Peter C. Williamson

Bio: Peter C. Williamson is an academic researcher from University of Western Ontario. The author has contributed to research in topics: Default mode network & Prefrontal cortex. The author has an hindex of 50, co-authored 102 publications receiving 11279 citations. Previous affiliations of Peter C. Williamson include Lawson Health Research Institute & Robarts Research Institute.

Toward discovery science of human brain function

Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

Spontaneous Low-Frequency Fluctuations in the BOLD Signal in Schizophrenic Patients: Anomalies in the Default Network

Abstract: Spontaneous low-frequency fluctuations in the blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A “default network” of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.

Neural Correlates of Traumatic Memories in Posttraumatic Stress Disorder: A Functional MRI Investigation

Abstract: OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann’s area 32), and the medial frontal gyrus (Brodmann’s area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers.

Abstract: OBJECTIVE: This in vivo 1H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in patients experiencing their first episode of schizophrenia. METHOD: Localized in vivo 1H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 never-treated patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects. No differences were found between groups in the levels of other metabolites in the anterior cingulate or thalamus. CONCLUSIONS: Higher than normal glutamine levels in the left anterior cingulate and thalamus provide in vivo evidence of greater than normal glutamatergic activity proposed by glutamatergic models of schizophrenia. In contrast to other studies in chronically ill patients, no differences were seen in the levels of N-acetylaspartate in either locati...

The Brain's Default Network Anatomy, Function, and Relevance to Disease

Abstract: Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Abstract: Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging.

Abstract: The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.