Hyperbaric Oxygen Therapy for Persistent Post Stroke Depression

Depression severity will be evaluated by structured interview based on the HDRS-17 guided structural questioner (Hamilton Depression Rating Scale from 0-53 ,Levels of depression is categorized according to the following accepted criteria:

• Not depressed: 0-7
• Mild (subthreshold): 8-13
• Moderate: 14-18
• Severe: 19-22
• Very severe: >23)

Beck depression inventory II. Each answer is scored on a scale value of 0 to 3 . The score ranges between 0 and 63, with higher scores indicating more severe depression symptoms.

Quality of life questionnaire, scale of 0-100, higher score means better outcome

The Brief Symptom Inventory-18 (BSI-18). self-report questionnaire which generates a summary scale, the global stress index (GSI), and three subscales: depression, anxiety, and somatization. Each item is rated on a 5-point scale, with distress ratings ranging from 0 (not at all) to 4 (extremely) .

Changes will be measured by The Stroke Impact Scale (SIS). The SIS version 3.0 includes 59 items, An extra question on stroke recovery asks that the client rate on a scale from 0 - 100 how much the client feels that he/she has recovered from his/her stroke.

Changes will be measured by Instrumental Activities of Daily Living (IADL) Scale. There are eight domains of function measured with the Lawton IADL scale. Clients are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women, and 0 through 5 for men.

computerized cognitive evaluation battery. each outcome parameter will be normalized and fit to an IQ-like scale (mean=100, STD=15), according to the participants' age and education.

Montreal Cognitive Assessment (MoCA). The maximum MoCA score is 30 points, with a 1-point scoring correction for individuals with 12 years of education or less. A score of 26 or above is considered normal and a score lower than 26 has been considered to be the optimal cutoff point for diagnosis of cognitive impairment.

computerized cognitive evaluation battery test, divided into 2 tasks: 1- Multitasking test (MTT)- attention, reaction time and executive functions, Multitasking test Incongruency cost - A higher incongruency cost indicates that the subjects takes longer to process conflicting information. 2-Paired associated learning (PAL)- visual memory and new learning, PAL Number of Patterns Reached (0-8), PAL Total Errors (Adjusted) (0-64), PAL Total Attempts(0-64).

At each of the evaluations, patients will undergo structural and functional MRI scanning. Images will be acquired on Vida 3 Tesla Scanner, configured with a 64-channel receiver head coils (Siemens Healthcare, Erlangen, Germany) at Shamir medical center radiology department.

Resting state fMRI(rsfMRI or R-fMRI)- a method of functional brain imaging that can be used to evaluate regional interactions that occur when a subject is not performing an explicit task. This resting brain activity is observed through changes in blood flow in the brain which creates what is referred to as a blood-oxygen-level dependent (BOLD) signal that can be measured using functional Magnetic Resonance Imaging (fMRI).

A general physical and neurological evaluation will be done. NIHSS - The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS), will be used as part of the neurological evaluation to objectively quantify the impairment caused by the stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4 .For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.

Quantitative EEG (qEEG) including task related EEG analysis. EEG analysis for each state within subject and between subjects will include frequency analysis (peak frequency and relative power), oscillations (proportions of the different bands alpha, beta, theta, delta activities) and power spectra distribution.

blood tests will include Inflammatory markers: IL-1 (IL-1β): pg/mL

blood tests will include Inflammatory markers: IL-6: pg/mL

blood tests will include Inflammatory markers: Tumor necrosis factor-alpha (TNF-α): pg/mL

blood tests will include Inflammatory markers: hsCRP (high-sensitivity C-reactive protein): mg/L

blood tests will include Inflammatory markers: Exosomes: particles/mL (by NTA) or µg protein/mL (by protein assay)

blood tests will include Inflammatory markers: Serum VEGF: pg/mL

blood tests will include Inflammatory markers: Testosterone (serum): ng/dL or nmol/L

blood tests will include Inflammatory markers: Estradiol (E2, serum): pg/mL or pmol/L

blood tests will include Inflammatory markers: DHEA-S (serum): µg/dL (commonly) or µmol/L

blood tests will include Inflammatory markers: Progesterone (serum): ng/mL or nmol/L

blood tests will include Inflammatory markers: Cortisol (serum): µg/dL or nmol/L

blood tests will include Inflammatory markers: Telomere length: kilobases (kb) or relative T/S ratio (qPCR, arbitrary units)