The Use of fMRI for Detecting Abnormal Neural Synchronization

Lay Summary

Using fMRI to Determine Whether Nerve Firing is Unsynchronized in Parkinson’s Disease

Based on the researchers’ Dana-supported demonstration that a new MRI imaging technique can non-invasively detect asynchronous firing of neurons, the investigators now will determine whether this abnormal firing occurs in patients with Parkinson’s disease.  If so, their research could provide a better understanding of the disease process and new approaches to treating it.

Previous studies have shown that Parkinson’s disease patients have pronounced cell loss within the brain’s basal ganglia, and a correspondingly low level of brain dopamine, a neurotransmitter that facilitates cell to cell communication.  Decreased dopamine levels disrupt the connection between the basal ganglia and the brain’s cortex.  This disruption results in the disease’s familiar symptoms of tremor, difficulty initiating movements, and muscle rigidity.  Surgical intervention in selective parts of the basal ganglia can alleviate most of these motor symptoms.

Yet some experimental findings suggest that this model is over-simplified.  The researchers hypothesize that brain cells in the basal ganglia do not fire synchronously in a coherent pattern.  This asynchronous firing decreases the brain cells’ connectivity locally in the basal ganglia and globally to the cortex, resulting in the Parkinson’s symptoms.  The investigators have shown that a new MRI technique, called “RCC” (Radical Correlation Contrast), can non-invasively reveal basal ganglia cell firing.  They will use this technique to compare synchronization patterns at rest and during activation in healthy and Parkinson’s disease model rats.  Thereafter, they will use MRI-RCC to compare synchronization patterns in Parkinson’s patients to those of healthy adults.  If the investigators are correct, this study would provide new insight into the disease process, a new method for diagnosing and defining the disease’s severity, and a way to assess therapies designed to re-synchronize nerve cell firing.

Significance:  If this imaging technique reveals that asynchronous firing of nerve cells in the basal ganglia occurs in Parkinson’s disease, the findings could lead to new insights into the disease process, improved early diagnosis, and assessment of treatments designed to restore synchronization.

Abstract

The Use of fMRI for Detecting Abnormal Neural Synchronization

At present the function of the basal ganglia (BG) in the control of motor and cognitive functions is still unresolved. The common models of the circuitry between the BG nuclei and the cortex that are used to understand BG clinical disorders can not explain all clinical symptoms of the disease or recent findings of pre-frontal overactivation. Our recent studies on MPTP, a primate model of Parkinson's disease (PD), suggest that temporal patterning and temporal coherence of neural signals may have a key role in the processing carried out by the basal ganglia - cortex circuit. We therefore hypothesize that the loss of processing in spatially and temporally independent channels in the basal ganglia-cortical networks, is an important pathophysiological principle of hypokinetic (e.g., Parkinson's disease) and hyperkinetic (L-DOPA induced dykinesias) movement disorders. However, today only invasive methods can be used for evaluating the synchronicity of neural network and even these methods give limited information.

In this project we propose to use our recently developed MRI Radial Correlation Contrast (RCC) method that, non-invasively, gives information on neuronal synchronization to study the changes in BG-cortex synchronization in Parkinsonian state. In the new RCC approach (as extension of the function connectivity MRI method), two complimentary types of images are obtained from each set of functional MRI data. One is proportional to the average neuronal synchronization of each volume element with its vicinity, and the other gives the weighted direction of this synchronization. The method was demonstrated on high spatial resolution data from rat brain. It was shown that functional clusters, like cortical layers, are distinguishable based on their different inter-communication. The RCC method will be optimized for human studies including its extension to 3D and will be used to map the changes in the BG-cortex synchronization circuit in human as well as in rodent 6-OHDA model of Parkinson's disease.

The expected outcome of the project is two-fold. One is better understanding the role of the BG in normal and pathological states and the other is a unique non-invasive method to map functional neuronal synchronization.