for Cognitive Mapping and Digital Therapeutics

Dr Jyoti Mishra NEUROTECHNOLOGY FOR COGNITIVE AND DIGITAL THERAPEUTICS

Environmental factors and genetics both play a part in how our function, whether that be in a healthy or disordered manner. Understanding the processes by which mental health disorders arise is an important step in developing effective therapies.Dr Jyoti Mishra founded NEATLabs at the University of California, San Diego, to work towards this goal. Her exciting research is advancing cognitive brain mapping to investigate brain functions as well as novel digital therapeutics that are personalised to individual needs.

Brain Function and Dysfunction Using innovative , Dr Jyoti Mishra is developing our knowledge Our brains are wonderfully complex surrounding this issue and pushing organs that help us to navigate the forward the field of . Within world. Webs of neurons interact the Department of at the through electrical signals to provide University of California, San Diego, Dr us with sensory information, thoughts Mishra founded the and emotions. However, when the and Translational Labs (NEATLabs). normal processes in the brain become Here, she is the director of human attention, working , rewards, dysfunctional, concerns with mental research and works on improving emotions) are processed in the brain. health arise. Depending on a variety of neurotechnology for cognitive brain An EEG is carried out by attaching factors such as which brain circuits or mapping (i.e., mapping of the brain small, metal electrodes (discs) all over which area(s) of the brain are affected dynamics underlying our cognitive the scalp. When a specific region of the in specific dynamic patterns, different abilities) as well as personalising digital brain is activated, electrical signals are issues can develop. These conditions mental health therapies to patients. Her generated through the firing of a large commonly manifest as , research has highlighted how contextual population of underlying neurons (brain anxiety, post-traumatic stress influences and environments can alter cells) and these are picked up by the disorder (PTSD) and attention deficit brain development and normal function electrodes. This information is passed hyperactivity disorder in the general as well as how closed-loop technology to the EEG machine, which records the population. is an exciting and promising opportunity activity at each electrode as peaks and to improve brain health. troughs on an electroencephalogram. Mental health disorders are on the rise, so uncovering the processes in the brain The Brain Engagement Platform The types of cognition the team that cause them is essential to evolving initially tested were selective attention, new, effective therapeutics. Traumatic At NEATLabs, Dr Mishra and her team response inhibition (i.e., successful life events can play a role in brain recently developed a scalable, mobile control of impulsive responses), working dysfunction in many people, but the platform called BrainE, which is short memory, and processing of object- biological mechanisms behind them are for Brain Engagement. This platform based and emotion-based interference. still not completely understood. uses wireless Over 100 healthy young adults were (EEG) recordings to rapidly test how given tasks that assess each of these essential aspects of cognition (such as functions separately and tested using

WWW.SCIENTIA.GLOBAL BrainE for cognitive brain mapping. The as increases the risk of suicide, meaning participants who had also self-rated platform allowed the team to carefully loneliness is related to high morbidity their sense of wisdom and loneliness. investigate the neural processes and mortality. Interestingly, the team found that taking place during the presentation loneliness was associated with slower of stimuli in these various cognitive At the other end of the spectrum, cognitive processing when angry contexts. Given its comprehensive wisdom is associated with better health emotional faces were presented. and rapid measurement of brain and well-being. It can be described in Loneliness also enhanced attentiveness function underlying different cognitive a number of ways, but one definition to threatening stimuli. Conversely, abilities, its cost-effectiveness and high is using your experience, knowledge, wisdom was associated with faster scalability, Dr Mishra believes BrainE will insight and empathy to influence your processing speed when happy be a useful tool for creating frameworks thoughts and actions. Wisdom is a emotional stimuli were presented. Using for mental health investigations. She complex component of personality the EEG data, they could identify which plans to use BrainE for understanding – it requires pro-social behaviours, relevant brain areas were activated the mechanisms of mental disorders emotional regulation and self-reflection. during these tests. in different contexts and for finding Research has shown that loneliness therapeutic targets. and wisdom are not frequently found According to Dr Mishra, these results together, perhaps because aspects of using BrainE, ‘show that loneliness and Loneliness Versus Wisdom wisdom like compassion (including wisdom may opposingly drive neural towards oneself) are sometimes circuits based on emotion context’. Recently Dr Mishra leveraged BrainE reduced in lonely individuals. In to study how two health indicators – addition, wisdom may act as a sort of The Impact of Negative Childhood loneliness and wisdom –drive neural protective factor from loneliness. Experiences on Brain Development circuits in an emotional context. Loneliness manifests when an As these are two opposing yet Dr Mishra believes it is very important individual’s social needs are not met, potentially linked characteristics, to understand brain function based and it is known to be a psychosocial Dr Mishra and her team decided to on life experiences and environmental determinant of poor health. The feeling investigate their neural and cognitive context. Environmental factors like can harm mental health and may also processing in the context of an trauma from neglect or abuse during negatively impact physical health. Acute emotion bias task. Faces showing the childhood years have a big impact stress disrupts the immune system and positive, negative, threatening and on how the brain develops and this can accelerates the risk of dementia as well neutral emotions were shown to 147 have bearing on a child’s behaviour into

WWW.SCIENTIA.GLOBAL increase in weather-related disasters like wildfires. In 2018, the Camp Fire in California was the deadliest in the state to date. Living through such an experience was undoubtedly traumatic so Dr Mishra systematically studied how the wildfire affected the mental health of residents in the vicinity of the fire.

Six months after the disaster, Dr Mishra and her team sampled 725 people who had had varying degrees of exposure to it and measured their mental health. The incidences of PTSD, depression and anxiety disorder were assessed, and participants additionally reported their personal resilience and mindfulness.

They found that direct exposure to the fire significantly increased the risk of mental health disorders, especially PTSD adolescence and adulthood. However, the biological reasons and depression. Notably, high resilience and mindfulness for this are not entirely clear. So Dr Mishra and her colleagues lowered these risks whilst childhood trauma and decided to investigate the effect of childhood trauma on brain disturbance exacerbated them. This study emphasises how the connections as well as executive dysfunction in a large sample climate change emergency may, ‘impact the mental wellbeing of 392 adolescents. The term executive dysfunction covers of the global population, and we must find ways to foster a range of emotional, cognitive and behavioural difficulties. individual resiliency’. For instance, issues with problem-solving, planning and organisation among others can be indicative of executive Mindfulness as a Digital Therapeutic Approach dysfunction. The team studied which brain connections are influenced by childhood trauma and thereby, underlie As we’ve already seen, adverse experiences during childhood executive dysfunction. Importantly, they took these findings to can significantly impact brain development. Dr Mishra predict future high-risk alcohol consumption in youth. wondered whether a mindful meditation approach that is digitally delivered can serve as an innovative therapy. The In this study, the team leveraged data from a National team in this study designed a closed-loop technology, which Institutes of Health dataset of adolescents, who self-reported is software that, ‘is adaptive to the performance capabilities of on childhood trauma and executive dysfunction. These the individual and uses reinforcing feedback to drive effective adolescents were interviewed about their alcohol and ’. This design was applied to a meditation programme substance use at the beginning and then every year for four for adolescents who had experienced neglect in their childhood years. In addition, the adolescents were given a functional living in a low/middle-income setting. magnetic resonance imagining (fMRI) scan, which shows the regions of the brain that are activated (displayed as an image After completing the period of meditation via closed-loop of the brain rather than on a time-graph as in an EEG) just while engagement, the adolescents showed great improvement resting. in several domains. Their academic performance was better and attention abilities were enhanced whilst hyperactive Perhaps unsurprisingly, experiencing trauma in childhood had behaviour was reduced. These improvements were linked a strong link to executive dysfunction in the adolescent years. to a strengthened connection in an area of the brain called The fMRI scans revealed functional brain networks particularly the dorsal anterior cingulate cortex which develops critically from core regions that control cognition, for example, the during adolescence. This study showed how new, personalised dorsal anterior cingulate cortex and the anterior insula, that (individually adaptive) can be implemented to mediate the link between executive dysfunction and childhood strengthen brain function, cognition and behaviour. trauma. Dr Mishra’s team further leveraged machine learning to show that the functional brain networks impacted by trauma An Exciting Future can help to accurately predict high-risk drinking in follow- up years. Therefore, this research is useful for developing a The innovative and novel research that Dr Mishra has prognosis of alcohol use disorder in individuals who have completed is guiding the field of neuroscience, particularly suffered adverse childhoods. clinical and translational research in an exciting direction. By providing insight into the effects of environmental factors A Climate and Mental Health Emergency on mental health and exploring personalised, accessible and sustainable mental healthcare solutions, her work is sure to Another environmental factor that is becoming ever more be at the forefront of a new age of digital medicine to improve concerning is climate change. With climate change comes an human well-being.

WWW.SCIENTIA.GLOBAL Meet the researcher Dr Jyoti Mishra University of California, San Diego Altman Clinical & Translational Research Institute La Jolla, CA USA

Dr Jyoti Mishra completed her BSc in Biochemistry at Delhi FURTHER READING University and went on to study for an MSc in Life Sciences at the National Center for Biological Sciences in India. PP Balasubramani, A Ojeda, G Grennan, et al., Mapping She achieved her PhD in Biology with specialisation in cognitive brain functions at scale, NeuroImage, 2021, 231, Computational Neurobiology from the University of California, 117641. San Diego (UCSD) in the USA. She is also completing her G Grennan, P Priyadharsini Balasubramani, F Alim, et al., MBA from the UCSD Rady School of Management. Having Cognitive and Neural Correlates of Loneliness and Wisdom fulfilled both academic and industry postdoctoral positions during Emotional Bias, Cerebral Cortex, 2021, 1-12. and receiving multiple honours, Dr Misha is now an Assistant Professor in the Department of Psychiatry at UCSD. She J Mishra, R Sagar, S Parveen, et al., Closed-loop digital founded NEATLabs within this department and directs their meditation for neurocognitive and behavioral development in human research into advancing neurotechnology for cognitive adolescents with childhood neglect, Translational Psychiatry, brain mapping and digital therapeutics for mental healthcare. 2020, 10(1), 1–13.

S Silveira, M Kornbluh, MC Withers, et al., Chronic Mental CONTACT Health Sequelae of Climate Change Extremes: A Case Study of the Deadliest Californian Wildfire, International Journal of [email protected] E: Environmental Research and Public Health, 2021, 18(4), 1487. W: http://neatlabs.ucsd.edu/ @neatneuro S Silveira, R Shah, KB Nooner, et al., Impact of Childhood Trauma on Executive Function in Adolescence—Mediating FUNDING Functional Brain Networks and Prediction of High-Risk Drinking, Biological Psychiatry: and University of California San Diego School of Medicine , 2020, 5(5), 499–509. Sanford Institute for Empathy & Compassion Hope for Depression Research Foundation

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