Dr. Arakaki, MD, PhD, is an Assistant Professor of Neuroscience and Head of the Cognition and Brain Integration Lab (CBIL) in the Department of Neurosciences at HMRI. Her research focuses on novel neurophysiological biomarkers of the conscious, subliminal and autonomic (CSA) system in pre-symptomatic Alzheimer’s disease (AD) and how their combinations will improve detection of pre-symptomatic AD and prediction of symptom onset. This work will characterize pre-symptomatic AD through a systemic lens and provide rich data for systems biology modeling in AD research and for other neurological diseases. Dr. Arakaki’s research also focuses on sodium disturbance underlying mechanisms of migraine.
Dr. Arakaki received her MD from the Medical College of Tongji University in Shanghai, China; her MS in neurobiology from the Medical Center of Fudan University in Shanghai; and her PhD in neuroscience from the University of Tennessee in Memphis, Tennessee. She pursued postdoctoral work at HMRI from 2007 to 2014 and was a research scientist and senior research scientist in neurosciences at HMRI from 2014 to 2021. In August 2021, Dr. Arakaki was appointed as Assistant Professor of Neurosciences. She is the recipient of R56 and R01 awards from the National Institute of Aging and National Institute of Neurological Disorders and Stroke.
Changes in biomarkers (amyloid/tau) and synaptic functions precede cognitive decline in Alzheimer’s disease (AD) by decades, and there is a critical need to detect these changes in order to plan and evaluate therapy. Changes in executive functions may signal AD progression and can guide both stage characterization and research on early diagnoses. Cognitive challenge tasks (working memory, Stroop interference and task shifting) reveal each core executive (implemented in prefrontal cortex) dysfunction in the pre-symptomatic stage of AD, which can potentially cause disinhibited subliminal and autonomic regulation from weakened top-down inhibitory controls. Dr. Arakaki’s team investigates novel non-invasive and systemic neurophysiological signatures of cognitively healthy individuals at elevated risk for cognitive decline, with collaborators Dr. Kloner (HMRI), Dr. Shimojo (Caltech) and Dr. Kleinman (UCI). The lab uses multidisciplinary approaches in their research, including neurobiology, cardiovascular biology, biochemistry, neuropsychology, electrophysiology and imaging techniques.
In addition, Dr. Arakaki and her team continue to investigate the role of sodium homeostasis dysfunction in migraine. Migraine is ranked among the top five leading causes of disability, and it is critically important to understand how migraine begins. Translational work demonstrates that changes in sodium concentration ([Na+]) in the cerebrospinal fluid (CSF) occur at migraine onset, and a possible cause is choroid plexus (CP) Na,K-ATPase dysfunction demonstrated by simulation. Dr. Arakaki’s team is looking into the roles of choroid plexus and sodium dysregulation in migraine, with collaborators Dr. Fonteh and Dr. Kloner (HMRI), Dr. Grant (FSU) and Dr. Petzold (UCSB).
Dr. Arakaki’s contributions to science:
Translational migraine studies in a cell and rodent model: Dr. Arakaki’s early work explored methods to monitor the sodium disturbance in a rodent migraine model. One study focused on how increased extracellular sodium elevates neuronal excitability using primary cultured neurons, which was replicated by NEURON simulation. Another study used immunostaining to show that the Na+,K+-ATPase isoforms maintain sodium homeostasis in the key CSF production location at the choroid plexus. In addition, Dr. Arakaki found that, in the rodent migraine model, brainstem auditory evoked potentials (BAEPs) peak latency and inter-peak latency ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged for two hours after nitroglycerin triggering of sensitization, reflecting changes in neurotransmitters and/or hypoperfusion in the midbrain. The results further validate the rodent migraine model for translational migraine research.
Arakaki X, Galbraith G, Pikov V, Fonteh AN, Harrington MG. Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine. Brain Res. 2014. 1563:110-21. PMID: 24680742
Arakaki X, McCleary P, Techy M, Chiang J, Kuo L, Fonteh AN, Armstrong B, Levy D, Harrington MG. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat. Fluids Barriers CNS. 2013. 10(1):14. PMID: 23497725
Harrington MG, Chekmenev EY, Schepkin V, Fonteh AN, Arakaki X. Sodium MRI in a rat migraine model and a NEURON simulation study support a role for sodium in migraine. Cephalalgia. 2011. 31(12):1254-65. PMID: 21816771
Arakaki X, Foster H, Su L, Do H, Wain AJ, Fonteh AN, Zhou F, Harrington MG. Extracellular sodium modulates the excitability of cultured hippocampal pyramidal cells. Brain Res. 2011. 1401:85-94. PMID: 21679932
Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. Severe Headache or migraine history is inversely correlated with dietary sodium intake: NHANES 1999-2004. Headache. 2016. 56(4):688-98. PMID: 27016121
Human EEG(ERP)/MEG studies: Dr. Arakaki’s recent work addresses objective EEG/MEG biomarkers in pre-symptomatic AD and mild traumatic brain injury (mTBI). In pre-symptomatic AD, cognitive challenge reveals the frontal hyperexcitability that indicates a transitional stage to further cognitive decline. In mTBI, cognitive challenge reveals the abnormal frontal alpha and delta waves and EEG/ERP signatures consistent with previous MEG findings.
Arakaki X, Lee R, King KS, Fonteh AN, Harrington MG. Alpha desynchronization during simple working memory unmasks pathological aging in cognitively healthy individuals. PLoS One. 2019. 14(1):e0208517. PMID: 30601822
Arakaki X, Shoga M, Li L, Zouridakis G, Tran T, Fonteh AN, Dawlaty J, Goldweber R, Pogoda JM, Harrington MG. Alpha desynchronization/synchronization during working memory testing is compromised in acute mild traumatic brain injury (mTBI). PLoS One. 2018. 13(2). PMID: 29444081
Lianyang Li, Arakaki X, Thao Tran, Harrington M, Padhye N, Zouridakis G. Brain activation profiles in mTBI: evidence from ERP activity of working memory response. Conf Proc IEEE Eng Med Biol Soc. 2016. 1862-1865. doi:10.1109/EMBC.2016.7591083. PMID: 26737894
Current work in Dr. Arakaki’s laboratory focuses on identifying systemic neurophysiological biomarkers for pre-symptomatic AD and continuing sodium dysregulation and choroid plexus role in migraine mechanisms.
Arakaki X, Hung SM, Rochart R, Fonteh AN, Harrington MG. Alpha desynchronization during Stroop test unmasks cognitively healthy individuals with abnormal CSF Amyloid/Tau. Neurobiol Aging. 2022. 112:87-101. PMID: 35066324
Arechavala RJ, Rochart R, Kloner RA, Liu A, Wu DA, Hung SM, Shimojo S, Fonteh AN, Kleinman MT, Harrington MG, Arakaki X. Task switching reveals abnormal brain-heart electrophysiological signatures in cognitively healthy individuals with abnormal CSF amyloid/tau, a pilot study. Int J Psychophysiol. 2021.
170:102-111. PMID: 34666107
Rochart R, Liu Q, Fonteh AN, Harrington MG, Arakaki X. Compromised Behavior and Gamma Power During working memory in cognitively healthy individuals with abnormal CSF Amyloid/Tau. Front Aging Neurosci. 2020. 12:574214. PMID: 33192465