Whole brain effects of deep brain stimulation

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In our latest study on deep brain stimulation we have found that deep brain stimulation (DBS) has large wide spread effects on the whole brain. It has long been thought that DBS relies on the specific structure of the stimulated tissue as well as the connectivity pattern from a brain area. This might indeed still be true and both necessary as well as sufficient for successful symptom alleviation. However this new study also shows a large spread of functional changes across the whole brain. It is conceivable that these changes contribute to any changes seen in non-motor symptoms.

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In this recent study we have looked at the effects of DBS on brain function and brain dynamics. We have used a truly unique opportunity to acquire MRI scans of patients with Parkinson’s disease who receive DBS treatment *. The results clearly show wide spread effects of DBS when turning stimulation ON compared to OFF. Furthermore, the brain dynamics when stimulation is turned ON approach the brain dynamics found in healthy controls. This is even found in areas not directly connected (structurally) to the brain area where the DBS electrodes are implanted, as can be seen in the figure below. The areas identified here are very similar to those areas found to show structural changes over time observed after long-term DBS in Parkinson’s disease.

Bifurcation for DBS-ON vs DBS-OFF

This study sheds new light on how DBS works and to what extend very local stimulation can affect whole brain dynamics through a sparsely connected underlying structural network. By adding this new evidence to the overall knowledge on DBS and how it works, we get again one step closer to created a complete and full picture. This of course will at some point provide us with enough information to improve current procedures (e.g. brain areas to target). It may also allow for the use of DBS in disorders that are as of yet difficult or even impossible to treat. Obviously we still need a lot more information, but combining the evidence we have with computational modelling would allow us to simulate and predict possible outcomes of treating disorders with DBS without the use of animals or people until the desired outcome is reached.


* It should be stated here that putting patients with DBS in an MRI scanner is only safe when following strict protocols to avoid any chance of adverse events. For this study all protocols and evidence from previously published studies have been implemented.


Source: Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson’s disease | Scientific Reports

One step closer to closed loop Deep Brain Stimulation

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Deep brain stimulation has been used systematically for nearly two decades now in a variety of disorders. One of the more prominent uses is for alleviation of tremor in Parkinson’s disease. Although considerable progress has been made and knowledge about brain stimulation is still growing, closed loop systems like those seen in artificial heart pacemakers since the early 1990s are still non-existent. Current deep brain stimulators deliver a constant stimulation, even at moments where this might not be necessary, e.g. in the momentary absence of an actual tremor. Using a closed loop system to detect when stimulation is needed and deliver stimulation accordingly could have great benefits. According to a recent study in Clinical Neurophysiology by Hirschmann and colleagues, this could significantly reduces battery usage if stimulation is activated less then 94% of the time. Read More

This would in turn mean that patients will have to come back less often to get batteries replaced, which involves minor surgery. In this study, conducted in Nijmegen in the Netherlands and Düsseldorf in Germany, the researchers used Hidden Markov Models to analyse and quantify the signals measured through the deep brain stimulation electrodes in the subthalamic nucleus. By employing these statistical models that are fully data driven, they were able to accurately measure when tremors occurred and when patients were temporarily tremor free.

There is of course a lot more information needed than rest versus tremor to successfully develop a closed loop deep brain stimulator. Other symptoms such as akinesia, bradykinesia or rigidity would still need to be alleviated as well. To complicate matters further, this would all need to be analysed within milliseconds while patients are also using different kinds of medication. This all still leaves out voluntary movement as well. So although there is clearly still much that needs to be investigated, this appears to be a great step forwards in the field of deep brain stimulation.

source: Parkinsonian rest tremor can be detected accurately based on neuronal oscillations recorded from the subthalamic nucleus

How Deep Brain Stimulation changes the human brain

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Structural plasticity in Parkinson's diseaseOur latest work on the effects of deep brain stimulation (DBS) on the structure of the brain has been combined in a book chapter published in “The Rewiring Brain” by Elsevier. In this book chapter we get to show you how exactly DBS works on the brain and which brain regions show specific changes after continued stimulation of the deeper parts of the brain. Most of this knowledge comes from patients with Parkinson’s disease where DBS is used as a last resort treatment when medication fails to alleviate the symptoms successfully.

As can be seen from the image, the changes we have observed after 6 months of continuous stimulation are located throughout the brain, but do not effect the entire brain equally. Some areas are more affected than others, whereas some brain areas show no changes as all. When the structure of the brain changes, it is of course also very likely to see changes in the brain function. One obvious behavioural change that we can observe is the reduction in symptoms related to Parkinson’s disease, including motor symptoms. Interestingly, patients receiving this type of treatment often show improvements and changes in other behavioural areas as well, such as their sense of smell.

The sense of smell is well known to be one of the most common symptoms on Parkinson’s disease occurring in up to 90% of patients. There have been studies in the past that show that these patients improve in certain areas of smell after receiving DBS treatment. Here we can also show that those brain areas involved in the sense of smell show structural changes after prolonged stimulation.

Other ways to show how DBS affects both brain structure and function is also described in our latest paper in Scientific Reports where we investigate the functional brain dynamics in patients with DBS. There we see a remarkable resemblance regarding the brain areas affected compared to the areas where we find long-term structural changes.

Source: Neural Plasticity in Human Brain Connectivity: The Effects of Deep Brain Stimulation – The Rewiring Brain – Chapter 25

Fingerprints of brain dynamics estimated from neuroimaging data and application to discrimination between individuals, tasks and/or conditions

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At the 26th Annual Computational Neuroscience Meeting this year in Antwerp (15 – 20 July 2017) I will be organising a workshop with my collaborator Matthieu Gilson from the Universitat Pompeu Fabra in Barcelona. During this workshop we will focus on brain dynamics and functional brain patterns or fingerprints and how we can apply such methods in individuals and tasks or conditions. This workshop will include talks by people such as Professor Karl Friston from UCL. Read More

Workshop abstract

The functioning of the brain relies on detailed interactions between specialised neuronal subsystems, implementing joint segregation and integration of information such as sensory stimuli, memory tokens and intentions. Nowadays, neuroimaging techniques (fMRI, EEG, MEG, etc.) provide indirect measurements of the neuronal activity at the whole-brain level. Recent efforts have focused on extracting fingerprints of the measured brain dynamics to discriminate between tasks, conditions (e.g., sleep vs. awake) or individuals. For example, given a dynamic network model, whole-brain effective connectivity describes the interaction scheme between regions for each condition, which can be quantitatively compared. The goal of this workshop is to review both data-analysis methods and model-based approaches that have attacked this problem.

Please see the programme for the line up of speakers.

An olfactory fingerprint in structural brain connectivity

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The olfactory system is much less studies compared to the visual and auditory systems. An added difficulty for those studies investigating how the olfactory system works or how it is affected in certain disorders comes from the fact that no accurate templates of the olfactory exist. Especially when using neuroimaging techniques, this could pose a major problem. There are some templates, but they are not always compatible with what we know from anatomical studies. For example some functional templates include secondary regions of the olfactory system in addition to the primary olfactory cortices. In this paper, the authors propose a new template for the primary olfactory cortex (POC).

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In this recent study multiple templates are compared and a single comprehensive template is created that can be used in both functional and structural neuroimaging studies. Using this new template, it should be possible to more accurately investigate the olfactory system in combination with neuroimaging. Furthermore, this study shows the exact connectivity patterns from the olfactory cortex and which part of the POC is connected to which higher order processing areas in the brain. In short, this study provides a new way to fully characterise the olfactory network and could be used as a diagnostic tool or biomarker in olfactory disorders.

Source: Brain fingerprints of olfaction: a novel structural method for assessing olfactory cortical networks in health and disease | Scientific Reports