Goodbye Drugs - Hello Stimulation

One of the most important neuroscience discoveries of the 20th century, or perhaps of all time, was that of Olds and Milner in the early 1950s (Olds 1973). They revealed cerebral circuits for pleasure and reward, and hence mechanisms for endowing hedonic tone to percepts and behaviour. This research was being conducted at the same time that others were unravelling additional neuroanatomical structures associated with the emotions, notably Papez and MacLean. Papez proposed a circuit for emotion, giving an organism “a stream of feeling”, MacLean (1990) defined for us the “visceral brain”. The latter became renamed limbic after the earlier anatomical designations of Broca, and the term limbic system is now familiar to all neuroscientists with an interest in brain-behaviour relationships.
    With the identification of such a neuroanatomy of the emotions, the possibility of altering emotional expression, and hence providing amelioration of neurobehavioral disturbances by influencing such circuitry became a possibility. Although most people are aware of the tissue destruction techniques such as those which dissected the frontal lobes from downstream structures, stimulation of the brain, whether indirectly across the scalp or directly by application of electrodes to the brain itself, was, until recently rather played down. In fact such ideas had been around for a long time, but the neuroanatomical knowledge and the technology needed for progress were not available, until the mid-part of the 20th century. One well acknowledged method, still widely used was electroconvulsive therapy (ECT), although quite how it worked to treat psychoses or depression was, and remains unclear. Nevertheless, it is a successful brain stimulation technique which has stood the test of time.
The early pioneers of direct stimulation had the right ideas, but lacked the sophistication that today’s electronic world has provided. Robert Heath (1954) was one such investigator, who, while at Tulane, began stimulation of what he referred to as the septal area (closely analogous to what is also referred to as the fundus striati, loosely the accumbens region), in patients with schizophrenia. The choice of target was interesting, as the subcortical controls over the cortex and hence behaviour were implicated in his theories (he also stimulated caudate, thalamus, hypothalamus and cerebellum). Since patients were usually conscious, their subjective responses could be recorded, which included sensations of pleasure, akin to the findings in animal models of Olds and Milner.
    The clinical work on treating psychiatric movement disorders by lesioning cortical or subcortical structures such as the cingulate gyrus, globus pallidus or the thalamus was quite successful, but the amount of operative tissue destruction led to unwanted neuropsychological deficits, and in any case, a new era of treatment evolved with the discovery of monoamine transmitters, especially dopamine and the development of an array of neuropsychoactive drugs the success of which soon diminished enthusiasm for the neurosurgery of neuropsychiatric disorders.
    There is now a renaissance of interest in brain stimulation, encouraged by the new technologies, and by the relative lack of success of psychotropic drugs in the treatment of so many neuropsychiatric conditions. Information gleaned from the earlier ablative studies is guiding current neurosurgical methods for deep brain stimulation (DBS), and helping reformulate hypotheses about the mechanisms of action of ECT. Other stimulation techniques, which have become available, and adopt indirect stimulation include Vagus Nerve Stimulation (VNS), Transcranial Magnetic Stimulation (TMS), and refinements of the ECT method with targeted pulses of energy with the intention of developing ECT without the convulsions. It is certain that other methods of brain stimulation will become available in the near future. If progress in this area is as rapid as it has been in the past few years, some form of brain stimulation will be a treatment, but I would predict the treatment modality, for a wide variety of neurological and psychiatric disorders in the near future. Acquaintance with basic principles of electricity will be essential for all who work in psychiatry and neurology, as is an understanding of say serotonin or dopamine today. Discussing treatment options with patients will necessitate an understanding of neuroanatomy, an explanation of the methods of action of various stimulation techniques, and the benefits and hazards of the options.
    There is clearly much to learn, but progress is fast. Soon implanted devices will be able to predict the onset of seizures and target pulses to stop them evolving, treat a wide spectrum of movement disorders and alter the progression of major psychopathologies, ameliorate addictions, slim the obese, revive memories in patients with dementia, prevent aggression, alter sexual orientation, and perhaps even make happy marriages. All this, with little apparent problem with either compliance or significant side effects.
    It is common to hear the wise with today’s knowledge disparage treatments of the past as naïve and misjudged. Who will not look back in say 50 years time at our current generation of therapies, and laugh at our predilection for giving drugs. They will surely wonder at the reason we advocated prescribing poisons, with so many side effects, given in such large doses that the whole body and brain becomes saturated with them, and whose mechanisms of action we were hardly aware of, when neuronal targeted therapies became an option. 

References:


Heath Rg, 1954. Studies in schizophrenia. A multi-disciplinary approach to mind-brain relationships. Cambridge, Harvard University Press.

MacLean PD, 1990. The Triune Brain in evolution. Plenum, New York.

Olds J, 1973. The discovery of reward systems in the brain. In: Valenstein ES, eds. Brain stimulation and motivation. Research and commentary. Glenview. Scott Foresman and company.