Periodic Reporting for period 4 - MEMCIRCUIT (Deconstruction of a neural circuit for working memory: hubs, coding mechanisms, and signal routing)
Reporting period: 2022-08-01 to 2024-01-31
Working memory is the basis of cognition. It allows behaviour to be governed by internal goals rather than by reflexive stimulus-response mappings. The neuronal mechanisms of memory maintenance are heavily contested. Seemingly contradicting results have been obtained in animal and human studies. This could be due to the use of different recording methods, which measure distinct brain signals. Alternatively, there might be fundamental differences in mnemonic coding between humans and animals. The key objective of this project is to investigate working memory coding at the cellular and circuit level and integrate across previously disconnected, species-specific lines of research. This will be achieved by an unprecedented one-to-one matching of behavioural tasks and recording methods with single-cell and split-second resolution in humans and rodents. The project represents a major step forward in understanding the cellular and circuit basis of a critical cognitive brain function.
At the end of the action, we could clearly demonstrate the feasibility of combining cellular-resolution brain recordings in human subjects and in trained animals (mice) performing comparable cognitive tasks. This line of research should propel forward efforts in the cognitive and systems neuroscience research community to formulate general, species-independent principles underlying higher cognitive functions and intelligent behaviour.
At the end of the action, we could clearly demonstrate the feasibility of combining cellular-resolution brain recordings in human subjects and in trained animals (mice) performing comparable cognitive tasks. This line of research should propel forward efforts in the cognitive and systems neuroscience research community to formulate general, species-independent principles underlying higher cognitive functions and intelligent behaviour.
To address our research questions in humans, we established reliable and robust acute multi-channel recordings using planar microelectrode arrays implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We achieved high-quality extracellular neuronal activity at the microcircuit, local field potential level, and at the cellular, single-unit level. Recording from parietal association cortex, a region rarely explored in human single-unit studies, we described travelling waves of oscillatory activity as well as single-neuron and neuronal population responses during working memory including operations with uniquely human number symbols.
To address our research questions in animals, we developed two different behavioural tasks for mice that allowed us to tap into the neuronal mechanisms of comparable cognitive functions. We could show that the neuromodulator dopamine plays a significant role when animals learn new tasks and flexibly associate sensory stimuli, own actions and rewarding outcomes. We then acquired large-scale recordings from both the rodent and the human brain in the identical working memory task, which is allowing us to make unique and unprecedented head-to-head, cross-species comparisons.
Our achievements in the field of cellular-resolution neurotechnology are providing the backbone for innovative new projects that will involve the use of chronically implanted brain-computer-interfaces for patients with disorders of cognition and mental health. We have put forward guidelines to support a new culture of neurotechnology research and development in which engineers work together with clinicians, neuroscientists, data scientists, ethicists and social scientists to co-create neurotechnological solutions for the most urgent healthcare challenges, with patients’ and caregivers’ needs at the center of all efforts. Our ongoing and future work will therefore heavily rely on and profit from close collaborations with researchers from these diverse fields.
To address our research questions in animals, we developed two different behavioural tasks for mice that allowed us to tap into the neuronal mechanisms of comparable cognitive functions. We could show that the neuromodulator dopamine plays a significant role when animals learn new tasks and flexibly associate sensory stimuli, own actions and rewarding outcomes. We then acquired large-scale recordings from both the rodent and the human brain in the identical working memory task, which is allowing us to make unique and unprecedented head-to-head, cross-species comparisons.
Our achievements in the field of cellular-resolution neurotechnology are providing the backbone for innovative new projects that will involve the use of chronically implanted brain-computer-interfaces for patients with disorders of cognition and mental health. We have put forward guidelines to support a new culture of neurotechnology research and development in which engineers work together with clinicians, neuroscientists, data scientists, ethicists and social scientists to co-create neurotechnological solutions for the most urgent healthcare challenges, with patients’ and caregivers’ needs at the center of all efforts. Our ongoing and future work will therefore heavily rely on and profit from close collaborations with researchers from these diverse fields.
By the end of the project, we expect to have a more detailed understanding of the cellular and circuit mechanisms that underlie our ability to learn new tasks and store behaviourally information in online in working memory.