Neuropsychiatric practice provides for the interested practitioner a bewildering yet exciting array of symptoms and syndromes. Some are quite common, such as a psychosis is in epilepsy, but many are rare, and sometimes the rarer they are, the more startling and challenging they seem. Take the Moebius syndrome. This is an unusual condition in which there is a congenital palsy of some cranial nerves—most notably the 6th and 7th—usually with hypoplasia or agenesis of the respective nerve nuclei. For example, the patient I was asked to see, because of unremitting seizures, was a girl in her late teens, who had never had any facial expression. She could not smile or express laughter, she could not look angry, she could not contort her face to tears or grief. But did she feel emotions? Of course. She got angry like the rest of us, teared when sad, and was able laugh. The vocalizations of her affects were all present, she simply could not show emotions.

Not surprisingly, this had affected her social development, and inhibited her interactions with her peers. She was frustrated by this inhibition and, in the course of her adolescence, had developed depression and panic attacks, which had been mistakenly diagnosed as epilepsy. This is one variant of the pseudoseizure spectrum.

Genetic contributions to phenotypic variation in general intelligence have been studied extensively. Less research has been conducted on genetic contributions to specific cognitive abilities, such as attention, memory, working memory, language, and motor functions. However, the existing data indicate a significant role of genetic factors in these abilities. Stages of information processing, such as sensory gating, early sensory registration, and cognitive analysis, also show evidence of genetic contributions. Recent molecular studies have begun to identify candidate genes for specific cognitive functions. Future research, identifying endophenotypes based on cognitive profiles of neuropsychiatric disorders, may also assist in the detection of genes that increase susceptibility to major psychiatric disorders.

How can functional neuroimaging be applied to clinical neurology and psychiatry? This article reviews selected contributions of functional neuroimaging to the clinical neurosciences. We review selected technical aspects of positron emission tomography, single photon emission tomography, and functional magnetic resonance imaging with a focus on the relative strengths and weaknesses of these techniques. Consumers of functional neuroimaging research are encouraged to consider the limitations of imaging techniques and theoretical pitfalls of cognitive task design when interpreting results of functional imaging studies. Then, we selectively review the contributions of functional neuroimaging to neurology and psychiatry, including the areas of epilepsy, stroke, chronic pain, schizophrenia, depression, and obsessive-compulsive disorder. Future directions of functional neuroimaging research are offered, with the emphasis that the best conclusions are informed by a convergence of research from functional neuroimaging, neurophysiological, and lesion studies.

Neuropsychological (NP) testing is now recognized as an important method for evaluating treatment effects. However, there are limitations to how these tests are currently used in most drug treatment protocols. Changes in cognition are typically defined in statistical terms, with little knowledge as to whether the observed differences are meaningful in any other sense. Methods for assessing changes in test scores need to account for test-retest reliability, practice effects, regression to the mean, and the impact of initial performance. All of these factors may vary according to the individual characteristics of the subject. This article reviews two methods from the NP literature that have attempted to account for these sources of test-retest bias. The reliable change index provides a confidence interval for predicted change by taking into account the test-retest reliability of the measure. Standardized regression-based measures use a more sophisticated statistical approach that enables them to better account for other potential sources of confound. Use of this methodology has been limited to studies of epilepsy surgery and sports-related concussion. These methods have the potential for enhancing the interpretation of NP test data in drug treatment protocols by providing an empirically based definition of clinically meaningful change.

Neuropsychological (NP) test batteries have evolved as an amalgam of intelligence tests, various individual measures of “biological” cognition, and sensory and motor testing. The early emphasis of NP testing was to identify “organicity” and central nervous system lesion localization. More recent approaches have emphasized the profiling of performance across individual neurocognitive domains (eg, attention, memory, and language) to facilitate diagnosis and treatment planning. However, the field is still hampered by the use of many tests that are antiquated, excessively long, or of dubious psychometric quality. Some of these problems may have contributed to the current under-utilization of NP testing in diagnostic workups of neuropsychiatric disorders. This paper reviews some of the recent changes in the field that hold promise for substantially shortening assessments, improving diagnostic reliability, and making NP testing more cost-effective and practical.