Earlier efforts to localize the symptoms of schizophrenia in a single brain region have been replaced by models that postulate a disruption in parallel distributed or dynamic circuits. Based on empirical data derived from both magnetic resonance and positron emission tomography, we have developed a model that implicates connectivity among nodes located in prefrontal regions, the thalamic nuclei, and the cerebellum. A disruption in this circuitry produces "cognitive dysmetria," difficulty in prioritizing, processing, coordinating, and responding to information. This "poor mental coordination" is a fundamental cognitive deficit in schizophrenia and can account for its broad diversity of symptoms.

Observing and assigning emotional value to unpleasant stimuli produced activations in subcortical limbic regions, whereas evaluation of pleasant stimuli produced activations in cortical limbic areas. These findings are consistent with the notion of a subcortical and archaic danger recognition system and a system detecting pleasantness in events and situations that is phylogenetically younger, involving primarily the prefrontal cortex.

Cognitive functioning in the nonsymptomatic phase and the long-term cognitive outcome of patients with mood disorders are both heuristic and important clinical issues in the study of mood disorders. Literature findings are inconsistent because of design confounds. We tried to address these issues while controlling for several confounds including age, education, gender differences in neurobehavioral functioning, and diagnosis. Nonsymptomatic patients with a history of chronic unipolar depression and bipolar affective disorder and healthy male individuals were administered neuropsychological tests to assess attention, visual-motor tracking, executive abilities, and immediate verbal memory. Subjects had comparable depression scores at the time of testing. Disease duration was 7.5 years (SD 5.1) for unipolar and 11 years (SD 7.3) for bipolar patients. Unipolar patients were more impaired than healthy normal comparison subjects on measures of visual-motor sequencing (Trail Making Test A, p < .05), executive function (Trail Making Test B, Stroop Test Color/Word Trial, p < .05), and immediate memory and attention (CERAD 1st trial, WAIS Digit Symbol subtest, p < .05). Differences between bipolar patients and normal comparison subjects did not reach significance in any of the selected measures. Male patients with a history of chronic unipolar disorder are at risk for cognitive impairment in the nonsymptomatic phase of their disease. Cognitive disturbance is the type seen with prefrontal dysfunction and may be assessed with standard neuropsychological assessments.

SummaryWhile the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [ 15 O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

This failure of the neural systems used to support emotional attribution is consistent with pervasive problems in experiencing emotions by schizophrenia patients. The widely distributed nature of the abnormalities suggests the importance of subcortical nodes in overall dysfunctional connectivity.

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In stroke and other medical illnesses, secondary depression may be associated with different factors in women than in men. The authors examined 301 consecutive admissions for acute treatment of cerebrovascular accident for gender differences in depression, psychosocial factors, physical impairment, and lesion location. Women were twice as frequently diagnosed with major depression as men. Women with major depression had a greater frequency of left hemisphere lesions than men. In men, major depression was associated with greater impairment in activities of daily living, and greater severity of depression was associated with greater impairment in daily activities and social functioning. In women, greater severity of depression was associated with prior diagnosis of psychiatric disorder and cognitive impairment. These findings suggest a different nature of poststroke depression in men and women and may have implications for its treatment.