Brain development is heavily influenced by geography, through a complex interplay of environment and genetics.
In Sub-Saharan Africa, home to 500 million children under the age of 18, brain development and mental health are impacted by both communicable and non-communicable diseases. Important contributors include brain infections (especially HIV and tuberculosis), brain injury (due to trauma and a range of other insults), non-communicable diseases (such as epilepsy, stroke, cancer and dementia), and other relevant risk and resilience factors, such as genetics, poverty, malnutrition and substance abuse.
Our interdisciplinary team investigates these strongly inter-dependent factors and works to create opportunities for globally-relevant scientific discovery, as well as tailored healthcare within an African context.
Through our four cross-cutting research themes we focus on all aspects of neurodevelopment, considering conditions across the lifespan, from before birth, through childhood and into adulthood.
The childhood years set the stage for human development. Children who have not met developmental expectations in their preschool years are at much higher risk of having academic and socio-emotional problems in their school years, and challenges in economic, interpersonal, social, and civic spheres in adult life.
At time-sensitive periods of childhood, including the foetal months, brain development can be promoted by a number of important resilience factors and disrupted by a wide range of adverse influences.
Understanding the mechanisms of how biological and environmental factors impact on the developing brain, as well as which assessments are valid in the African context, can support locally-relevant and effective preventative strategies, early diagnosis, and interventions to optimise development.
This focus area informs aspects of all three of the following themes and, given that by 2100, nearly half of the world’s children will be African, represents one of the most important scientific threads for the African continent and for our institute.
Home to more than 70% of the estimated 37 million people living with HIV worldwide, sub-Saharan Africa remains the epicentre of the global tuberculosis and HIV epidemic. We seek to understand the precise mechanisms underlying the impact of HIV infection and exposure on the human nervous system, and to investigate screening approaches and scalable interventions to reduce this impact across the lifespan.
TB meningitis is the most lethal form of this disease. Mortality rates remain exceptionally high and those who survive usually have significant neurological disability. With world-leading clinical experience with the disease in children and adults, as well access to sophisticated infrastructure, NI researchers have novel opportunities to study the disease in pathogenesis, pathophysiology, neuro-immunology, drug development and optimization, neuroimaging, and biomarker research. These investigations also provide a model for understanding the molecular mechanisms of brain injury, and the acute and subacute inflammatory responses of the brain to insult.
Emerging global infections, not least of which includes the current pandemic caused by the novel SARS-CoV-2 virus, frequently behave differently in environments where socio-economic disadvantage and other infectious diseases are highly prevalent. We work to address the implications of these new challenges on the neurological and mental health of African populations.
Africa has the highest rates of traumatic brain injury worldwide, and acquired brain injury is a leading cause of death and neurological disability, especially among children and young adults. Infectious diseases (meningitis and encephalitis), epilepsy, and stroke also contribute heavily to the overall burden.
The neurobiological mechanisms that underlie the impact of brain injury across these conditions have important common elements. Many of these conditions are preventable or at least treatable, and the outcomes for patients are strongly influenced by early diagnosis and appropriate clinical care.
To optimise the outcomes of prevention and intervention methods, we pursue point-of-care diagnostics, using novel imaging or biomarker methods to enable early diagnosis, and investigate how secondary mechanisms of injury cause progressive brain damage.
There is a wide spectrum of mental, neurological, and substance-use disorders that manifest in particular ways in the African context, and which can be grouped together as non-communicable diseases.
Our focus areas in this theme range from fundamental neuroscience to specific neurological and neuropsychiatric conditions as they manifest in the sub-Saharan African context. We are particularly cognizant of the unique scientific opportunities that lie in studying the African genome and, conversely, of the threat of widening health disparities should such a focus be neglected.
Additionally, non-infectious neuro-inflammatory disorders in Africa are different to elsewhere and may be triggered by local infections such as tuberculosis. There is a critical need to understand these relationships in terms of patient management, and to differentiate between those with a short-lived infectious-immune trigger, and those at risk of requiring long-term immunosuppression.
We have access to exceptional clinical resources, a number of state-of-the-art neuroscientific methodologies locally, including MRI and PET-CT, and an expanding capacity for molecular diagnoses for a range of disorders. Exciting opportunities exist to discover novel therapies and to pursue these in translational trials. This is particularly relevant in both inherited neuromuscular disorders and epilepsy syndromes across the lifespan.
Our scientific strategy emerged from the successes of the following well-established programmes:
Brain-Behaviour Unit (BBU)
Led by A-rated scientist Professor Dan Stein, the Brain-Behaviour Unit (BBU) is a world-leading multi-disciplinary, UCT-accredited collaborative hub of psychiatric neuroscience research. The BBU focuses on work particularly relevant to the South African and African context, and comprises three interlinked Groups:
The BBU uses a range of methods, including neurogenetics, neuroimaging, and animal models, with the aim of ultimately advancing diagnostic tools and treatments for people with mental disorders. Each of the BBU Groups houses a number of ongoing collaborative projects, all of which are focused on the common theme of psychiatric neuroscience. Specific aims of the BBU are: To bring together expertise in psychiatric neurogenetics, psychiatric neuroimaging and translational neuroscience To apply these psychiatric neuroscience research approaches to areas of particular relevance to the developing world and South Africa To encourage Masters, Doctoral and post-Doctoral students with an interest in brain and behaviour studies. The BBU collaborates with a broad range of Universities locally, in Africa, and across the world and has an exceptional record of attracting funding locally and internationally.
Upon his return to South Africa in 2012 following a Rhodes Scholarship-funded DPhil and a mini-postdoc at the EPFL, Dr Joseph Raimondo started building on a long history of world-class neurophysiology at UCT. His group addresses the beguiling simple question: why do brains seize? Their research attempts to answer this question by examining the cellular and circuit level interactions between brain cells, which result in the development of epileptic seizures, with a focus on how changes to inhibitory synaptic transmission and neuroinflammatory responses relate to the emergence and termination of epileptic seizures. With access to a wide range of state-of-the-art techniques, including patch-clamp electrophysiology and local field potential recordings, in vitro optogenetics, fluorescence microscopy including Ca2+ imaging, in vivo EEG wireless telemetry, organotypic hippocampal slice cultures, maintaining a colony of Taenia crassiceps larvae, and computational and theoretical modelling, Dr Raimondo’s research projects fall into 2 broad areas:
Joseph currently holds a FLAIR Fellowship from the Royal Society and also receives funding from the Wellcome Trust, NIH and NRF.
Dr Dorit Hockman, recently appointed a Lecturer in the Division of Cell Biology, is developing an exciting research program in Developmental Neurobiology and gene expression in the nervous system. Dr Hockman received her undergraduate and MSc degrees from UCT, her MSc research investigating the molecular mechanisms of bat limb development. She did her PhD at the University of Cambridge as part of the Wellcome Trust 4 Year PhD Programme in Developmental Biology, where she explored the evolution and development of vertebrate hypoxia-sensitive cells. In 2013, Dorit joined Trinity College (University of Oxford) as a Junior Research Fellow and began work on her current research into the evolution of the neural crest gene regulatory network. From 2016, she worked as a Leverhulme Trust funded post-doctoral researcher in the Sauka-Spengler lab at the Weatherall Institute of Molecular Medicine. During this period, Dorit also held the Sydney Brenner Post-Doctoral Fellowship, which allowed her to establish a new collaboration between the University of Cape Town, the University of Oxford and the California Institute of Technology. Dorit now runs her own lab in the Department of Human Biology at UCT where she is continuing her research into the evolution of the neural crest (funded by a National Research Foundation Competitive Support for Unrated researchers Grant). Dorit has also embarked on a new research programme (funded by the Global Challenges Research Fund FLAIR fellowship) investigating the gene regulatory dynamic of human brain maturation, which involves close collaboration with other Neuroscience Institute members, including Dr Joseph Raimondo and Prof. Anthony Figaji.
HIV Mental Health Research Group
The HIV Mental Health Research Unit (HIV MHU) is located in the Division of Neuropsychiatry, Department of Psychiatry and Mental Health and is led by Prof John Joska and Prof Jackie Hoare. The Unit's platform of clinical service, teaching and research, extending to numerous hospitals and clinics in greater Cape Town, was established in response to the growing recognition of the burden of mental disorders in people living with HIV – including depressive, anxiety, substance abuse and neurocognitive disorders. The group has a long history of pioneering work in the region, with a teaching and research programme supported by several large grant awards, with well-established international recognition. The HIV MHU is organised into the Adult Group (Joska) and Adolescent Group (Hoare). Each Group is active in researching the behavioural and neurological consequences of HIV, and holds/has held several NIH and other international grants. The Unit has extensive local and international collaborations in neuro-imaging, neuro-psychology, and biomarker science. Current projects include investigations into psychotherapies for PLWH and care engagement, neurologic sequelae of dolutegravir (adults). Adolescent studies include projects focused on mental health, neurocognitive disorders, neuroimaging, epigenetics and developing adherence and sexual and reproductive interventions in adolescents living with HIV.
Medical Research Council Unit on Risk and Resilience in Mental Disorders
The Medical Research Council Unit (MRC) on Risk and Resilience in Mental Disorders is a cross-university unit at the Department of Psychiatry at Stellenbosch University (SU) and the Department of Psychiatry and Mental Health at the University of Cape Town (UCT). This unit builds on the legacy of the MRC Unit on Anxiety and Stress Disorders that was initiated at SU in 1997. The MRC Unit on Risk and Resilience in Mental Disorders came into effect 1st April 2017, headed by Professors Dan Stein (UCT) and Christine Lochner (Stellenbosch University). Disorders of the psyche are fast becoming one of the greatest contributors to the burden of health disorders in both the developing and developed worlds. The current unit goes beyond anxiety and stress, to embrace a number of additional conditions, that are linked to, amongst others, compulsivity and impulsivity. With a focus on cohorts that allow examination of risk and resilience, the research covers a wide spectrum including basic science (laboratory-based work) and clinical trials, using animal models, to genetics and brain imaging studies, as well as a variety of appropriate aspects of community psychology and culture, capitalising on expertise from both universities. In practical implementation of these findings the unit support through the Mental Health Information Centre
Neurology Research Group
Led by Professor Jeannine Heckmann, this group pursues research in a wide range of neurological conditions of relevance to Africa. Research into myasthenia gravis includes the optimal use of immune therapies, determining prognostic clinical and plasma biomarkers and the genomics underlying complex subphenotypes. In Amyotrophic Lateral Sclerosis (ALS) the group performs cognitive phenotyping and genomic and biomarker development studies. Other research areas include inflammatory conditions related to HIV-infection such as stroke mechanisms in younger patients (HIV-1 proteins and varicella zoster virus), tuberculous and syphilitic meningitis and non-infectious neuromyelitis optica. Areas of growing interest include the medical and surgical management epilepsy and a program to bring definitive molecular diagnoses to Africans with inherited Neuromuscular Diseases.
Professor Mark Solms is best known for his discovery of the brain mechanisms of dreaming and for his integration of psychoanalytic theories and methods with those of modern neuroscience. He trained at the University of the Witwatersrand and following a highly successful career in London he was appointed to the Chair of Neuropsychology at UCT. He established the profession of Neuropsychology with the HPCSA and the South African Psychoanalytical Association with the IPA.
Prof Solms is a NRF ‘A1’ rated researcher, has received numerous awards in recognition of his work, and has published more than 350 articles and book chapters, and 8 books. He is the authorised editor and translator of the forthcoming Revised Standard Edition of the Complete Psychological Works of Sigmund Freud (24 vols), and the Complete Neuroscientific Works of Sigmund Freud (4 vols). He is currently working closely with Karl Friston (UCL) and a teacher to UCT physicists and computer scientists on the ‘hard problem’ of consciousness.
Other major research topics in Neuropsychology at UCT are various aspects of sleep and dreaming, opioid and dopaminergic mechanisms in depression, testosterone mechanisms in dominance behaviour, cardiovascular mechanisms of cerebral lateralisation, Urbach-Wiethe disease, autism spectrum disorders, theory of mind in anosognosia, and the rehabilitation of traumatic brain injury.
The pain team is an interdisciplinary group of 20 clinician researchers focusing on acute and chronic pain. Our work ranges from basic laboratory work with healthy humans to increase our understanding of the mechanisms which contribute to the development of chronic pain to clinical trials of the effectiveness of various treatments for acute and chronic pain.
The laboratory-based team is led by Dr Tory Madden who is specifically exploring the mechanisms by which psychosocial distress upregulates spinal cord mechanisms of nociception increasing vulnerability to chronic pain. The clinical research team is led by A/Prof Romy Parker with discreet research groups focusing on: acute pain management (Dr Alma de Vaal); mechanisms, prevalence and treatment of phantom limb pain (Katleho Limakatso); epidemiology of chronic pain in different South African populations; paediatric pain (Dr Anisa Bhettay); chronic pain management (Dr Janieke van Nugteren).
The team has successfully obtained funding from the MRC, NRF, an NIH K-award, and the International Association for the Study of Pain. The team is also involved in undergraduate (MBChB; BSc Physiotherapy) and postgraduate (2020 – 4 PhD candidates; 6 MMed candidates; 3 MSc candidates; 16 PG Diploma in Interdisciplinary Pain Management candidates) education. In 2019 the team published 14 papers. In 2020 we have had 8 papers published thus far.
Paediatric Neuroscience - Neurodevelopment | Paediatric Neurology
The sub-specialty Divisions of Paediatric Neurology (led by Prof Jo Wilmshurst) and Developmental Paediatrics (led by Prof Kirsty Donald) operate as discreet training units and are different sub-specialties, however the support and combined expertise of the consultant staff across both sub-specialties allows a depth of inter-disciplinary input which has resulted in a highly productive research team and research mentorship programme. Research has sought to address fundamental questions by longitudinally mapping brain and cognitive growth across the early years of life in association with infant nutrition, parent-child interaction, substance exposure, infections and environmental stress.
Performed in low resource settings, where there is paucity of information and where children are at highest risk of poor developmental outcomes, results from this research help quantify relative impact of modifiable factors on infant brain growth/cognition, clarifying time-periods where impact is greatest and potential windows for interventions for amelioration of childhood cognitive stunting. Recent research, using multiple MRI brain imaging methods, has facilitated a deeper understanding of the timing and potential mechanisms underlying neurological and neurocognitive complications associated with multiple biological and social risk factors, including HIV and substance exposure in infant brains. Evolving research areas include a number of multi-disciplinary and cross-disciplinary collaborative projects in neuroimaging and genomics. In the areas of NCDs in paediatric neurology the group has active interest areas across epilepsy, with ongoing epidemiological studies, neurobehavioural and comorbidity study, epilepsy genetics, vitamin D levels and epilepsy, management of status epilepticus in resource limited settings, the use of home videos, epilepsy surgery in resource limited settings, delineation of specific seizure syndromes, such as Dravet syndrome, epileptic spasms and Lennox Gastaut Syndrome.
Neuromuscular interests include longitudinal study of patients with Duchenne muscular dystrophy (RCWMCH is an internationally accredited care centre), collaborative projects with international centres for centronuclear myopathy patients, nemaline myopathy, Charcot Marie Tooth disease, spinal muscular atrophy, role of home ventilation, and acute flaccid paralysis (GBS, post enteroviruses). An additional group of study generated by the patients managed in the dedicated neurocutaneous clinics (neurofibromatosis and tuberous sclerosis complex) have resulted in phenotypic, genetic and neuropsychology studies. The combined outputs of this group include active supervision of 12 PhDs, 10 Masters and 26 publications in peer reviewed journals.
SARChI Brain Imaging
Professor Ernesta Meintjes is Head of the highly productive Magnetic Resonance Imaging Group in the Division of Biomedical Engineering and holds the SARChI Chair in Brain Imaging, which was established through the efforts of Prof Dan Stein and the Brain-Behaviour Initiative. Their research in Magnetic Resonance Imaging (MRI) focuses on applications of MRI to neuroscience, cardiac MRI, MRI technology development and MRI physics.
This work is conducted at the Cape Universities Body Imaging Centre (CUBIC), situated adjacent to the Neuroscience Centre, a joint initiative between Siemens, Stellenbosch University, UCT and the MRC. At any time, there are roughly 30 active research projects being conducted at CUBIC, most of which focus on addressing diseases or conditions that present major public health problems to South Africa, including HIV, Fetal Alcohol Syndrome, substance abuse, trauma, and mental disorders.
SARChI Clinical Neuroscience
Professor Anthony Figaji is Head of Paediatric Neurosurgery Unit at RCWMCH and the first and only surgeon in South Africa to be appointed to a Research Chair. The SARChI Chair in Clinical Neuroscience Research was initially established through the efforts of Professor Bongani Mayosi as Head of the Department of Medicine. The first incumbent was Prof Marc Combrinck who subsequently took up the Chair of Geriatric Medicine, and following Prof Figaji’s appointment in 2015, the Chair has been reviewed and upgraded to Tier 1.
His approach is to combine clinical expertise and laboratory research to advance cutting edge clinical care, with a focus on bedside to bench to bedside translation. His major areas of interest include mechanisms of brain injury in trauma, meningitis and stroke, increasing capacity in Africa for molecular biology study of brain tumours, understanding brain metabolism, brain perfusion, neuroinflammation neurophysiology and the effect of treatment interventions on the brain. More recently, his group has pioneered the use of genomics, transcriptomics and proteomics to the study of various brain disorders in Africa. An exceptional feature of this group’s work is the close relationship between clinical and laboratory investigation.