The ADD Centre® & The Biofeedback Institute of Toronto®

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AFFECT DISORDERS
Depression, Anxiety, Panic

Neurofeedback combined with heart rate variability biofeedback can be an effective tool to help with symptoms of:

• Anxiety / Panic
• Depression or mood regulation
• Stress

During training sessions at the ADD Centre clients learn to achieve a calm, focused and relaxed state. This is accomplished by getting real-time feedback about brain and physiological functioning. Clients receive positive feedback from the computer in the form of music, or video when they are in an optimal state.
We use a variety of feedback screens that combine single channel neurofeedback and heart rate variability training. The screen below is a favourite because it induces a sense of competition between the boats with the client attempting to have the top (circled) green boat win. When a client plays this game, their brainwave patterns are being measured in real-time. To win the race the client must be very calm while they focus, eliminate all unnecessary thoughts and ruminations, relax, and concentrate. In training clients also learn to breathe in a way that maximizes the change in their heart rate. This is called heart rate variability training and is an effective tool for improving balance in the nervous system, managing stress and improving brain function. On this screen the client is asked to try to maintain synchrony between the variations in heart rate (red line) and their breathing (inspiration and expiration shown by the blue line) while allowing their shoulder and neck muscles to relax and their hands to feel warm.


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Figure 2: Screen for simultaneous EEG and HRV feedback

All clients complete a comprehensive initial assessment prior to commencing neurofeedback training. Interventions are then customized according to assessment findings. Conventional single-channel neurofeedback at FCz combined with heart rate variability and breathing training has been effective in the vast majority of our clients who have problems with mood. Recently we have been able to add more advanced techniques such as LORETA z-score NFB. LORETA allows us to work on many sites in the brain at once and also allows training of communication between areas of the brain that may be involved in anxiety and mood related difficulties. This type of training may decrease the number of sessions that are required to obtain a good clinical result.

Other biofeedback modalities, such as electromyogram (EMG), finger temperature, or electrodermal response (EDR) are added based on the stress assessment results for a particular client.



Below is a little More Background For Professionals:
Neuroanatomical structures affected by Neurofeedback (NFB) plus Biofeedback (BFB) that relate to affect network(s):
A neural network consists of interconnected, functionally related, groups of neurons. In the cortex, these networks typically involve adjoining Brodmann Areas. These areas are shown in the figure below:

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Lateral View to show Lobes of the Brain, Brodmann Areas, and 10-20 Electrode Sites
Figures are adapted from The Neurofeedback Book (Thompson, L. (2003) The Neurofeedback Book: An Introduction to Basic Concepts in Applied Psychophysiology, Wheat Ridge, CO: Association for Applied Psychophysiology). Figures by Thompson, J., Wu, W. (Drawing by Amanda Reeves & Bojana Kenezevic)

For an explication of Brodmann Areas, their primary functions, and their relation to International 10-20 electrode placement sites, a booklet, authored by L. Thompson, can be ordered on the ISNR website, with the $20 fee going to their research fund.) Each Brodmann Area (BA), in addition to its primary function, can be involved in many different functional networks. A network serves to synchronize the functions of groups of neurons in widely distributed but functionally related areas of the cerebral cortex. Networks also involve cortical–subcortical connections (Thompson L., 2007). This perhaps explains why NFB practitioners have obtained good results when doing NFB over a single site, such as Cz, that influences not just that site, and an area with a radius of 6 cm around that site, but, by influencing activity in the anterior cingulate cortex, this single channel training can have an effect on whole neural networks.

The cingulate gyrus that lies below the central midline (FZ, CZ, PZ) is involved in many networks, including the executive, affect, salience, and default networks. Influencing the cingulate gyrus when the patient’s affect network is actively engaged may be assumed to have indirect effects on many deeper structures that cannot be directly affected by NFB at the surface site.

Areas deeper in the cortex can, alternatively, be directly trained using LORETA z-score NFB. This is a variation on regular NFB which uses a 19-channel cap and a process by which the mathematics of low resolution electromagnetic tomography (Pasqual-Marqui et al., 1994; 2002) are applied so that a number of parameters are simultaneously trained. LORETA mathematics, virtually instantaneously, identifies sources in the cortex of the EEG that is being recorded on the surface of the scalp. (See ‘MEDIA’ section of this web site for videos of LORETA NFB.) Thus LORETA is used to identify the source deeper in the cortex of activity measured on the scalp and, with LORETA z-score NFB, it is hypothesized that one can influence these areas more directly. With z-score NFB training the patient’s data is automatically being compared to a large data base of persons who do not have symptoms of any disorder. Dr. Thompson decides which areas that are outside the data base ‘norms’ are likely to be involved in the patient’s major symptoms. The patient attempts to maintain z-scores in these designated areas within a z- score “window” set by the trainer. Ideally this would be between + 1.5 & - 1.5 SDs but the window will be larger at the outset of training. One would expect that about 95% of the population would be less than 2 SDs from the data base means for any of the measurements of amplitude, coherence, and phase. Below we show a figure from an EEG assessment that included LORETA analysis.

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The ‘slices’ shown above are Horizontal, Sagittal, & Coronal respectively.
This figure, taken from an analysis done with the Neuroguide program, shows the ‘slices’ of the brain as they are seen using LORETA. It shows a LORETA source correlation in Brodmann Area (BA) 23, anterior cingulate gyrus, and the activity was 2.49 standard deviations above the database mean. This finding reflected excessive activity at 20 Hz in a 42-year-old woman who had anxiety symptoms (affect network).

A key structure for us to consider in the central midline structures is the anterior cingulate cortex (ACC) (Devinsky et al, 1995). The LORETA image shown in the above figure indicates that, in this person, the ACC Brodmann Area 23 was 2.49 standard deviations (SD) above the data base mean. As noted in the following discussion of anxiety and the stress response, the ACC has direct links to other key cortical areas that are involved in affect networks, including the medial and orbital prefrontal cortex and the insulae, in addition to key basal ganglia areas such as the amygdala, as well as to the hippocampus. Changes in the ACC will therefore also affect the hypothalamus and, through it, the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. These connections have a major role in the human stress response. All of these structures are involved in depression. Influencing these structures using a combination of NFB + HRV (heart-rate-variability) training, especially when combined with appropriate diet, sleep, and exercise routines, can alleviate depression and improve stress management (Thompson & Thompson, 2007; Paquette et al, 2009). The ACC is involved to different degrees in all the major neural network systems, affect, executive, salience and default networks. Thus NFB & HRV training to influence the ACC can have an effect on many different systems.

Central Midline Structures involved in Depressive Disorders:
Patients who are depressed demonstrate symptoms that relate to both executive and affect networks. Figure 1 illustrates three networks involved in different aspects of depression based on a presentation by neurosurgeon Dirk de Ridder (2010 ISNR presentation). Areas in the green box relate primarily to the Executive network involved in depression. More specifically, this dorsal compartment modulates attention and sensory-cognitive symptoms, such as apathy, attentional and executive deficits. It includes the dorsolateral prefrontal cortex (BA 9 & 46), the dorsolateral anterior cingulate (area 24b), posterior cingulate (BA 31), the inferior parietal lobe (BA 40), and the striatum. The dorsal prefrontal components, including the ACC, are also involved in the cognitive control of emotion including reappraisal, evaluation, and explicit reasoning concerning emotional stimuli. Areas in the orange box relate primarily to the affect network involved in vegetative symptoms that often appear in depressive disorders. These vegetative/autonomic nervous system symptoms involve a ventral compartment that relates to symptoms such as: sleep disturbance, loss of appetite and libido. Here we find the hypothalamic-pituitary-adrenal axis, hippocampus, insula (BA 13), subgenual cingulate (BA 25), and the brainstem. In red is an area involved in the integration and connection of the other two areas. Information concerning cognition and emotion from the two compartments (dorsal & ventral) is integrated by the rostral anterior cingulate (BA 24), medial frontal cortex (BA 9 & 10), orbital frontal cortex (BA 11), and frontopolar areas.

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Figure 1: Areas involved in Depression

Different treatments influence different affect networks:
Cognitive Behaviour Therapy (CBT) appears to have its effects on the more dorsal and executive aspects of depression by increasing activity in the ACC, BA 24. It may also decrease activity in the “connecting” areas including the medial prefrontal Cortex (MPFC), BA10, and the orbital frontal cortex (OFC), BA11 (Goldapple, 2004).

Medications can increase the activity of the more ventral, vegetative areas, such as the prefrontal cortex (PFC), BA 9, and the brain stem. They decrease activity in BA 25 and the hypothalamus according to one research group studying the regional metabolic effects of fluoxetine in major depression and the relation to clinical response (Mayberg et al, 2003).

Deep brain stimulation can directly affect BA 25. It requires a surgical procedure to implant leads in the ventral anterior cingulate gyrus connected to a pacemaker placed under the skin near the collarbone. Helen Mayberg and collaborators successfully treated a number of depressed people, individuals virtually catatonic with depression despite years of talk therapy, drugs, even electroconvulsive shock therapy, using deep brain stimulation in Brodmann Area 25 (Mayberg et al, 2005, Kennedy et al, 2011). BA25 is said to be metabolically overactive in treatment-resistant depression and stimulation, once it has been properly adjusted (which can takes months) has been shown via a PET scan follow-up to decrease activity in BA 25 and OFC BA 11. It will also increase activity in the dorsolateral prefrontal cortex (DLPC) BA 9, 46 and the ACC BA 24 and parietal cingulate cortex (PCC) BA 31. In addition, it will increase parietal activity in BA 40. These effects are seen in responders, about half of the patients.

Interestingly, for the most part, the same areas that respond to deep brain stimulation showed changes after combined NFB and psychotherapy in a group of patients who had been medication non-responders (Paquette, 2009). One month after the end of treatment, responders showed significantly reduced absolute power of high-beta (18–30 Hz) in the orbitofrontal cortex (BA 11/47), insula (BA 13), amygdala/parahippocampal cortex (BA 36/37), temporal pole (BA 38), lateral prefrontal cortex (BA 10 and BA 6/8), and subgenual cingulate cortex (BA 25). In addition, responders showed an increase of high-beta activity in the bilateral precuneus/posterior cingulate cortex (BA 40/31). This makes sense because other research has shown abnormally low amplitude of high-beta activity (>20 Hz) in these cortical areas (BA 40/31) in individuals with major depressive disorder (Pizzagalli et al.,2002; 2004). Increased activity in precuneus/posterior cingulate cortex has additionally been shown to correlate with symptom remission following pharmacological treatment (Mayberg, 2003) and with interpersonal therapy (Martin et al., 2001). Since the highest level of cortical glucose metabolism during resting state occurs in these brain regions in healthy participants (Raichle et al., 2001), it is a plausible hypothesis that pharmacological treatment, interpersonal therapy and the neurofeedback plus counselling utilized by Paquette all contribute to restoring the appropriate functioning of the default mode (network) of the brain.

Neurofeedback (NFB) + Heart-Rate-Variability (HRV) Training for Depression that is accompanied by Anxiety:
We have previously described the importance of BA 25 in the ventral rostral anterior cingulate cortex in very serious, often intractable, depression. Brodmann Area 25 is also called the subgenual area (literally “below the knee” referring to its location below the bend in the corpus callosum), area subgenualis or subgenual cingulate. NFB may influence affect networks that involve the more superior aspect of the cingulate gyrus under Cz and the medial aspect of the frontal lobe under Fz but BA 25 is very deep in the midline cortex. Thus LORETA NFB may, theoretically, have a much more direct effect than single channel training at one site. BA 25 is rich in serotonin transporters and is considered to influence the following areas: hypothalamus and brain stem, which are involved in changes in appetite and sleep; the amygdala and insula, which affect mood and anxiety; the hippocampus, which plays an important role in memory formation; and some parts of the frontal cortex responsible for self-esteem. Of importance to the practitioner who uses a combination of NFB + BFB, the solitary nucleus in the medulla (nucleus solitarius) has direct feedback concerning heart rate and blood pressure. This nucleus in the brain stem has direct connections to BA 25. It also has connections to all the other areas involved in the affect / limbic network and will influence the patient’s responses to stress, Since HRV training strengthens the vagal response and will send vagal afferent feedback to the solitary nucleus in the medulla, it can also influence BA 25 and thus, perhaps, the symptoms of depression related to dysfunction in this area of the cortex.

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Diagram by Maya Berenkey from The Companion to The Neurofeedback Book (in press)

TH = Thalamus
IN = Insula
HTH = Hypothalamus
P = Pituitary
CNA = Central Nucleus Amygdala
A = Amygdala
ANS = Autonomic Nervous System
PVN = Paraventricular Nuc.
HI = Hippocampus
PBN = Parabrachial Nucleus
NTS = Nucleus Tractus Solitarius

The above diagram is shown for professionals. It illustrates many of the central midline areas that are important in depression, anxiety, and the human stress response.

Heart Rate Variability (HRV) Training:
Heart rate variability refers to the constantly oscillating variations in heart rate that are observed in healthy individuals. These variations may be measured in terms of their frequencies, amplitudes, the range of heart rate changes in each cycle, and the standard deviations of the interbeat intervals (IBI). The standard deviation of these interbeat intervals (IBI), computed after all artifacts have been removed, is called SDNN. We are concerned when SDNN falls below 50 mille-seconds (ms) and prefer to see it above 80 to 100 ms (Gevirtz, 2010). Heart rate changes are being measured using a plethysmograph which measures red light reflected from blood vessels in a finger or thumb. Measuring pulse to pulse in the thumb gives the same figures at rest (though may not do so during tasks) for SDNN as do electrocardiogram (EKG) sensors on the chest (Giardino, 2002). SDNN is calculated using the Cardiopro program from Thought Technology, which was developed to meet research criteria and provides the statistics used internationally for heart rate variability measures.

There are now studies that show that HRV training can have a positive effect on depression. Katsamanis et al reported significant improvements after HRV TRAINING in the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI-II) with concurrent increases in SDNN. They noted that SDNN decreased to baseline levels at the end of treatment and at follow-up, but clinical statistically significant improvement in depression persisted (Katsamanis et al, 2007). Hassett et al found that, in addition to relief of pain in patients who have fibromyalgia, HRV biofeedback significantly improved overall functioning and depression (Hassett, 2007).

LORETA z-score NFB for Affect Disorders
In depressed patients (and often in patients with concussion / Traumatic Brain Injury (TBI) or with other disorders) LORETA analysis indicates that significant deviations from the normative data base have their source in one or more areas. These areas can include the anterior cingulate (BA24), the medial frontal area, the rostral-ventral cingulate gyrus (BA 25), uncus, parahippocampal gyrus and other central midline structures. These areas are deep in the midline and, as previously mentioned, surface NFB can only influence them indirectly based on influencing part of the network that includes them. LORETA NFB, on the other hand, allows the practitioner to choose up to 24 areas and measurements (amplitude, phase, coherence) in the cortex for feedback. It is more time consuming because LORETA mathematics requires input from 19 channels to determine source localization. The 19 channel ‘cap’ takes a few minutes to put on properly. This is important because, to be accurate, the data should be as free of artifacts as is possible.

The hope is that faster and perhaps more complete results can be obtained. Faster results would then justify the more complex procedure. Controlled research has yet to be done to investigate the merits of LORETA as compared to regular neurofeedback. In the meantime, both can be used and both can be combined with HRV training. When doing LORETA NFB, HRV training can be done at the beginning of the session when the cap is being put on and impedance checked, which takes upwards of ten minutes. The patient can continue the HRV or just breathe in this relaxed regular manner through the remainder of the session while doing the NFB. NFB and HRV training are ‘learning’ methods. Unlike medications or surgery, nothing invasive is being carried out. The brain is ‘plastic’ and learning methods can be very powerful for allowing change to occur in the desired direction (Doidge, N., (2010) The Brain that Changes Itself; Other references can be found in that section of this Website).

Example of Results of LORETA z-score NFB Training
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In the above diagram, the X axis shows z scores (standard deviations (SDs) from a database). Each coloured line is from a distinct Brodmann Area (BA) that was being trained using this program. The Y axis shows session numbers. Z- scores compare the patient to a normal population. The reader will recall that about 95% of the population would be less than 2 SDs. This man, in addition to other difficulties, was depressed and anxious. The figure above shows that, when he began LORETA z-score NFB, the first session statistics were between 2 and 7 SDs for magnitude of various EEG frequencies at many of the BAs that were being trained. Within 6 sessions he had brought all these areas to under 2 SDs. He then had to leave Canada for several months for family reasons. When he came back to Canada some of his symptoms had returned. Session 7 was carried out and the z-scores in a number of areas had risen to between 2 and 3 SDs. The figure shows that highest z-score (3.04 SD) for session 7 was Beta 2 (15-18 Hz) from the right insula, BA 33. This is an important area in the affect network. Both these z-scores and his symptoms decreased with further training. He remained in training for more than 30 sessions to solidify these gains. Working with his family doctor, he gradually came off his medications.







For more information please contact, Dr. Lynda Thompson at the ADD Centre® (905) 803 8066 or (416) 488-2233