Mild traumatic brain injury (mTBI) can produce persistent cognitive and behavioral deficits. These impairments result in a reduced quality of life and difficulty returning to work, school, or other activities. Individuals with repeated injuries show increased risk for greater cognitive impairment and persistence of symptoms. A variety of pharmacological approaches have been tried to limit cognitive symptoms and other aspects of secondary injury following mTBI. However, their efficacy and ability to treat the sequela of mTBI remains disputed and no FDA-approved drug exists for mTBI. However, neurotrophins have considerable promise as regenerative therapies for mTBI by exhibiting procognitive, neuroprotective, and anti-inflammatory actions. One neurotrophin, hepatocyte growth factor, and its receptor MET (HGF/MET) are upregulated in response to CNS injury within the prefrontal cortex and other regions supporting memory and higher cognitive function impaired by TBI. HGF/MET activation can be anti-inflammatory and neuroprotective, yet an understanding of its actions on cognitive function after mTBI is limited. Using a closed-head midline impact model of mild TBI, we characterized the actions of the HGF/MET system on working memory performance after repeated injury. Following repeated mild TBI, the HGF/MET-positive modulator dose-dependently rescued the working memory deficits following injury. These actions indicate that neuroptrophic transmitter systems, including HGF/MET, may hold critical pharmacological targets for treating the neurosequela of TBI.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slices ex vivo or under different anesthetics or during wakefulness in vivo. LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes ("tonic" or "phasic"), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders.

Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed “off-label”. The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.

The prefrontal cortex (PFC) and extended frontostriatal circuitry play a critical role in executive cognitive processes that guide goal-directed behavior. Dysregulation of frontostriatal-dependent cognition is implicated in a variety of cognitive/behavioral disorders, including addiction and attention deficit hyperactivity disorder (ADHD). Psychostimulants exert dose-dependent and opposing actions on frontostriatal cognitive function. Specifically, low and clinically-relevant doses improve, while higher doses associated with abuse and addiction impair, frontostriatal-dependent cognitive function. Frontostriatal cognition is supported by the coordinated activity of neurons across this circuit. To date, the neural coding mechanisms that support the diverse cognitive actions of psychostimulants are unclear. This represents a significant deficit in our understanding of the neurobiology of frontostriatal cognition and limits the development of novel treatments for frontostriatal cognitive impairment. The current studies examined the effects of cognition-enhancing and cognition-impairing doses of methylphenidate (MPH) on the spiking activity of dorsomedial PFC (dmPFC) and dorsomedial striatal (dmSTR) neurons in 17 male rats engaged in a working memory task. Across this frontostriatal circuit, we observed opposing actions of low- and high-dose MPH on the population-based representation of delay: low-dose strengthened, while high-dose weakened, representation of this event. MPH elicited a more complex pattern of actions on reward-related signaling, that were highly dose-, region- and neuron-dependent. These observations provide novel insight into the neurophysiological mechanisms that support the cognitive actions of psychostimulants.

Goal-directed behavior is dependent on neuronal activity in the prefrontal cortex (PFC) and extended frontostriatal circuitry. Stress and stress-related disorders are associated with impaired frontostriatal-dependent cognition. Our understanding of the neural mechanisms that underlie stress-related cognitive impairment is limited, with the majority of prior research focused on the PFC. To date, the actions of stress across cognition-related frontostriatal circuitry are unknown. To address this gap, the current studies examined the effects of acute noise-stress on the spiking activity of neurons and local field potential oscillatory activity within the dorsomedial PFC (dmPFC) and dorsomedial striatum (dmSTR) in rats engaged in a test of spatial working memory. Stress robustly suppressed responses of both dmPFC and dmSTR neurons strongly tuned to key task events (delay, reward). Additionally, stress strongly suppressed delay-related, but not reward-related, theta and alpha spectral power within, and synchrony between, the dmPFC and dmSTR. These observations provide the first demonstration that stress disrupts the neural coding and functional connectivity of key task events, particularly delay, within cognition-supporting dorsomedial frontostriatal circuitry. These results suggest that stress-related degradation of neural coding within both the PFC and striatum likely contributes to the cognition-impairing effects of stress.

Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodulator systems. The neuromodulatory locus coeruleus-norepinephrine (LC-NE) system is central to regulating cognitive function in a behaviorally-relevant and arousal-dependent manner. Through its nearly ubiquitous efferent projections, the LC-NE system acts to modulate neuron function on a cell-by-cell basis and exert a spectrum of actions across different brain regions to optimize target circuit function. As LC neuron activity, NE signaling, and arousal level increases, cognitive performance improves over an inverted-U shaped curve. Additionally, LC neurons burst phasically in relation to novel or salient sensory stimuli and top-down decision- or response-related processes. Together, the variety of LC activity patterns and complex actions of the LC-NE system indicate that the LC-NE system may dynamically regulate the function of target neural circuits. The manner in which neural networks encode, represent, and perform neurocomputations continue to be revealed. This has improved our ability to understand the optimization of neural circuits by NE and generation of flexible and adaptive goal-directed behaviors. In this review, the rat vibrissa somatosensory system is explored as a model neural circuit to bridge known modulatory actions of NE and changes in cognitive function. It is argued that fluid transitions between neural computational states reflect the ability of this sensory system to shift between two principal functions: detection of novel or salient sensory information and detailed descriptions of sensory information. Such flexibility in circuit function is likely critical for producing context-appropriate sensory signal processing. Nonetheless, many challenges remain including providing a causal link between NE mediated changes in sensory neural coding and perceptual changes, as well as extending these principles to higher cognitive functions including behavioral flexibility and decision making.

A variety of cognitive assessment tools are used to determine the functional status of the brain before and after injury in athletes. Questionnaires, neuropsychological tests, and electroencephalographic (EEG) measures have been recently used to directly assess brain function on and near the playing field. However, exercise can affect cognitive performance and EEG measures of cortical activity. To date, little empirical evidence exists on the effects of acute exercise on these measures of neurological function. We therefore quantified athlete performance on a standardized battery of concussion assessment tools and EEG measurements immediately before and after acute exercise to simulate conditions of athletic competition. Heart rate and arterial oxygen levels were collected before and after the exercise challenge consisting of a 1-mile run. Together these data, from a gender-balanced cohort of collegiate athletes, demonstrated that moderate to hard levels of acute exercise improved performance on the King-Devick test (K-D test) and Standardized Assessment of Concussion (SAC) component of the Sport Concussion Assessment Tool (SCAT3). Gender played an important role in these effects, and performance was most affected by exercise in female athletes. EEG activity in the theta band (4–8 Hz) was decreased during periods of quiet resting with eyes open or eyes closed. Additionally, exercise produced a slowing of the EEG during the K-D test and a shift to higher frequencies during the balance assessment of the SCAT3. Together, these data indicate that exercise alone can influence outcome measures of cognitive assessment tools used to assess brain function in athletes. Finally, care must be taken to acquire postinjury measurements during a comparable physiologic state to that in which baseline assessment data were measured, and further research is needed into the factors influencing outcome measures of these tests.

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction.SIGNIFICANCE STATEMENT The dorsomedial PFC and its striatal targets play a critical role in higher cognitive function. PFC-dependent cognitive dysfunction is associated with many psychiatric disorders. Although it has long-been known that corticotropin-releasing factor (CRF) neurons are prominent within the PFC, their role in cognition has remained unclear. Using a novel chemogenetic viral vector system, the present studies demonstrate that PFC CRF neurons impair working memory via activation of local PKA-coupled CRF receptors, an action associated with robust degradation in task-related frontostriatal neuronal coding. Conversely, suppression of constitutive PFC CRF activity improved working memory. Collectively, these studies provide novel insight into the neurobiology of cognition and suggest that CRF may represent a novel target for the treatment of cognitive dysfunction.

Stress, pervasive in modern society, impairs prefrontal cortex (PFC)-dependent cognitive processes, an action implicated in multiple psychopathologies and estimated to contribute to nearly half of all work place accidents. However, the neurophysiological bases for stress-related impairment of PFC-dependent function remain poorly understood. The current studies examined the effects of stress on PFC neural coding during a working memory task in rats. Stress suppressed responses of medial PFC (mPFC) neurons strongly tuned to a diversity of task events, including delay and outcome (reward, error). Stress-related impairment of task-related neuronal activity included multidimensional coding by PFC neurons, an action that significantly predicted cognitive impairment. Importantly, the effects of stress on PFC neuronal signaling were highly conditional on tuning strength: stress increased task-related activity in the larger population of PFC neurons weakly tuned to task events. Combined, stress elicits a profound collapse of task representations across the broader population of PFC neurons.

Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its ability to detect sports concussion in collegiate athletes. Background: Non-invasive biomarkers are emerging as essential tools as diagnostic aids to primary care physicians and neurologists. Static imaging (MRI/PET/SPECT) and fluid based (blood and CSF) biomarkers are limited in their ability to capture the inherent dynamics of brain physiology. The present study evaluates a telemetric EEG during a series of cognitive tasks to assess test-retest reliability of this approach, classify injured athletes, and collect longitudinal data during recovery. Methods: Recent advances in wireless EEG hardware have enabled Cerora to develop a novel activated EEG system (Cerora BorealisTM) to focus the physiological assessment of brain health while activating various neural circuits during cognitive tasks. In a 3 year study, baselines scans consisting of 16 tasks were conducted on N=274 varsity athletes. Longitudinal data was collected from N=49 concussed athletes (and N=48 non-injured comparator subjects) during the symptomatic and asymptomatic phase at 6-10 time points per subject. Results: Retest reliability analyses indicated that spectral values were not statistically different across 10 separate recording scans. Additionally, we observed that performance on components of the task battery were similar across scans (e.g. SAC Immediate Memory rmANOVA F(3,6) = 0.25, p = 0.93). In contrast, performance on the cognitive test battery was significantly different following concussion (e.g. Wilcoxon p=0.001). Conclusions: A physiologically focused battery of activated EEG tasks is able to probe elements of brain circuits not presently assessed with standard resting state (Eyes Open or Eyes Closed) quantitative EEG. These measures can be stable and reliable across multiple testing sessions occurring over months. Concussion alters these measures that can be followed longitudinally during recovery.

Objective: Determine the degree to which acute moderate exercise impacts performance in several concussion assessment tools and electrocortical measures of cognitive function used in the detection of concussion. Background: The effects of acute exercise on cognitive function are dependent on a number of factors, including the assessment type, exercise intensity, and recovery time before testing. Recently, emphasis is being placed on using cognitive assessment tools before and after injury in athletes, however little empirical evidence exists on the influence of exercise on these measures. Methods: A gender-balanced cohort (N=8 /gender) was assessed with a single channel telemetric EEG recording device and cognitive test battery (Cerora Borealis, Cerora Inc.) immediately before and after moderate exercise (1-mile run). Heart rate and arterial oxygen levels were collected to control for the level of exertion. Results: We provide novel evidence that moderate exercise modestly improves performance on the King-Devick neuro-ophthalmologic saccade test (43.94+/-2.23 to 39.875+/-1.62 (mean+/-SEM total time(sec), Wilcoxon p = 0.0044) and standardized assessment of concussion (SAC) tool (27.9+/-0.43 to 29.125+/-0.26 mean(sec)+/-SEM, Wilcoxon p = 0.0039). During standard EEG recording methodology (bouts of quiet resting with eyes open or eyes closed) activity within the Theta band (4-8Hz) was decreased. However during the working memory component of the SAC, exercise produced a complex array of changes in EEG activity. Surprisingly, the majority of these effects were dependent on gender. Conclusions: Exercise can impact outcome measures of cognitive tests and direct measures of brain function used to identify concussion that may lead to biases in the interpretation of post-injury assessment measures. Although these observations are from a limited sample size, these findings which include evidence that gender plays an important role in the actions of exercise in these measures, indicate that further research is needed into the factors influencing outcome measures of these tests.

Objective: To validate a novel neuro-ophthalmologic set-shifting task in healthy subjects against current neuro-ophthalmologic tools used in the detection of concussion. Background: Saccade-based tasks evolved from the Pierce task, through the King-Devick (KD) Test, to the Developmental Eye Movement (DEM) test and are used for developmental assessment and concussion testing. Although the DEM test improves on both tasks by introducing reading direction in the horizontal and vertical orientation to deconvolve number naming automaticity from saccade performance, the majority of field testing continues to use the KD test and sensitivity of these tests can be further improved. Methods: The present study compared performance on the novel Cerora Saccade task (CST) to the KD test. The CST uses 2 vertical cards and 2 horizontal cards. Test card 1 and 3 contains numerals 0 - 9, whereas card 2 and 4 use a hexadecimal system (0-9 and capital A-F). The addition of letters incorporates a set-shifting component to the task. Set shifts are initially made between blocks of 5 elements then subsequently are made element wise. The CST and KD test were administered in a randomized cross-over design and performance was analyzed in a matched pairs analysis in JMP v11 (SAS, Cary, NC). Results: In a sample of N=31 collegiate subjects, we observed a Pearson correlation coefficient of 0.67 (p<0.0001) between the total task time (seconds) of the three KD test cards and the total time of the 4 CST card. Additional subjects will be recruited until the sample size approaches 100. Conclusions: The high degree of correlation between these two tasks begins to indicate that the CST is a valid measure of neuro-ophthalmologic assessment. Future studies will need to determine the sensitivity of this set-shifting saccade task to assess developmental abnormalities and concussion.

Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its ability to detect sports concussion in collegiate Background: Non-invasive biomarkers are emerging as essential tools as diagnostic aids to primary care physicians and neurologists. Static imaging (MRI/PET/SPECT) and fluid based (blood and CSF) biomarkers are limited in their ability to capture the inherent dynamics of brain physiology. The present study evaluates a telemetric EEG during a series of cognitive tasks to assess test-retest reliability of this approach, classify injured athletes, and collect longitudinal data during Methods: Recent advances in wireless EEG hardware have enabled Cerora to develop a novel activated EEG system (Cerora BorealisTM) to focus the physiological assessment of brain health while activating various neural circuits during cognitive tasks. In a 3 year study, baselines scans consisting of 16 tasks were conducted on N=274 varsity athletes. Longitudinal data was collected from N=49 concussed athletes (and N=48 non-injured comparator subjects) during the symptomatic and asymptomatic phase at 6-10 time points per subject. Results: Retest reliability analyses indicated that spectral values were not statistically different across 10 separate recording scans. Additionally, we observed that performance on components of the task battery were similar across scans (e.g. SAC Immediate Memory rmANOVA F(3,6) = 0.25, p = 0.93). In contrast, performance on the cognitive test battery was significantly different following concussion (e.g. Wilcoxon p=0.001). Conclusions: A physiologically focused battery of activated EEG tasks is able to probe elements of brain circuits not presently assessed with standard resting state (Eyes Open or Eyes Closed) quantitative EEG. These measures can be stable and reliable across multiple testing sessions occurring over months. Concussion alters these measures that can be followed longitudinally during recovery. Disclosure: Dr. Simon has received personal compensation for activities with Cerora, Inc. as an owner, director, officer, and employee. Dr. Devilbiss has received personal compensation for activities with NexStepBiomarkers LLC and Cerora, Inc. as an owner.

Identifying the network structure of a neuron ensemble beyond the standard measure of pairwise correlations is critical for understanding how information is transferred within such a neural population. However, the spike train data pose significant challenges to conventional statistical methods due to not only the complexity, massive size, and large scale, but also high dimensionality. In this article, we propose a novel "structural information enhanced" (SIE) regularization method for estimating the conditional intensities under the generalized linear model (GLM) framework to better capture the functional connectivity among neurons. We study the consistency of parameter estimation of the proposed method. A new "accelerated full gradient update" algorithm is developed to efficiently handle the complex penalty in the SIE-GLM for large sparse datasets applicable to spike train data. Simulation results indicate that our proposed method outperforms existing approaches. An application of the proposed method to a real spike train dataset, obtained from the prelimbic region of the prefrontal cortex of adult male rats when performing a T-maze based delayed-alternation task of working memory, provides some insight into the neuronal network in that region.

Objective: To assess the predictive accuracy of multivariate models from novel wireless single lead electroencephalography (EEG) system data to detect diagnostic features of sports concussion. Background: Non-invasive biomarkers are emerging as essential tools as diagnostic aids to primary care physicians and neurologists. Static imaging (MRI/PET/SPECT) and fluid based (blood and CSF) biomarkers are limited in their ability to capture the inherent dynamics of brain physiology. The present study evaluates a telemetric EEG device and multivariate classifiers for the physiological assessment of brain health. Methods: Recent advances in wireless EEG hardware have enabled Cerora to develop a novel activated EEG system (Cerora BorealisTM) to focus the physiological assessment of brain health while activating various neural circuits during cognitive tasks. A 5 minute Cervey™ scan was conducted on N=45 control and N=26 mild Traumatic Brain Injury subjects while wearing the brainwave biosensor. Univariate and multivariate classifiers were constructed from the extracted features. Results: Several features derived from over 150 published or proprietary EEG biomarkers can independently show good diagnostic accuracy across 5 of these cognitive tasks. Clinical performance of a random forest model resulted in a substantially greater predictive accuracy of nearly 80[percnt] (ROC AUC=0.79) in a hold-out validation set (45[percnt] of the sample, 55[percnt] training set). Conclusions: A cognitive task battery designed to produce dynamics in the EEG can probe elements of brain circuits not presently assessed with standard resting state (Eyes Open or Eyes Closed) quantitative EEG. Multivariate models can enhance diagnostic accuracy, although further work extending these preliminary results is required to validate activated EEG signatures to map the brain for its age-related, normal and abnormal signatures. Disclosure: Dr. Simon has received personal compensation for activities with Cerora, Inc. as an owner, director, officer, and employee. Dr. Devilbiss has received personal compensation for activities with NexStepBiomarkers LLC and Cerora, Inc. as an owner.

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. In contrast, while the striatum is a critical participant in PFC-dependent cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g., working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation.

We have developed a novel approach to elucidate several discriminating EEG features of Alzheimer’s disease. The approach is based on the use of a variety of continuous wavelet transforms, pairwise statistical tests with multiple comparison correction, and several decision tree algorithms, in order to choose the most prominent EEG features from a single sensor. A pilot study was conducted to record EEG signals from Alzheimer’s disease (AD) patients and healthy age-matched control (CTL) subjects using a single dry electrode device during several eyes-closed (EC) and eyes-open (EO) resting conditions. We computed the power spectrum distribution properties and wavelet and sample entropy of the wavelet coefficients time series at scale ranges approximately corresponding to the major brain frequency bands. A predictive index was developed using the results from statistical tests and decision tree algorithms to identify the most reliable significant features of the AD patients when compared to healthy controls. The three most dominant features were identified as larger absolute mean power and larger standard deviation of the wavelet scales corresponding to 4–8 Hz (\(\theta\)) during EO and lower wavelet entropy of the wavelet scales corresponding to 8–12 Hz (\(\alpha\)) during EC, respectively. The fourth reliable set of distinguishing features of AD patients was lower relative power of the wavelet scales corresponding to 12–30 Hz (\(\beta\)) followed by lower skewness of the wavelet scales corresponding to 2–4 Hz (upper \(\delta\)), both during EO. In general, the results indicate slowing and lower complexity of EEG signal in AD patients using a very easy-to-use and convenient single dry electrode device.