Monthly Archives: July 2013

Cranial Electrotherapy Stimulation (CES) Vignette 1

Vignette # 1

John, a fourteen year old Caucasian male with a history of psychiatric treatment including medication intervention for depression and developmental deviation with a hyperkinetic element. His history of school functioning had been poor although he was not reported to display excessive body movement or squirminess difficulty attending was a problem. During the initial psychological evaluation on a measure of depression he scored at the 76th percentile, while on a measure of anxiety he scored at the 81st percentile with present moment (state) anxiety and at the 68th percentile with general proneness (trait) anxiety. On the Wechsler Intelligence Scale for Children-Revised (WISC-R) Full Scale intellectual functioning was in the Average range (Full Scale IQ = 108) with verbal area functioning also in the Average range (Verbal IQ = 107) and performance area functioning in the Average range
(Performance IQ = 107) as well.

After thirty days daily usage of at least forty-five minutes with the CES device he was again administered a psychological evaluation. On the same measure of depression John scored at the 74th percentile, while on the same measure of anxiety he scored at the 7th percentile with present moment (state) anxiety and at the 47th percentile with general proneness (trait) anxiety, a very noticeable decrease with his levels of anxiety. On the WISC-R Full Scale intellectual functioning was in the High Average range (Full Scale IQ = 114) with verbal area functioning in the Average range (Verbal IQ = 102) and Performance area functioning in the High Average range (Performance IQ = 126). Higher scores in the Performance area indicated a gain of more than three standard deviations which by chance alone would occur in less than two in ten thousand cases (p<.0002). These results were obtained even though John was physically ill during the post CES evaluation. In the psychologist's opinion there would have been more of an increase if he had been feeling better.

The Use of CES in the Maintenance of Health and Wellbeing

Following the initial research in the U.S., several units began to be sold for clinical use before the 1976 Amendment gave the FDA control over medical devices. The Amendment gave the FDA power to determine the safety and effectiveness of medical devices prior to allowing them into the U.S. marketplace, and all electrosleep devices which were on the open market prior to the Amendment were grandfathered and left on the market, with a provision that the FDA could call them in later to have them show their safety and effectiveness, a process costing up to an estimated $800 million.

The FDA also decided to call electrosleep devices Cranial Electrotherapy Stimulation devices, since by then their clinical uses had expanded from sleep to include depression and anxiety. A preliminary look at CES by the FDA’s Neurology Panel in 1978 suggested they should be accepted for the safe and effective treatment of addictions, and that the other treatment claims should be looked at again as more research became available.

When one looks back at specific neurotransmitter systems that are influenced and possibly rebalanced by CES one finds himself confronted directly with the body’s neurohormonal stress system.

Stress is caused by a person entering a dangerous fight-or-flight situation, and is relieved when the person is no longer in that situation. To operate effectively in such a situation, the body has to dramatically shift its neurohormonal balance out of its normal homeostasis. Stress, in that situation, is very healthy and can even be life saving, such as when a person runs out of the path of an automobile that is swerving toward him out of control, or jumps away from a snake, poised to strike, suddenly encountered on a trail in the woods.

Chronic stress, however, is a different matter and occurs when a person is living in a threatening situation he can not escape… a job, an unfortunate relationship, driving daily in dangerous commuter traffic, watching the evening news on T.V., with every “Oh, my god,” story the news producer can find to put on (“if it bleeds, it leads”14). When under chronic stress, the body’s neurohormonal system does not come back into its normal homeostatic balance, and the resulting imbalance is said to cause up to 90% of the physical illnesses brought to the attention of physicians.

Major symptoms of a system under chronic stress number among them, insomnia, depression, anxiety, posttraumatic stress disorder, various compulsive behavior disorders, not the least of which are the various addictions in which the person uses various drugs (or medications) in an effort to alter the neurohormonal system back to a more acceptable level. Physical problems also increase, such as heart attacks, strokes, diabetes, cancer, obesity, and infections such as colds and flue, among any number of others.

And where does CES treatment interface with this syndrome? From the earlier animal and later human research,17 CES can best be described as an adaptogen, in which CES acts to increase the body’s resistance to adverse influences by reestablishing the homeostatic balance between the body’s various neurotransmitters that have been thrown out of balance by chronic stress. In basically rebalancing the physiological system, CES influences a wide range of physical, chemical and biochemical factors that have a normalizing effect on the body. CES, then, acts to alleviate stress, and in the process improve all kinds of conditions that have been generated by that stress.

For example in 18 studies of insomnia, the average improvement was 62%, in a similar number of depression studies, the average improvement was 47%, while in 38 studies of anxiety, the average improvement was 58%. Those were the average improvement scores. In 31 double blind studies of various psychological problems, while the average improvement was found to be 56%, the range of improvement went from a low of 23% to a high of 91%, a treatment effect never seen in pharmaceutical treatment of those types of disorders.

Highly positive treatment effects have also been found in other areas of dysfunction, such as in persons recovering from the effects of addiction, in children and adults suffering from Attention Deficit Disorder, in persons suffering from stress related memory loss, and in patients suffering from headaches and other types of stress related pain syndromes. And more importantly, no significant negative side effect has ever been reported in more than 46 years of CES research and treatment in the U.S

More recently, following the Vietnam War the Post Traumatic Stress Disorder or PTSD is being given much attention. During World Wars I and II, the disorder was known as shell shock and thought to be caused by the immediate stress of battle. The cure, at the time, was to let the men lie quietly in or just outside the medical tent away from the battle area, and rest until their nerves settled down.

Once the syndrome was described, it was discovered that perhaps 25% or more of persons who have never been in the military have experienced PTSD. It has been precipitated by such things as child abuse or other childhood trauma such as emotional abandonment by parents or parental surrogates. In older persons and adults it has been precipitated by serious car accidents, major surgery, rapes, muggings, and in general by any other event in which the person felt helpless during an event he/she perceived as life threatening. Nine times more females than males are now known to experience PTSD, and up to 75% of persons suffering from fibromyalgia have PTSD either currently or in their background.

It is now known that PTSD represents a basic split off of parts of the brain in which the emotional trauma was recorded, so that the waking brain remains unaware of it. The problem is that the part of the brain storing the memory often reactivates during sleep and the event is recalled in very stressful nightmares. Also, during the day, any number of small stimuli that occur can reactivate that section of the brain, and a flashback occurs. Accompanying a nightmare or flashback, the entire sympathetic nervous system is called into play and the resulting stress, both physical and emotional can be overwhelming.

Because so many things can trigger a flashback, the person slowly but surely closes off ever more sections of the day to day experience and activities in order to not provoke an episode. The brain actually becomes phobic of those activities that can act as triggers, and closes them off from its daily activities and awareness. The person, as a result, remains in hyper aroused alert status, with an ever narrower life view and experience. To those looking on, the person become quieter, less sociable, and tends to limit activities in all areas of his/her life more and more.

CES treatment in PTSD should have a pronounced effect in that PTSD symptoms always increase when the person is under stress of any other kind. Also, the research with CES in phobic patients indicates that phobic fear can not be experienced while CES treatment is in progress, and at least for a time thereafter.21 It is the panic felt by patients when the phobic areas are roused, with the accompanying uncontrolled system wide sympathetic physiological arousal that gives them their greatest fear and dread. To have CES available during those times of panic should be very helpful immediately, and contribute markedly to a longer term cure as those feelings of helplessness dissipate via its use. Also, researchers are warned not to encourage the patient to call up the traumatic event(s) until they have a ready brake or safe spot they can go to if the emotion gets too high and might go out of control otherwise.22 CES might well act as a brake that the patient could use if he could not readily break off the traumatic imagery and get to his safe spot mentally.

For this reason, it has been suggested that the use of CES during desensitization therapy such as Prolonged Exposure Therapy (PET), a therapy found very effective in treating PTSD, should allow desensitization therapy proceed at a much more rapid rate, and possible be much more effective if it reduced or eliminated the fear while the desensitization was in process. It should also be helpful for use during the several other major forms of PTSD treatment that are presently being used.

If nothing more, CES should reduce or eliminate many phobic areas within the personality, allowing the person to come down from his hyper aroused state and begin interacting in more areas of his life experience once again. That would be a type of desensitization therapy process on its own.

Clinical experience has shown that PTSD patients initially never go out without their CES device handy for use at a moment’s notice. The presence of the device gives them a needed feeling of security they can not get in any other way.

Similar uses could be mad of CES in the treatment of Obsessive Compulsive Disorders, whose symptoms also become more pronounced as the patient comes under ever greater amounts of stress. A type of desensitization treatment, Response Prevention Therapy (ERP) has also been found of real value in treating OCD. In this treatment approach, the patient and the therapist record various stimuli that trigger the OCD response, and rate them in terms of emotional valence. They then attack those with less emotional impact by having the patient put himself in the presence of the stimulus, then deliberately refrain from performing the compulsive ritual that is usually attached to the stimulus. Over several trials the patient habituates to the stimulus and it loses its effectiveness in triggering the self-protective, anxiety reducing OC response.

As the therapy progresses, the patient goes on to those stimuli of ever increasing emotional impact. It might well be that CES, in helping the patient control his anxiety when facing each stimulus until such time as it habituated could also synergize this therapeutic approach and shorten the time to recovery.

How much treatment is required to produce these effects with CES? Patients respond to differing amounts of CES treatment, depending on which of their neurohormonal systems CES is intended to rebalance. And while effects begin to be felt from the first treatment, almost all patients are expected to come back within normal homeostatic limits with 60 minutes to 1 hour of treatments every day for 14 to 21 days, depending on the availability of any required neurohormonal precursors in their diet, their level of activity and so on.

By Ray B. Smith, Ph.D.

Activation of Prefrontal Cortex by Transcranial Direct Current Stimulation

Activation of Prefrontal Cortex by Transcranial Direct Current Stimulation Reduces Appetite for Risk during Ambiguous Decision Making

As adult humans, we are continuously faced with decisions in which proper weighing of the risk involved is critical. Excessively risky or overly cautious decision making can both have disastrous real-world consequences. Weighing of risks and benefits toward decision
making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but its role remains unclear.

Repetitive transcranial magnetic stimulation studies have shown that disruption of the DLPFC increases risk-taking behavior. Transcranial direct current stimulation (tDCS) allows upregulation of activity in the DLPFC, and we predicted that it might promote more cautious decision making. Healthy participants received one of the following treatments while they performed the Balloon Analog Risk Task: (1) right anodal/left cathodal DLPFC tDCS, (2) left anodal/ right cathodal DLPFC tDCS, or (3) sham tDCS.

This experiment revealed that participants receiving either one of the bilateral DLPFC tDCS strategies adopted a risk-averse response style. In a control experiment, we tested whether unilateral DLPFC stimulation (anodal tDCS over the right or left DLPFC with the cathodal electrode over the contralateral supraorbital area) was sufficient to decrease risk-taking behaviors.

This experiment showed no difference in decision-making behaviors between the groups of unilateral DLPFC stimulation and sham stimulation. These findings extend the notion that DLPFC activity is critical for adaptive decision making, possibly by suppressing riskier responses. Anodal tDCS over DLPFC by itself did not significantly change risk-taking behaviors; however, when the contralateral DLPFC was modulated with cathodal tCDS, an important decrease in risk taking was observed. Also, the induced cautious decision-making behavior was observed only when activity of both DLPFCs was modulated. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling.

Morphological changes of the aging brain

During healthy aging, the brain experiences complex structural and biochemical changes, including modification in dendritic morphology, synaptic connectivity (Anderson and Rutledge, 1996), Ca2+ dysregulation (Toescu et al., 2004), gene expression (for review see Burke and Barnes, 2006) and a decrease in the availability and level of neurotransmitters (Roth and Joseph, 1994). Cholinergic and dopaminergic reductions are particularly pronounced compromising motor, attention, and memory processes (Volkow et al., 1998; Braver and Barch, 2002). Furthermore, extensive studies reported that the function of the dopaminergic system gradually declines as we grow older due to degeneration of dopaminergic neurons and receptors (Zaman et al., 2008).

Age-related decreases in white matter integrity appear to be a common process in the brain (Resnick et al., 2003; Stadlbauer et al., 2008). Recent morphological studies using diffusion tensor imaging (DTI, for review see Pierpaoli et al., 1996) in old healthy subjects have consistently shown a correlation between aging and reduction of fractional anisotropy, suggesting a rarefaction of directionally oriented axonal membranes, and increased mean diffusivity reflecting an alteration in cellular membranes and other structures hindering diffusion (Sullivan and Pfefferbaum, 2006).

These age-related differences in white matter integrity are seen throughout the brain, with an increasing magnitude of the difference in anterior white matter structures compared to posterior regions, which most authors refer to as a “anterior–posterior gradient,” with age-related changes occurring earlier in the frontal lobe (Bennett et al., 2010). The corpus callosum represents the largest white matter structure connecting the two hemispheres in the brain. Age-related changes in the topology of the corpus callosum primarily affect the genus; however, recent studies using more sensitive techniques of DTI also demonstrated changes in the splenium (Bastin et al., 2010).

Until now, there is no consensus of the etiology and the functional repercussion of these changes in white matter structure, but recent data from healthy individuals and patients with mild cognitive impairments and dementia converge on highlighting correlations between cognitive performance and fractional anisotropy (Persson et al., 2006), indicating that the decline in white matter might be associated with cognitive impairment.

Healthy aging

Healthy aging is accompanied by changes in cognitive and motor functions that result in impairment of activities of daily living. This process involves a number of modifications in the brain and is associated with metabolic, structural, and physiological changes; some of these serving as adaptive responses to the functional declines. Up to date there are no universally accepted strategies to ameliorate declining functions in this population. An essential basis to develop such strategies is a better understanding of neuroplastic changes during healthy aging. In this context, non-invasive brain stimulation techniques, such as transcranial direct current or transcranial magnetic stimulation, provide an attractive option to modulate cortical neuronal assemblies, even with subsequent changes in neuroplasticity. Thus, in the present review we discuss the use of these techniques as a tool to study underlying cortical mechanisms during healthy aging and as an interventional strategy to enhance declining functions and learning abilities in aged subjects.

During the last century, average life expectancy in developed countries was prolonged approximately 30 years. In addition, a significant decline in fertility generated a shift in the distribution of the population with important socio-economic, political, and public health consequences (UN-Report, 2005). The fact that there are more old people today than ever before, and that this tendency is expected to increase further, underlines the importance of understanding the mechanisms of healthy aging as well as developing novel innovative strategies to adapt for age-relate declines.

Besides age-associated diseases, like cardiovascular diseases or cancer (Balducci and Extermann, 2000), age-related neurobiological changes with consecutive declines in cognitive functions, perceptual, and motor abilities impair activities of daily living, independence, and quality of life (Logsdon et al., 2002; Craik and Bialystok, 2006). In cognition, age-related deficits encompass multiple domains, including attention, memory, reasoning, and executive functions (Celsis, 2000; Hogan et al., 2006). Age-related motor impairments are also ubiquitous, with deficits in the planning, the execution and the control of movement (Krampe et al., 2002; Sawaki et al., 2003). Physiologically, aging consists of a dynamic process in the brain, involving a number of modifications associated with metabolic, structural, and functional changes, part of them hypothesized as adaptive responses to the functional declines (Burke and Barnes, 2006).

In recent years, different forms of non-invasive brain stimulation techniques have been explored in patients and healthy volunteers offering the attractive option to modulate neuronal plasticity and to improve behavior and learning processes (Hummel and Cohen, 2006; Nitsche et al., 2008; Reis et al., 2009). In the present review, we will focus on studies using non-invasive brain stimulation techniques to evaluate cortical mechanisms during healthy aging, especially the one involved in preserving cognitive and motor funcNon-2010.00149tions. Furthermore, the novel field of applying these techniques to increase behavior, neuronal plasticity and learning, e.g., in the sensorimotor domain as a model system, will be presented. Rather than attempting to be comprehensive in terms of reviewed work, this article intends to provide a clearly structured framework of the application of these techniques to understand and support plastic changes in the aging population.