Current Research

Deep Brain Stimulation

All DBS projects are carried out in close collaboration with Prof Morten Kringelbach and with Prof Tipu Aziz and Alex Green from Oxford Functional Neurosurgery.

Deep brain stimulation (DBS) is a well-established treatment for several neurological conditions including Parkinson’s disease (PD), as can be seen in the video. Unfortunately, the underlying neural mechanisms of DBS and its long-term effects on brain connectivity remain unclear. This limitation restricts the efficacy of DBS since the identification of individual DBS targets and the settings of stimulation parameters cannot be optimally performed beforehand. Uncovering these aspects will improve the clinical benefits of DBS in the treatment of such diseases.

In general terms, the effects of DBS must be closely linked to at least three factors: 1) the stimulation parameters such as frequency, amplitude, pulse width and duration; 2) the physiological properties of the neural tissue (which may be dependent on disease state); and 3) the interactions between the electrode and the surrounding neural tissue and specific anatomy of the targeted region (see Kringelbach et al 2010). This third factor includes the extended brain-wide connectivity pattern from the electrode where this specific structural “fingerprint” of connectivity is an important factor for the efficacy. You can read more about that in our article here. Thus rather than solely acting locally, the evidence clearly shows that DBS affects a network of neural elements; foremost myelinated axons, and to a lesser degree cell bodies. The most likely mechanism of DBS seems to be through stimulation-induced modulation of the activity of macroscopic brain networks. This has been confirmed by optogenetic experiments in rodents, which show that the therapeutic effects within the subthalamic nucleus (STN) can be accounted for by direct selective stimulation of afferent axons projecting to this region. It is not clear, however, which of the many connections from a given DBS target are most influential in providing a clinical benefit and whether DBS creates long-term changes in brain connectivity.

Neural Plasticity

All projects on neural plasticity are carried out in close collaboration with Prof Morten Kringelbach and Prof Gustavo Deco.

It has been almost a century since one of the most important pioneers in neuroscience, Ramon y Cajal, stated unequivocally that nerve paths in the adult central nervous system are fixed and cannot be regenerated once damaged. This view dominated the field for nearly half a century until the first studies in the 1960s and 1970s were showing neuronal regeneration. Since the discovery of regeneration and structural plasticity in the adult brain, this topic has been of increasing interest to a large number of researchers. In the past decades it has become clear that structural plasticity and learning are closely related to each other. Whereas plasticity allows for new skills and knowledge to be stored, the act of learning stimulates this process. The best example of this happens on a micro-scale where task repetition leads to strengthened neural connections. This mechanism is often referred to as Hebbian learning although other mechanisms could also be at play. Our recent studies have shown that these changes in the brain can occur on a macro scale following deep brain stimulation (DBS). Constant DBS strengthens some connections between brain areas, in a similar fashion as Hebbian learning, resulting in long-term structural changes in the whole-brain network.

Sense of Smell

All projects on olfactory functioning are carried out in close collaboration with Prof Morten Kringelbach and with Prof Therese Ovesen, Dr Alexander Fjældstad and Dr Henrique Fernandes at the Flavour Institute.

Olfaction, or as it is more commonly known, the sense of smell, is of great importance for species survival in terms of both reproduction and food selection, especially when taken together with the sense of taste (gustation). Taste and smell are so closely linked that when people talk about, for example, the flavour of food, they in fact talk about this multimodal experience, which also includes vision, hearing and touch. Studies on, among others, single-cell organisms indicate that the combined chemical sense of taste and smell is possibly the oldest of the senses and the most universally employed.

Humans and other animals rely strongly on olfaction to locate and identify food sources. Most animals also rely heavily on olfaction for mate selection and to identify their offspring. Further evidence for the importance of olfaction can be found in the size of the olfactory organ and system in a vast majority of species. For example, dogs have about 100 times more olfactory receptor cells compared to humans.

But what happens when things don’t work the way they are supposed to? Olfactory dysfunction is associated with apathy, depression, and a lower quality of life. These observations combined with the fact that olfactory neurons project directly to the amygdala and hippocampus without a thalamic relay suggests a prominent role for olfaction in mediating hedonic experience. Taken together, the weight of the evidence shows that olfaction is a very important sensory system in humans, which needs to be fully functioning to support not only our survival, but also very much our sense of well-being in general.

The Caregiving Project

Tim van Hartevelt

The Caregiving Project is being led by Prof Morten Kringelbach in collaboration with Prof Alan Stein and includes Dr Joana Cabral and Dr Henrique Fernandes.

The bond between a parent and an infant often appears to form effortlessly and intuitively, and this relationship is fundamental to infant survival and development. Parenting is considered to depend on specific brain networks that are largely conserved across species and in place even before parenthood. Efforts to understand the neural basis of parenting in humans have focused on the overlapping networks implicated in reward and social cognition, within which the orbitofrontal cortex (OFC) is considered to be a crucial hub. This review examines emerging evidence that the OFC may be engaged in several phases of parent-infant interactions, from early, privileged orienting to infant cues, to ongoing monitoring of interactions and subsequent learning. Specifically, we review evidence suggesting that the OFC rapidly responds to a range of infant communicative cues, such as faces and voices, supporting their efficient processing. Crucially, this early orienting response may be fundamental in supporting adults to respond rapidly and appropriately to infant needs. We suggest a number of avenues for future research, including investigating neural activity in disrupted parenting, exploring multimodal cues, and consideration of neuroendocrine involvement in responsivity to infant cues. An increased understanding of the brain basis of caregiving will provide insight into our greatest challenge: parenting our young.