Brain organization and function is a complex topic. We are good at establishing correlates of perception and behavior across forebrain circuits, as well as manipulating activity in these circuits to affect behavior. However, we still lack good models for the large-scale organization and function of the forebrain. What are the contributions of the cortex, basal ganglia, and thalamus to behavior? In addressing these questions, we often ascribe function to each area as if it were an independent processing unit. However, we know from the anatomy that the cortex, basal ganglia, and thalamus, are massively interconnected in a large network. One way to generate insight into these questions is to consider the evolution and development of forebrain systems. In this talk, I will discuss the developmental and evolutionary (comparative anatomy) data on the thalamus, and how it fits within forebrain networks. I will address questions including, when did the thalamus appear in evolution, how is the thalamus organized across the vertebrate lineage, and how can the change in the organization of forebrain networks affect behavioral repertoires.

About 30% of children with cerebral palsy have congenital hemiplegia, resulting from periventricular white matter injury, which impairs the use of one hand and disrupts bimanual co-ordination. Congenital hemiplegia has a profound effect on each child's life and, thus, is of great importance to the public health. Changes in brain organization (neuroplasticity) often occur following periventricular white matter injury. These changes vary widely depending on the timing, location, and extent of the injury, as well as the functional system involved. Currently, we have limited knowledge of neuroplasticity in children with congenital hemiplegia. As a result, we provide rehabilitation treatment to these children almost blindly based exclusively on behavioral data. In this talk, I will present recent research evidence of my team on understanding neuroplasticity in children with congenital hemiplegia by using a multimodal neuroimaging approach that combines data from structural and functional neuroimaging methods. I will further present preliminary data regarding functional improvements of upper extremities motor and sensory functions as a result of rehabilitation with a robotic system that involves active participation of the child in a video-game setup. Our research is essential for the development of novel or improved neurological rehabilitation strategies for children with congenital hemiplegia.

It is increasingly recognized that epilepsy affects human brain organization across multiple scales, ranging from cellular alterations in specific regions towards macroscale network imbalances. My talk will overview an emerging paradigm that integrates cellular, neuroimaging, and network modelling approaches to faithful characterize the extent of structural and functional alterations in the common epilepsies. I will also discuss how multiscale framework can help to derive clinically useful biomarkers of dysfunction, and how these methods may guide surgical planning and prognostics.

Connections between nerve cells called synapses are the fundamental units of communication and information processing in the brain. The accurate wiring of neurons through synapses into neural networks or circuits is essential for brain organization. Neuronal networks are sculpted and refined throughout life by constant adjustment of the strength of synaptic communication by neuronal activity, a process known as synaptic plasticity. Deficits in the development or plasticity of synapses underlie various neuropsychiatric disorders, including autism, schizophrenia and intellectual disability. The Siddiqui lab research program comprises three major themes. One, to assess how biochemical switches control the activity of synapse organizing proteins, how these switches act through their binding partners and how these processes are regulated to correct impaired synaptic function in disease. Two, to investigate how synapse organizers regulate the specificity of neuronal circuit development and how defined circuits contribute to cognition and behaviour. Three, to address how synapses are formed in the developing brain and maintained in the mature brain and how microcircuits formed by synapses are refined to fine-tune information processing in the brain. Together, these studies have generated fundamental new knowledge about neuronal circuit development and plasticity and enabled us to identify targets for therapeutic intervention.

Topographic maps are a prominent feature of brain organization, reflecting local and large-scale representation of the sensory surface. ​​Traditionally, such representations in early visual areas are conceived as retinotopic maps preserving ego-centric retinal spatial location while ensuring that other features of visual input are uniformly represented for every location in space. I will discuss our recent findings of a striking departure from this simple mapping in the secondary visual area (V2) of the tree shrew that is best described as a sinusoidal transformation of the visual field. This sinusoidal topography is ideal for achieving uniform coverage in an elongated area like V2 as predicted by mathematical models designed for wiring minimization, and provides a novel explanation for stripe-like patterns of intra-cortical connections and functional response properties in V2. Our findings suggest that cortical circuits flexibly implement solutions to sensory surface representation, with dramatic consequences for large-scale cortical organization. Furthermore our work challenges the framework of relatively independent encoding of location and features in the visual system, showing instead location-dependent feature sensitivity produced by specialized processing of different features in different spatial locations. In the second part of the talk, I will propose that location-dependent feature sensitivity is a fundamental organizing principle of the visual system that achieves efficient representation of positional regularities in visual input, and reflects the evolutionary selection of sensory and motor circuits to optimally represent behaviorally relevant information. The relevant papers can be found here: V2 retinotopy (Sedigh-Sarvestani et al. Neuron, 2021) Location-dependent feature sensitivity (Sedigh-Sarvestani et al. Under Review, 2022)

While time-averaged dynamics of brain functional connectivity are known to reflect the underlying structural connections, the exact relationship between large-scale function and structure remains an unsolved issue in network neuroscience. Large-scale networks are traditionally observed by correlation of fMRI timecourses, and connectivity of source-reconstructed electrophysiological measures are less prominent. Accessing the brain by using multimodal recordings combining EEG, fMRI and diffusion MRI (dMRI) can help to refine the understanding of the spatio-temporal organization of both static and dynamic brain connectivity. In this talk I will discuss our prior findings that whole-brain connectivity derived from source-reconstructed resting-state (rs) EEG is both linked to the rs-fMRI and dMRI connectome. The EEG connectome provides complimentary information to link function to structure as compared to an fMRI-only perspective. I will present an approach extending the multimodal data integration of concurrent rs-EEG-fMRI to the temporal domain by combining dynamic functional connectivity of both modalities to better understand the neural basis of functional connectivity dynamics. The close relationship between time-varying changes in EEG and fMRI whole-brain connectivity patterns provide evidence for spontaneous reconfigurations of the brain’s functional processing architecture. Finally, I will talk about data quality of connectivity derived from concurrent EEG-fMRI recordings and how the presented multimodal framework could be applied to better understand focal epilepsy. In summary this talk will give an overview of how to integrate large-scale EEG networks with MRI-derived brain structure and function. In conclusion EEG-based connectivity measures not only are closely linked to MRI-based measures of brain structure and function over different time-scales, but also provides complimentary information on the function of underlying brain organization.

The emergence of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms govern the diversity of these developmental processes? There are many existing descriptive theories, but to date none are computationally formalized. We provide a mathematical framework that specifies the growth of a brain network over developmental time. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over development. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the developmental simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity of childhood brain development, capable of integrating different levels of analysis – from genes to cognition. (Pre-print: https://www.biorxiv.org/content/10.1101/2020.08.13.249391v1)