http://web.mit.edu/swg/ImagingPubs/connectivity/horwitz.neuroimage.2003.pdf

The elusive concept of brain connectivity.

Functional connectivity among brain regions has been investigated via an analysis of correlations between regional signal fluctuations recorded in magnetic resonance (MR) images obtained in a steady state. In comparison with studies of functional connectivity that utilize task manipulations, the analysis of correlations in steady state data is less susceptible to confounds arising when functionally unrelated brain regions respond in similar ways to changes in task. A new approach to identifying interregional correlations in steady state data makes use of two independent data sets. Regions of interest (ROIs) are defined and hypotheses regarding their connectivity are generated in one data set. The connectivity hypotheses are then evaluated in the remaining (independent) data set by analyzing low frequency temporal correlations between regions. The roles of the two data sets are then reversed and the process repeated, perhaps multiple times. This method was illustrated by application to the language system. The existence of a functional connection between Broca's area and Wernicke's area was confirmed in healthy subjects at rest. An increase in this functional connection when the language system was actively engaged (when subjects were continuously listening to narrative text) was also confirmed. In a second iteration of analyses, a correlation between Broca's area and a region in left premotor cortex was found to be significant at rest and to increase during continuous listening. These findings suggest that the proposed methodology can reveal the presence and strength of functional connections in high-level cognitive systems.

/pdf/detection-of-functional-connectivity-using-temporal-53dcmkqdfo.pdf

Detection of functional connectivity using temporal correlations in MR images.

• In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessivecompulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus.

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine.

In a sample of chronic schizophrenic patients, a group of symptoms which included poverty of speech and lack of spontaneous movement was found to be associated with poor performance in tests of conceptual thinking, object naming and long-term memory, and also with cortical neurological signs. A second group of symptoms which included formal thought disorder and inappropriate affect was associated with poor performance in tests of concentration, immediate recall and word learning, and with cortical neurological signs. The findings suggest that these two syndromes are associated with dysfunction at two different sites within the frontal lobes. A third group of symptoms, comprising various delusions and hallucinations, was associated with poor figure-ground perception, and might reflect temporal lobe dysfunction.

Schizophrenic syndromes, cognitive performance and neurological dysfunction.

A method for using blocked and event-related fMRI data to study “resting state” functional connectivity

This article describes a method for partitioning metabolic variability found in positron emission tomography/[18F]fluorodeoxyglucose studies. For the 15 subjects examined, 74.8% of the total metabolic variability could be ascribed to individual differences in global metabolic rate, whereas 15.8% of the total variability was consistent regional variation or pattern across subjects. Subsequently, the method of Q-component analysis is described for the identification of strong- and weak-pattern subjects. In addition, a standardization procedure that amplifies the observed pattern by removing systematic individual differences is described. Finally, the implications of these findings and methods for future and clinical studies are discussed.

Alternative statistical models for the examination of clinical positron emission tomography/fluorodeoxyglucose data.

Correlational methods for determining regional coupling of cerebral glucose metabolism: a pilot study.

The ability to study patterns of cerebral metabolism in humans noninvasively is clearly one of the great advantages of positron tomography. The development of the 18F-labeled 2-fluorodeoxyglucose (218FDG) method has produced a powerful tool for studying cerebral energy metabolism with positron tomography (Huang et al. 1980). Given the tight coupling normally existing between cerebral function and energy metabolism (Sokoloff 1977, 1981), 218FDG has been used to study resting patterns of metabolism in resting subjects (Mazziotta et al. 1981), subjects undergoing neuropsychological activations (Greenberg et al. 1981), and schizophrenic subjects at rest and off medication (Buchsbaum et al. 1982).

C. M. Clark

Papers

Alternative statistical models for the examination of clinical positron emission tomography/fluorodeoxyglucose data.

Correlational methods for determining regional coupling of cerebral glucose metabolism: a pilot study.

Regional Correlations in Patterns of Glucose Use in Patients with Schizophrenia and Normal Subjects During Mild Pain Stimulation