Treatment of Depression with Quantitative Electroencephalography (QEEG) of the TQ-7 Neurofeedback System Increases the Level of Attention of Patients

Valdenilson Ribeiro Ribas1*, Mariana Veríssimo De Souza2, Viviane Wisnievski Tulio3, Mariana De Souza Pavan4, Gislaine Azzolin5, Renata De Melo Guerra Ribas6, Diélita Carla Lopes De Oliveira7, Jean de Almeida Nóbrega8 and Hugo André De Lima Martins9 1Postgraduate degree in Neuropsychiatry and Behavioral Sciences, Federal University of Pernambuco (UFPE), Recife/PE, Brazil 2Center of Biological Sciences, Federal University of Pernambuco (UFPE), Recife/PE, Brazil 3Department of Psychology, Pontifical Catholic University of Paraná (PUCPR), Curitiba/PR, Brazil 4Department of Pedagogy, State University of Campinas (UNICAMP), Campinas/SP, Brazil 5Department of Psychology, Tuiuti University of Paraná, Curitiba/PR, Brazil 6Department of Nutrition, Federal University of Pernambuco (UFPE), Recife/PE, Brazil 7Department of Psychology, Catholic University of Pernambuco (UNICAP), Recife/PE, Brazil 8Department of Electronic Engineering, Campina Grande/Paraiba, Brazil 9Postgraduate degree in Neuropsychiatry and Behavioral Sciences, Federal University of Pernambuco (UFPE), Recife/PE, Brazil


Introduction
Depression is characterized by a feeling of deep sadness associated with physiological and cognitive symptoms [1]. Both the ICD-10 and the American Psychiatric Association in their statistical manual of mental illness (DSM-V) characterize depression as a set of symptoms that include depressed mood (sadness, hopelessness), loss of interest and pleasure for previously satisfactory activities, and decreased energy, leading to a significant lack of enthusiasm that interferes with the life of the individual [2,3]. However, in relation to the etiology, most of the scientific community shares the idea that depression has multifactorial causes [4] that can originate from endogenous (neurobiological, genetic) [5], exogenous (psychosocial) [6] or traumatic factors (shock, letdown or a tumor) [7]. A biochemical alteration in the brain caused by a deficiency of serotonin [8], especially in the synaptic cleft, is implicated in the psychogenesis of neurobiological nature, possibly causing an imbalance of both mood and sense of well-being in the individual. distribution and attention capacity [10]. The deployment/distribution of attention, the ability to channel attention to specific stimuli and sustain the focus on these stimuli, is divided into three aspects. The first is the stage of wakefulness (arousal), and refers to the level at which the individual is awake, sleepy, torporous or comatose [11]. The second aspect is focused attention, which concerns the individual's ability to select the stimulus of interest from several stimuli. The third aspect is sustained attention, which is determined by the individual's ability to concentrate on the selected stimulus during the time of interest [12]. The union of these abilities demonstrates the full functioning dimension of human attention with characteristics that add alertness, focus on attention, maintaining focus, information storage, mental information processing and resisting interference [29]. However, these skills may be impaired if there is interference from intervening variables such as stress. Although there are studies demonstrating the difficulty of attention due to depression, there are no findings in the literature investigating the treatment of depression and consequently improvement in attention using The Learning Curve (TLC) technique and the neurofeedback TQ-7 system [13]. Thus, the aim of this study was to evaluate changes in the level of attention of patients with depression resulting from treatment using quantitative electroencephalography (QEEG) of the neurofeedback TQ-7 system.

Subjects
Thirteen male and 28 female patients from the Brain and Neurofeedback Clinic in Recife were evaluated. Subjects were submitted to clinical evaluations under standard room conditions at a temperature of 22° ± 2°C. All the evaluations were performed in a neutral manner, that is, an agreement was reached with each patient so that no symptoms would be revealed before the QEEG examination based on the protocol of The Learning Curve (TLC) Trainer's QEEG (TQ-7) system. The evaluation was divided into three steps. TLC research protocol of the TQ-7 system was used in the first; in the second stage, the level of attention of patients was evaluated before treatment and in the last stage, the level of attention was evaluated after treatment. Patients were informed about the application of attention tests the day before and all subjects agreed to sleep at 8:00 p.m. Each patient was submitted to a total of 40 sessions of neurofeedback of one hour and a half each over twenty weeks. The Digit symbol, d2, Digit Span in correct and inverse order and the Paced Auditory Serial Addition (PASAT) tests were used to assess attention. The inclusion criteria were a clinical diagnosis of depression, signing of written consent forms and age greater than 18. Patients with other medical diagnosis of a psychiatric condition and those unable to follow the treatment process were not included.

TQ-7 System Specifications
The TRAINERS' QEEG (TQ-7) was organized by Peter Van Deusen [13] and is a system consisting of an amplifier, called Q-wiz, with four simultaneous channels of 24-bit resolution and a maximum sampling rate of 512 samples per second; this means that signals of up to 256 Hz (half the sampling rate) are acquired. Each channel has a 0.2 Hz high-pass filter to eliminate frequencies below this value. Thus, the frequency range of each channel varies between 0.2 Hz and 256 Hz. The TQ-7 uses the Bioexplorer program for signal analysis. Bioexplorer is a software from CyberEvolution Inc for real time biological signals acquisition, processing, display, recording and playback. It permits the user to mount graphically a setup (also called a "design") for processing raw signals from the Q-wiz amplifier interconnecting various processing, display and audio objects for biofeedback. The processing objects include various types of low-pass, bandpass, high-pass filters, Fast Fourier Transforms (FFTs), mathematical and logical operations. The audio and display objects include display bars with automatic and manual thresholds, graphical trends, power spectrum, audio and MIDI playback, video player and flash game players, all of them controlled by processing objects.
A standard was established for TLC investigation protocol of the TQ-7 system [13,14] in relation to the expected conformation of depression symptoms. In TLC protocol for the TQ-7 system, it is possible to identify a pattern of brain electrical activity that signals the presence of symptoms of depression named by Van Deusen as Reversal 13. It was demonstrated that within this category it is possible to find specific symptoms for two types of depression: depression with symptoms of hopelessness and symptoms of agitated depression [13].
The symptoms of depression with hopelessness are: sadness, loss or significant decline of interest in performing activities previously considered pleasurable, social withdrawal, altered appetite, changes in sleep quality, slowing of speech and in some cases mutism, fatigue, guilty feelings, cognitive disorders and thoughts related to death. These symptoms are associated to a reversal or asymmetry of alpha waves (8)(9)(10)(11)(12) [13,15,16]. Thus, the importance of the right hemisphere, represented by eight even points (Fp2, F4, F8, C4, T4, P4, T6 and O2) [13,17] in the international 10-20 electroencephalography mapping system, is observed. These points contain around 10-15% more alpha waves when compared to the left hemisphere represented by eight odd points (Fp1, F3, F7, C3, T3, P3, T5 and O1) as alpha waves emit less energy compared to beta waves [18]. This same ideal alpha pattern is expected in the posterior region of the brain at five points (T5, P3, Pz, P4 and T6) when compared to the anterior region also at five points (F7, F3, Fz, F4 and F8) giving a total of 26 points, divided in two groups of 13 [13].
From this expected profile, training protocols were set up taking into account the individual needs of each client. For example, if the 10-20 EEG System identified alpha inversions, reversals or asymmetry [13] in the P4, T6 and O2 regions of the right hemisphere, that is, a lower percentage of alpha waves compared to the P3, T5 and O1 regions of the left hemisphere, a protocol would be established to increase alpha percentages in these deficient regions. However, since depression is not a single-cause disease, other areas of the brain related to other emotional states need to be trained. These may include anxiety control by inhibiting beta waves in a range that produces anxiety, hypervigilance, fear, insecurity or even panic (23-38 Hz), especially in the T3 and T4 regions near the amygdalas and in the posterior areas of the brain such as those mapped as P3, P4, T5, T6, O1 and O2 by the 10-20 system. Another emotional state that might be trained is related to deficient restorative sleep due to lack of control of physical relaxation in the sensory-motor areas C3, Cz and C4. Training would increase the sensory-motor rhythm (12-16 Hz) and inhibit high Beta (23-38 Hz) as well as prioritize an increase in beta waves (13)(14)(15)(16)(17)(18)(19)(20)(21) and reductions in Delta (2-4 Hz), Theta (4-8 Hz) and Alpha waves (8)(9)(10)(11)(12) in the Fp1, Fp2, F3, F4, F7, F8, Fz and Cz regions with the ultimate aim of increasing the level of concentration and attention. The attention theory of Mateer and Mapou (1996) [9,10,19,20] guided this study. The deployment/distribution of attention can be evaluated in tasks of fast exploration of target identification with the Digit Symbol, Trail Making and d2 tests and others. The Digit Symbol and d2 tests were used in this experiment to evaluate focus and maintaining the focus, respectively [20]. The Digit Symbol test requires the subject to pair symbols with their respective numbers from 1 to 9 within 1 minute and 30 seconds. Whereas in the d2 test, the individual should cross out the letter d when it has one or two lines above or below it on a specific form of 14 lines with 47 letters on each including distractors [9].
Attention capacity/encoding refers to the situation where the individual can capture and store data in order to process them mentally while resisting external interference [11]. The Correct Order Digit test starts with a 2-digit sequence that increases progressively. The subject is asked to repeat this sequence correctly. This is an indirect way of measuring the amount of information that the subject is able to retain. The Reverse Order Digit test is similar to the Correct Order Digit test but the subject must repeat the sequence of digits in reverse order. For example, if the sequence is 1-9-3, the individual should say 3-9-1 [20]. In this test, in addition to retaining information in the memory, the subject must also mentally manipulate this information; the subject remembers the sequence, reverses the order, and says the new order out loud. The Paced Auditory Serial Addition test (PASAT) is a test that evaluates the mental capacity of the subject to process information as well as to resist divided attention [9]. This resistance to external interference is the third sector that should be evaluated to verify attention capacity. In this test, the subject must sum dictated numbers. The examiner says two numbers, and the individual must add them up and say the answer (for example, for 9, 8 the client should say 17). When the examiner says the next number, the subject should add it on to the last number of the previous pair, that is, eight and not its total seventeen. The subject must remember the last number spoken and discard the sum of the previous two numbers. This test demands that the person is able to mentally process information and, at the same time, resist interference [9,19].

The groups
This longitudinal cross-sectional study (before and after) was performed in subjects with ages ranging from 32 to 67 years old, divided into two groups: female patients (n = 28) and male patients (n = 13). The Chi-Square Distribution was used and the Simple Random Method (90% confidence level with 10% probability of error) [21].

Data analysis
The individually applied attention tests were analyzed using the paired t-test and the results are expressed as mean ± standard error of the mean (SEM) and presented in table. Significance was set for p-values ≤ 0.05.

Auditory attention or Short-term memory -Correct Order Digit Span test
Only female subjects (before: 8.36 ± 0.17; after: 9.04 ± 0.10) presented better short-term memory after training compared to before training with neurofeedback (p-value <0.001) ( Table 1).

Mental manipulation -(Reverse Order Digit Span test)
Female (before: 4.57 ± 0.15; after: 4.68 ± 0.14) and male subjects (before: 5.92 ± 0.31; after: 7.54 ± 0.62) presented higher results in the reverse order Digit Span test after training with neurofeedback compared to the results prior to training. However, no statistically significant improvements were found with neurofeedback training (p-value = 0.083 and p-value = 0.082, respectively).

Discussion
This study found increased attention with better sustained attention, auditory attention/short-term memory and resistance to interference in patients of both genders with hopeless depression and agitated depression trained using the TQ-7 system of TLC neurofeedback technique [13]. Although the mental manipulation capacity presented higher values in the reverse order Digit Span test for both genders, no statistically significant difference was found. Perhaps, this result is related to the low number of subjects enrolled in this study as the result is very close to the significance level of p-value <0.05. Added to the results found in the attention tests, there was also a congruence in the patients' reports regarding the reduction of DSM-V symptoms associated with depression and reversal or asymmetry of alpha and beta waves using the neurofeedback TQ-7 system of TLC technique [13,14]. This study corroborates the findings of Simkin et al. [22] on the question of treating depression even though the methodological processes used were different. Simkin et al. used neurofeedback with low-resolution tomography (LORETA) 32 due to physiological restrictions linked to possible patterns captured by the human electroencephalogram assessed using the standard statistical chart of the normal curve called the z-score [23] validated by Thatcher et al. [24]. However, in this study we used the standard TQ-7 system in TLC protocol which is specific for depression, that is, asymmetry [18,25] or reversal category [13]. Regardless of the neurofeedback system used, several studies in the area of neurophysiology [13,22,24,26] have already shown that brains are organized by means of rhythmic oscillations expressed in different frequency ranges produced by the constant firing of the neurons. The constant changes in the patterns of these brain waves seem to be directly related to mental states and these changes are only possible due to neuronal neuroplasticity, which can be accessed using the electroencephalogram [27].
With QEEG it is possible to observe several patterns that include optimal states of psychic balance, but also states of fear, anxiety, panic, anger, impatience and depression. According to Fisher, these states arise from developmental trauma disorders [27,28], above all, from affective regulation problems. These patients live in the absence of the mother [27]. The infant's early developing right hemisphere has deep connections to the limbic and autonomic nervous systems and is dominant for human stress response, and in this manner the attachment relationship facilitates the expansion of the child's coping capacities [29]. Thus, these patients find it difficult to develop the sense of self, and brain training with neurofeedback may help build new circuits that minimize fear, shame, and anger [27], that is, impaired brain development can affect emotional control, control of verbal or behavioral impulses and neurocognition such as intelligence, memory, perception and attention. In this sense, this study demonstrated that, among the neurocognitive impairments caused in a brain with depression, the attention, indeed, was affected. However, after 40 sessions of brain training with neurofeedback, it was possible to reestablish a high level of distribution and attention capacity in these patients. Although all patients were asked to sleep at 8:00 the day before the attention tests were applied, it is difficult to verify whether this really happened. As data on this subject are scarce in the literature, it is still difficult to compare these results with other researchers. It is therefore important that further research is carried out with larger cohorts to confirm the results found in this study. Data are represented as means ± standard error of the mean (SEM) (Paired t-test).