Transcranial Direct Current Stimulation for Fatigue and Attentional Disorders

Introduction

Fatigue and attention disorders are common in modern society and can cause significant difficulties in the lives of those afflicted. Increases in cognitive fatigue are typically characterized by a decline in attention, difficulties concentrating, and increased reaction times ( ). In fact, cognitive impairments caused by just moderate levels of fatigue have been shown to exceed those caused by alcohol intoxication at a blood–alcohol content (BAC) of 0.08 ( ). While the cause of the fatigue or attentional symptoms vary, there is a growing body of evidence that suggests a benign form of noninvasive brain stimulation known as transcranial direct current stimulation (tDCS) can augment brain activity in a manner that provides therapeutic relief of major symptoms, improves mood, and reduces associated cognitive performance declines.

Medical Causes of Fatigue and Chronic Fatigue Syndrome

Fatigue is a common symptom in a variety of neurological disorders such as major depressive disorder (MDD), cancer, anxiety, multiple sclerosis (MS), mitochondrial diseases, stroke, traumatic brain injury (TBI), chronic pain, and chronic fatigue syndrome (CFS). Patients often describe fatigue as quickly reaching exhaustion while engaged in activity, attention and vigilance declines, reduced energy levels, feeling sleepy or tired even at rest, high inertia, low endurance, and low vigor ( ). Sometimes fatigue symptoms can manifest with no apparent underlying cause. When such symptoms persist for more than six months, it is referred to as “chronic fatigue syndrome” ( ).

divide fatigue into two types: central fatigue (CF) and peripheral fatigue. As the name implies, CF is caused by abnormal function or physiology in the central nervous system (CNS). Conversely, peripheral fatigue arises from bioenergetics, excitation-contraction uncoupling, or peripheral nerve changes ( ). For the purposes of this chapter, the focus will be on CF.

CF can be caused by a variety of medical disorders. Perhaps one of the more debilitating is Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This is characterized by persistent incapacitating fatigue that lasts for more than 6 months. This level of fatigue impairs normal activities, is accompanied by nonspecific somatic symptoms, and has no identifiable medical or psychological problems to account for it. In addition to fatigue, people may complain of loss of memory or concentration, headaches, unrefreshing sleep, depression, enlarged lymph nodes, unexplained muscle or joint pain, sore throat, and hypotension. ME/CFS is classified as a disease of the CNS but is only diagnosed when other conditions have been ruled out. There is no diagnostic test and the symptoms vary in presence and severity from patient to patient. ME/CFS is poorly understood as it seems to be a combination of the malfunctioning of the short-term (autoimmune and/or autonomic nervous system) and long-term (hypothalamus–pituitary–adrenal (HPA) axis, psychological) stress response systems ( ).

There is evidence for both altered immune functioning and for perpetuating psychological factors in the development or maintenance of CFS that may be mutually reinforcing ( ). The onset of CFS is often sudden and precipitated by an infectious episode ( ). Subsequent infections may play a large part in worsening of fatigue symptoms ( ), signaling an autoimmune response. There is also a growing body of evidence that the immune system of patients with CFS might respond differently to exercise when compared to healthy, sedentary controls, potentially triggering an increase in symptoms ( ). The HPA axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions ( ). Dysfunction of the HPA axis in ME/CFS patients may manifest as hypocortisolism, which is relevant to fatigue and due to cortisol’s role in energy metabolism ( ) and response to stressors ( ).

The presence of infectious agents, immune dysfunctions, psychological influences on the illness, and the dysfunctional HPA axis may be the outcome of hypersensitivity of the CNS (i.e., central sensitization). The increased sensitivity to a variety of stimuli (including mechanical pressure, chemical substances, light, sound, cold, heat, and electricity) results in a decreased load tolerance ( ), as the nervous system gets regulated in a persistent state of high reactivity. This persistent hypersensitivity may maintain dysfunction, even after its trigger has been alleviated.

ME/CFS shares abnormalities along with other CNS disorders, including fibromyalgia and MS. All three disorders are associated with widespread pain, fatigue, sleep disturbance, depression, sensory and motor impairments, and reduced quality of life (QOL) ( ) due to a lack of optimal options for symptom management. In a neuroimaging study comparing MS and ME/CFS, the neuroimages are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels ( ).

The pathophysiology of fatigue in MS remains unclear but it has been suggested that functional (reduction of glucose metabolism, communication disruption) and structural (lesions, atrophy) alterations in the frontal cortex play a role in fatigue severity ( ). MS-related fatigue has also been attributed to atrophy within the parietal lobe ( ). Because fatigue may derive from frontal or parietal area hypoactivation, tDCS may benefit patients by restoring activation in these areas ( ).