Connections, Disconnections, and Neuromodulation: Advancing Prognosis and Therapy in PPA

Most individuals with primary progressive aphasia (PPA) initially have trouble retrieving names and spelling.  However, subsequent decline in language may be rapid or slow, or evolve to near muteness or fluent jargon with little comprehension of language.  We report new ways to identify individuals with the semantic variant early in the disease – those who will later progress to fluent jargon with poor comprehension of language – before they show these deficits on traditional testing. Their eye movements give away their lack of confidence in identifying which picture matches a spoken word, and provide clues to the difficulty they will later have in understanding spoken words.

            Relatively new imaging techniques show which areas of the brain have similar activation patterns at rest and indicate that these areas are functionally connected.  This “functional connectivity MRI” can also show how strongly these areas are connected with each other (by how closely they activate together).  We show that the degree of connectivity between the right and left prefrontal cortex predict how quickly the individual will decline in language.  Lower connectivity across prefrontal cortices (areas important for many higher level cortical functions) is associated with more rapid decline.

            Speech and language treatment is the main intervention for PPA, for reducing decline or even bringing about temporary improvement.  We show that response to treatment depends on both the variant of PPA and the degree of atrophy in right inferior frontal gyrus.  Finally, transcranial direct current stimulation (tDCS), a noninvasive, nonpainful electrical stimulation over the skull, can sometimes enhance the effects of speech and language intervention, at least for  a few months. Individuals with PPA showed more improvement in with language treatment during periods when treatment was accompanied by tDCS. Furthermore, people with PPA who received tDCS with language treatment showed increased functional connectivity between left and right inferior frontal gyrus (IFG), while those who received sham tDCS with language treatment showed no change in connectivity.   This increase in connectivity positively correlated with the volume of the right IFG and also positively correlated with improvement in language with treatment. Together, results indicate that the ability to improve or maintain language, at least temporarily, may depend on the health of the right frontal cortex and its connectivity with left frontal cortex.  Functional connectivity might be augmented with language intervention plus tDCS.