The importance of subject control in reinforcing brain stimulation

A comparison between the reinforcement strength of self-administered and externally imposed brain stimulation was undertaken. Rats performed on a chain schedule in order to receive brain stimulation, either selfadministered or imposed, during the second component of the chain. Response rates during the first component of the chain schedule indicated that self-stimulation was more reinforcing than imposed stimulation. In addition, contrast, both positive and negative, seemed to be present. It was concluded that reinforcement strength may be enhanced when the subject controls the presentation of reinforcement.     

The opportunity for aggression as an operant reinforcer during aversive stimulation

Squirrel monkeys were provided with a chain-pulling response which produced an inanimate object that could be attacked. In the absence of pain-shock, little or no chain-pulling occurred. When pain-shocks were delivered, chain-pulling responses increased. The chain-pulling response was successively reinforced, extinguished, reinforced, and again extinguished by presenting or withdrawing the opportunity to attack as the reinforcing event. Aggression appears to be a distinctive motivational state which is produced by aversive stimulation and which can be used to condition and maintain new behavior.     

Electrical stimulation of the brain for psychiatric disorders

Despite advances in therapies, there remain psychiatric patients who are extremely ill and cannot be helped by classic psychiatric treatments, including psychotherapy and drug therapy. Certain of these patients may be helped by use of bilateral brain lesioning. The complication rate of standard stereotactic psychosurgery techniques is very low. The main rationale for the continued experimental use of deep brain stimulation (DBS) in neurosurgery for mental disorders is its reversibility. This reversibility is not an advantage in terms of the benefits obtained, but rather if side effects emerge. In addition, electrical stimulation may provide patients with some autonomy for their treatment. The first, very preliminary results of electrical stimulation for obsessive-compulsive disorder and for a small heterogeneous group of patients with other psychiatric disorders have been published. Electrical stimulation of the brain for psychiatric disorders may become a new treatment option for certain intractable psychiatric disorders. Nevertheless, the mechanism of action of DBS in psychiatric disorders is unknown, and the experience with this modality is extremely limited. The first results look promising, but this treatment option may prove unusable for some time because of a lack of knowledge of appropriate brain stimulation targets and technical problems such as the availability of sufficient current supply.     

Putative common pathways in therapeutic brain stimulation for affective disorders

Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment-resistant depression with limited results. DBS may be of potential use in rare cases of treatment-resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.     

Foraging for brain stimulation: toward a neurobiology of computation

The self-stimulating rat performs foraging tasks mediated by simple computations that use interreward intervals and subjective reward magnitudes to determine stay durations. This is a simplified preparation in which to study the neurobiology of the elementary computational operations that make cognition possible, because the neural signal specifying the value of a computationally relevant variable is produced by direct electrical stimulation of a neural pathway. Newly developed measurement methods yield functions relating the subjective reward magnitude to the parameters of the neural signal. These measurements also show that the decision process that governs foraging behavior divides the subjective reward magnitude by the most recent interreward interval to determine the preferability of an option (a foraging patch). The decision process sets the parameters that determine stay durations (durations of visits to foraging patches) so that the ratios of the stay durations match the ratios of the preferabilities.     

A multifunctional on-line brain stimulation system

A flexible on-line electrical brain stimulation system designed for brain stimulation reward (BSR) research is described. A Cromemco Z-2D microcomputer is interfaced with a constant-current stimulator and a standard operant chamber. The system programs, written substantially in BASIC, calculate BSR threshold by two rate-independent methods, measure rate of operant responding, and determine resistance of the brain. Other software programs are used for training rats on complex schedules of reinforcement, for system hardware calibration, and for sophisticated statistical data analyses.     

Vagus nerve stimulation: a new form of therapeutic brain stimulation

Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.     

Lessons learned in deep brain stimulation for movement and neuropsychiatric disorders

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.