Psychosis is a sign of severe brain disorders including schizophrenia and is characterised by disturbances of perception such as hallucinations. These are subjective phenomena that have traditionally been difficult to study biologically.

We recently established a new behavioural-computational approach to capture hallucination-like perception in humans and mice. Hallucination-like perception increased after hallucinogenic manipulations in mice and correlated with self-reported hallucinations in humans. Using optical imaging, optogenetics and pharmacology in behaving mice, we found evidence for a causal role of striatal dopamine in psychosis-like perception. Finally, computational modelling showed that hallucination-like perception occurred when expectations about upcoming stimuli were high.

Our results suggest that hallucination-like perception can serve as a translational marker of hallucinations across humans and mice, and provide circuit-level evidence for the long-standing dopamine hypothesis of psychosis. We propose that increased striatal dopamine biases perception to rely more on expectations, signalled by cortical inputs, as compared to sensory evidence, signalled by thalamic inputs, thereby producing hallucinations.

In our current work, we investigate neural and immunological upstream regulators of these psychosis-relevant neural circuit mechanisms. Thereby, we hope to identify new biological targets for the treatment of schizophrenia, and to understand how the brain generates perception.

SPEAKER BIOGRAPHY

Katharina Schmack received her MD/PhD equivalent from Charité, Berlin in 2009. She then completed her postdoctoral training, clinical scientist fellowship and psychiatry specialization at Charité, Berlin. In 2018, she was awarded a research fellowship from the German National Academy of Sciences, Leopoldina, and joined Cold Spring Harbor Laboratory, New York, as a research investigator in Adam Kepecs’ group. In September 2021, she opened her own lab at the Francis Crick Institute, London. As a Clinical Group Leader, her appointment is shared with the UCL – Division of Psychiatry, and she splits her time between research and patient care.

Her research focuses on psychosis. Her group investigates the neural circuits and immune processes giving rise to hallucinations and other psychotic symptoms. Using a cross-species approach, they study both patients and mice with behavioural tests, computational models, and in-vivo measures and manipulations.