Based on our research background, we hypothesize that LIFUS has neuromodulation effects on brain cortex and the active LIFUS on left-DLPFC would improve negative symptoms in schizophrenia patients. It would firstly verify the safety of LIFUS on human as well. The multimodal MRI will be contributed to investigate the possible mechanism of negative symptoms.

Firstly, we plan to explore the short-term effects of LIFUS on cortical excitability by detecting the MEP amplitude. 40 patients and relatively well matched healthy-control would be enrolled. After MEP detection and baseline evaluations, the two groups will be treated with one-single intervention on the primary motor cortex. The cognitive function and MEP amplitude will be assessed respectively at the moment, after 15 minutes and 30 minutes. Then, it is a randomized double-blind sham-controlled LIFUS intervention trial in schizophrenia patients. After screening and baseline evaluations, the 40 patients with schizophrenia will be treated with active LIFUS or sham stimulation for 3 weeks on the left DLPFC. The multimodal MRI will be acquired. Clinical symptoms and cognitive function will be assessed respectively at baseline, at the end of fifth treatments and after the end of the treatment.

• Inclusion Criteria (patients):

  1. Meet the DSM-5 diagnostic criteria for schizophrenia or schizoaffective disorder;
  2. Age18-50, right-handed, Han nationality;
  3. the score of at least 1 item from N1 to N7 is ≥4 (moderate or above);
  4. Be in a stable condition, received second-generation antipsychotics for at least 4 weeks or more;
  5. Written informed consent;

• Exclusion Criteria (patients):

  1. Current or past neurological illness, severe physical diseases, substance abuse or alcohol dependence, mental retardation, pregnant or lactation;
  2. Uncooperative or risky patients with high excitement, stupor, disorder of words and deeds, negative suicide, etc.;
  3. A history of MECT or other physical therapy within 6 months;
  4. A history of epilepsy, or epileptic waves on the baseline EEG;
  5. Ruled out share antiepileptic drugs, carbamazepine, valproic acid salt) or larger doses of benzodiazepines drugs (> 10 mg/day, diazepam clonazepam 2 mg/day, 1 mg/day, alprazolam lorazepam 2 mg/day, midazolam 10 mg/day, 20 mg/day, Mr Shah diazepam triazolam 0.5 mg/day), avoid the use of chlorine drug, (in principle, to avoid the use of antiepileptic drugs and clonazepam;Other antipsychotic drugs, if necessary, remain unchanged during the course of treatment;
  6. Contraindications to LIFUS and MRI are present.