Research project P7/11 (Research action P7)
1. To study functional brain networks supporting perception, action and cognition in normal and diseased human subjects and non-human primates (NHP). There will be a strong focus on anatomical, functional and effective connectivity and causality-oriented research to develop and to test biologically-relevant theoretical models for understanding brain function. The consortium will build heavily on joint expertise and collaborative experiments performed during previous phases of the IUAP program in which monkey imaging, developed by the pilot group, plays a crucial role to link human imaging studies with knowledge obtained through monkey electrophysiology.
2. To support cognitive neuroscience in Belgium and promote independence of young researchers. More than ten new young principal investigators joined the present consortium compared to IUAP-phase VI. We aim to foster collaborations between groups with different expertise based on the principle that „the whole is greater than the sum of its parts‟. Wherever possible, we will investigate similar cerebral functions in normal subjects, patient populations, and in monkeys, and using similar experimental paradigms. We will develop and implement novel comparative analytical methods and share imaging and analysis technology. We will organize general meetings, symposia, joint seminars and workshops and joint doctoral training programs.
3. The project will cover a number of collaborative research topics in humans and monkeys with an emphasis on the visual system at large, including its output stages; interactions with related cognitive processes such as numerical and symbolic processing, and how higher order executive control structures and extraretinal factors such as attention and reward modify and shape visual processing and perception. As during the previous program, several of the partners will continue to study the visual representation of 3D and 2D biological (e.g. faces and bodies) and non-biological objects and how these are linked with action observation and action execution systems. To achive these goals we will integrate single-unit (SU) and local field potential (LFP) data with human and NHP fMRI data. There will be a multi-site single unit-fMRI study on the perception of quantity in humans and NHP. Several of the partners will jointly focus on integrated brain networks involved in cognitive control such as self referential processing, selective attention, short and long term memory, inhibition and feedback, multi tasking, and task switching. Comparisons will be made between normal and aged subjects and impaired integration will be explored in patients i) with Alzheimer‟s disease, ii) with focal cortical lesions due to stroke, iii) with developmental disorders (autism), and iv) with minimal consciousness. Moreover, the consortium will investigate adult brain plasticity induced by perceptual and motor learning and after (ir)reversible lesions.
4. The ongoing sleep EEG-fMRI studies in humans will be complemented with comparative NHP studies and with consciousness studies on coma and locked-in patients by a new PI in our consortium S. Laureys (ULg). State-dependent variations in functional connectivity using resting state data will be compared between awake and anesthetized patients and NHP using novel analytical approaches.
5. Following the recommendations of the ex-post evaluation we reduced the number of work packages from 6 to 4. Actually, the expanded number of individuals involved in the present IUAP implies that we will cover the individual work packages (WPs) in great detail. Thus, although we propose fewer WPs compared to phase VI, more experiments per WP will be conducted. In WP1 on visual perception, we will focus on the representation of faces and bodies, 3D shape and how representations are shaped by perceptual learning and extra-retinal influences such as attention and reward. An explicit comparison will be made between multi voxel pattern analysis (MVPA) and adaptation-based measures of selectivity. There is a gradual transition from WP1 to WP2 as attention will be studied in both work packages. WP2 focuses on executive control functions, including long- and short-term memory, inhibition, and their relations to numerical representations and task rules. WP3 is entirely devoted to actions: action observation and execution as well as goal and intention coding. Finally, WP4 is a technical work package that aims to improve different types of connectivity measures and perturbation methods to perform causality-oriented experiments, mainly applied to data and paradigms of the other WPs. This work package also includes a number of aims to improve significantly the spatial resolution of fMRI measurements.
Methodology:
1. We will build on the previous technological developments within the consortium that were praised highly in the ex-post evaluation of IUAP phase VI. The new project will capitalize on causal-oriented experiments that require the (ir)reversible perturbation of parts within a functional network while concurrently measuring its behavioral consequences as well as its local and distant functional effects using single unit and/or fMRI measurements. We will use a battery of perturbation methods each with its own spatio-temporal specifics and invasive character. All methods are already implemented or are currently under development within the consortium. They include transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in humans and NHP (eventually combined with (concurrent) fMRI or concurrent event related potentials), simultaneous fMRI-electrical microstimulation (EM) and single unit (SU) recordings in NHP, pharmacological and cell-specific optogenetic-based stimulation and inactivation protocols together with fMRI and SU recordings in NHP. To test for the critical contribution of human cortical brain regions we will also compare TMS results with those obtained from patients with focal cortical lesions.
2. Building on our recent success with implanted Rx coils in NHP, we also aim to develop and implement very high resolution (≤0.1mm3) fMRI with full-brain coverage in NHP which potentially will allow us to perform laminar and columnar-specific studies. Novel functional contrast agents will be instrumental to this goal and will be developed and tested within the consortium.
3. We will develop novel analytical methods to analyze fMRI and electrophysiological data using decoding strategies, non-parametric statistics, quantification of diffusion data using probabilistic methods, novel methods to study functional interspecies correspondences using graph theoretical approaches, and inter-species activity correlations. There will be a consortium-wide effort to compare adaptation, ICA and classifier-based measures of stimulus-selectivity using fMRI and single units. Several technically-oriented groups including the new UA partner J. Sijbers and the new foreign partner H. Benali will play a key-role in optimizing the measurement and analytical tools.
4. We will combine efforts of the different groups to study effective and functional connectivity between brain regions based on resting state and task-specific fMRI signals in humans and monkeys, and SU data acquired simultaneously in multiple regions of the monkey. On the structural side, novel MRI-based methods for in-vivo tract tracing in NHP will be developed. Data based on high-resolution and optimized diffusion MRI experiments, including diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging will be integrated to construct atlases of diffusion measures. These indirect connectivity measures will be compared to the ground truth using real anatomical tractography by one of the world leaders in the field (i.e., the Uparma partner).
