Schizophrenia is a mental disorder with a multi-factorial aetiology . Because of its chronic nature, it leads to numerous limitations in the activities of daily living of patients in professional, family and social settings. These limitations are due to the progressively deteriorating cognitive functions, such as concentration, attention, working memory, emotions, and executive functions [1–10].
The deepening dysfunctions are associated with disturbances in the activity of various brain regions, mainly the frontal and temporal regions, limbic and midline brain structures and basal ganglia [2–9]. They can be alleviated by systematic pharmacological treatment and rehabilitation.
Among the various methods that can be effectively used in the rehabilitation of patients suffering from schizophrenia, the most commonly mentioned ones are transcranial magnetic stimulation (TMS), transcranial direct current stimulation (t-DCs) and Biofeedback [11, 12].
The therapeutic effect of these methods is based on a stimulation mechanism that leads to the restructuring of neuronal connections [11–14] by inducing changes in the bioelectric activity of the brain and activating the glutamate receptors NMDA (an excitatory neurotransmitter), AMPA (an ionotropic transmembrane receptor) and BDNF (brain derived neurotrophic factor, a member of the nerve growth factor family of proteins) [15–22].
The anatomical reorganization of neural circuits depends on biochemical changes and the accompanying changes in the action potentials in dendritic spines (sprouting) [12, 13], which increase neurotransmitter release, allowing the formation of new connections based on long-term potentiation (LTP) [23–26].
There are many biomarkers that participate in these biochemical structural changes. One of them is extracellular matrix metalloproteinase-9 (MMP-9), which is necessary for the transformation of pro-BDNF (a glycosylated precursor protein) into mature BDNF (a non-glycosylated protein) [16, 18, 27–33].
MMP-9, as an extracellular catalyst of metabolism plays an essential role in the cycle of changes associated with the activation of BDNF (a dopaminergic neurotransmitter protein), which is responsible, among others, for the improvement of cognitive function [34, 35]. Abnormal MMP-9 levels inhibit BDNF activity and lead to the so-called deficit syndrome (negative symptoms, cognitive deficits) which characterizes individuals diagnosed with schizophrenia [30, 35–39].
The deficit symptoms caused by disease-induced changes in the brain's bioelectric activity  can be confirmed in studies using modern neuroimaging techniques (magnetoencephalography MEG, positron emission tomography PET, functional magnetic resonance fMRI) as well as studies of qualitative (EEG) and quantitative (QEEG) changes in brain activity [41, 42] and changes in event related potentials (ERP) [40, 43]. These methods and the physiological markers associated with signalling and reorganization may also turn out to be effective in assessing the outcomes of rehabilitation therapy [42, 44–46].
This present study is an attempt to assess the role of BDNF and MMP-9 in structural synaptic modulation in people with schizophrenia following two different rehabilitation programs and to find out whether there exists a relationship between the rehabilitation interventions used and changes in the investigated parameters. The aim of the experiment was to compare two groups of male patients with a clinical diagnosis of schizophrenia, in the remission period, recruited according to inclusion criteria. Group 1 were men who followed a standard rehabilitation program and Group 2 were men who received galvanic skin response (GSR) Biofeedback training (GSR-BF).
The working hypothesis was that GSR-BF training should improve the cognitive functions of schizophrenic patients with an efficiency similar to or higher than that of standard rehabilitation interventions, as demonstrated by:
a reduction in cognitive deficits (changes in ERP),
a reduction in the severity of psychopathological symptoms (PANSS scale),
quantitative changes in the EEG (attention – theta/beta ratio, concentration – theta/SMR ratio),
changes in blood serum levels of BDNF and MMP.