Synopsis

Twelve Years’ Challenge of BrainConnects

Toshiharu Nakai, Graduate School of Osaka University, Suita, Japan,
BrainConnects Coordinator

BrainConnects was launched in 2014, merging several bilateral collaborations in cognitive neuroimaging and informatics in the pacific Asia. The topic in BrainConnects was initially application of neuroimaging in aging researches to evaluate the effects of physical and cognitive interventions on the older adults. Based on this collaboration platform, the annual meetings covered not only clinical applications but also adjacent fields such as artificial intelligence, nutrition, health promotion, and education. In order to surmount recent drastic changes in research environments, BrainConnects has been encouraging collaborations among the participating facilities to grow mutual reliability and partnership. In the next decade, further developments in neural network modeling, decoding, neuro-intervention and cognitive assistance will be promoted using neuroimaging with AI technologies. The program of this 12th meeting will serve you a good opportunity to review the cutting edge of neuroimaging and obtain your insights towards next step. 

Neural Effects and Cognitive Gains from the BrainTrain Intervention: A Mobile App-Based Cognitive Training Program for Patients with Mild Cognitive Impairment

Prof.  Ha Thi Thanh Huong, Vietnam National University

Mild Cognitive Impairment (MCI) represents a crucial opportunity for preventing or delaying the onset of Alzheimer’s disease, especially in low- and middle-income countries (LMICs). In this lecture, I will present our recent study investigating the cognitive and neural effects of BrainTrain – a mobile application developed based on principles of cognitive neuroscience, featuring 12 interactive games that target essential domains such as memory, attention, language, and mathematics.

The study involved recruiting patients with MCI, instructing them to engage with the app for 30 minutes daily over a three-month intervention period. Participants were categorized based on their frequency of app usage. Cognitive changes were measured using neuropsychological assessments, while neural activity was evaluated through EEG by analyzing power spectral density and functional connectivity. Correlation and causal analyses were performed to examine whether app usage frequency directly contributed to cognitive improvements. Additionally, a post-intervention survey was conducted at the end of the three-month program to gather insights into patients’ subjective experiences. Responses were analyzed using thematic analysis, which identified key themes that provide a deeper understanding of the intervention’s impact.

The study findings demonstrated statistically significant enhancements in cognitive performance among patients with high app usage. Notably, their MMSE scores showed substantial improvement after both one and three months of use. EEG data revealed a decrease in power spectral density and coherence during task performance, indicating more efficient neural processing following the intervention. Furthermore, the app usage frequency was positively correlated with cognitive improvements, as evidenced by increasing MMSE scores throughout the intervention period. Importantly, causal analysis identified app usage frequency as the only statistically significant factor driving improvements in MMSE scores over time. Thematic analysis of post-intervention survey responses identified five key themes: (1) Diverse emotional experiences, (2) Technical issues and content limitations, (3) Perceived cognitive benefits and belief in effectiveness, (4) Social support and sharing experiences, (5) Personal barriers. These themes provide valuable insight into the multifaceted nature of patient engagement, highlighting both facilitators and challenges to long-term adherence.

This lecture will underscore how mobile-based tools like BrainTrain can offer scalable, user-friendly, and effective cognitive intervention strategies while emphasizing the importance of integrating both quantitative and qualitative outcomes in evaluating digital health interventions.

Artificial Intelligence in Brain Machine Interfaces – Trends and Updates

Angelito A. Silverio, PhD, Nuvoton Technology Singapore, Pte, Ltd.

With the increase in computing power over the past decade, we have witnessed more implementations of Artificial Intelligence (AI) especially in the medical field. One of its very promising applications is in Brain Machine Interfaces (BMI) leading to a technology called smart BMI.  With the help of AI to process signals, the applications of BMIs have been extended greatly, such as cursor control, auditory sensation, limb control, spelling devices, somatic sensation, thoughts to speech, and visual prosthesis. These smart BCIs have achieved notable clinical success, improved the quality of paralyzed patients’ lives, expanded the athletic ability of common people and accelerated the evolution of robots and neurophysiological discoveries. In this talk, we shall look at the technical foundations of smart BCI, its current state of the art, design and implementation challenges, and a preview of what we are to expect in the near future.

The potential use of navigation dysfunction as a very early marker of Alzheimer's disease

Prof. Epifanio Bagarinao, Brain and Mind Research Center, Nagoya University, Nagoya, Japan

 Studies have shown that brain regions implicated in the initial stages of Alzheimer’s disease (AD), such as the entorhinal cortex and the retrosplenial cortex, are also essential for spatial navigation. For instance, neurofibrillary tangles, which are indicative of AD, initially develop in the entorhinal cortex and gradually spread through the limbic cortex to the neocortex. However, the entorhinal cortex is also known to contain grid cells that provide periodic self-location representations of the environment and are crucial for path integration, which underpins the navigation capabilities of the brain. Considering this regional overlap, there is a growing interest in leveraging navigation dysfunction as an early marker of AD. In this talk, I will present the results of our ongoing study using functional MRI to investigate the neural correlates associated with poor navigation performance in cognitively healthy older adults.

NEUROMAP-PH and its Complexity Perspectives for Brain Health Research in the Philippines

Prof. Johnrob Y. Bantang, National Insitute of Physics, University of the Philippines 

In this talk, I will provide a brief overview of complexity science and the perspectives that it can offer for brain health research. Existing complexity models will be discussed and explain how they can elucidate the unique dynamical features present in brain activity and their potential connection to holistic view of human health. I will then introduce our on-going project NEUROMAP-PH that aims to form part of the nucleus of the brain mapping efforts in the Philippines with the St. Luke’s Medical Center in cooperation with different government institutions such as the Department of Science and Technology’s Philippine Council for Health Research and Development (PCHRD-DOST) and the University of the Philippines.

Human neuroimaging using 7T-MRI 

Tomohisa Okada, Kenichi Ueno, Chisato Suzuki, Kazuki Kunieda, R. Allen Waggoner. Riken CBS, Japan

Technical developments in the field of MRI have brought 7 Tesla (7T) MRI system into clinical practice in some countries. Although my experience is limited to research, I would like to inform you on the clinical and research applications of the 7T-MRI (1). High signal-to-noise ratio enables acquisition in submillimeter isotropic resolution, leading to detailed imaging of small deep-brain structures, cortical structures and so on. High contrast-to-noise ratio increases T2*-weighted contrast including blood oxygenation-dependent (BOLD) contrast, which is highly advantageous functional MRI (fMRI). In addition, increased spectral resolution facilitates separation of overlapping metabolite peaks in MR spectroscopy. In structural brain imaging, T1-weighted imaging (T1WI) is commonly performed using the MPRAGE sequence. At 7T, however, transmit field (B1⁺) inhomogeneity highly matters and MP2RAGE, which mitigates this issue and enables quantitative T1 mapping in high resolution with 0.5 – 1 mm isotropic. Such resolution facilitates research into cortical thickness and its relevance in Parkinson’s and Alzheimer's diseases (2). It also supports detailed imaging of various deep and superficial brain structures, including Nigrosome-1, locus coeruleus, and habenula. FMRI at 7T also get benefits from high spatial resolution and enables detailed mapping, such as finger-wise primary sensory areas (3) and layer-wise activity of the cortex as superficial-layer input and deep-layer output. Improved functional connectivity analysis can also be conducted based on small, previously unresolved structures. Neuroimaging at 7T provides new findings on structural and functional information and is expected to refine the imaging biomarkers of the human brain. 

References: (1) Okada T, et al. Neuroimaging at 7 Tesla: a pictorial narrative review. Quant Imaging Med Surg. 2022;12(6):3406-3435. (2) Yoshimura K, et al. Neural substrates underlying distinct dual cognitive syndromes in Parkinson's disease. Eur J Neurol. 2025;32(1):e70022. (3) Wang L, Zhang Z, Okada T, et al. Population Receptive Field Characteristics in the between- and Within-Digit Dimensions of the Undominant Hand in the Primary Somatosensory Cortex. Cereb Cortex. 2021;31(10):4427-4438. 

Understanding individual differences in exercise-related cognitive gains: the role of neurophysiological and lifestyle mediators

Alicia Goodwill, Assistant Professor at Physical Education and Sports Science (PESS) Academic Group at National Institute of Education (NIE), Nanyang Technological University (NTU).  

 It is well-established that exercise is associated with improved cognition, slower cognitive decline, and reduced risk of dementia. Yet, outcomes from well-designed randomised controlled trials (RCTs) remain mixed, highlighting the need to move beyond a “one-size-fits-all” approach to exercise prescription for brain health. One likely explanation lies in the individual variability of exercise dose–response relationships, particularly the influence of exercise intensity and habitual lifestyle factors. This talk will explore key predictors and mediators of exercise-induced changes in executive functions in healthy young adults, with a focus on physiological markers such as lactate and heart rate variability (HRV), alongside lifestyle factors including habitual physical activity and diet. By identifying the mechanisms and moderators of exercise effects on cognition, this work aims to help inform personalised exercise prescriptions for brain health. Such insights will have important clinical implications for tailoring interventions to optimise cognitive outcomes earlier in the lifespan, with potential to delay or prevent cognitive decline in later-life.

Walking Brain in the Human Maze  

Prof. Makoto Miyakoshi, University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience, USA

Spatial navigation in humans is traditionally studied in stationary, screen-based paradigms, yet real-world navigation involves multisensory integration during movement. We developed the AudioMaze, a room-sized “human maze task” inspired by classic mouse maze experiments, in which blindfolded participants navigated virtual mazes defined by sparse auditory feedback while EEG and motion capture were recorded simultaneously. Sixteen adults explored mazes across repeated trials, totalling 220 meters, showing behavioral learning through reduced completion times, faster movement, and fewer wall probes. EEG revealed trial-dependent decreases in low-frequency power near the lingual gyrus, a posterior parahippocampal place area region, and effective connectivity from occipital to midcingulate cortices, reflecting shifts from egocentric exploration to allocentric map formation. These results demonstrate the feasibility of mobile EEG for capturing “walking brain” dynamics and provide novel evidence of neural correlates of spatial learning in real-world scale navigation.  

Science of Learning for Brain Health: Neuroplasticity, Reserve, Resilience and Vitality

SH Annabel Chen, Professor of Psychology, CRADLE, LKCMedicine, Nanyang Technological University, Singapore

Learning as we age involves continuous changes in the brain, shaped by neuroplasticity across cognitive, social, and lifestyle domains. The Science of Learning provides a framework for understanding how these processes contribute to brain health across the lifespan. This overview introduces cognitive reserve, resilience, and vitality as complementary constructs for explaining how individuals maintain or enhance function later in life. Reserve reflects efficiency in tolerating pathology, resilience denotes adaptability in the face of insult or degeneration, and vitality emphasizes proactive enrichment through engagement and learning. Evidence from neuroimaging and neuromodulation highlights how lifelong learning, cognitively challenging activities such as dancing and square stepping, social participation, and other enrichment factors can strengthen flexibility, support active aging, and promote lifelong brain health.

Nuclear Medicine and Neuroimaging in Dementia

Prof. Dr. Subapriya Suppiah, Universiti Putra Malaysia

In this era of digital expansion and artificial intelligence (AI), medical imaging and precision medicine using nuclear medicine and neuroimaging have come to the forefront as important and relevant diagnostics and treatment of the future. The revolution that is being seen in the development of radiopharmaceuticals, multimodality imaging and therapy tools, as well as better clinical workflow has led to faster time-to-treatment, better patient survival, and increased quality of life. Now, clinicians also have powerful tools that aid in the early and accurate diagnosis of dementia, which is a rising concern in countries with aging populations, such as Malaysia.  Traditional imaging techniques like CT and MRI while providing structural insights, may be better utilized with the integration of functional imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). These hybrid imaging can offer unique metabolic, functional, and molecular information that is pivotal in dementia care. Specifically, ¹⁸F-FDG PET-CT and amyloid imaging using PET-CT enable non-invasive visualization of brain glucose metabolism and amyloid plaque burden, respectively.  This information can characterise and distinguish Alzheimer's disease (AD) from frontotemporal dementia (FTD) or dementia with Lewy bodies (DLB). Amyloid PET tracers like florbetapir and tau imaging agents further enhance specificity by directly targeting hallmark proteinopathies of AD. With the advent of these molecular biomarkers, in vivo confirmation of neuropathology can be achieved, even before cognitive symptoms become overt. Whereas, using SPECT-CT imaging, dopaminergic imaging (e.g., DaTscan and TRODAT scans) assist in diagnosing DLB and Parkinson’s disease dementia by visualizing nigrostriatal degeneration. Beyond diagnostics, nuclear neuroimaging is also used for monitoring disease progression, evaluating therapeutic response, and facilitating patient selection for clinical trials. Hybrid imaging systems such as PET/MRI are also pushing the boundaries by integrating structural, functional, and molecular data into a single session with reduced radiation dose. In conclusion, nuclear medicine and radiology play a central and expanding role in the clinical and research settings of dementia. Visual and quantitative assessment can be made in a non-invasive manner, gaining clinic-pathological insights that offers "pearls" that not only enable precision diagnostics but provide hope for theragnostics of the future in solving the problem of neurodegenerative diseases.

Using a Rodent Model to Evaluate Novel Treatments for Addiction in the Philippines

Rohani Cena-Navarro, National Institutes of Health, University of the Philippines Manila

Gregory J. Quirk, PhD, National Institutes of Health, University of the Philippines Manila

Substance abuse is a chronic brain disease that poses a major public health challenge worldwide. Rodent models of drug addiction are valuable for studying the long-term effects of drugs and for testing novel interventions. In the Philippines, solvent use (particularly toluene) is highly prevalent, especially among street children, yet the effects of toluene on females and on social behavior are still poorly understood. We recently reported that repeated toluene inhalation enhanced conditioned place preference (CPP) and impaired social novelty preference during abstinence. In this presentation, we will highlight findings on low-cost pharmacological (N-acetylcysteine) and behavioral (exercise) treatments for mitigating these effects. We will also demonstrate the use of cFos immunofluorescence to evaluate the brain circuitry involved in toluene addiction. New directions for our lab include social interactions in morphine and methamphetamine addiction.

Diffuse Tensor Imaging and Voxel Based Morphometry

Prof. Gloria Fan-Pei Pang (Virtual), National Tsing Hua University, Taiwan 

Diffusion Tensor Imaging (DTI) and Voxel-Based Morphometry (VBM) are advanced MRI-based neuroimaging techniques widely employed to study brain microstructure and anatomy. DTI measures the directional diffusion of water molecules in brain tissue, providing quantitative insights into white matter integrity and enabling visualization of fiber tract pathways through tractography. This technique is particularly useful for understanding white matter connectivity and detecting microstructural changes linked to neurodegenerative diseases, psychiatric disorders, and brain injuries. While advancements in DTI processing pipelines have enhanced accuracy, challenges related to standardization and artifact management persist.

VBM complements DTI by utilizing a fully automated voxel-wise statistical approach to identify regional gray and white matter volume differences across populations. It facilitates whole-brain investigations into structural brain changes associated with atrophy or tissue expansion, supporting research in aging, neurodegeneration, epilepsy, and psychiatric conditions. Despite sensitivity to registration and segmentation artifacts, VBM has demonstrated biological relevance when validated against manual methods. Together, DTI and VBM offer a comprehensive toolkit for studying structural brain changes at both microstructural and macrostructural levels, deepening our understanding of brain organization and pathology. This talk will explore their principles, methodologies, applications, and future directions in neuroscience research.

Autism: Networks and Biomarkers

Prof. Lourdes Tanchanco, Ateneo School of Medicine and Public Health Philippines

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with early atypical brain growth—often cerebral overgrowth in toddlerhood—followed by altered maturation across cortico-cerebellar and fronto-limbic systems. Neuroimaging and postmortem data show regionally mixed cortical thickness/gyrification changes (frontal, temporal/STS, parietal, cingulate, fusiform), amygdala-hippocampal cell-size/density differences, reduced cerebellar Purkinje neurons, excess extra-axial CSF in infancy, and white-matter microstructural changes affecting corpus callosum and long association pathways. 

The “second brain,” the gut, communicates bidirectionally with the CNS via the vagus nerve, immune signaling, shared neurotransmitters (e.g., serotonin largely produced in the gut), and microbial metabolites (e.g., SCFAs), and children with ASD experience significantly higher rates of GI symptoms, underscoring the clinical relevance of gut–brain interactions. 

Building on these insights, a DOST-funded study by the Ateneo Autism Study Group will compare children with ASD and age-matched neurotypical peers to define clinical profiles and multi-omic biomarkers—including molecular, nutritional, metabolic, inflammatory markers—and characterize the gut microbiome; it will correlate biomarker patterns with symptoms and establish a biobank to support precision diagnostics and future interventions.

Biophysical Generative Mechanism of Scalp-Recorded EEG

Prof. Makoto Miyakoshi, Cincinnati Children’s Hospital Medical Center, USA

This lecture will explore the biophysical generative mechanisms of scalp-recorded EEG across multiple spatial scales, from the activity of a single synapse to whole-head dynamics. At the microscopic level, I will distinguish between intracellular and extracellular currents and introduce the concept of dendritic electrotonic conduction, illustrated through cable theory simulations. These simulations also clarify how low-pass filtering arises in extracellular electrophysiological recordings. I will then contrast the traditional passive, subthreshold model with the more recently developed active, suprathreshold model of EEG generation. At the macroscopic level, I will discuss how EEG signals emerge from the laminar structure of the cortex, drawing on classical in vivo depth-recording studies. This discussion will extend to the role of thalamo-cortical networks and, finally, to the principles of volume conduction. The lecture is grounded in Electric Fields of the Brain by Nunez and Srinivasan (2006), which I am currently translating in official collaboration with the authors.

Neurometabolic Changes in Disorders of Consciousness 

Dr. Niall Duncan, Graduate Institute of Mind, Brain and Consciousness, Taipei Medical University

Disorders of consciousness (DoC), including unresponsive wakefulness syndrome and minimally conscious state, are conditions in which patients show no or limited signs of conscious awareness while retaining arousal transitions. Such disorders can arise from different insults to the brain and can have quite different prognoses. At the same time, accurate diagnosis of consciousness level is challenging and often inaccurate. As such, developing a better understanding of what set of brain alterations can lead to consciousness loss is important. Considerable work on anatomical and functional correlates of DoC has been conducted, helping to build an initial picture. Less work has been done on the cellular processes that may also underlie consciousness loss. We therefore sought to study brain metabolism and neurochemical changes in DoC patients through a combination of [18]F-fluorodeoxyglucose PET and magnetic resonance spectroscopy (MRS). We probe the topography of metabolic changes in DoC patients, relating them to canonical functional gradients. Further, we study changes in a set of neurotransmitters and neurometabolites. Together, our investigation helps elucidate neural correlates of consciousness and provides initial pointers towards neurometabolic feature that may be targeted by treatments for DoC.

Rapid AI in Acute Stroke Management

Dr. Ma. Cristina Macrohon-Valdez, St. Luke’s Medical Center Philippines

This lecture explores the clinical utility of RAPID AI CT Scan technology in rapidly diagnosing acute ischemic stroke. The session begins with an overview of the principles behind swift stroke diagnosis, emphasizing how RAPID AI enhances this process. Key focal points include the system's proficiency in detecting large vessel occlusion (LVO), and its critical role in assessing patient suitability for intravenous thrombolysis and mechanical thrombectomy. A significant portion of the talk is dedicated to the revolutionary role of RAPID AI in extending treatment time windows, allowing for more flexible and effective intervention strategies. This extended window has expanded possibilities for acute stroke treatment, offering hope to patients who may have previously been beyond the optimal timeframe for traditional interventions. The lecture concludes with practical insights through case studies from our practice. These cases highlight the successful application of RAPID AI, demonstrating its value in clinical settings and enhancing patient outcomes. This real-world evidence reinforces the transformative impact of RAPID AI on stroke management and its potential to save lives by enabling timely and accurate treatment decisions.

Transcranial Magnetic Stimulation

Ludwig Damian, St. Luke's Medical Center Institute for Neurosciences, Philippines

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique that uses magnetic pulses to influence brain activity. Originally developed for psychiatric applications, it has gained increasing attention in pain medicine. High-frequency stimulation over the primary motor cortex has shown promising results in several high-level evidence studies, demonstrating potential benefits for patients with neuropathic pain, fibromyalgia, and central post-stroke pain. Its analgesic effects are believed to stem from enhanced cortical excitability and modulation of descending pain pathways, offering a novel therapeutic avenue for patients with chronic pain.

Since its U.S. FDA approval in 2008 for treatment-resistant depression, rTMS has steadily expanded in clinical application. In 2016, St. Luke’s Medical Center pioneered the establishment of the first rTMS treatment center in the Philippines, marking a milestone in local neuromodulation practice. While its use for pain management is still in the early stages of development in our setting, its potential is promising. 

In this session, we will take a closer look at the principles behind rTMS, share real-world insights from our institutional experience, and highlight its promising applications in chronic pain management

HIFU/ MRgFUS FOR X-LINKED DYSTONIA-PARKINSONISM

Roland Dominic G. Jamora, MD, PhD, University of the Philippines Manila

X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder found only among Filipinos with ancestry from Panay Island. Recently, patients have also been reported from Sultan Kudarat and South Cotabato.

Aside from the motor presentation (dystonia and parkinsonism), patients with XDP also presents with nonmotor features, such as depression and cognitive impairment. This cognitive impairment involves the general intellect, episodic memory, and attention and executive function and affect. 

At present, there is no known cure for XDP. Medical management is limited to oral medications such as biperiden, clonazepam, zolpidem, and even levodopa/ carbidopa. Some patients undergo chemodenervation with botulinum toxin A. The response to deep brain stimulation has been very good, but is somehow limited by the cost involved. 

I will present our experience on the use of high intensity focused ultrasound or magnetic resonance-guided focused ultrasound among patients with XDP.

Innovative Neuroscience Research at the National Institutes of Health: Investigating the Genetic Epidemiology of X-linked Dystonia Parkinsonism

Eva Maria Cutiongco-de la Paz, Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila

X-linked Dystonia Parkinsonism (XDP) is a rare, severe neurodegenerative disease that is exclusively manifested among individuals with maternal ancestry tracing back to the Panay region of the Philippines due to a genetic founder effect. It is caused by an SVA retrotransposon that contains a hexameric repeat expansion in the TAF1 gene. XDP is inherited in an X-linked recessive manner and affects mostly males. Individuals with the disease exhibit symptoms of focal dystonia in their fourth decade of life, progressing to generalized dystonia and followed by the appearance of parkinsonism. The disease leads to deterioration of the quality of life and eventually, premature death. There is no available data regarding the national prevalence of the causative gene for XDP. This information is important for the development of health services and allocation of resources that can improve the quality of life of individuals affected by XDP. Using randomly selected de-identified residual dried blood spots (rDBS) from the PhilippineNewborn Screening Program, a qPCR-based assay, fitted in an automated workflow, was used to identify the XDP-associated genetic variant DSCn1. The results of the study showed that XDP is more common than what is currently reported based on clinical cases.

Brain Research in the Philippines

Dr. Jaime C. Montoya, Executive Director III Philippine Council For Health Research and Development

The Philippine Council for Health Research and Development (PCHRD), as lead coordinator of the Philippine National Health Research System (PNHRS), advances brain and mental health research through strategic agenda-setting, funding, and partnerships. Guided by the National Unified Health Research Agenda (NUHRA) and the Harmonized National R&D Agenda (HNRDA), PCHRD has elevated neuroscience and mental health as national priorities. Key milestones include creation of the Brain and Mental Health Research and Development Program last 2019 through the National Mental Health Research Agenda, and the development of the Philippine Brain Research Agenda in 2024. These activities fostered a surge in supported innovative projects, from the country’s first brain mapping study the Neuromap-PH, to novel animal models for addiction, molecular studies on autism, and therapeutic rare neurological disorders such as X-linked dystonia parkinsonism. Moving forward, PCHRD remains committed to inclusive funding, regional capacity building, and sustained local and international partnerships to ensure that research translates into better policies, diagnostics, and interventions, ultimately improving the brain health of all Filipinos.

Tractography in Neurosurgery

Dr. Ibet Sih, Institute for Neurosciences, St. Luke's Medical Center, Philippines

The use of tractography to visualize white matter pathways in modern Neurosurgery is key to reducing postoperative neurological deficits while achieving maximal safe resection. The advantages and limitations of tractography, preoperative planning of surgical corridors, case-based applications and challenges, and future directions are elucidated.