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18 May 2022

How CANTAB helps us to explore the cognitive electrophysiology of the deep brain

We caught up with Martin Gillies from the University of Oxford, who told us how CANTAB™ tasks help his team to probe the cognitive electrophysiology of the deep brain, particularly focusing on the cognitive role of the dorsal Anterior Cingulate Cortex (dACC) in decision-making.

Hello! My name is Martin Gillies, Senior Research Fellow and Lecturer in Oxford Functional Neurosurgery Group, University of Oxford, senior author of ‘Spatial and Temporal Distribution of Information Processing in the Human Dorsal Anterior Cingulate Cortex’ (Keogh et al., 2022).  

Can you tell us more about your research?

We perform functional neurosurgery (deep brain stimulation or DBS) as part of our practice.  This involves implanting specially designed electrodes into specific parts of the brain, connected to an internal cardiac pacemaker-like device for the brain (an implanted pulse generator).  This delivers gentle electrical stimulation to neural targets to treat patient symptoms.  

The bulk of the practice involves treatment of movement disorders such as Parkinson’s disease, different types of dystonia and essential tremor.  But our practice includes targeting areas of the brain for neuropathic pain – pain caused by damage to the nervous system caused by stroke or traumatic limb loss amongst other causes.  

As part of the procedure, some patients may have the electrodes externalised for a few days before implanting with the pacemaker device.  This to allow clinical testing of stimulation before the implantable pulse generator is implanted.  This means the electrodes implanted into the brain are connected to extension leads under the skin that are tunnelled and come outside the body.  This allows electrical signals to be recorded from the target areas.  Patients are awake during this period, therefore this allows electrical activity to be measured from areas below the cortical surface where the electrodes are targeted while patients perform tasks.  This can be harnessed to study the electrophysiology of areas of the brain for research too. These deep brain targets can be difficult to study with standard EEG.  

We primarily use this opportunity to study the electrophysiology of movement disorders, particularly Parkinson’s disease, to better understand the pathology and treatment of these disorders. In addition, we support clinical trial work to explore the clinical utility of the technique for existing and novel indications. DBS has been used for a host of disorders in other centres including epilepsy, depression, and obsessive-compulsive disorder.  

However, we have recently begun to explore a new area with the aid of Cambridge Cognition’s CANTABTM software suite (specifically CANTABTM eclipse): the cognitive electrophysiology of the deep brain.  These areas are targets for treatment of neurological symptoms, specifically the basal ganglia and the dorsal anterior cingulate cortex. They have also been implicated in reward-based decision making.  Since Parkinson’s disease in particular can be associated with cognitive symptoms, we were originally motivated to acquire the CANTABTM software suite to allow us to probe and compare cognitive functions in our movement disorder patient group.  We were particularly keen to explore the difference between dystonic and Parkinson’s disease patients since dystonia is associated with normal dopaminergic function and Parkison’s is not.  We found that the design of some of these tasks meant we could correlate electrophysiological events measured from patients’ electrodes to events in the CANTABTM tasks.  

Which CANTABTM tasks did you use and why?

Through our pain practice, we were presented with an exciting opportunity to study what some researchers have described as the most interesting part of the brain – the dorsal anterior cingulate cortex.  This is a key part of the salience network, which is a large-scale brain network involved in decision making, but also involved in functions such as internally generated movement as well as pain perception.  

Given the patients had electrodes externalised from both right and left dACC and multiple electrodes were present in each side, we had a unique opportunity to not only study decision making in real time in a real-world task, but also study the interaction of functional nodes within and between right and left dACC.  This is difficult with scalp-based EEG and fMRI.  This allowed us to probe an issue that has been raised recently in the anterior cingulate cortex generally – are functions spatially segregated or are functions intermixed?  The rationale for the study was therefore to examine the spatial and information flow in the dorsal anterior cingulate cortex, left and right simultaneously.

We harnessed the features of the Intra- Extra-Dimensional set shift task (IED) to probe these aspects of the cognitive role of the dorsal anterior cingulate cortex (dACC).  The features of the IED task that are particularly useful to explore the cognitive electrophysiology of the dACC are the prediction-action-outcome nature of each trial within the task, the changing reward environment of the task as rules change, and the flexible learning required to pass the task.  The large numbers of trials in the task allow signal averaging, which offers a high signal to noise ratio for event-related potentials.  

We were able to show functional nodes within each hemisphere, which responded to various cognitive events in the task, including anticipation, movement and response to the outcome of the movement (correct or wrong), and that learning occurred in the network over successive trials.  We found activity in the left (dominant) dACC preceded similar activity in the right (non-dominant) dACC. 

How did Cambridge Cognition support this work?

Making use of the IED task in this way required the kind assistance of Cambridge Cognition, who we found to be helpful and supportive of our perhaps a little unusual endeavours! We made use of Cambridge Cognition’s additional service which rapidly provides extra technical information. We needed this to make use of the IED task to interpret the electrophysiology. They also kindly allowed us to use images of the task in publication to explain how the IED task could be used for event-related potential analysis related to cognitive events.  I feel the CANTABTM suite has a lot of potential for electrophysiology research and the support we have had from Cambridge Cognition makes me confident that we will continue to find new uses in our research for the CANTABTM suite.

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Author:

Martin Gillies

University of Oxford

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