BY TZIPI HOROWITZ-KRAUS
Read Part 1 of this interview here.
Tzipi Horowitz-Kraus (THK): What do you consider to be the greatest scientific discovery that was made possible by neuroimaging?
Karl Friston (KF): That's a difficult question. I think we all have to acknowledge that there is no field in systems neuroscience that hasn't been profoundly touched by neuroimaging. However, I think the impact and import of neuroimaging is not about discovery, it is seismic in a slower and subtler way; basically, neuroimaging makes a lot of sense of stuff that we already knew. In other words, I would not point to what has been discovered as the validation of brain mapping but point to how it makes sense of the vast amount of knowledge that has been accrued through the centuries of anatomy, physiology and psychology. We knew a lot of things in the past but now we know how to put them together. Neuroimaging can contextualize mesoscopic – and indeed synaptic or molecular – findings and say why that is important and how it relates to this, and how those findings could drive the next wave of imaging neuroscience.
THK: What do you think are the most pressing issues in neuroimaging for your area of interest?
KF: More detailed and mechanistic modeling of distributed neuronal responses. For instance, getting the right kind of connectivity and determining how to best integrate structural and functional connectivity. Other issues include connecting behavior to physiology and connecting functional connectivity to the underlying synaptic processing, and connecting synaptic processing to microcircuits – and microcircuits to whole brain connectomes.
When people ask me “What is the most important issue for you?” I respond "the issues that I work on"; namely, biophysical modeling (at least in my day job). In short, getting better and better modeling tools that enable people to ask evidence-based questions about the mechanisms that underlie the functional integration they are interested in.
THK: What do you think is the future of neuroimaging for basic research, for translation and maybe for applications as well?
KF: There are many avenues for neuroimaging in the future and I guess it depends where you place yourself in the spectrum of basic to clinical neuroscience. I think neuroimaging is not a field, it's a tool: it provides data or evidence for ideas and hypotheses. In this sense, the integration of neuroimaging with other modalities of enquiry probably holds the greatest promise. For example, one can see this in the use of whole brain imaging to contextualize invasive electrophysiology – which takes us into the realm of basic neuroscience and, if we put pharmacology and genetics on top of that, molecular neuroscience. A nice example of this is the molecular basis of neuromodulation and its effect on effective connectivity at the synaptic and molecular level. To get to this future, we need mechanistic, biophysically grounded, models in place – that can generate and make predictions about the molecular biology of synaptic plasticity; for example, models based on the short-term changes in synaptic efficacy that also explain a BOLD response in the fusiform gyrus. When we get that far, I think the future will no longer be brain mapping – it will be brain metrology.
I started in schizophrenia research. The future for people like me is ultimately translational in nature. Clearly, it will be nice to predict outcome trajectories of neuropsychiatric syndromes based on a psychopathology and pathophysiology. I suspect that this ambition has led to the emergence of computational psychiatry in recent years. Interestingly, most people working in computational psychiatry come from neuroimaging. There is a clear reason why that might be the case: if you're a doctor and you're worried about your patients, a non-invasive neuroscience is very appealing. Neuroimaging is par excellence, the non-invasive tool that can harness computational and basic science advances; hopefully, in the service of refining our understanding and treatment of neuropsychiatric conditions.
THK: Fifty years from now where do you think the neuroscience field will be?
KF: I think the interesting challenges I see around at the moment are in artificial intelligence. I think there are going to be big advances in artificial intelligence – and they will inform us at many different levels in neuroscience, clinical management and possibly well-being. From a personal perspective, this is largely the focus of my Sunday job.
I love the idea of having sentient curious machines living in your computer and working with you. One can imagine interactions with e-creatures that live in an electronic world and that have a purpose beyond minimizing some cost function. They have a purpose that is epistemic – and they want to learn what they can do and learn about you – like a proactive personalized Wikipedia. They will know that you are information hungry and might create novel situations for you that you have to explore.
THK: So it will be an extension of yourself without limits. ..
KF: I was thinking more of an extension of your parents. :)
Karl Friston is a theoretical neuroscientist and authority on brain imaging. He invented statistical parametric mapping (SPM), voxel-based morphometry (VBM) and dynamic causal modelling (DCM). These contributions were motivated by schizophrenia research and theoretical studies of value-learning formulated as the dysconnection hypothesis of schizophrenia. Mathematical contributions include variational Laplacian procedures and generalized filtering for hierarchical Bayesian model inversion. Friston currently works on models of functional integration in the human brain and the principles that underlie neuronal interactions. His main contribution to theoretical neurobiology is a free-energy principle for action and perception (active inference). Friston received the first Young Investigators Award in Human Brain Mapping (1996) and was elected a Fellow of the Academy of Medical Sciences (1999). In 2000 he was President of the international Organization of Human Brain Mapping. In 2003 he was awarded the Minerva Golden Brain Award and was elected a Fellow of the Royal Society in 2006. In 2008 he received a Medal, College de France and an Honorary Doctorate from the University of York in 2011. He became of Fellow of the Royal Society of Biology in 2012, received the Weldon Memorial prize and Medal in 2013 for contributions to mathematical biology and was elected as a member of EMBO (excellence in the life sciences) in 2014 and the Academia Europaea in (2015). He was the 2016 recipient of the Charles Branch Award for unparalleled breakthroughs in Brain Research and the Glass Brain Award, a lifetime achievement award by OHBM (the Organization for Human Brain Mapping) in the field of human brain mapping. He holds Honorary Doctorates from the University of Zurich and Radboud University.
Special thanks to Jeanette Mumford for her assistance in transcribing and editing this interview.