Projects in the lab are concerned with cognitive/psychiatric disorders and comparative evolutionary neuroscience. We are interested in the relationship between brain structure and function - particularly language and social cognition.
The disorders investigated in the lab are autism, schizophrenia and dementia. All are characterised by relatively subtle, pervasive abnormalities but each takes hold at a different stage in the human lifespan: autism in early development, schizophrenia in adolescence/early adulthood, and dementia in late life. Our investigations into the anatomy of these disorders reveal that brain changes can only be understood with reference to the background trajectory of brain growth, stabilization, and ageing. For example, the transition from vigorous early developmental neuroplasticity to more subtle persistent adult neuroplasticity is an extended process in human association cortex which is particularly vulnerable to abnormalities in each of these disorders.
Current work on autism is funded by a 3 year project grant from Autism Speaks, begun in April 2011. The goal of the study is to investigate the neuroanatomy of the social cognitive network in autism. The study investigates minicolumn organisation as increased number and narrowed width of minicolumns is one of the most prominent neuropathological findings in autism.
This study exploits the contrasting predictions made by two structural hypotheses: the minicolumn hypothesis (Casanova 2002), and the association cortex hypothesis (Buxhoeveden et al 2006 -the argument that neuropathology is more marked in areas of association cortex due to their involvement in higher cognitive functions while primary sensory cortex does not differ from controls). To enable these contrasts we are studying association cortex and two primary sensory regions not previously examined in autism - primary auditory cortex which does contain minicolumns, and a control region, piriform olfactory cortex, which is neither association cortex nor typically columnar.
In collaboration we have also compared putative anomalies of the sub-ependymal zone and rostral migratory stream in autistic brains. This is of interest as progenitor cell proliferation in the sub-ventricular zone may be at fault in autism (Pontious et al 2008).
The minicolumn structure of the cerebral cortex is remarkably sensitive to hierarchical differences between cortical regions - narrow in primary sensory and wide in association cortex. The neuropil space around the minicolumn thins with age in association cortex unlike primary sensory cortex (Chance et al 2006). It demonstrates regionally selective correlations with cognitive measures (ie. only in those regions associated with the measured function) in primates (Cruz et al 2009), and we have recently extended this finding to humans. A two-stage process appears to occur: 1) a loss of neuropil associated with normal ageing and minicolumn thinning, and (2) a loss of cells associated with dementia symptoms and microanatomical disruption.
Recent developments in the clinical and neuropsychological profiling of mild cognitive impairment (MCI) indicate that this category contains members who appear to be worsening with time and are presumed to be progressing to dementia as well as members who appear to have a mild impairment that is relatively stable (eg. De Jager & Budge 2005). It is of considerable aetiological and clinical interest to identify the distinguishing markers of these different groups (Portet et al, 2006). We have been pursuing the neuropathological differentiation of these two subgroups within the MCI cohort in OPTIMA.
The relative expansion of neuropil in the more neuroplastic, human neocortex (and its vulnerability to pathology) is thought to depend on gene expression. Gene expression associated with neuroplasticity and its interaction with ApoE genotype, the most prominent genetic risk factor for Alzheimer's disease, is of interest.
Previous work on schizophrenia indicates that the transition from early developmental plasticity to the mature state does not occur successfully in patients who suffer a failure of this adult neuroplasticity at a time point that may be linked to the age of illness onset (Chance et al 2008). This hypothesis is supported by recent meta-analysis of age related effects on cell organisation in schizophrenia (Chance et al 2009). The neuroanatomical focus of some of this work has been the auditory cortex due to its role in language and auditory hallucinations.
More recently we have begun investigating the inferior parietal lobe in schizophrenia patients due to its role in social cognition, as well as possible candidate genes involved in age-associated changes in neuroplasticity in schizophrenia.
Our research concerns the neural basis of human cognition. The lab is interested in how this has evolved in primates and how it has shaped and constrained human behaviour and cultural expression.
We have investigated brain asymmetries in auditory cortex, including within 'Wernicke's area'. We have found that the structure of these areas and the interhemispheric connections between them tend to be different between the sexes. Semantic processing and verbal fluency analysis are interesting in dementia and schizophrenia where they appear to reveal altered organisation or access to semantic memory. Ongoing work aims to understand how semantic space (the map of word meanings) develops in humans and degrades in disease. We are also using a mechanistic interpretation of cortical microcircuits (minicolumns) as a hypothesis to investigate the neural basis of this.
Recent work includes a chimpanzee-human comparison of the anatomy of the area of the brain that supports face processing (the fusiform gyrus) and a chimpanzee-human comparison of facial expression categorisation for con-specific faces. The indications are that brain structure in chimpanzees and in the human right hemisphere fits with the bias towards holistic face processing, but humans are distinguished by the presence of asymmetry related to more categorical processing in the language-biased left hemisphere.
We have previously found that fusiform cortex structure changes with age in humans which may be involved in the tendency for dedifferentiation of face recognition in older people. We also found that in schizophrenia the anatomical ageing changes are not observed which may be due to the absence of neuroplastic modification of brain microstructure.
A network of brain regions is thought to play a prominent role in social cognition. We are investigating several of these regions in different disorders. For example, we have found that some patients with mild dementia have specific deficits in recognising known individuals and these patients have selective atrophy of the anterior medial temporal lobe. Future work is intended to make further measurements for comparisons between several primate species. The development of these structures may be influenced by social group size and social dominance of the individual animals.
Comparative neuroanatomical work in the lab has demonstrated that the chimpanzee brain does not have as much diversity of structure as that seen in human brains, with less hemispheric asymmetry. However, chimpanzees have a relatively well developed prefrontal cortex microstructure. Ongoing work is designed to assess the extent of difference between trajectories of development for individual brain regions in chimpanzees and humans. We are interested in the implication that nutritional requirements and gene expression may consequently have greater effects at different points in the lifespan.