Treating Depression with Neurotherapy

Major depression is a disorder of the brain’s affective system. Major depression is characterized by a triad of symptoms:

(1) low or depressed mood;

(2) loss of interest or pleasure in almost all activities (anhedonia); and

(3) low mental and physical energy or fatigue.

Other symptoms such as sleep and psychomotor disturbances, pessimism, guilty feelings, low self-esteem, suicidal tendencies, and food-intake and body weight dysregulation, are also frequently present but not essential to making the diagnosis.

For more information on depression and the symptoms of depression, GOTO:
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Findings from Brain Imaging Studies

Early brain mapping studies using Positron Emission Tomography (PET) to examine resting cerebral glucose metabolism and Functional Magnetic Resonance Imaging (fMRI) to examine regional cerebral blood flow in depressed versus normal individuals have generally found decreased activity in the prefrontal cortex (PFC) of those suffering from depression. This reduced metabolic activity is positively correlated with severity of depression and has been found to reverse with recovery from depression.

The onset of major depression has also been associated with brain injuries that damage the frontal lobes, especially the left frontal pole.

A more recent PET study of treatment-resistant patients with depression found, in addition to the usual decreased prefrontal metabolism, an increase of metabolic activity in the subgenual cingulate gyrus (a part of the limbic system). This is the same area that demonstrates increased blood flow in normal subjects when sadness is induced. This area of the brain also responds to treatment with antidepressant drugs.

Numerous brain imaging studies over the last few decades have been broadly consistent in showing sadness and depressed mood to be associated with abnormal neuronal activation in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC), including the anterior cingulated gyrus (ACC) and orbito-frontal cortex (OFC). These areas in the cortex receive input through the anterior nucleus of the thalamus from the hippocampus (HC), amygdala (Am), and mammilary bodies of the hypothalamus (MB).

Figure A.  Areas of the brain involved in depression.

Of particular relevance to depression are the ventromedial and dorsolateral prefrontal cortices. The ventromedial PFC plays an important role in negative affect. Damage to this brain area results in a reduction of negative affect such as guilt, shame, embarrassment, and regret. Disturbances of the vmPFC are believed to lead to these depressive symptoms. 

The dorsolateral prefrontal cortex is important for "cognitive" and "executive" functions such as working memory, intention formation, goal-directed action, abstract reasoning, and attentional control. Moreover, this brain area is believed to be important for the regulation of negative affect. This area is important for the reappraisal/suppression of negative affect. A defect in this regulation of negative affect due to dysfunction of the dlPFC appears to be involved in depression.

There is some evidence suggesting that a reduction in dlPFC activity and/or over-activity of the vmPFC may play a major role in the development of depression. 

Brain imaging studies to date suggest that depression is largely a result of reduced activation/metabolism in a number of brain areas and reports of increased activation of any particular brain area have not consistently been associated with depression. Anxiety, on the other hand, correlates with increased regional cerebral blood flow (rCBF) in posterior cingulate and bilateral inferior parietal lobules. Since comorbid depression and anxiety are quite common, it is important to recognize the different areas that are activated or inhibited by both depression and anxiety.  

Electroencephalographic (EEG) studies have largely confirmed these findings by demonstrating increased alpha (8-12 Hz) EEG power in the left frontal regions of the brains of depressed individuals. Since alpha is generally viewed as a cortical idling rhythm and is inversely related to neuronal activity, increased left frontal alpha results in deactivation of the left prefrontal cortex and a functional dominance of the right prefrontal cortex. Indeed, a number of brain researchers have suggested a laterality of the brain’s affective system; with negative emotions having a bias in activating the right hemisphere and positive emotions activating the left hemisphere. The left frontal lobes may be considered to include an “approach behavior” circuit whereas the right frontal lobes may include an “avoidance-behavior” circuit. As the left becomes more active, we tend to see things as generally more interesting, more rewarding, more approachable. In contrast, activation of the right circuit causes us to see things as potentially more dangerous and less rewarding. Brain research suggests that a person's mood may largely depend on which side of the prefrontal cortex is more active.

In this vein, Henriques & Davidson (1990, 1991) examined frontal EEG asymmetry in currently depressed versus never depressed individuals and found elevated left frontal alpha power in the depressed individuals. Other researchers have confirmed these findings as well as observing that individual differences in frontal asymmetry emerge early in life and are associated with individual differences in “approach-withdrawal” behavior and the “introversion-extroversion” personality dimension. Taken together, these findings suggest that EEG asymmetry marked by relative left frontal hypoactivation may be a biological marker of familial and, possibly genetic risk for mood disorders.

Figure B.  Nx-Link QEEG brain maps of an elderly male suffering from severe depression.
Note the excessive relative power in alpha band in the left temporo-frontal region.

Neurological patterns found associated with depression are asymmetry of frontal lobe activity, deficiency of slow-wave (theta) activity or excessive fast wave (beta) activity in the occipital or posterior region of the brain, as well as deficiency in 13-15 Hz activity over the sensorimotor cortex.

Figure C. LORETA image showing the source distribution of low Alpha (8-10 Hz) recorded from the scalp in an individual diagnosed with major depression. Note that the bottom row of brain images follow the "medical-neurology" convention of showing the images as if they were film negatives with the right and left sides reversed. This is a confusing but common practice in representing images from CAT and MRI scans.  

These findings with respect to depression are quite consistent with the more general notion that abnormal activity in the EEG reflects psychopathology and, conversely, normalizing the EEG can improve brain function and reduce psychopathology.

Neurotherapy to Treat  Depression

While there are as yet no published randomized controlled trials (RCTs) of EEG neurofeedback or any of the other neurotherapies offered by Edmonton Neurotherapy to treat depression, a small number of published clinical and case studies as well as the reported clinical experience of hundreds of neurotherapy practitioners around the world all point to EEG and HEG neurofeedback and such neurotherapies as audio-visual entrainment, cranial electrostimulation therapy, and transcranial DC stimulation as promising alternatives to pharmacological and electroconvulsive therapies in the treatment of major depression.

Based on the common finding of reduced activation of the left prefrontal cortex as being associated with depressed mood and the indication from neurobiological studies of depression that left frontal activation is important to being happy, most neurotherapy treatment protocols focus on increasing brain activation in the left frontal/prefrontal region.

To see a YouTube video by Dr. Clare Albright on EEG neurofeedback for the treatment of depression, please click on this link... http://www.youtube.com/watch?v=jjY9ILDDOaM&feature=BF&list=ULOy74rq6Q3WQ&index=3

EEG neurofeedback protocols commonly focus on downtraining slow wave EEG in the range of 2-7 Hz and uptraining faster 15-18 Hz activity from left frontal/prefrontal locations. Similarly, Hemoencephalographic (HEG) neurofeedback focuses on increasing perfusion of oxygenated blood within the left prefrontal cortex and transcranial DC stimulation (tDCS) therapy focuses on modifying the electrical potential in the left frontal cortex to increase the ease with which these neurons are activated. Together, these three modalities appear to actively support each other and, in our experience, speed up the process of recovery from depression and reduce the possibility of future relapse. This is especially true when these neurotherapies are combined with Cognitive-Behavioral Therapy (CBT), a type of goal-oriented psychological "talk" therapy that teaches individuals to solve problems related to the interactions between how they think, feel, and behave. CBT helps individuals recognize and change dysfunctional patterns of thinking and behaving that increase and help maintain negative mood. CBT is a good partner with neurotherapies in the treatment of depression because it encourages the patient to engage the frontal lobe "executive functions" of  the brain to more consciously and actively regulate cognitions and behaviors. 

For more information on cognitive-behavioral therapy...
GOTO: www.drmueller-healthpsychology.com/treatments_psychotherapies.html 

In some cases of depression, especially when there is a significant anxiety component present, other forms of neurotherapy, such as audio-visual entrainment (AVE) or cranial electrotherapy stimulation (CES), and peripheral biofeedback, such as heart rate variability (HRV) training, may be valuable adjunctive therapies to help the individual better manage his/her day to day stresses, generalized feelings of anxiety, and help induce relaxation and improve sleep. 

Edmonton Neurotherapy can offer a multi-modality approach to treating clinical depression that is both effective and comprehensive.

Transcranial DC Stimulation to Treat Depression

Transcranial direct current stimulation (tDCS) is a way of non-invasively stimulating the brain using a small amount of electricity. This treatment is actually very different than electroconvulsive therapy (ECT), which is another way to stimulate the brain with electricity. ECT requires a person to have anaesthesia and gives the brain a full one ampere jolt that causes a seizure. ECT causes massive changes in brain functioning and can be effective for many brain disorders such as depression and schizophrenia that fail to respond to other treatments. Transcranial direct current, on the other hand, is a much more selective and benign treatment. Instead of 1 ampere of electricity, tDCS uses 1-2 milliamps of current (a thousand times less than ECT). tDCS can be performed on a person when they are fully awake and conscious. The only noticable side effect is a transient mild scalp irritation (itchy feeling) that occurs when the electricity is turned on. So basically for this technology, researchers place two sponge electrodes on specific areas of your head. These sponge electrodes are connected to the anode and cathode parts of a nine volt battery. The sponge electrode that is connected to the anode increases brain activity underneath it, while the sponge electrode attached to the cathode tends to decrease brain activity. So neurotherapy practitioners are able to selectively increase or decrease brain activity in cortical brain regions that are near to the electrodes.

To view a brief Youtube video on transcranial DC stimulation therapy, please click on this link...   http://www.youtube.com/watch?v=hp6bBs16g28&NR=1  

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option.

Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last few years tDCS protocols have been optimized and application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies.

Transcranial direct current stimulation is attracting widespread attention as a promising new treatment for Major Depressive Disorder on the basis of its low cost, good safety profile, and promising reports of clinical efficacy.

Fregni, et al. (2006) reports on a randomized, sham-controlled, clinical trial of tDCS in the treatment of 10 patients diagnosed with major depression. Level of depression was evaluated before and after treatment by means of the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Patients were randomly assigned to one of two groups, an active treatment group that received 1.0 mA anodal (+) DC stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal (-) stimulation over the contralateral supraorbital area (just above right eyebrow) versus a sham treatment group that received the identical treatment but with the tDCS device turned off. Both groups received 20 minutes of actual or sham stimulation once a day for five consecutive days. All patients remained blind to treatment conditions and the treatment was well-tolerated with no significant adverse effects. Four of the five patients in the active treatment group were treatment responders whereas none of the five patients receiving sham were treatment responders. The active treatment group showed a significantly greater reduction in depression scores on the post-treatment HDRS and BDI as compared to the sham treatment group (70% vs 30% respectively).

Boggio, et al. (2008) followed up and expanded on Fregni’s earlier small clinical trial by examining the effects of 2.0 mA tDCS treatment on major depression with a larger group of 40 unmedicated patients. In this study, the patients were randomly assigned to one of three groups in a 2:1:1 ratio: active treatment (n = 21), active control (n = 9), and sham treatment (n = 10). As with Fregni’s study, all patients were evaluated pre- and post-treatment using the HDRS and BDI depression scales but this time the scales were administered at the beginning of treatment (baseline), immediately after treatment, and again at 15 and 30 days post-treatment.

All patients received ten 20-minute treatment sessions over a period of two weeks. The active treatment group was treated with anodal (+) tDCS over the left DLPFC. The active control group was treated with anodal (+) tDCS over the occipital cortex. The sham group was treated exactly as the active group but with the electricity turned off. In all cases, the cathode (-) was placed over the right eyebrow.

Treatment response was defined as a 50% or greater reduction in HDRS scores from baseline. Remission was defined as HDRS scores below 7. On average, the active treatment group obtained a 40% reduction in HDRS scores with treatment as compared to 21% and 10% for the active control and sham groups respectively.

The results of this study demonstrated that ten brief sessions (10 x 20 minutes) of cortical stimulation with tDCS is associated with clinically significant reductions in depression scores on clinical symptom rating scales that is specific to the site of stimulation and lasts for at least 30 days post-treatment. Moreover, 10 days of tDCS treatment resulted in only minimal and temporary adverse effects in less than 15% of the patients that did not carry on beyond the end of treatment.

The most recently published study of tDCS for the treatment of depression (Martin, Alonzo, Mitchell, et al., 2011) found that 20 treatment sessions over 4 weeks with the anode placed over the left dorsolateral prefrontal cortex (F3) and the cathode attached to the left bicep was successful in reducing depression symptoms by an average of 43% in the 11 patients treated. All patients in this study had failed to respond to conventional treatments for depression.

Suggested Readings on Neurotherapies for Depression

Baehr, E., Rosenfeld, P., Baehr, R. (2001). Clinical use of alpha asymmetry neurofeedback protocol in the treatment of mood disorders: Follow-up study one to five years post therapy. Journal of Neurotherapy, 4(4): 11-18.

Baehr, E., Rosenfeld, J., Baehr, R., & Earnest, C. (1998). Comparison of two EEG asymmetry indices in depressed patients vs. normal controls. International Journal of Psychophysiology, 31: 89-92.

Baehr, E., Rosenfeld, J., Baehr, R., & Earnest, C. (1999). Clinical use of an alpha asymmetry neurofeedback protocol in the treatment of mood disorders. In J. Evans & A. Abarbanel (Eds). Introduction to Quantitative EEG and Neurofeedback. (pp. 181-203). New York, NY: Academic Press.

Boggio, P., Nitsche, M., Pascual-Leone, A. (2005). Correspondance: Transcranial direct current stimulation. Briish Journal of Psychiatry, 186: 446-447.

Boggio, P., Rigonatti, S., Ribeiro, R., Myczkowski, M., Nitsche, M., Pascual-Leone, A., Fregni, F. (2008). A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. International Journal of Neuropsychopharmacology, 11(2): 249-254.

Cantor, D., Stevens, E. (2009). QEEG correlates of auditory-visual entrainment treatment efficacy of refractory depression. Journal of Neurotherapy, 13(2): 100-108.

Dell'Osso, B., Zanoni, S., Ferrucci, R. et al. (2011). Transcranial direct current stimulation for outpatient treatment of poor-responder depressed patients. European Journal of Psychiatry, July 2011.

Fregni, F., Boggio, P. Nitsche, M., Marcolin, M., Rigonatti, S., Pascual-Leone, A. (2006). Treatment of major depression with transcranial direct current stimulation. Bipolar Disorders, 8(2): 203-205.

Fregni, F., Pascual-Leone, A., et al. (2007). Technology Insisight: Non-invasive brain stimulation in neurology - Perspectives on the therapeutic potential of rTMS and tDCS. Clinical Practice in Neurology, 3(7):383.

Hagemann, D., Hewig, J., Naumann, E., Seifert, J., Bartussek, D. (2005). Resting brain asymmetry and affective reactivity: Aggregated data support the right-hemisphere hypothesis. Journal of Individual Differences, 26, 139-154.

Iyer, M., Mattu, U., Grafman, J., et al. (2005). Safety and cognitive effects of frontal DC polarization in healthy individuals. Neurology, 64(5): 872-875.

Martin, D., Alonzo, A., Mitchell, P., et al. (2011). Fronto-extracephalic transcranial direct current stimulation as treatment for major depression: An open-label pilot study. Journal of Affective Disorders, August 2011.

Nitsche, M. (2002). Transcranial direct current stimulation: A new treatment for depression? Bipolar Disorders, 4(Suppl. 1): 98-99. 

Nitsche, M., Boggio, P., Rigonatti, S., Pascual-Leone, A. (2009). Treatment of depression with transcranial DC stimulation (tDCS). Experimental Neurology, 219(1): 14-19.

Rigonatti, S., Boggio, P., Myczkowski, M., et al. (2008). Letters to the Editor: Transcranial direct stimulation and fluoxetine for treatment of depression. European Psychiatry, 23: 74-76.

Walker, J., Lawson, R., Kozlowski, G. (2007). Current status of QEEG and neurofeedback in the treatment of clinical depression. In: J.R. Evans (Ed.), Handbook of Neurofeedback: Dynamics and Clinical Applications. (chapter 14, pp.341-352). New York, NY: Haworth Medical Press.