The cerebral organization of word identification processes in reading was examined using functional magnetic resonance imaging (fMRI). Changes in fMRI signal intensities were measured in 38 subjects (19 males and 19 females) during visual (line judgement), orthographic (letter case judgement), phonological (nonword rhyme judgement) and semantic (semantic category judgement) tasks. A strategy of multiple subtractions was employed in order to validate relationships between structure and function. Orthographic processing made maximum demands on extrastriate sites, phonological processing on a number of frontal and temporal sites, and lexical-semantic processing was most strongly associated with middle and superior temporal sites. Significant sex differences in the cerebral organization of reading-related processes were also observed.

This study linked 2 experimental paradigms for the analytic study of reading that heretofore have been used separately. Measures on a lexical decision task designed to isolate phonological effects in the identification of printed words were examined in young adults. The results were related to previously obtained measures of brain activation patterns for these participants derived from functional magnetic resonance imaging (fMRI). The fMRI measures were taken as the participants performed tasks that were designed to isolate orthographic, phonological, and lexical-semantic processes in reading. Individual differences in the magnitude of phonological effects in word recognition, as indicated by spelling-to-sound regularity effects on lexical decision latencies and by sensitivity to stimulus length effects, were strongly related to differences in the degree of hemispheric lateralization in 2 cortical regions.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.

A paired-associate learning (PAL) test was administered to 22 community volunteers without disruptive disorders and 197 children (7.5-13.5 years-old) presenting with the inattentive and combined subtypes of attention-deficit/hyperactivity disorder (ADHD) either in combination with or without oppositional defiant disorder (ODD). Participants were screened for learning disorders. In comparison to non-ADHD participants, children with ADHD achieved worse PAL and made errors rated as more acoustically and less semantically similar to the correct paired associates. These deficits were not related to hyperactivity-impulsivity or comorbid ODD. These results suggest that ADHD children are less competent at PAL and use less efficient learning strategies than their non-ADHD peers.

During a health supervision visit, the father of a 7.5-year-old African American second-grader asked about his son's progress in reading. He was concerned when, at a recent teacher-parent conference to review Darren's progress, the teacher remarked that Darren was not keeping up with reading skills compared with others in his class. She said that he had difficulty sounding out some words correctly. In addition, he could not recall words he had read the day before. The teacher commented that Darren was a gregarious, friendly child with better-than-average verbal communication skills. His achievement at math was age-appropriate; spelling, however, was difficult for Darren, with many deleted letters and reversals of written letters. A focused history did not reveal any risk factors for a learning problem in the prenatal or perinatal periods. Early motor, language, and social milestones were achieved on time. Darren had not experienced any head injury, loss of consciousness, or chronic medical illness. He had several friends, and his father denied any behavioral problems at home or at school. His teacher completed a DSM-IV-specific behavioral survey for attention-deficit/hyperactivity disorder (ADHD). It did not show any evidence of ADHD. Darren's father completed 1 year of college and is currently the manager of a neighborhood convenience store. His mother had a high school education; she recalled that she found it difficult to complete assignments that required reading or writing. She is employed as a waitress. Darren does not have any siblings. The pediatrician performed a complete physical examination, the results of which were normal, including visual acuity, audiometry, and a neurological examination. It was noted that Darren seemed to pause several times in response to questions or commands. On two occasions, during finger-nose testing and a request to assess tandem gait, directions required repetition. Overall, he was pleasant and seemed to enjoy the visit. His pediatrician concluded that he had a learning problem but she was uncertain about the next step. She asked herself, "Is there anything else I can do in the office to evaluate Darren's problem with learning? Should I quickly refer him for educational testing or encourage a reading tutor? What questions can I ask his teacher that would be helpful? Am I missing a medical disorder?"