Human/ Clinical studies

Recording of single units

The recording of activity from single neurons is the gold standard for neuroscientific research, giving insight into the neural mechanisms underlying cognitive processes ranging from visual perception to memory formation. However, until recently, single-neuron recordings were only possible in animal models. Recent work has shown that it is possible to record from single human neurons during treatment for intractable epilepsy.
We study the neural basis of cognitive functions (such as memory and visual processing) in multiple areas of the human brain while the patient performs a simple cognitive task. A schematic drawing of the electrodes that are implanted in these patients is shown below. They have been developed in the lab of Itzhak Fried (and are known as Behnke-Fried electrodes). With these micro-wires we record local field potentials as well as single neuron activity. These signals provide unique, direct evidence (contrary to imaging techniques such as PET and fMRI) on the functioning of different brain areas and their interplay during cognitive processing in awake behaving humans. Moreover, it is possible to study elements of cognition such as perception and imagery which are impossible to study in animals. Therefore, these experiments do not only verify previous findings in animal literature in the human brain, but they also provide unique insights for which there is no alternative method available.

Development of a visual prosthesis

Approximately forty million people across the world suffer from blindness (World Health Organization, 2010). Patients whose visual system is damaged can be broadly classified into two groups: those for whom the damage occurs somewhere along the visual processing pathway up to and including the photoreceptor layer in the retina; and those for whom damage occurs after this processing stage. Significant progress has been made in the development of retinal prostheses for the former group of patients (SecondSight; Bionic Vision Australia; Retinal Implant AG), with clinical trials underway. However, the loss of vision sustained by the latter group is more challenging to address.

Visual cortex stimulation hold the promise of restoring vision in the latter group: by inserting microstimulating electrodes into the visual cortex, and applying weak electrical pulses to the surrounding tissue, one may artificially generate small visual percepts within the visual field, which are termed ‘phosphenes.’

We are carrying out a comprehensive investigation of how monkeys perceive these artificial percepts, elicited via microstimulation of ~1000 implanted electrodes per subject. The use of such large numbers of electrodes is unprecedented; with these high-density implants, we can send meaningful information directly to the visual cortex, and explore the capacity of the primate brain to perceive, interpret, and learn from complex phosphene imagery.

The stability and durability of the implanted device is continually monitored, and the quality of the microstimulation protocol will be assessed over an extended period of time. Importantly, our work lays the foundations for the clinical development of a cortical neuroprosthesis in blind human patients.

Deep brain stimulation

Deep brain stimulation (DBS), the chronic electrical stimulation of the deeper areas of the brain, has a long history as a treatment for motor problems associated with Parkinson’s disease. In more recent years, its applicability has spread into the domain of cognition where it is now rather successfully used as a treatment for psychiatric disorders like Obsessive Compulsive Disorder, depression, or addiction. The problem with DBS in psychiatry is however that the precise brain mechanisms responsible for the positive clinical outcomes are poorly understood. To resolve this issue, we closely collaborate with the Neuromodulation & Behaviour Group at the NIN, and the Amsterdam UMC’s Department of Psychiatry, where patients with a range of mental disorders are treated with DBS. Together, we attempt to unravel the functional brain networks that are influenced by DBS and map their relation to cognitive behaviors that are associated with the psychiatric symptoms for which DBS has successfully been applied. Our primary focus herein is on the neural networks of reward processing and cognitive control since. Stimulating clinically relevant brain areas within these known functional brain networks, while simultaneously measuring the impact of this stimulation on broad patterns of brain activity using fMRI, and on cognitive functioning using diverse behavioral paradigms will hopefully provide the operational knowledge necessary to fully harness the exciting potential of DBS as a treatment for a range of psychiatric disorders.