TIS for Improving Cognitive Impairment in Schizophrenia

The MATRICS Consensus Cognitive Battery (MCCB) can be used for cognitive assessment of schizophrenia, bipolar disorder, and other neuropsychiatric diseases. The MCCB covers nine cognitive domains, including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function, and fine motor skills. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.

Range from 30 to 210, higher score indicates more severe positive and negative symptoms.

The score range is 0-120; the higher the score, the more severe the negative symptoms are.

Ranges from 0 to 27; a higher score indicates more severe affective symptoms.

Functional MRI (fMRI) is based on the blood oxygen level dependent (BOLD) contrast that can detect changes in blood oxygenation to analyze the change of brain function after intervention.

The changes of neuroelectrophysiological signals were collected under the task-based electroencephalogram.

Global function will be measured by the Global Assessment of Functioning (GAF). GAF is a 0-100 numerical scale used by clinicians to subjectively rate a person's overall psychological, social, and occupational functioning. Higher scores (91-100) indicate superior functioning, while lower scores (1-10) indicate severe danger or impairment.

Social function will be assessed by the Global Functioning: Social (GF:Social) and Role (GF:Role) scales (GFS) and the Social Functioning Scale (SFS). The GFS is a clinician-rated, 1-10 point tool designed to measure social and occupational functioning. They focus on development, allowing for the assessment of change over time, and avoid confounding functioning with psychiatric symptoms. The SFS is a 79-item self-report measure designed to assess social functioning in schizophrenia. Items assess ability and performance related to social engagement, interpersonal contact, recreation, independence and competence in activities, activities of daily living, and employment.

The aperiodic component of the neural power spectrum, quantified as the slope of the 1/f-like signal recorded by electroencephalogram, will be used as an index of excitation/inhibition balance. The unit of measure is the exponent (unitless).

Long-range temporal correlations of neural oscillations recorded by electroencephalogram will be measured as an index of the temporal stability of excitation/inhibition balance. The unit of measure is the Hurst exponent (unitless).

The ratio of excitatory to inhibitory neural activity derived from electroencephalogram signals will be calculated as a functional excitation/inhibition balance index. The unit of measure is a ratio (unitless).

The power of neural oscillations across all frequency bands (e.g., delta, theta, alpha, beta, gamma) recorded by electroencephalogram will be measured. The power values from all bands will be averaged to produce a single composite oscillation power index. The unit of measure is microvolts squared (μV²).

The 40 Hz auditory steady-state responses recorded by electroencephalogram will be measured, including both evoked power and inter-trial phase coherence. The unit of measure for evoked power is μV², and the unit of measure for phase coherence is unitless.

The mismatch negativity amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).

The P300 amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).

Behavioral performance will be evaluated using the Sternberg Item-Recognition Paradigm, a memory task that measures reaction time and accuracy. The unit of measure for reaction time is milliseconds (ms), and the unit of measure for accuracy is percentage correct (%).

Behavioral performance will be evaluated using the Mnemonic Similarity Task, a memory task that measures pattern separation and recognition memory. Three indices will be derived and reported separately: the Lure Discrimination Index (LDI), the similarity object recognition index, and the old object recognition index. All three indices are measured in d-prime (unitless).

Approximately 10 mL of blood will be collected intravenously to measure peripheral blood biomarkers: brain-derived neurotrophic factor (BDNF) in ng/mL, C-reactive protein (CRP) in mg/L, interleukin-6 (IL-6) in pg/mL, Kynurenic acid in nM, high-density lipoprotein (HDL) in mg/dL, low-density lipoprotein (LDL) in mg/dL, and triglycerides (TG) in mg/dL. These biomarkers will be combined into a single allostatic load index using a standardized high-risk count algorithm. For each biomarker, a cutoff score based on population norms or clinical thresholds (e.g., highest-risk quartile) will be applied to determine high-risk status (1 = high-risk, 0 = not high-risk). The allostatic load score is the sum of high-risk indicators across all biomarkers. The unit of measure is the allostatic load score (unitless, integer count).