Functional Neuroimaging

Research activities

The Functional Neuroimaging Laboratory focuses on the study of mammalian brain organization at the macroscale.

We are interested in understanding how large scale functional activity and network dynamics originate, develop and govern behavioural states. A major goal of our research is to unravel the elusive neurophysiological basis of macroscale functional connectivity as measured with neuroimaging methods, and the underpinnings of its aberrations observed in human brain disorders such as autism spectrum disorders. To achieve these goals, we have pioneered the use of advanced magnetic resonance magnetic (MRI) methods to image the structure and function of the living mouse brain under resting conditions, or upon pharmacological, neuromodulatory or genetic preconditioning. The combined use of high resolution structural (e.g. Diffusion Tensor imaging - DTI and voxel-based morphometry -VBM) and functional MRI (fMRI) defines a novel investigational platform that we have successfully employed to describe the intrinsic organization of the mouse brain in unprecedented detail. We aim to combine these novel approaches with cell type-specific optogenetic manipulations to establish causal relationship between local activity and its propagation at the systems level.

Projects

Macroscale functional organization of the mouse brain

This research leverages on the use of resting-state fMRI to obtain an integrated portrayal of the macroscale mouse functional connectome, i.e. the complex network of elements and connections that govern and compose the brain at the macroscale. As part of this effort, we provided the first demonstration of the presence of distributed resting-state functional connectivity networks in the mouse brain including a plausible homologue of the human salience and default mode network (DMN). We are now using multidisciplinary approaches to investigate the function, behavioural relevance and directional topology of the mouse DMN and other connectivity networks via the use of canonical and advanced computational frameworks, including multivariate Granger Causality and dynamic causal modelling. Our efforts complement ongoing activities aimed at mapping the macroscale organization of the laboratory mouse, with the final goal of describe brain function as the integration of processes occurring at multiple scales.

Collaborations
  • Stefano Panzeri, Neural Computation, IIT.
  • Michele Caselle, University of Torino.

Neurobiological basis of aberrant functional connectivity in autism

Deficits in large-scale structural and functional connectivity have been highlighted for autistic patient populations, but investigational approaches to unravel the elusive pathophysiological basis and significance of these phenomena are limited. By using fMRI in transgenic mouse lines mouse we have begun to establish causal relationships between genetic ASD-related mutations, neurodevelopmental processes and functional connectivity alterations. This line of research will provide testable hypotheses concerning the mechanisms underlying a key patho-physiological feature of autism, thus shedding light into the origin and clinical significance of these aberrations. Importantly, the use of readouts commonly used in the clinic offers a means to translate our findings from and to analogous patient populations.

Collaborations
  • Massimo Pasqualetti, University of Pisa.
  • Alessandro Usiello, Cienge Napoli.
  • Maria Luisa Scattoni, ISS, University of Torino.

Endogenous modulation of functional connectivity

At the cellular level, local functional connections giving rise to a specific circuit output are configured by neuromodulatory environment. According to this view, axonal connectivity itself only establishes potential circuit configurations, whose availability and properties depend critically on local neuromodulatory state. However the degree to which similar dynamics may shape macroscale intrinsic brain function remains unknown. We are using optogenetic methods to determine the role of endogenous neuromodulation in shaping network activity as measured with resting state fMRI. Our research will help understand how local neuronal perturbation propagate at the network level, and the degree to which alterations in internal states affect macroscale network configurations

Collaborations
  • Massimo Pasqualetti, University of Pisa.
  • Ferruccio Pisanello, IIT Lecce.

Facilities

The Functional Neuroimaging Laboratory is equipped with state-of-the-art instrumentation for

  • Structural and functional brain imaging (7 Tesla multi-channel MRI scanner, high resolution microendoscopic probes and optical systems for recording the brain intrinsic signal)
  • Electrophysiology (dual-channel patch-clamp amplifiers and multichannel extracellular amplifiers)
  • Optogenetics (laser sources and optical devices for single- and two-photon patterned excitation)
  • Transgene expression (transgenic Cre-lox models and various gene delivery approaches)

Selected Publications

Members

Principal investigator

Alessandro Gozzi

After receiving a master degree in Biotechnology at the University of Verona (Italy) in 1998, I joined the neuroscience centre of GlaxoSmithKline (GSK), a large research-based pharmaceutical company based in Verona (Italy) and Harlow (UK), where I pioneered the use of functional magnetic resonance imaging (MRI) to describe the neural substrates modulated by pharmacological agents, a line of research that I also pursued to obtain a PhD degree in biomedical imaging with the University of Verona.