Clinical trial NCT05412901: Scaffolding of Brain Operations
Official title: Scaffolding of Brain Operations: the Role of Beta Oscillations in Forming Flexible Neural Ensembles
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Behavioral Performance
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
First posted: 2022-06-09
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Brain activity will be recorded while participants rest and/or perform perceptual discrimination tasks. These tasks include the presentation of sensory stimuli and require participants to detect and discriminate these stimuli, and to report about the objective properties of the stimuli as well as about their subjective perceptual experience using ratings of confidence, visibility, and/or alertness/sleepiness. All sensory stimuli used are neutral and consist of visual stimuli presented on a computer screen (either basic visual stimuli, e.g. an arrow, a grating or a dot, or neutral pictures of e.g. objects, buildings, landscapes), or auditory stimuli presented via headphones (either basic sounds, e.g. a beep or noise, or more complex sounds, e.g. a spoken word or rhythm). The experimental tasks may require participants to compare between sensory stimuli presented at different spatial locations or at different times, and/or to focus their attention on specific stimuli while suppressing distracting information; additionally, tasks may require participants to remember these stimuli for a delayed report. In these tasks, participants' performance will be quantified by motor responses (i.e., button press), reaction times and subjective ratings (confidence, visibility, alertness/sleepiness).

Brain activity will be recorded by means of electroencephalography (EEG), a non-invasive technique consisting of electrodes placed along the scalp that record electrical field potentials generated by cortical neurons. EEG will be used to record brain activity prior to and in response to the sensory stimuli presented during the cognitive and perceptual tasks as well as during the participants' responses. Additionally, EEG may be used to record brain activity during a baseline resting state, while participants are not engaged in any particular tasks. In particular, the analysis of the EEG signal will focus on event-related brain activity (i.e., in response to the stimuli) such as event-related potentials (ERP), as well as ongoing and spontaneous and/or induced brain activity quantified as oscillations: wave-like signal fluctuations reflecting rhythmic variations of membrane potentials of cortical neurons. In addition, the investigators will use MRI to take an anatomical image of the brain to facilitate localizing the sources of the activity measured with EEG.

Detailed description: The brain constantly makes decisions based on perceptual input as well as internal signals, quickly weighing and processing information, leading to goal-directed behavior. One key aspect crucial to all these processes is communication the transfer of information from one brain network to the next. However, we are only beginning to understand how the brain accomplishes this. Here, the investigators propose to study exactly this question. The overarching goal of this project is to elucidate how the brain sets up the functional neural architecture involved in working memory and decision-making. The investigators argue that brain oscillations in the beta frequency band 1530 Hz play a critical role in forming flexible neural ensembles. The investigators propose a novel theoretical framework, delineating how the beta rhythm flexibly sets up transient networks, linking neuronal circuits that are relevant to current task demands, especially in terms of endogenous information processing e.g., working memory, decision-making. In this view, beta provides the scaffolding for information transfer,routing information through the brain by temporarily connecting relevant nodes such that exchange of information can take place. The investigators propose that the beta rhythm briefly activates a neural ensemble, allowing it to broadcast its message encoded in population spike activity such that it can be efficiently and effectively received. To test this framework, the aim here is to (1) examine the role of beta oscillations in dynamic neural ensemble formation and its relation to behavioral performance, (2) identify the underlying circuit-level physiology of beta-mediated ensemble formation, and (3) establish the generality of beta-mediated ensemble formation and identify non-invasive biomarkers. The investigators will use a combination of EEG recordings in healthy human subjects, and intracranial electrophysiology and optogenetic neuromodulation in awake-behaving rodents. Both human subjects and animals will perform a spatial working-memory paradigm, critically allowing vertical integration across recording levels. Human subjects will additionally perform working-memory tasks in different sensory modalities and at higher levels of abstraction to guarantee generalizability of results, and to allow for identification of biomarkers to be used in future patient studies. This approach is designed to answer core mechanistic questions how are local ensembles formed and how are these modulated Critically, the investigators will determine the effect of these mechanisms on behavior. The project will provide fundamental insights that will set the stage for further detailed investigations in healthy human subjects and patients with impaired beta functioning and cognitive impairment, such as in Parkinson's disease and schizophrenia.

Eligibility criteria: Inclusion Criteria:

* English speaking
* Normal (or corrected-to-normal) vision, normal hearing

Exclusion Criteria:

* Epilepsy, past brain surgery, neurological or psychiatric disorders for which they are on medication

Primary outcomes:
measure: EEG spectral beta power
timeFrame: during procedure
Secondary outcomes:
measure: behavioral performance: accuracy
timeFrame: during procedure
measure: behavioral performance: reaction time
timeFrame: during procedure
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: NYSPI
name: Saskia Haegens, PhD
role: PRINCIPAL_INVESTIGATOR
References: