Clinical trial NCT06108336: Cerebellar Involvement in Cognitive Sequencing
Official title: Investigation of Cerebellar Involvement in Cognitive Sequencing
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Effects of Cerebellar Stimulation on Brain Activation
Keywords: sequencing
cerebellum
transcranial magnetic stimulation
TMS
functional MRI
fMRI
verbal working memory
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2023-10-31
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cerebellar and Occipital stimulation groups will be tested under sequence-demanding and non-sequence demanding tasks (in counterbalanced order)
Primary purpose: BASIC_SCIENCE

Brief summary: Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. One theory that might account for both motor and cognitive contributions of the cerebellum is that the cerebellum is involved in sequencing of relevant events or stimuli. Previous experiments have suggested that disruption of the cerebellum impairs the prediction of the next event in a sequence. The present experiment will examine the impact of cerebellar stimulation on brain activation during the performance of both sequence-demanding and non-sequence-demanding tasks.

Detailed description: Although there is increasing recognition that the cerebellum, which contains half of the brain's neurons, is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. The uniform circuitry of the cerebellum and the extensive connectivity of the cerebellum with numerous neocortical regions has suggested to some researchers that there is a common computation that the cerebellum performs for both motor and cognitive functions. The cerebellar sequencing hypothesis posits that the cerebellum acquires sequence information, makes sequence predictions, and detects sequence violations. These functions, executed via a forward model, could underlie cerebellar involvement in both motor and cognitive behavior. In motor control, such predictions can be used to guide limb trajectory without reliance on movement-generated sensory feedback. In cognition, sequencing requirements are prominent in both verbal working memory (VWM) and language acquisition; eg, in VWM, keeping a phone number in mind requires encoding and rehearsing a sequence of digits. In language, words consist of sequences of syllables, and the learning of syllable transition probabilities is an important component of recognizing legal words in a language. Importantly, prominent cerebellar activation has been observed in many functional MRI (fMRI) VWM and language studies. However, the brainstem/cerebellar neural correlates of sequencing in cognition, and the influence of cerebellar sequence predictions on neocortical targets, are poorly understood. In this experiment, studying healthy individuals the investigators will Investigate the cerebellum as a source of sequence prediction and its influence on forebrain areas. The cerebellum is hypothesized to provide its forward model sequence prediction to forebrain targets, but to date no study has attempted to visualize with concurrent TMS/fMRI the consequences of disrupting this cerebellar input on forebrain activation. In the investigators previous work, the investigators show that transcranial magnetic stimulation (TMS) during the rehearsal of a sequence of letters results in errors in determining if a probe letter matches the next letter in the sequence, suggesting that TMS disrupted this predictive input. In accordance with this finding, the investigators hypothesize that, using concurrent TMS/fMRI, TMS disruption during a sequencing task will produce greater changes in neocortical activation relative to an analogous control task that does not have the predictive component brought out by sequencing demands. The investigators further hypothesize that different patterns of neocortical activations in response to cerebellar TMS will be observed depending on whether a probe letter matches the expected next letter in a sequence.

Eligibility criteria: Inclusion Criteria:

* 1) Age 18-50;
* 2) educational attainment of at least 8 years;
* 3) capable of giving informed consent;
* 4) fluent speaker of English by self-report;
* 5) right handed.

Exclusion Criteria:

* 1) illicit drug use within 30 days of MRI scanning;
* 2) neurological or systemic disorder which can cause dementia or cognitive dysfunction;
* 3) history of an Axis I psychiatric disorder including substance use disorder;
* 4) history of definite stroke;
* 5) focal lesion on MRI exam;
* 6) uncorrected visual deficits by self-report
* 7) contraindications for MRI scanning
* 8) use of anxiolytic, antidepressant, neuroleptic, or sedative medication
* 9) Additional exclusion criteria recommended by Wassermann for TMS neuromodulation, including: History of seizure or a family history of epilepsy, heart disease, intracardiac lines, increased intracranial pressure, history of head trauma, and history of respiratory disease

Primary outcomes:
measure: functional magnetic resonance imaging brain activation
timeFrame: during scan up to 1 hour
Secondary outcomes:
measure: percent correct of behavioral responses
timeFrame: during scan up to 1 hour
measure: behavioral reaction time (milliseconds)
timeFrame: during scan up to 1 hour
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: John E Desmond, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: