In addition, the number of output neurons is much smaller when the square cosine encoding scheme is employed. Furthermore, SpikeTemp is benchmarked against a selection of existing machine learning algorithms, and the results demonstrate the ability of SpikeTemp to classify different data sets after just one presentation of the training samples with comparable classification performance.

DL-ReSuMe: A Delay Learning-Based Remote Supervised Method for Spiking Neurons.

Recent research has shown the potential capability of spiking neural networks (SNNs) to model complex information processing in the brain. There is biological evidence to prove the use of the precise timing of spikes for information coding. However, the exact learning mechanism in which the neuron is trained to fire at precise times remains an open problem. The majority of the existing learning methods for SNNs are based on weight adjustment. However, there is also biological evidence that the synaptic delay is not constant. In this paper, a learning method for spiking neurons, called delay learning remote supervised method (DL-ReSuMe), is proposed to merge the delay shift approach and ReSuMe-based weight adjustment to enhance the learning performance. DL-ReSuMe uses more biologically plausible properties, such as delay learning, and needs less weight adjustment than ReSuMe. Simulation results have shown that the proposed DL-ReSuMe approach achieves learning accuracy and learning speed improvements compared with ReSuMe.

Novelty detection using level set methods.

This paper presents a level set boundary description (LSBD) approach for novelty detection that treats the nonlinear boundary directly in the input space. The proposed approach consists of level set function (LSF) construction, boundary evolution, and termination of the training process. It employs kernel density estimation to construct the LSF of the initial boundary for the training data set. Then, a sign of the LSF-based algorithm is proposed to evolve the boundary and make it fit more tightly in the data distribution. The training process terminates when an expected fraction of rejected normal data is reached. The evolution process utilizes the signs of the LSF values at all training data points to decide whether to expand or shrink the boundary. Extensive experiments are conducted on benchmark data sets to evaluate the proposed LSBD method and compare it against four representative novelty detection methods. The experimental results demonstrate that the novelty detector modeled with the proposed LSBD can effectively detect anomalies.

Compensating for thalamocortical synaptic loss in Alzheimer's disease.

The study presents a thalamocortical network model which oscillates within the alpha frequency band (8-13 Hz) as recorded in the wakeful relaxed state with closed eyes to study the neural causes of abnormal oscillatory activity in Alzheimer's disease (AD). Incorporated within the model are various types of cortical excitatory and inhibitory neurons, recurrently connected to thalamic and reticular thalamic regions with the ratios and distances derived from the mammalian thalamocortical system. The model is utilized to study the impacts of four types of connectivity loss on the model's spectral dynamics. The study focuses on investigating degeneration of corticocortical, thalamocortical, corticothalamic, and corticoreticular couplings, with an emphasis on the influence of each modeled case on the spectral output of the model. Synaptic compensation has been included in each model to examine the interplay between synaptic deletion and compensation mechanisms, and the oscillatory activity of the network. The results of power spectra and event related desynchronization/synchronization (ERD/S) analyses show that the dynamics of the thalamic and cortical oscillations are significantly influenced by corticocortical synaptic loss. Interestingly, the patterns of changes in thalamic spectral activity are correlated with those in the cortical model. Similarly, the thalamic oscillatory activity is diminished after partial corticothalamic denervation. The results suggest that thalamic atrophy is a secondary pathology to cortical shrinkage in Alzheimer's disease. In addition, this study finds that the inhibition from neurons in the thalamic reticular nucleus (RTN) to thalamic relay (TCR) neurons plays a key role in regulating thalamic oscillations; disinhibition disrupts thalamic oscillatory activity even though TCR neurons are more depolarized after being released from RTN inhibition. This study provides information that can be explored experimentally to further our understanding on the neurodegeneration associated with AD pathology.