By Douglas Labar, MD, PhD

Professor of Neurology, Weill Cornell Medical College

Dr. Labar reports no financial relationships relevant to this field of study.

SYNOPSIS: In this pilot study, transcranial direct current stimulation appeared to improve some aspects of verbal object identification and naming in a small number of patients with primary progressive aphasia.

SOURCE: Teichmann M, Lesoil C, Goddar J, et al. Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia. Ann Neurol 2016;80:693-707.

Transcranial direct current stimulation (tDCS) delivers stimulation via conducting sponges affixed to the patient's skull. A steady state current is passed through the scalp and skull and into the brain. The resultant changes in resting membrane potentials alter neuronal firing rates, thus influencing brain function. Historically, current has been passed through large brain regions, often in a multilobar fashion from hemisphere to hemisphere. Recent technical advances have allowed more selective stimulation of topographically discrete zones. This permits isolation of unique cortical functions for detailed investigation.

One such small cortical area of interest is the temporal lobe tip. This area can be targeted for excitatory (anodal) or inhibitory (cathodal) focal stimulation. In primary progressive aphasia (PPA) patients, the left temporal tip shows hypoactive metabolism, on positron emission tomography (PET). Thus, it may be hypothesized that excitatory anodal tDCS of the left temporal tip may improve language function in PPA. Furthermore, inhibitory cathodal stimulation of the right temporal tip may reduce its interference with left side function, restoring interhemispheric balance, and in turn improving language.

In 2016, Teichmann et al treated 12 PPA patients with tDCS. Patients were tested before and after single 20-minute sessions of active or sham tDCS. Several features of the research were designed to segregate specific from nonspecific treatment effects. Patients were selected for the presence of very focal (and testable) deficits, which is a characteristic of the semantic variant of PPA. Clinical evaluation employed tests involving materials matching. Presented items for the matching tasks were subdivided into living (e.g., animals) vs. nonliving (e.g., inanimate objects) items, and into visual vs. verbal modalities. Normal control subjects were included to eliminate any performance changes that might not be related to treating the PPA.

In the verbal modality, which covered the most important deficits in these patients, left-excitatory plus right-inhibitory tDCS improved post-stimulation performance. In the visual modality, there were no changes due to stimulation. When the testing material was in the verbal modality and the living category, right-side inhibitory tDCS, but not left-side excitatory tDCS, improved performance. There were no nonspecific tDCS-associated changes in overall cognitive and attentional functions.

COMMENTARY

This study design and results by Teichmann et al demonstrated a thoughtful application of our knowledge concerning tDCS physiological effects to a disease state’s physiological functional disturbances. Most likely, excitatory stimulation, to antagonize the patients’ depressed cortical activity state (as demonstrated on their baseline PET scans), truly led to improved verbal semantic function. This leads to the interesting concept of selecting and targeting brain illnesses and treatments based on baseline imaging functional assessments, such as the baseline hypometabolic temporal tips, seen in the patients in this study.

However, it is not just the location and nature of the brain hypofunction treated in this study that is of interest. The authors provided evidence that an imbalance between hemispheres, and an intervention to help re-establish appropriate interhemispheric balance, were significant operative components in producing a good outcome. This is an example of an evolution into neurological assessments and treatments directed toward restoring and maintaining critical neural networks and balances, as opposed to focusing on the discrete functions of isolated brain nuclei or fiber pathways.

This study may have several avenues for follow-up research. Do the abnormalities on baseline PET scans improve in parallel with the improvements in semantic functions? Finally, the durability of the effects would be of interest. Is tDCS somehow temporarily boosting neural function, which then returns to baseline? Or are the effects more long-lasting? Were the latter true, this would be of considerable interest for future clinical applications.