May 10th, 2016
It’s a great time to be a neuroimaging researcher, especially in Europe and the United States where a lot of money is currently being invested by the government; to better understand this mass of tissue between our ears. Full disclaimer – I am a functional neuroimaging researcher. Claiming that this field of interdisciplinary neuroscience research is at perhaps the most important crossroad in time in terms of impact research, is not a hyperbole.
This past decade has seen an enormous increase in the number of papers published using functional Magnetic Resonance Imaging (fMRI) to image the brain and its successful incorporation with simultaneous Positron Emission Tomography (PET) imaging. Optical imaging techniques like conventional 2-D intrinsic optical imaging or advanced microscopic methods like 2-photon microscopy or optical coherence tomography are beginning to take center-stage for viewing the brain anatomy and function with unprecedented spatial and temporal resolutions, respectively. There are a few labs that have also used newer techniques like photoacoustic tomography, coupling optogenetic methods, and developing concoctions that clear the brain for imaging ex vivo.
Over the last decade, the above mentioned imaging modalities are being widely used for investigating the origins of neurovascular coupling, which can be broadly defined as the change in cerebral blood flow following neuronal activity due to an external stimulus. However, this is not a novel question that researchers are attempting to answer. The quest to solve this problem has been going on for over a century. In the Journal of Physiology in 1890, Roy and Sherrington concluded that the brain has an intrinsic mechanism to alter flow locally in response to local variations in activity. And, lost in a library in Turin, Italy were the original manuscripts of Angelo Mosso – a 19th century Italian physiologist. If William James’ accounts of 1890 are true, Mosso’s work is the earliest record of measuring changes in cerebral blood flow following any activity.
In a new publication in Brain, Sandrone et al. have brought to light the earliest known works in understanding cerebral blood circulation. In this column, the authors have brilliantly outlined the design and construction of the ‘human circulation balance’ and described the experiments carried out by Mosso to prove his hypothesis on blood flow changes in the brain. Mosso’s first attempt was a plethysmograph but this experiment was short-lived as this could only measure changes in blood flow in patients with skull defects and couldn’t be successfully translated to healthy subjects. The balance was a wooden table (with some padding for comfort) lying on a fulcrum. The subjects were told to lie down and be at rest so as to ensure the blood was distributed equally within the body tissues, before the barycenter and central pivot of the fulcrum overlapped. Mosso had thought through this experiment to such a fine detail that respiration, respiration induced fluctuations, head and other movements, and changes in volume in other peripheries were all either recorded or corrected for. Remarkably, his experiment paradigm is a model we use even today. He was shrewd enough to take a baseline reading (resting state, if you may) and proceeded to use a series of stimuli with increasing cognitive processing (in a block or event-related design as used in fMRI). He found that the balance tilted faster towards the head as the task increased in complexity. The much finer details of this set-up is explained in more detail in this manuscript.
The beauty and simplicity of Mosso’s method does not end with his work. A pair of researchers in the United Kingdom, in response to Sandrone et al., detailed their work on reproducing Mosso’s balance, albeit with some modern adjustments. They not only recreated the balance, but also made all efforts to control for any or all physiological artifacts that can affect their response, similar to what Mosso did. They were successful in providing evidence of local changes in blood volume in response to neuronal activity in the brain.
In a world where there is growing number of scientific research maleficence and its associated publication retractions (written about recently in this magazine), it is very hard to comprehend that a lost manuscript, initially written in Italian, can be found, successfully translated, and the work within reproduced. As a researcher in this field, it is both amazing to know that functional neuroimaging methods had such modest beginnings and scientifically inspiring to see the novelty of imaging modalities today. The future is indeed looking bright for this interdisciplinary field of neuroscience research.
Photo: Flickr, Felix Salazar
Field, D., & Inman, L. (2014). Weighing brain activity with the balance: a contemporary replication of Angelo Mosso’s historical experiment Brain, 137 (2), 634-639 DOI: 10.1093/brain/awt352
Sandrone, S., Bacigaluppi, M., Galloni, M., Cappa, S., Moro, A., Catani, M., Filippi, M., Monti, M., Perani, D., & Martino, G. (2013). Weighing brain activity with the balance: Angelo Mosso’s original manuscripts come to light Brain, 137 (2), 621-633 DOI: 10.1093/brain/awt091