Personalised brain stimulation

Computer simulations, based on an individual's connectome, can predict stimulation outcomes

While many psychiatric and neurological conditions are treated with pharmaceutical drugs, side effects remain severe. Brain stimulation of distinct regions of the brain offers a potential route to new treatments. However, for neuromodulation to replace drugs in the future, interventions need to be targeted, personalised and non-invasive.

We are developing computational models based on a subject's connectome to predict global neuromodulation effects. Using focused ultrasound stimulation (FUS), we develop approaches to change brain connectivity and thus cognitive function for the long-term. The aim is to improve cognitive function for mental and brain health conditions.

We also develop models to predict stimulation effects at the local tissue model using the VERTEX brain tissue simulator.

Predicting intervention outcomes

Removal of hub nodes in simulated lesions has severe effects for network architecture

Why do some lesions cause more severe deficits than others? We found that cortical networks behave similar to scale-free networks after the removal of regions or connections with drastic effects for removing network hubs (Kaiser et al., European Journal of Neuroscience, 2007).

Connectome information can indicate regions involved in epilepsy and predict surgery outcome

Can epileptic seizure patterns be related to brain connectivity? Based on structural connectivity for temporal lobe epilepsy, we can already predict starting points for epileptic seizures (Hutchings et al. PLOS Computational Biology, 2015).

Moreover, changes within regions are more informative than changes between regions for predicting surgery outcome (Chen et al., 2021).

Connectome development
in health and disease

Spatial and temporal features can lead to small-world and modular networks

A simple model for the development of networks in space, spatial growth, can generate networks with small-world properties (Kaiser & Hilgetag, Physical Review E, 2004). The algorithm can generate networks with similar properties than cortical networks (Kaiser & Hilgetag, Neurocomputing, 2004). However, multiple clusters only arise in few cases.

The existence of multiple clusters can be secured if there are time windows for connection establishment so that some parts of the network develops earlier than others and there is a higher probability to form connections if both regions have similar time windows for synaptogenesis (Kaiser & Hilgetag, Neurocomputing, 2007).

Following an old-gets-richer model, hub nodes arise early during development

Observing birth-times of neurons in C. elegans we could show that 70% of long-distance connections potentially arise early on during development, before hatching when the worm only has 20% of its final body size. In addition, hub nodes were also generated early on indicating that the time that neurons have available to receive connections from later neurons can explain the increased node degree (Varier & Kaiser, PLoS Computational Biology, 2011).

More about connecto
me develoment can be found in my MIT Press book 'Changing Connectomes'.

Connectome organisation

Hierarchical modular network architecture prevents widespread activation and facilitates functional specialisation

Neural systems also show a hierarchical architecture with modules and sub-modules covering different levels of organization, from cortical columns to visual, auditory, and sensorimotor cortices (Kaiser et al. Frontiers in Neuroinformatics, 2011).

Recent work includes the characterization of the specific modular organisation of human structural connectivity (Kim et al. Phil. Trans. Roy. Soc. B, 2014) and an overview of network features across species (Kaiser, Current Biology, 2015).

Non-optimal component placement improves information propagation and switching between brain states

For the human brain, regions are not positioned to minimize the total length of their connections (Hayward et al., 2023). This nonoptimal organization, previously shown for C. elegans and rhesus monkeys (Kaiser & Hilgetag, 2006), better allows distant brain regions to communicate. In addition, this suboptimal spatial arrangement of the connectome promotes fluctuations in human brain dynamics, potentially enabling the brain to undertake flexible behavioral responses.