Author: Oliver The Brainy Owl

– Buddhi Clinic’s Brain and Behaviour Dialogue with the legendary Prof. Michael R Trimble of University College, London, curated and presented by Neurokrish

The Buddhi Clinic virtual programme   on 26/12/2020 was  a ‘ Brain and Behaviuor  Dialogue‘. Prof Ennapadam S Krishnamoorthy, who was Raymond Way Fellow  in Behavioural Neurology and Neuropsychiatry, UCL, from 1997, under the mentorship of Prof. Michael R. Trimble, introduced his guru of many years. He gave a brief outline of Trimble’s illustrious career and observed that there could be no better person to elucidate the Brain and Behaviour interface . 

As Chair in Behavioural Neurology and Neuropsychiatry of the Raymond Way Research unit, Institute of Neurology, Queen Square, London, and Professor in the same disciplines, Trimble established a unique system of academic mentorship over three decades. This led to neuropsychiatry worldwide remaining associated with the Raymond Way group long after the trainees and fellows left Queen Square. As a sensitive clinician, committed researcher and erudite scholar, Trimble had chosen the less trodden path, to establish neuropsychiatry as a recognised global academic and clinical discipline.

Krishnamoorthy set the ball rolling with “What made you choose Neuropsychiatry?”  Trimble observed that the term ‘Neuropsychiatry’ was always a problem, with neurologists in Europe using it vaguely to indicate psychosomatic disorders; Freud unable to give it true meaning in his attempt, through a psychoanalytic viewpoint; the Behaviourists reluctant to give up their  simplistic ‘stimulus-response paradigm’! 

Trimble observed that it was the dawn of a new era when EEG evidence of the pathophysiology in a neurological disorder, with associated psychological problems, emerged in the late 1950s. Frederic Gibbs’ pioneering EEG studies in Boston, recorded the anatomical localisation of a form of seizure  to the  temporal lobe, which was replicable over a number of patients. This established the relationship between anterior temporal lobe abnormality and the psychopathology of epilepsy. Modern Neuropsychiatry took a definitive step forward in the 1960s and 1970s, with the discovery of the structure, function and circuitry of the limbic system of the brain. Trimble recalled that as the only Behavioural Neurology consultant in UK for a long spell, he participated in the ‘neuropsychiatric awakening’ of the 1970s, and enjoyed lecturing on limbic neuroanatomy. Neuroimaging resulted in several other revelations in the brain-behavior link. The Raymond Way group, were involved in early PET studies in the 1990s that showed the volume of the hippocampus to be smaller in schizophrenia patient. 

Trimble’s dictum is that every neurologist must aim at proficiency in  neuroanatomy. This should include brain dissection and not learning through anatomical waxwork models! One wonders if every step in Trimble’s higher education and training trajectory, toward specialisation in Behavioural Neurology, was planned by him well ahead, in order to achieve the thoroughness and authority in his field, which his professional career reflects. Trimble’s first degree was in Neuroanatomy with Sir Solly Zuckerman, followed by MPhil in Psychopharmacology before he trained at Radcliffe Infirmary for MRCP, at National Hospital, Queen Square in Neurology and at Maudsley in Psychiatry. As Johns Hopkins Fellow, he was exposed to American psychiatry for the first time. Though there was demand for his expertise in new drug development, in temporal lobe epilepsy, in particular, he opted for association with the legendary Prof Lennart Heimer, in his research lab. Trimble enjoyed being in his old familiar ground of animal studies, primatology  and  neuroanatomy, but this time round with years of clinical and scientific expertise behind it. In the four-author publication on  ‘Anatomy of Neuropsychiatry’ (dealing with the latest discoveries in limbic system-basal ganglia circuitry, structure, function and pathology), with Heimer as lead author, Trimble, provided the valuable  link between  basic science sections and clinical neuropsychiatry.

Why did Prof. Trimble go into the field of Neuraesthetics?

As emeritus professor, since 2004, Prof. Trimble had the ‘leisure’ to consolidate his kaleidoscopic professional experiences and find the link to integrate them with his natural inclination towards  creativity and the Arts. This resulted in three  book publications, which go to form the subject of this online Brain and Behaviour dialogue. The rich fare presented, moved seamlessly from ‘Psychoses of Epilepsy’, championing the right brain along with other neuroscientist thinkers, to the power of the human voice in music at a Wagner opera; why Gana the gorilla at the Muenster zoo, who grieved the loss of her son  did not cry ? or why humans, on occasion, find the need to move beyond the  mundane, towards ‘a transcendental state of consciousness’?

   The Soul in the Brain: The Cerebral Basis of Language, Art, and Belief 

                                  Johns Hopkins University Press  (2007) 

This was the first book discussed. In this provocative study, Prof. Trimble alludes to the interrelationship between brain function, language, art—especially music and poetry—and religion. Inspired by the writings and reflections of his patients, Trimble was drawn into the study of their individual artistic ability, in which he observed a clear pattern. He came to the conclusion that writing effective poetry is probably incompatible with certain disorders-schizophrenia being one, and seems to be highly restricted by epilepsy. Even in the literature, there are very few acknowledged poets with schizophrenia- as the content, metre and prosody cannot be sustained by them. “To be a musician of the canon with schizophrenia seems impossible, as a compositional score, of say Wagner or Brahms, have notes that go on and on and must follow a trend to cohere with the same narrative over a long period”. However, there were patients with manic depressive psychosis (bipolar disorder) who were capable of poetry and music. Another study by the Raymond Way group showed that some patients with temporal lobe epilepsy were ‘hyperreligious’, well above the expected  range of involvement in religion. Hypergraphia was another unique temporal lobe phenomenon, but the content of the voluminous pages of writing was poor and lacked cogency.

The  ‘Soul in the Brain’ brings together poetry, music (and going back to Greek culture, which offers a third element within Greek theatre) and dancing. This  ‘total work of art’, integrating music, poetry and dancing, has  ‘movement’. Trimble referred to the German term–‘Gesamkunstwerk’ for this integration of different art forms to create a single cohesive whole. This term finds acceptance in English in the field of aesthetics. “Movement in the arts affects our brain and ourselves in a different way, and that is where neuroaesthetics comes in” Trimble explained. His own keen interest in opera, drew him deeper into the realm of Neuroaesthetics and the role of the brain and mind. 

The story of creativity started with language.  Broca localized language to a small area in the left anterior frontal region, based on the study of his stroke patients. Hughlings Jackson, a contemporary of Broca, was skeptical about his findings and maintained that a higher order brain function like language could not be confined to a small circumscribed area.  Hughlings Jackson, with his visionary understanding of the working of the human brain and mind, well ahead of his times, could be called the founder of modern Neuropsychiatry, Trimble opined. 

Scientists were preoccupied with language syntax, and if this was in place and a lesion did not involve the left hemisphere, language was assumed to be normal. It took  deeper study of patients with lesion of right anterior frontal region by experts, to spot the subtler missing elements in language,  elements which boost its richness, namely, the emotional tone and prosody, (the latter so important to poetry). There was poverty of creative expression, of metaphors and other   semantic aspects of language. Language is accompanied by gesticulation. There was slow acceptance, that it required the coordination of both hemispheres to make language. 

Going back in time to ancient Greek culture, Trimble traced it to Athens and  to the Festival of Dionysus, celebrated to this day, with much  music , dance, revelry and abandon, in the spirit of freedom, reminiscent of the romantic era. Of the arts, linking music with religion became prominent during the Renaissance period and resulted even in moving small operas into churches. Opera marked the highpoint of Western musical culture in the 19^th and 20^th century. Trimble observed that the propensity to art occupies a spectrum, and varies between individuals and also periods in history, e.g., between the Baroque  and  Romantic periods of Western culture. Ancient Greek cultural music and art forms had a profound impact in shaping European culture through the ages.Interestingly, Iain McGilchrist conceives that it is “the brain that has shaped the world”, in his  book, ‘The Master and His Emissary’!McGilchrist, neuropsychiatrist, philosopher and thinker, it was, who put creativity and art forms in the field of neuroaesthetics. 

Trimble recalled how another undisputed champion of the right brain, John Cutting and he, had long discussions on this subject, while at the Maudsley as colleagues. Cutting was a neuropsychiatrist, with special interest in schizophrenia. His vehement disagreement with the right brain being assigned ‘minor hemisphere’ status, featured in his profuse writings. Trimble had also associated with Norman Geschwind, who had published his elaborate work on the laterality of brain function.

 Why Human Like to Cry :Tragedy, Evolution and the Brain 

 Oxford University Press (2012)

The second book discussed:

What makes humans *cry?

In 2007, Gana the gorilla in the Muenster zoo, held up her son who died suddenly, and indicated her distress and grief, but did not cry, even as the humans watching her shed tears of compassion. Crying is an attribute exclusive to humans, adding to the other evolutionary attributes of  homo sapiens.

 Tears can signal pain or distress from one person to the other. When the mother sees the baby’s tears, it signals hunger or perhaps some discomfort. She cuddles and comforts the baby and each time this repeats, the bonding becomes stronger. When one looks at the large human face, and then within a short span of time, tears roll down the cheek of that face, the latter state of intense feeling creates a surge of emotion and compassion  in the beholder. 

Tears can also emerge as a result of aesthetic experience. Beauty, the art forms, and relating to memories of the past can evoke strong emotions. Proust describes 

*Crying’  involves shedding of tears. It may be in the form of sobbing, weeping, etc

the archaeologist who bursts into tears on beholding an ancient Assyrian sculpture. It was a spontaneous mark of reverence for an artifact of the past. Trimble expressed concern that the Western world seems to be moving away from the past – be it from parents and family, a historical monument, or even the four walls of the house where one spent one’s childhood. This is a great pity, as these memories and emotions form the core of aesthetic values and in its absence, one may not be moved by a strain of music or a beautiful face – and  probably be the loser!

Crying may follow a deep religious experience or listening to music or while at an opera. “Music appears to be the art form most likely to make us cry”, says Trimble. A study by his team, interviewing participants of the study, revealed that 80% cried to music, and 60% to poetry. Reading a novel, with continuity of the narrative almost equaled music in its impact on the reader. Another study of lottery participants left the team puzzled over why the winner cried. It came about that the ‘tears of joy’ made their appearance when the winner shared the news and bonded with the family and dear ones. Trimble confessed that tears well up in his eyes when he is at a Wagner opera, where the power of the human voice in music can raise the emotional response to its heights. It was acceptable to cry at the opera or in church, especially for men !   

Greek tragedy explored many themes around human nature and it heavily influenced the theatre of the Renaissance.In the Renaissance period, in church, every member of the congregation was expected to cry, especially the men.  If they failed to concur, they could be severely reprimanded, as crying was  considered  part of  the religious experience, sacred and symbolic of grieving for the loss. He referred to the practice of lamentation,the passionate expression of grief or sorrow, from the Book of Lamentations of the Old Testament. He made a biblical reference to ‘Lacrima Christi’, which literally means ‘Tears of Christ’. William James, the modern psychologist and great thinker elaborated on a variety of religious experiences. He observed that the human mind is in search of a transcendental idea. A deep religious experience can provide this. William James on  consciousness : “Consciousness, does not appear to itself chopped up in bits”. There is a continuous flow of thought in our minds, one leading to the other, which he referred to as ‘stream of consciousness’.

Trimble observed that our emotional response to tragedy and crying for emotional reasons have evolved over several millions of years. Then, why are people ashamed of crying ?  

 One of the more recent major discoveries of highest significance to neuropsychiatry is the mirror neuron. It goes beyond the scope of functional neuroimaging in some areas, as the presence of mirror neurons in the human brain allows identification with the other. This could be through the other person’s facial expression. But tears are an even surer signal from one person to another of emotional feelings; it arouses  ‘with’= ‘com’- passion and feeling  ‘in’= ‘em’ -pathy.  Though the appearance of tears may be physical, put in the metaphysical context, it is a link from one person to the other, by what is termed empathy. ‘Theory of Mind’ is a complex human ability of social cognition, which is required to empathise and must have evolved towards fulfilling emotional reaction; chimpanzees do not have this highly evolved ability of  social cognition,  though they may imitate an action, like picking  up a banana, due to the presence of some mirror  neurons, but not beyond this.  

Though the human brain circuitry for emotional tears is widespread, it links the cerebral cortex, especially anteriorly, with those areas associated with the representation of emotion-the limbic system and to the autonomic nervous system for the release of emotional tears. This highly evolved circuitry is not present  in primates, again pointing to the hand of evolution.

 The Intentional Brain: Motion, Emotion  and the Development of Modern Neuropsychiatry  Johns Hopkins University Press  (2016 )                    

This was the third book discussed:

 ‘The Intentional brain’ puts together information it has accumulated over several hundred years-over 2000 years. Trimble’s purpose of the book may be conveyed briefly, by quoting from the preface to the book. “The book is not simply about Neuropsychiatry as a medical discipline, but it is in many ways much more a reflection on the way the brain and its functions have been viewed over the centuries, as well as the huge change in orientation, germinating within romanticism, which has given us an understanding of our dynamic, active, creative brain”. This was in stark contrast to the Baroque period, which was restrictive and had some strict formulations for literature, music, and other art forms. 

Modern research has focused on the brain as a predictive organ. Trimble’s view of the dynamism of the brain and how we receive the world, borders on the transcendental!  “The way we greet the world and the way the world greets us and the world is embodied within us and our need to control it”, he says and goes on to “ We go out in the world expecting something, greet the world with hope of fulfillment, moment by moment. If not fulfilled, there has to be some reconciliation.” If this does not happen, an alternative path is taken, as each situation demands, laying down a novel brain circuitry. The belief that the brain is a passive organ with a stimulus evoking a response, assumes that with repetition of this pattern, neural tracks are laid down, which subsequently guide the automatic response which has been preset.

Trimble spoke about the Baroque period, which was restrictive. The Age of Enlightenment brought further strictures in the belief that science offered the solution to everything. Almost as a reaction to the progressively tightening fetters, both political and social, imposed by earlier periods, there  arose an intellectual movement, and with it an explosion of art, music, literature, and the glorification of nature and the past in poetry by the romantics  of the 19^th century. We enjoy much of this freedom, culture and art forms even today, but  some nations show signs of repression, curbing freedom of speech and of the press and increasing inequity which could be possibly labelled the post-post modern age! McGilchrist puts the blame of all the unsavoury components of modernity squarely on people paying less heed to the right brain.

Iain McGilchrist, in his voluminous book, “The Master and His Emissary’,  describes the evolution of Western culture, as influenced by specialised hemispheric functioning. He designates the right brain, with its greater contributionto creativity and the arts, (and perhaps to humanity) as the Master, and the left brain as the emissary in the “divided brain”. He is wary of the Western world today becoming increasingly dominated by the left brain which he believes may be to our detriment. 

Prof Trimble concluded with “The Intentional Brain is how the brain works and we have got it wrong for 2000 years!”  His appeal to appreciate the art forms in order to live life fully continues into his  next book, from which he shared a sentence – “ A world without music is not human”.

Dr. Subbulakshmy Natarajan MBBS, DCN (Lond.), PhD, FRCP (Edin.)

Research Consultant, Neuroscience India Group (NSIG)

Adjunct Faculty Public Health Foundation of India

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Prof. Michael Trimble is no stranger to the Chennai audience as he has visited at our invitation on several occasions.  He came first  at the invitation of Prof. Krishnamoorthy Srinivas  as the TS Srinivasan orator for 1998. It is of interest to note that in the topic of his oration ‘Towards a Neuropsychiatric Theory of Literary Creativity’, the central neuroaesthetic theme of the books discussed here was already taking shape, to be consolidated in his retirement days. At several points of the dialogue  Prof. Trimble, in a chatty way,  would stop to address Prof. Ennapadam S Krishnamoorthy to revive the memories of the significant clinical and research work done together in the Raymond Way unit.

The programme saw good audience participation. During question time there was reference to Indian art forms and some thought-provoking questions, which Prof. Trimble answered at length.

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 Every decade of TS Srinivasan orations, marks yet another significant milestone in the global neuroscience arena.

Prof. Ralph L. Sacco

Ralph L. Sacco, MD, MS, is the Chairman of Neurology, Olemberg Family Chair in Neurological Disorders, Miller Professor of Neurology, Public Health Sciences, Human Genetics, and Neurosurgery, Executive Director of the Evelyn McKnight Brain Institute, Senior Associate Dean for Clinical and Translational Science, Director of the Clinical and Translational Science Institute at the Miller School of Medicine, University of Miami, and Chief of the Neurology Service at Jackson Memorial Hospital.  He was previously Professor of Neurology, Chief of Stroke and Critical Care Division, and Associate Chairman at Columbia University before taking his current position.

Prof. Sacco has been a member of the World Stroke Organization since 2008 and past chair of the WSO Research Committee, and is on the Board of Directors. He has published extensively with over 600 peer-reviewed articles and 250 invited articles in the areas of stroke prevention, disparities, treatment, epidemiology, risk factors, vascular cognitive impairment, and human genetics. He has been the recipient of numerous awards including the AAN Wartenberg Lecture.  He is the founding Principal Investigator of the NINDS-funded Northern Manhattan Study among several other NIH – funded research projects. He is the immediate past-President of the American Academy of Neurology and was the first neurologist to serve as the President of the American Heart Association, 2010-2011. Fifty years ago, the American Heart Association’s journal Stroke was conceived, and now it is the premier journal in the field. Ralph L. Sacco, will take the reins as Stroke’s editor-in-chief beginning with the July 2020 issue.

 Preventing Stroke and Maintaining Brain Health in 2020

Prof. Ralph L. Sacco, the 40^th TS Srinivasan orator observed that the impact of the Srinivasan lectures was felt not only in India but the world over. Looking at the impressive list of 39 orators before him, he elaborated on how nine among them had touched his life in varied capacities. To mention the role of two, Prof JP Mohr (the 2004 orator) was his mentor in Stroke, and he took over as the third Chair in Neurology at University of Miami from WG Bradley (the 1996 orator). He acknowledged the vision of the TS Srinivasan family, the significant contribution of the programme distinguished mentors and the amazing hospitality and  meticulous organisation that went into the success of the mammoth event that marked the neuroscientific calendar year after year.  

Prof. Sacco outlined the global burden of stroke and dementia, and the alarming projected figures for 1. Stroke, a major cause of mortality and the second highest cause of disability and for 2. cognitive  decline and dementia with the progressive increase in the greying population. The urgency to deal with ‘Brain Health’ globally and to adopt preventive strategies was the focus of Prof. Sacco’s oration. He dwelt on the interplay between vascular disease, stroke and dementia and on the convergence of the pathogenic mechanisms in vascular and neurodegenerative processes. He had devoted much effort and thought to this concept and as the first neurologist to be elected President of the American Heart Association (AHA) 2010-2011, his Presidential address was ‘Achieving Ideal Cardiovascular and Brain Health – Opportunity Amid Crisis’ bringing the two vital organs under a common lens to establish the link between factors leading to carotid artery stenosis due to atheromatous plaques, atrial fibrillation releasing embedded clots, and heart failure with brain health and cerebrovascular events. 

The multidimensional stroke disability burden (Global Burden of Disability 2016) risk factors for stroke are hypertension, high blood sugar and cholesterol levels, and kidney disease- 72% ; smoking, poor diet control and poor physical activity – 66.3 % and  air pollution 28.1 %, risk factors total – near 90%. Stroke and cognitive decline/dementia being life–course illnesses, preventive steps must be taken before midlife and not later, when adverse consequences result. A Presidential Advisory from ASA/American Stroke Association, 2017, is ‘AHA’s Life simple 7 ‘ (which the professor believes are not so simple and the average score falls short by 2-3  of the ideal ). The 7 metrics to define optimal brain health in adults are ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m²) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL).  The professor shared the large cohort study stretching over 27 years -the Northern Manhattan Study (NOMAS), where his team established that timely intervention in behaviours and control of other health factors could prevent stroke and slow cognitive decline when compared with those in the study who did not adhere to lifestyle modifications in diet, physical activity, etc. NOMAS studies moved on to include baseline values of cognitive performance with follow up records after 5 years, conducted subtle cognitive neuropsychiatric test based on executive function, semantic memory, episodic memory and processing speed, where the cognitive decline was less in those who took preventive measures early to alter the course. The study of novel determinants, namely inflammatory and infectious markers,  MRI  markers of subclinical brain ageing –small vessel disease, white matter hyperintensities, microbleeds, silent infarcts and brain atrophy, and predisposing candidate genes were other advanced aspects of the study, yielding promising research data, toward  speeding up early risk prediction and prevention.

The professor discussed the ethnic variations, and socio-economic factors influencing the course of stroke and cognitive decline. There was an urgent need for setting population health goals and policies towards preventive measures for non-communicable diseases, lifestyle changes, healthcare of the elderly, and government advocacy measures to improve these areas of health policy, more so for LMIC countries with mounting public health concerns. He stressed the need for effective communication to the public on preventive measures and on recognition of early symptom of stroke to hasten hospitalization within the stipulated golden  period. The scope of research in the branches of this field are phenomenal and must be exploited effectively with adequate funding. Moving closer to equitable global healthcare should be the goal and  national and international collaboration is the key, he observed 

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A Report by Dr. Subbulakshmi Natarajan, MBBS, DCN (Lond), FRCP (Edin), Clinical Neuroscientist & Science Writer.

December brings the promise of pleasant, cool days to Chennai, south India, along with the annual Indian classical music and dance festivals and church choral music, to mark a month-long atmosphere of peace, joy and festivity.  It was in this part of the year, in the serenity of the colonial era milieu of Madras Club, that an international cast of experts discussed the brain, mind and their rich interface, sharing the global trends in the field and their individual and team experiences at the exclusive closed door meeting (by invitation) of the International Neuropsychiatric Association. The theme of the INA Colloquium 2019 was “New Horizons in Neuropsychiatry’ 

Prof. Ennapadam S Krishnamoorthy, the INA President, extended a warm welcome. It was an honour to have the inaugural President of INA , Prof. Colin Shapiro (1998-2002) and INA’s third President , Prof. Perminder Sachdev (2004-2006)  as colloquium faculty. Other eminent, senior members of INA also comprised the colloquium faculty.

Prof. Krishnamoorthy called upon faculty members to light the ‘Lamp of Knowledge’ , to the background chant to Saraswathi, the Goddess of Learning. “The overall  theme ‘Brain and Behaviour’ belongs to all present,” he said and announced that those attending the colloquium could register free for a year to become members of INA, and receive ‘the INA pin’ In the hands of the experts and over several decades, the complexities of  mind, brain and behaviour captured separately by the specialities of  Neurology and Psychiatry, have been brought together in a holistic manner under the INA banner, much to the benefit of Neuroscience, the clinician and the patient. It was keenly felt that this knowledge deserved to be shared by a wider medical fraternity towards global excellence in brain and mind healthcare and research. 

The colloquium was sponsored by the ever-flowing generosity of the TS Srinivasan family. The handsome endowment towards this was in honour of the philanthropist industrialist, TS Srinivasan.

Inaugural Address

Prof ES Krishnamoorthy opened the scientific session with  ‘Innovation: An Integrated Care Model in Neuropsychiatry’  as  practiced in the Buddhi Clinic, Chennai,  founded by him in 2010. The Integrated Brain and Mind care at Buddhi Clinic , towards ‘Restoration, Rehabilitation and Rejuvenation ‘ has over the years  developed protocols and procedures which make them sustainable, replicable and measurable. More gratifying is the qualitative measure of patient response. Here, CAM enjoys a common platform with Modern Neuropsychiatry and Neurorehabilitation.

Presidential Session

Perminder Sachdev, Professor of Neuropsychiatry at UNSW, Co-Director of the Centre for Healthy Brain Ageing (CHeBA), UNSW, Australia, took us through the exciting present day ‘Biomarker Approach to the Diagnosis of Dementia’, and the dilemmas in this unrelenting quest for the Holy Grail. The heterogeneous presentation of person-specific contribution of neuropathologies to cognitive loss  (more so in  old age), makes the search for an AD biomarker elusive.  It is only with pooling of multiple data that we can hope to arrive at a biomarker complex to detect at the pre-AD phase. NIA AA has proposed an effective Research Framework for AD biomarker grouping AT(N)  (Jack C et al, 2018). He touched on the consensus study (VICCCS) on the vascular causes of dementia, for which he was an international collaborator along with two other speakers, Prof. Ingmar Skoog and Prof. Raj Kalaria.

Raj Kalaria , Professor of Neuropathology, Newcastle University, UK shared with us his twenty- year experience and  heading the Neurovascular Group at the Institute of Neuroscience, Newcastle,  in ‘the Cognitive Function after Stroke’ ( CogFAST) study. Being a strong proponent of the concept of cognitive decline due to vascular causes, he observed that the understanding of lifestyle diseases and the preventable nature of the risk factors led to a renewed interest in refinement and classification of vascular dementias (VaD). It resulted in ‘Vascular Impairment of Cognition Classification Consensus Study (VICCCS)’, with international collaborators, on sensitive and specific clinical and research criteria to diagnose the earliest phase of Vascular Cognitive Impairment (VCI). He went on to say that cerebral vessel disease may be an under-recognised risk factor for AD dementia-the vascular pathology in AD is arteriosclerosis and capillary degeneration. Changes in vessel wall causes chronic hypoperfusive state (oligaemia) and the white matter changes and may result in either stroke or degeneration (to AD) or in a mixed type which includes both. 

Epilepsy and Behaviour  – Learning through case studies

This session saw four interesting presentations by leading Indian experts.

The Many Ramifications of Post-ictal Psychosis

 Bindu Menon, Professor and Head of Dept. of Neurology, Apollo Specialty Hospital, Nellore, south India, was a case based presentation.  A 38 year lady, single, living with her parents, diagnosed as complex partial seizures with secondary generalization, based on clinical, EEG and imaging parameters. She was on optimum dose of levetiracetem, with a history of poor drug adherence and with recurrent episodes. She presented  in a confused, agitated state, with auditory and visual hallucinations and with persecutory delusions and aggressive behaviour. Her mother reported a cluster of seizures two days prior to this admission and reported that she had had two similar bizarre episodes earlier. Dr. Menon took us through the differential diagnosis of such a presentation and elegantly argued her opting for Post-ictal Psychosis (PIP), based on Logsdail and Toone criteria.  

Epilepsy and Neurodisability

Prof. Nirmal Surya, Consultant Neurophysician, Bombay Hospital Institute of Medical Sciences, shared his experience in neurorehabilitation of  young patients with neurodevelopmental disabilities (NDD)  with associated epilepsy at the Epilepsy Foundation Centre and his rural community-based outreach programmes. His multidisciplinary team offers management of the physical, cognitive, language, psychosocial and behavioural problems of these patients.  He presented video clips of 4 cases, with various levels and types of disability. The lack of awareness, the continuing stigma attached to epilepsy and all forms of disability, poor availability and accessibility of rehabilitation centres, and the out-of-pocket expenditure are major concerns in India

Paediatric Psychogenic Non-epileptic Seizures

Dr.  Praveen Kumar Jakati,  Consultant Child and  Adolescent Psychiatrist, Institute of Neuroscience, Kolkata, India-spoke on Paediatric Psychogenic Non-epileptic Seizures PNES, and showed video- EEGs of typical episodes in a few patients. Comprehensive psychiatric assessment points to a conversion disorder or occasionally a dissociative disorder. Gold standard for diagnosis is a prolonged video EEG. Early recognition of PNES and early intervention offers the best results

Epilepsy and Behaviour: the gentle overlap

Prof Manjari Tripati, Head of Dept. of Neurology, AIIMS, Delhi  outlined  the ‘Good, Bad and the Ugly’ in surgical intervention for  intractable epilepsy in her study of over 200 cases in the dedicated epilepsy neurosurgical dept. of AIIMS, Delhi.  The ‘good’ was the 10-fold improvement in the seizure episodes and significant improvement clinically and on the Child Behaviour Checklist, and Paediatric Quality of Life Measure The ‘ugly’ were two patients, both teenage boys, who underwent posterior temporo-parietal resections; one became seizure- free following surgery, the other continued to have about 4 seizures a month.  In both cases, post operative ASD was diagnosed, with severe behavioural  problems. There was  little improvement  after therapies over several years.

Why is ASD in such cases underreported in world literature? The posterior brain location of both these lesions could perhaps account for the post-op ASD, as the parieto-occipital region represents ‘autistic functionality’ and ‘theory of mind’.   

Stand ups:

‘If you have anything interesting to say, you must be able to convey it within eight minutes- these are what these stand ups are about, following which they will be open  for discussion’. The 4  Buddhi team members were game for the challenge !

Mr. Vivek Misra, Neuroscientist & Neuromodulation consultant of the Buddhi team spoke on Integrating Neuromodulation in a Multidisciplinary Care Paradigm. He contributes to the neuromodulation with brain  stimulation with repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS). He outlined  the beneficial effects of rTMS on the Parkinson’s disease patients at Buddhi Clinic and discussed future plans for brain stimulation in the lab.  rTMS not only improves the motor performance but also the cognitive and behavioural outcomes- 20 sessions bilateral motor area stimulated  following the standard protocol  showed benefit  not only on the UPDRS scale but also showed progressive improvement on MoCA and NPI assessment at baseline, mid treatment and end of brain stimulation, WHOQOL BREF showed positive scores on the social domain. The audience suggested more cases in the series under controlled conditions are required to launch the study on a research basis.

Dr. VG Srivatsa, Neuropsychiatrist presented on  intractable behavioural difficulties, anxiety, aggression, below average intelligence  in a 14 year old treated with a multidisciplinary  integrated approach including neurodevelopmental therapy, behavioural therapy , family focused therapy and  rTMS.  It was a diagnostic dilemma. The Buddhi clinic team came to a diagnosis of ASD with intellectual disability and severe anxiety state.  Rapidly escalating anxiety and panic in the wake of below average intelligence, with the added effect of early life trauma was  suggested by two experts reviewing the case who ruled out autism.

Indhu Rajagopal, Clinical Psychologist, Buddhi clinic 

Case presentation was of  a 17 year old girl Treatment-resistant  depression following a single seizure – found with LOC, vomited once, aggressive on admission, EEG normal initially, subsequent prolonged  EEG showed bilateral temporo-parietal and occipital epileptiform activity . CT brain normal, stressors at school and home with maladaptive responses. History of recurrent attacks of migraine.Patient was treated  as a case of seizure disorder with Levetiracetam and Clobazam. Subsequently, Levetiracetam was tapered and Lamotrigine introduced, with some improvement all round. Paroxetime CR was continued.

The final diagnosis was  AED –induced mood and anxiety disorder with accompanying insomnia.

Dr. Krishnaswamy Viswanathan, Senior Neurosurgeon – is Director of the Buddhi Clinic at Porur. He operates at Sri Ramachandra Medical College and Research Centre- He is an MRCS Edinburgh, and received special training in DBS at the Sai Baba Hospital at Whitefield, Bengaluru. 

He explained the procedure for DBS electrode implantation in the brain,   in some detail and the brain stimulation. The videograph, of his patient, an elderly male with dystonia, pre and post operative, and following three months of therapy, was impressive. 

Clinical Neuropsychiatry- The Child

Prof. Valsa Eapen, Chair, Infant, Child and Adolescent Psychiatry, University of New South Wales, Australia elaborated on ‘The Burden of Neurodevelopmental Disability- Call for Action’ Globally NDD affects 52.9 million children, accounting for 29.3 million years lived in disability; and 23% of 2-9year olds.  She outlined ‘A New- to- World Integrated Approach’ to Child Development covering the first 2000 days. Each stage of integrated service delivery needs to build on to the next a form of ‘cumulative buffering’ to counter cumulative risks. New South Wales Child Development Study is ‘A Longitudinal, Multiagency, Trans-generational Record Linkage Study’ in which 77, 062 children and their parents are under review- Carr et al 2019. The message of hope is that advances in Neuroscience, molecular biology, genomics and the Behavioural and Social Sciences could be leveraged to catalyse innovative policies and practices across sectors.

KP Vinayan  Prof. and Head, Dept. of  Paediatric Neurology, Amritha Advanced Centre for Epilepsy,  Amrita Institute of Medical Sciences, Kochi, Kerala demystified ‘Developmental Encephalopathies: A New Terminology or a Conceptual Progress?’ He broke down the elements in the most recent International League Against Epilepsy (ILAE) Commission Report definition of Epileptic Encephalopathies. There is an underlying brain pathology, either congenital or acquired. The epileptic activity itself contributes to severe cognitive and behavioural deficits which is well beyond what might be expected from the underlying brain pathology and these impairments can worsen over time. Treatment of the seizures or EEG abnormalities, a herculean task in this group, would be expected to improve the cognitive and behavioural deficits and also reduce the seizures. He discussed Lennox- Gastaut syndrome and Davert syndrome as examples.

Keynote Address:

Mustafa M. Hussain, Prof. of Neurology, Psychiatry and Internal Medicine , Director Neuromodulation and Therapeutics, UT Southwestern Medical Centre, Dallas, USA, recounted his over twenty years experience in neuromodulation procedures in ‘Dawn of a New Era in Depression’ The remarkable value of ECT in depression cannot be underestimated, he said. However, the more modern Magnetic Seizure Therapy enters the brain unimpeded, the seizure is focal, mild and only on the targeted regions, there is better control over the induced seizure, it does not affect cortical regions responsible for cognitive side effects, and the recovery after a session is quick.  The induced seizure modulates the neuronal activity within the brain to effect change. He confessed that Neuromodulation is  expensive therapy, and if Fluoxetine could do the job, he would go for it. 

Clinical Neuropsychiatry : The Adult 

Colin Shapiro, Professor, Dept of Psychiatry and Ophthalmology, University of Toronto, Canada Director, International Sleep Clinic spoke on ‘Sleep and the Expansion of Neuropsychiatry’ with conviction that “Every psychiatrist must be doing a sleep study on every patient they see!” There may be an underlying history of sexual abuse or PTSD. Sleep deprivation can have  its impact on many psychiatric conditions, depression in particular, and anxiety, and lead to excessive dependence on sleeping dose medication, and to drug and alcohol abuse. Sleep apnoea is more common than estimated. Non-communicable diseases may be exacerbated due to sleep deprivation.    Polysomnography   provides the critical information on sleep disorders. The factors to be studied in a sleep EEG record are

• 1. Sleep continuity disturbances
• 2. Slow wave sleep deficit
• 3. REM sleep disorder
• 4. Short sleep duration. 

Prof Niruj Agrawal, Consultant Neuropsychiatrist and Hon. Senior Lecturer, St George’s Hospital, London, dealt with the topic Dementia following Traumatic Brain Injury (TBI) – a reality. After TBI or repetitive injury as in contact sports, a gap of several decades, may be followed by aggressive behaviour, cognitive decline and  memory deficit. The inflammation following TBI, the white matter changes, brain atrophy and subsequent ‘immunotoxicity’, can trigger a progressive neurological degeneration, a condition called chronic traumatic encephalopathy. There is a progressive increase primarily of phosphorylated tau, and also of amyloid beta and alpha synuclein associated with a clinical presentation of  Alzheimer’s  disease, fronto-temporal dementia or Parkinson’s disease.

Neurotheology- A Thought Leadership Session

Dr Sudhir Shah, Neurologist, Ahmedabad,   has a regular consulting clinic, but his unique research interest borders on Neurotheology, dipping into the neural correlates of religious and spiritual belief. He elaborated on ‘Happiness, Meditation and the Brain’ – the merits of positive emotions and the role of gratitude, compassion, forgiveness, appreciation of others and acceptance of what cannot be changed, the ancient day wisdom for physical, mental and psychological well-being.  “We are our own enemies when negative emotions take over” he emphasized. The four paths of yoga of karma, gnana, bhakthi and the classical raja yoga help in control of the mind.  He presented functional neuroimaging scans of studies (in some of which he was part of the study group) where meditation activates the neural structures  involved in attention and control of the autonomic nervous system and emotions positive or negative show  response in the limbic areas. 

Biological Psychiatry:

Prathima Murthy Prof. and Head, Dept.of Psychiatry- Chief of De-addiction Services, NIMHANS, Benguluru, when faced with the question Neurostimulation for Addictive Disorders, Fad or Fact? started her talk by confessing “I am a clinician and a ‘mechanistic agnostic’, but if it helps my patient, I am willing to go along with it”. She went on to describe the various stimulation modalities used on her patients, and the human research studies conducted in her lab on  some newer modalities.  Addictive drugs cause activation of reward pathways. Biological, sociological and psychological factors influence the vulnerable. Transcranial direct current stimulation (tDCS) is safe , employs low intensity current, is non-invasive, and achieves neuronal sensitivity through weak intensity current stimulation. Modulation of prefrontal cortical excitability with tDCS may reduce alcohol craving and cue-reactivity. Periodic follow up is required as the effect of the neuromodulation wanes over time.

Dr. Adith Mohan, CheBA, Sydney, Australia elaborated on the ‘Psychosis of Suspected Autoimmune Origin- proposed model for co-ordinated clinical care at the Neuropsychiatric Institute, Sydney’. He opened his talk quoting  Susannah Cahalan  who describes her experience of the condition and recovery  in her book  ‘Brain on Fire’ (2018) where she agonises  on  “How many people currently are in psychiatric wards and nursing homes denied the relatively simple cure of steroids, plasma exchange, (or) more intense immunotherapy?”. What is important is to pick these patients early clinically, and treat, the red flags being- 1^st week of viral prodrome ;1-2 weeks of psychotic symptoms, delusions, hallucinations, mania, agitation, speech changes, disorganized thinking, catatonia , insomnia,  and often seizures; weeks to months of neurological complications, movement abnormalities, dysautonomia, hypoventilation and seizures, coma. This is the inflammatory phase and tapers, followed by months to years of prolonged deficits- executive dysfunction, impulsivity, disinhibition, and sleep abnormalities. The pathomechanism: Antibodies of IgG class targeting  NMDAR subunits on dendritic clusters. 40 % triggers are paraneoplastic (ovarian teratoma)-  As NMS is a major risk, one  must be  wary of use of antipsychotics.

Prof.Krishnamoorthy quoted the example of the 13 year female patient in his  Buddhi clinic  in 2013, with  bizarre,  acquired, acute behavioural psychosis and cognitive deficit. Under the guidance of Prof. Angela Vincent, the patient tested positive for NMDA receptor antibodies and recovered well with a course of Methylprednisolone, with a relapse after a few years. It is  important to create awareness among Psychiatrists  when to suspect autoimmune psychosis, a reversible condition.

Dr Mohan suggested the latest  article underlining the red flags –  ‘Autoimmune Psychosis – an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin’ – Thomas Pollak,  Lancet Psychiatry,  Nov 2019 . 

John P John, Prof of Psychiatry, NIMHANS , has a special research interest in  ‘Multimodal brain imaging in Schizophrenia and Dementia’. The Multi- modal Brain Imaging Analytic Lab (MBIAL) of NIMHANS has state of the art equipment, funded by Department of Biotechnology, Government of India. The research is conducted with the collaboration of the DST-sponsored clinical group at NIMHANS. One test for the schizophrenia participant in the research was the semantic word fluency test (word generation) against repeating  what is produced on the screen. In this task, activation is as important as is deactivation. In normal subject, anterior prefrontal activation is accompanied by posterior brain deactivation.  In the patient of schizophrenia, there is less deactivation of posterior brain. There is hyperconnectivity in Default mode network (DMN) in schizophrenia and  a positive relation between DMN connectivity and the psychotic symptoms. (Whitfield Gabrieli et al, PNAS, 2009). The reason why the  DMN is  of particular relevance in the study of dementia is because these areas are where AB amyloid is deposited even in early MCI. The DMN shows less connectivity.

Dementia:

Ingmar Skoog, Prof of Psychiatry, University of Gothenburg, Director, Centre for Health and Ageing and  Leader for the Neuroepidemiology Unit, Gothenburg,  Sweden stressed  that  the first biomarker appearance and preclinical AD can have a gap of 20 years,  the order  being CSF abeta , PET amyloid, CSF tau, PET tau, MRI atrophy, memory symptoms, MCI, Dementia – ( ‘Temporal ordering of the pathological processes of AD’. Jack et al, Lancet, 2013.)  Prof. Skoog has a large series  of CSF studies,  as the study participants give consent for lumbar puncture and even for a follow up study. Other concomitant  pathological markers in CSF he has  studied in 85 year olds: total tau a biomarker for neuronal damage; neurogranin a marker for synaptic degeneration, a post synaptic protein, CSF levels of which increase significantly in MCI and AD; phospho tau 18, a marker for tangle pathology, phosphorylation of tau appearing to be  specific to AD, showing a 2-3-fold increase in CSF; YKL -40, a marker for reactive astrocytosis, increase of which coccurs in the CSF in AD and FTD.

Mathew Varghese, Prof. of Psychiatry, Geriatric Dept., NIMHANS spoke on the ‘Psychosocial Interventions in Dementia’ with particular reference to the Indian scenario and as practiced in his department. He emphasised that in India it is mainly informal caregiving at home. Education of the caregivers with the ABC symptoms of dementia, namely problems with activities of daily living (ADL) and the behavioural  and cognitive symptoms, which require attention is provided in the clinic through family counseling. The need for progressive coping is underlined. The care recommended is a whole -day structured activity schedule, simple, tasks, keeping the general health, nutrition and exercise of the patient in mind, in a safe environment, preserving the dignity of the patient and avoiding confrontation. Prof. Varghese has been involved in modules for dementia healthcare from 2003. Agencies and Societies  providing service are ARDSI (the Indian chapter of ADI),  HelpAge India and Senior Citizens Forum. The Mental Healthcare Act- has outlined some positive steps towards a national level preparedness.  National Health Mission, the flagship programme of GoI, is in the process of preparing district clinic manuals for rehabilitation centres.

Amithaba  Ghosh, Consultant Neurologist from Kolkata, spoke about Frontotemporal dementia in the Indian setting presenting unique biological, cognitive, behavioural and psychosocial data from this setting. 

The impressive cast of Indian chairpersons for the colloquium included Professors :

• Lakshminarasimhan R, Chennai
• Mehndiratta MM, Delhi
• Bharat Srikala, Bangalore
• Bhattacharya Kalyan, Kolkata,  
• Padmavathi R, Chennai, 
• Lakshminarayanan R, Chennai, 
• Sudhakar TP, Tirupathi, 
• Thara R, Chennai,
• Vijayakumar Lakshmi, Chennai.  

Chennai being a hub of Indian Neuroscience, it does not stop with the advantage of inviting local experts, but for opting for among the best in the field.

In all the INA Colloquium was a meeting of minds, Western & Eastern, modern scientific and ancient integrative, discussing many aspects of the brain and mind interface.   Truly a feast for the brain, mind & soul, with the wonderful fusion cuisine of Madras Club satisfying also the palate.