Mid-frontal Delta/Theta and Cognitive Control

Summary

Abstract Cognitive symptoms of Parkinson's disease (PD) include deficits in attention, working memory, and reasoning. These deficits affect up to 80% of PD patients and lead to mild cognitive impairment (PD-MCI) and dementia in PD (PDD). There is a critical need to better understand cognitive impairment in PD to develop new targeted treatments. The long-term goal is to define the mechanisms of PD-related cognitive impairment. PD involves diverse processes such as dopamine and acetylcholine dysfunction, synuclein aggregation, and genetic factors. During the past funding period, the investigators linked PD-related cognitive impairment to dysfunction in frontal midline delta (1-4 Hz) and theta (5-7 Hz) rhythms, which the work has established as a marker of cognitive control. However, it is unknown why PD patients have deficits in these low-frequency brain rhythms. The preliminary magnetic resonance imaging (MEG) and magnetoencephalography (MRI) implicate the anterior midcingulate cortex (aMCC) as a potential source of frontal midline delta/theta rhythms. In the next funding period, the objective is to determine the mechanisms and predictive power of delta/theta rhythms in PD, which will help to better understand the pathophysiology of PD-related cognitive impairment. Collaboration between the University of New Mexico (UNM) and University of Iowa (UI) that will bring together MEG, MRI, longitudinal EEG, and adaptive subthalamic (STN) deep-brain stimulation (DBS). The investigators will test the overall hypothesis that frontal midline delta/theta dysfunction contributes to cognitive impairments in PD. In Aim 1, the investigators will determine the structural basis for delta/theta rhythm deficits in PD. In Aim 2, the investigators will determine the predictive power of delta/theta rhythm deficits in PD. In Aim 3, the investigators will determine how tuned low-frequency STN DBS impacts cortical activity and cognition. The results will have relevance for basic-science knowledge of the fundamental pathophysiology of cognitive impairment in PD and related dementias. Because this proposal will study patients with PDD, the findings are directly relevant to Alzheimer's-related dementias (ADRD).

Interventions

• Deep-brain Stimulation · DEVICE

  a neurosurgical procedure that uses implanted electrodes and electrical stimulation to treat movement disorders and certain neuropsychiatric conditions when medications are ineffective or cause significant side effects.

• Transcranial Magnetic Stimulation · DEVICE

  Transcranial magnetic stimulation (TMS) is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain.

• Transcranial Alternating Current Stimulation · DEVICE

  Transcranial Alternating Current Stimulation (tACS) is a non-invasive brain stimulation technique that uses weak, alternating electrical currents applied to the scalp to modulate brain activity and potentially influence cognitive processes by entraining brain oscillations.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

We will study individuals with idiopathic mild-moderate Parkinson's Disease. Diagnosis will be confirmed by Dr. Narayanan - a neurologist.

Inclusion criteria:

GROUP 1: Parkinson's disease without cognitive impairment

1. Parkinson's disease, with MOCA \> 26
2. under stable PD medication
3. able to walk independently, make their own decisions
4. age range = 18 - 89 years old

GROUP 2: Parkinson's disease with mild cognitive impairment

1. Parkinson's disease, with MOCA 23-26
2. under stable PD medication
3. able to walk independently, make their own decisions
4. age range = 18 - 89 years old

GROUP 3: Parkinson's disease with dementia

1. Parkinson's disease, with MOCA \< 23
2. under stable PD medication
3. Make their own decisions
4. age range = 18 - 89 years old

GROUP 4: Parkinson's disease with STN-DBS 1) Parkinson's disease with functioning bilateral STN-DBS electrodes 2) under stable PD medication 3) able to walk independently, make their own decisions 4) age range = 18 - 89 years old 5) THIS GROUP WILL NOT UNDERGO TMS

GROUP 5: Parkinson's disease without DBS and with no seizure history for EEG-TMS study

1. Parkinson's disease with MOCA 23-30
2. under stable PD medication
3. able to walk independently, make their own decisions
4. age range = 18 - 89 years old

GROUP 6: Essential tremor with VIM-DBS

1\) Essential tremor with functioning bilateral VIM-DBS electrodes 2) able to walk independently, make their own decisions 3) age range = 18 - 89 years old 4) THIS GROUP WILL NOT UNDERGO TMS

GROUP 7: Parkinson's disease without DBS and with no seizure history for EEG-HD-tACS study 1) Parkinson's disease with MOCA 23-30 2) under stable PD medication 3) able to walk independently, make their own decisions 4) age range = 18 - 89 years old

Exclusion criteria:

Patients with dementia with Lewy Bodies and Alzheimer's disease, drug-induced parkinsonism, Parkinson's-plus, on investigational drugs, with hearing loss will be excluded, or with color-blindness will be excluded. Subjects with a history of neuropsychiatric disorders, like Schizophrenia or Depression will be also be excluded.

For the TMS sub-study, PD patients with DBS leads will be excluded and any subject with a seizure disorder will also be excluded. For the HD-tACS sub-study, PD patients with DBS leads will be excluded and any subject with a seizure disorder will also be excluded.

Control Group: patients with Alzheimer's Disease (AD) and dementia with Lewy Bodies (DLB) A group of patients with AD and DLB will be recruited for the cognitive tasks to compare data with PD. Since AD is non-dopamine deficiency disease so they can serve as another control group for the study.

Inclusion criteria:

1\) age range = 18 - 89 years old (will have to match with the age of subjects with Parkinson's Disease)

Exclusion criteria:

1\) with any neurological disorders, including epilepsy

Control Group: patients with mTBI A group of patients with mTBI will be recruited for the cognitive tasks to compare data with PD.

Inclusion criteria:

1\) age range = 18 - 89 years old (will have to match with the age of subjects with Parkinson's Disease)

Exclusion criteria:

Control Group: patients with 16pDel Autism A group of patients with 16pDel Autism will be recruited for the cognitive tasks to compare data with PD.

Inclusion criteria:

1\) age range = 18 - 89 years old (will have to match with the age of subjects with Parkinson's Disease)

Exclusion criteria:

Control Group: patients with Brain Lesions A group of patients with Brain Lesions will be recruited for the cognitive tasks to compare data with PD.

Inclusion criteria:

1\) age range = 18 - 89 years old (will have to match with the age of subjects with Parkinson's Disease)

Exclusion criteria:

Control Group: Older Normal Subjects A group of older healthy individuals will be matched with subjects with Parkinson's disease in terms of age, sex, and years of education. We will also recruit a small group of older healthy individuals specifically to pilot new behavioral tasks.

Inclusion criteria:

1\) age range = 35 - 99 years old (most of this group will have to match with the age of subjects with Parkinson's Disease. One subset from this group (N = 40) will be independent from the demographics of the subjects with Parkinson's Disease, so they can have a wider age range).

Exclusion criteria:

1\) with any neurological disorders, including epilepsy

Control Group: Older Subjects with Mood Disorders A group of older individuals with Mood Disorders will be recruited to perform cognitive tasks to compare data with both PD with Mood Disorders and PD without Mood Disorders.

Inclusion criteria:

1\) age range = 18 - 89 years old (will have to match with the age of subjects with Parkinson's Disease)

Exclusion criteria:

1\) with any neurological disorders, including epilepsy

Control group: Healthy young and middle-aged adults

* A group of healthy young and middle-aged adults without Parkinson's disease or other neurological issues.
* 1\) age range = 18-60 years old
* Exclusion criteria: 1) any neurological disorders, including epilepsy

Control subjects' mothers

\- The group of mothers of the healthy young adult control subjects.

Sites (1)

• University of Iowa, Iowa City, Iowa