DBS in the treatment of major depression To date, a few case reports suggest that DBS might be a useful treatment for refractory depression. Recently, Mayberg and colleagues158 found that DBS of the white matter tracts adjacent to the subgenual cingulate gyrus was associated with improvement in depressive symptoms in 6 patients with refractory depression. By 1 and 6 months, two and four Inhibitors,research,lifescience,medical patients met criteria for clinical response, respectively Remission was achieved by three patients after 6 months.158 Deep brain stimulation

of the ventral caudate CP-690550 nucleus improved anxiety, depressive, and compulsive symptoms in one patient who suffered from resistant obsessive-compulsive disorder and resistant major depression.159 Deep-brain stimulation of the inferior thalamic peduncle improved depressive symptoms in one patient suffering from recurrent

unipolar Inhibitors,research,lifescience,medical depression and borderline personality disorders.161 Adverse effects Major side effects of DBS are seizure (1% to 3%), hemorrhage (1% to 5%), infection (2% to 25%, usually superficial infections but rarely cerebritis or brain abscess) and hardware-related complications (about 25%) that include Inhibitors,research,lifescience,medical fracture of leads, disconnection, lead movement, and malfunction.162,163 Stimulation-induced adverse effects such as parasthesia, muscle contraction, dysarthria, or diplopia are usually reversible with changes in stimulation Inhibitors,research,lifescience,medical parameters.164 Mechanism of action Investigating the mechanism

of deep brain stimulation reveals a basic paradox: the clinical effect of deep brain stimulation, which is usually regarded as a method of activating neurons, is similar to the traditional ablation of specific brain areas.165 Studies aimed at resolving this paradox have led to the development of four major theories regarding the mechanism of action of DBS. The first theory suggests that irregular activity in neurons converging with Inhibitors,research,lifescience,medical other neurons can result in a loss of information transfer and thus cause clinical pathology. The therapeutic effect of DBS may be due to its driving neurons at regular frequencies, and thus modulating the pathological network activity and increasing neuronal activity in the output nuclei.166 Many studies using functional imaging demonstrate increased GSK-3 cortical activity during DBS treatment. For example, activation of the thalamus and basal ganglia was demonstrated by fMRI studies167 and activation of motor cortex and supplementary motor area was demonstrated by PET studies.168,169 The second theory suggests that excitation of axon terminals near the stimulation electrode releases inhibitory factors that cause synaptic inhibition of the neuron.170 The third theory suggests that high-frequency tetanus produces a blockade of the spontaneous activities of neurons as a result of a strong depression of intrinsic voltage-gated currents,171 and thus DBS causes a depolarization blockade.