Cerebellar Stimulation and Verbal Working Memory in Early Course Psychosis: Insights From Functional Neuroimaging

Project: Research project

Description

An emerging body of evidence suggests that cerebellar-thalamic-cortical-cerebellar (CTCC) circuits play an important role in articulatory control (frontal-superior cerebellar) and phonological storage (parietal-inferior cerebellar) functions supporting verbal working memory (VWM) in healthy individuals. This may have significant relevance for psychosis, which is characterized by abnormalities in cerebellar activation as well as marked deficits in VWM. Because the ability to hold and manipulate verbal information is central to achieving goals and problem solving, deficits in this VWM disrupt every-day interactions, and contribute to diminished quality of life, and to disability. However, recent studies have demonstrated that among healthy individuals, excitatory stimulation of the lateral posterior cerebellum with transcranial direct current stimulation (tDCS) can modulate VWM function. While preliminary evidence indicates cerebellar hypofunction abnormalities during WM in psychosis patients, there is limited knowledge about the role abnormal CTCC function plays in VWM deficits in psychosis and to date, there have been no investigations designed to determine if cerebellar tDCS can improve VWM in psychosis. This is particularly noteworthy as the cerebellum is central to prominent theoretical conceptualizations such as cognitive dysmetria, but has been largely overlooked in functional imaging studies aimed at evaluating etiology and treatment target development studies. In this randomized double-blind cross-over study, 40 patients with early course psychosis (ECP) will be administered an excitatory cerebellar stimulation (2mA, unipolar anodal montage) or sham (placebo) for 25 minutes immediately before participating in a functional magnetic resonance imaging (fMRI) experiment designed to assess neural networks utilizing a validated Sternberg VWM task. Participants will later return for a second visit after seven days and receive the counterbalancing condition (sham or stimulation) as well as the subsequent fMRI experiment. A group of 40 healthy control (HC) participants will be assessed with the fMRI experiment as well (receiving sham stimulation). The study will first aim to map out differences between the ECP and HC group in cerebellar-cortical network activation and task performance (reaction time and accuracy). Evaluating group contrasts between the ECP and HC participant’s performance following the sham stimulation condition (for both groups) will provide an invaluable perspective of cerebellar contributions to VWM deficits, and also help to provide benchmark for interpreting the predicted normalizing effects of the stimulation trial. Then, the study will evaluate potential changes in circuit activity between the sham and active excitatory stimulation sessions in ECP participants, in conjunction with changes in the behavioral VWM performance. This aim will test the potential of excitatory stimulation to address the putative contributions cerebellar-cortical circuit hypofunction to higher order VWM. Further, the highly innovative strategy of examining the effects of cerebellar excitatory stimulation on VWM with an fMRI paradigm will provide a new understanding for how these critical circuits behave when modulated in individuals with psychosis, yielding a dynamic perspective of CTCC dysfunction and clearer picture about potential mechanism of action. Taken together, this study will improve our understanding of the role that CTCC circuits play in contributing to cognitive deficits in psychosis, and lay the groundwork for p
StatusActive
Effective start/end date3/15/18 → 3/14/20

Funding

  • Brain & Behavior Research Foundation (25780)

Fingerprint

Functional Neuroimaging
Short-Term Memory
Psychotic Disorders
Magnetic Resonance Imaging
Memory Disorders
Cerebellum
Healthy Volunteers
Cerebellar Diseases
Benchmarking
Cerebellar Ataxia
Aptitude
Task Performance and Analysis
Cross-Over Studies
Action Potentials
Reaction Time
Placebos
Quality of Life