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.     

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.     

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.     

Mind matters: A narrative review on affective state-dependency in non-invasive brain stimulation

Variability in findings related to non-invasive brain stimulation (NIBS) have increasingly been described as a result of differences in neurophysiological state. Additionally, there is some evidence suggesting that individual differences in psychological states may correlate with the magnitude and directionality of effects of NIBS on the neural and behavioural level. In this narrative review, it is proposed that the assessment of baseline affective states can quantify non-reductive properties which are not readily accessible to neuroscientific methods. Particularly, affective-related states are theorized to correlate with physiological, behavioural and phenomenological effects of NIBS. While further systematic research is needed, baseline psychological states are suggested to provide a complementary cost-effective source of information for understanding variability in NIBS outcomes. Implementing measures of psychological state may potentially contribute to increasing the sensitivity and specificity of results in experimental and clinical NIBS studies.     

Memory in schizophrenia and affective disorders*

The purpose of the present study was to investigate the stability of memory and information processing in schizophrenics and affectively disturbed patients. Twenty-two schizophrenics, eight affectives and 14 normal controls were tested twice, with an interval of approximately one year. Results showed that normals performed better than schizophrenics and affectively disturbed patients on almost all of the cognitive measures. The differences reached a level of significance on a reaction time test, a vigilance task and a long-term memory task. The only measure where the difference did not reach a level of significance was on a short-term memory test. Groups' performance to some extent changed over time on most of the measures, but the changes were not significantly different for different groups.     

Continuous opportunity for reinforcing brain stimulation

The performance of a rat provided with continuous opportunity to obtain reinforcing brain stimulation over a 20-day period is described in detail. The animal averaged 29.2 responses per min during the entire time. Testing session was terminated by experimenters, but a day-by-day analysis of behavior provided no evidence that the animal would have stopped responding.     

Affective disorders and aggression disorders: evidence for a common biological mechanism

Ever since the discovery that the classical antidepressants--tricyclics and MA oxidase inhibitors--exert an influence on central 5-HT, this neurotransmitter has been studied in depression, particularly in those forms responsive to this type of treatment. This chapter reviews the evidence in favor of a relationship between depression and central 5-HT dysfunctions. Most of the findings have been derived from patients with depression as the principal diagnosis. Some data have originated from patients suffering from a somatic illness and from depression as well. Both peripheral and central data are discussed. Although no single 5-HT-related finding in depression has so far been unequivocally established, the available evidence, in balance, justifies the tentative conclusion that disturbances in 5-HT metabolism can occur in depression. Lowered CSF 5-HIAA, the major indicator of disturbed central 5-HT metabolism in depression, has also been reported in aggression disorders, both in patients who had committed suicidal acts and in those with outward-directed aggression. The finding can not be explained by a concomitant state of depression. Rather than to discard the classical 5-HT-depression hypothesis, in favor of a 5-HT-aggression hypothesis, the hypothesis is launched that disturbances in serotonergic regulation can give rise to both mood and aggression disorders. This would provide a biological explanation for the clinical observation that those disorders frequently go hand in hand.     

Developing connections for affective regulation: age-related changes in emotional brain connectivity

The regulation of affective arousal is a critical aspect of children’s social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of “hot” executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional magnetic resonance imaging (fMRI), we investigated the brain mechanisms involved in the development of affective regulation in typically developing 5- to 11-year-olds and an adult comparison sample. Children and adults displayed differing patterns of increased anterior cingulate cortex and decreased amygdala activation during episodes in which emotion regulation was required. Specifically, amygdala activation increased in adults but decreased in children during recovery from a frustrating episode. In addition, we used effective connectivity analyses to investigate differential correlations between key emotional brain areas in response to the regulatory task demands. We found reliable increases in effective connectivity between the anterior cingulate cortex and the amygdala during periods of increased demand for emotion regulation. This effective connectivity increased with age.     

Sex differences on the revised Beck Depression Inventory for outpatients with affective disorders

The revised Beck Depression Inventory (BDI) was administered to 174 male and 276 female psychiatric outpatients diagnosed with affective disorders. The mean BDI scores, mean number of symptoms claimed, and corrected item-total correlations were comparable for both sexes, and the coefficient alpha for each sex was .88. Principal components analyses found four dimensions of depression underlying both sexes' BDI item-intercorrelation matrices. Although men and women had comparable dimensions with respect to weight loss, self-blame, and somatic-performance symptoms, men had affective and performance symptoms loading on the same factor, whereas women had affective and cognitive symptoms loading on the same dimension.     

Longitudinal changes in time estimation in affective disorders: a preliminary study

8 patients with hospital diagnoses of major affective disorder were studied by repeated measurements of time estimation using the three different methods of metronome adjustment, verbal estimation and operative estimation (production) of short time intervals. Retrospective estimations of longer intervals were also studied. The diagnoses were evaluated according to DSM III criteria. The degree of mental disturbance was rated with subscales of the Comprehensive Psychopathological Rating Scale. Earlier findings had indicated that manic patients tend to overestimate short time intervals and that some depressed patients underestimated time, but some investigators have reported different results. A longitudinal study could possibly support the earlier findings if the time estimations should vary with the clinical states of the patients. Such a variation was suggested by the results of 5 of the 8 patients. In several cases there were statistically significant correlations between the results of time estimations and the rating scores. This partly supports earlier findings. Associations between time estimations and changes in clinical state seem to be present in some cases of major affective disorders. Operative estimations were best correlated with ratings in most cases.     

Pharmacological treatment of affective disorders: A review and guide for the non-medical practitioner

Mental health professionals who lack medical training may also lack knowledge and understanding of the potential utility of medications in the treatment of emotional disturbance. They may also lack information regarding the effects and side-effects of medications which their clients may already be taking, or be uncertain when the nature of their client's situation suggests a psychiatric assessment regarding drug therapy. This paper offers an educational review in one such area: the pharmacological treatment of depression. It includes a brief review of theories regarding the aetiology of affective disorder, examines the methodes, mechanisms and efficacy of anti-depressants, and draws conclusions regarding the appropriate use of pharmacological treatment.     

Social brain development and the affective consequences of ostracism in adolescence

Recent structural and functional imaging studies have provided evidence for continued development of brain regions involved in social cognition during adolescence. In this paper, we review this rapidly expanding area of neuroscience and describe models of neurocognitive development that have emerged recently. One implication of these models is that neural development underlies commonly observed adolescent phenomena such as susceptibility to peer influence and sensitivity to peer rejection. Experimental behavioural evidence of rejection sensitivity in adolescence is currently sparse. Here, we describe a study that directly compared the affective consequences of an experimental ostracism manipulation (Cyberball) in female adolescents and adults. The ostracism condition led to significantly greater affective consequences in the adolescents compared with adults. This suggests that the ability to regulate distress resulting from ostracism continues to develop between adolescence and adulthood. The results are discussed in the context of models of neurocognitive development.     

Validity of the Millon Clinical Multiaxial Inventory in the assessment of affective disorders

The Millon Clinical Multiaxial Inventory (MCMI) was administered to 270 adult outpatients with major affective disorders at the same time that a semistructured, diagnostic interview was conducted by a clinician. The mood of the patient was then rated, and the clinician completed the Hamilton Depression Rating Scale and the Mania Rating Scale. A consensual diagnosis was arrived at by the team of investigators using DSM-III criteria. Significant correlations were found between four MCMI affective scales and the global mood state of the patient. Analysis of covariance indicated that the MCMI affective scales are significantly related to DSM-III affective disorders even after the effect of the current mood of the patient is partialled out. The clinical usefulness of each of the scales is discussed.     

Mental disorders,brain disorders,neurodevelopmental disorders: challenges for the philosophy of psychopathology after DSM-5

The publication of DSM-5 has been accompanied by a fair amount of controversy. Amongst DSM's most vocal ‘insider’ critics has been Thomas Insel, Director of the US National Institute of Mental Health. Insel has publicly criticised DSM's adherence to a symptom-based classification of mental disorder, and used the weight of the NIMH to back a rival research strategy aimed at a more biology-based diagnostic classification. This strategy is part of Insel's vision of a future, more preventative psychiatry in which mental disorders are not only understood as biological disorders of the brain, but also as neurodevelopmental disorders. This paper examines the interest and merit of Insel's views of mental and neurodevelopmental disorder for the philosophy of psychopathology, with a special focus of his neurodevelopmental model of schizophrenia. Pitman's ‘moderate materialism’ will be used both as a philosophical lens through which to examine Insel's position, as well as an example of a philosophical framework that may require updating and revision in the light of moves towards a neurodevelopmental conception of mental 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.