Causal Connections of the cortical face network studied with TMS and fMRI

Whether meeting someone for the first time, or seeing someone we have known all our lives, we will understand the mood and intentions of that person by looking at their face. This understanding is formed not only by the verbal and non-verbal cues that she or he makes but also by the size and shape of their face and by how they move their head, eyes and mouth. Our brains are so efficient that, to us, instantly processing this wealth of socially relevant information appears to happen effortlessly. Yet even the simplest function, like recognizing someone's identity, or their facial expression, requires the interaction of specialized face-selective regions distributed across the brain. While the locations of these regions have been established this is only the first step in understanding how we recognize faces. We currently lack any real comprehension of how face-selective regions interact with each other when we recognize a friend, or how that friend feels based on their facial expression. New experimental paradigms are required that will transiently, and safely, disrupt brain function, to causally demonstrate how face-selective regions operate with each other and with brain regions that process different cognitive functions such as emotion and memory. Studying the effects of disruption in this manner will help us to better understand how brain damage and brain disorders (e.g. autism) can impact human behaviour.

The experiments in this proposal address this issue using a novel combination of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and neuropsychology. TMS can transiently, and safely, disrupt a targeted brain region and, when combined with fMRI, it offers a powerful experimental tool for causally studying the cognitive functions of brain networks. Transiently disrupting the brains of neurologically normal participants with TMS and measuring the effects of this disruption with behaviour and fMRI is a safe and replicable way to build on more than two hundred years of neuropsychological research.

We will use TMS to disrupt brain regions implicated in social perception, such as those that process facial expression and speech, and measure what impact this has on the brain. The results of these studies will be used to generate detailed maps of the causal functional connectivity of the face-processing network. The behavioural relevance of these functional connections will also be tested in behavioural TMS experiments and neuropsychological studies of a patient with face recognition deficits, to further establish how disruption impacts face-processing behaviour. Then, in the final stages of the project, we will perform a meta-analysis of all acquired combined TMS/fMRI, TMS and neuropsychological data to produce a new causal model of the face-processing network.

A new causal model of the connections and cognitive operations of the face-processing network is important because it will give us a better description of how complex cognitive functions are processed across multiple brain regions. This model will also have clinical relevance. Abnormal face-processing performance has been shown in individuals with brain disorders, such as autism and schizophrenia. Mapping the functional connections of the face-processing network will enhance understanding of how brain connectivity can be impaired in these social brain disorders. For example, by identifying target nodes in social disorders, such as the face-selective STS region, for future study and possible treatment.

Highly influential models of primate visual cortex propose that it is divided into two functionally distinct pathways for processing either the identify, or the location of an object. While remaining highly influential these models require revision. The aim of this proposal is to define the cortico-cortical connections and functions of a third visual pathway, specialised for social perception. This will be achieved using a novel combination of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and neuropsychology. The model system in which this will be demonstrated is the human cortical face processing network. At present, these types of studies are not widely used but they offer a powerful way to establish the impact of disruption on the brain networks that underpin behaviour. Establishing the effects of this disruption in the neurologically normal brain with TMS offers a novel approach for modelling how the brain could be disrupted in brain disorders that impair social interaction such as autism.

Across a series of experiments we will demonstrate that motion is an essential component of this third pathway and that the third pathway is lateralised to the right hemisphere. This will be achieved by disrupting facial expression and spoken language discrimination tasks with TMS. The functional connections of the third pathway will also be established in two combined TMS/fMRI experiments and in an fMRI study of an acquired prosopagnosic patient with a lesion to his right ventral occipitotemporal cortex. Taken together this series of experiments will demonstrate the behavioural impact of disrupting the third pathway on human behaviour. In the final stages of the project we will perform a meta-analysis of all acquired brain and behavioural data to build a new causal model of the face processing network. This will be of great value to researchers studying the brain networks that underpin human behaviour.

The principle beneficiaries of this research will be medical professionals involved in diagnosing autism and social deficit disorders.

Using the cortical face perception network as a model system to better understand ASD is pertinent because of the behavioral impairments exhibited by autistics. Compared to control participants, individuals with ASD are impaired during social interactions, and faces are one of the most salient social stimuli we encounter. This suggests that face-selective regions in the ASD population may also be impaired. Consistent with this hypothesis prior neuroimaging studies have demonstrated that individuals diagnosed with ASD show abnormal neural responses to faces in face-selective regions of the brain such as the fusiform face area (FFA). Disrupting the face processing network with TMS and measuring how this disruption impacts both the brain and behaviour can improve autism diagnostic techniques. In addition it may also suggest possible treatments, for example by identifying brain areas for future brain stimulation experiments.

Autism spectrum disorders (ASD) are at least four times more likely to be diagnosed in males than females but the biological basis of this gender discrepancy is not understood. This makes identifying biological markers of the behavioral differences between the genders an important issue for autism research. If differences in face discrimination abilities exist between females and males in the neurologically normal population then this could suggest one reason why males are more likely to be diagnosed with ASD than females.

The proposed research will collect a large volume of brain and behavioural data from a mixed gender neurologically normal experimental participant group. We will then be able to examine whether the cortical disruption induced by TMS has a differential effect between the genders. For example, it may be the case that female participants are less susceptible to TMS disruption of social brain areas, such as the superior temporal sulcus (STS). If this is the case then this may aid individuals engaged in diagnosing autism and social deficit disorders. To facilitate this outcome we will establish connections with the Leeds Autism Diagnostic Service (LADS) to investigate whether any of their diagnostic criteria can directly inform the proposed research. (http://www.leedsandyorkpft.nhs.uk/our_services/Specialist-LD-Care/LADS).