Over the next 2 years, CNS Spectrums will be publishing a series of articles on neuroanatomy. The purpose of these articles is to broaden knowledge and interest in neuroanatomy, with a special reference to some key brain structures that are important for neuropsychiatry. Interest in nuclear structures and hodology, in connectivity and circuitry between brain regions, and in neurochemical associations has increased in the last 3 decades due to new neuroanatomical staining methods, brain imaging, and new treatments, such as deep brain stimulation.These columns will enliven an understanding of the clinical neuroscience interface but also provide a solid framework of contemporary neuroanatomy for psychiatrists and neurologists.

The first in the series reviews the ventral striatum. Henk J. Groenewegen, MD, PhD, in a column dedicated to the late Lennart Heimer, MD, reveals the importance of this structure and its connectivity for a contemporary understanding of brain-behavior relationships. In earlier conceptions, the basal ganglia were solely related to motor function, uninvolved with emotion or cognition. This conception arose from a misunderstanding of basic neuroanatomy, which has been unravelled by careful neuroanatomical studies in the last 30 years with new tissue staining and tracing techniques.The basal ganglia are the main target structures of the limbic system, hence the motion in emotion.

Dr. Nierenberg is associate director of theDepression Clinical and Research Program atMassachusetts General Hospital and associate professor of psychiatry at Harvard MedicalSchool in Boston. He is also director of the National Institute of Mental Health Bipolar Trials Network, a federally funded infrastructure for the next generation of clinical trials to help patients with bipolar disorder. He was the site principal investigator for the Systematic Treatment Enhancement Program for Bipolar Disorder and was involved in the Sequenced Treatment Alternatives to Relieve Depression study. His research interests focus on bipolar disorder, treatment-resistant depression, and the longitudinal course of affective disorders. Dr. Nierenberg has been listed in The Best Doctors in America for the treatment of mood and anxiety disorders in every edition since 1994.

Williams syndrome is a neurodevelopmental disorder that results from the deletion of ~25-30 genes spanning about 1.5 megabases in the q11.23 region of chromosome 7. Patients with this syndrome present with a combination of a distinctive elfin-like facial appearance; growth retardation; mild mental retardation; an inconsistent cognitive profile that includes visuospatial impairments with good facial discrimination and relatively preserved expressive language skills; and cardiovascular abnormalities. In addition, a striking behavioral feature of the syndrome is the high sociability and empathy that these patients show for others. The study of patients with “partial” deletions of the chromosome band 7q11.23, mutated genes in this region and knockout mice with deletions of specific genes in the homologous G1–G2 region of mouse chromosome 5 are clarifying some genotype/phenotype relationships. Futhermore, genes located in this region that are prominently expressed have been implicated in brain development and function.The neuropsychological profile of patients with Williams syndrome is heterogeneous, highlights important dissociations between cognitive functions and suggests that the behavioral dimensions of sociability, empathy, engageability, and talkativeness may be independent of, or not easily explained by, the cognitive deficits. Williams syndrome has enormous heuristic value because its pathological feature of heightened “sociability” can be a “deficit” symptom of major complex neuropsychiatrie disorders, such as schizophrenia and autism. Data consistent with a core inability of patients with Williams syndrome to inhibit social approach suggest that this disorder may afford an opportunity to study the biological basis of the “drive” toward socialization. From a research perspective, the syndrome lends itself to neurobiological studies of sociability as a dimension that varies independently of cognition (or at least many separable cognitive processes). Importantly, from a clinical perspective, the syndrome challenges us to administer strategic psychosocial interventions that take advantage of the opportunities that “pathological” sociability provide, while avoiding its threats. An illustrative example of an effective strategically planned psychosocial intervention for a patient with Williams syndrome is briefly presented.

Somnambulism, a previously unreported side effect of quetiapine, is described in two cases. Both cases involved individuals who had no prior or family history of somnambulism and had attention-deficit/hyperactivity disorder. The possible significance of this will also be discussed. Somnambulism is a common parasomnia that reflects an impairment in the normal mechanisms of arousal from sleep in which motor behaviors are activated without full consciousness. Motor behaviors are initiated during deep non-rapid eye movement or slow-wave sleep (stages 3-4), and may be limited to relatively simple manifestations, such as sitting up, fumbling with objects or bedclothes, or mumbling.

Our objective is to report a coincident reduction in headache pain in patients treated with repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD). Two patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, non-responsive to prior antidepressant treatment who were enrolled in a sham-controlled, double-blind study of rTMS for MDD. After the study, it was revealed that both were in the active-treatment arm. Both patients suffered from near daily headaches and kept logs of headache frequency and severity before, during, and after the study. Headache pain was significantly reduced under double-blind conditions with rTMS treatment, but returned to baseline following cessation of rTMS treatment. Ultimately, when receiving rTMS post-study as a maintenance intervention for MDD (~2 rTMS sessions/week), the positive effects on headache amelioration were sustained. Headache pain is frequently comorbid with mood disorders and has been reported as the most common side effect with rTMS. In these subjects, rTMS was, in fact, associated with relief of depressive symptoms and preexisting headache pain. This indicates that rTMS may be beneficial for both disorders in some patients.