Neural activation patterns during working memory tasks and OSA disease severity: preliminary findings.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cognitive impairments in working memory (WM). Neuronal activation during WM tasks can be indirectly assessed by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). The purpose of this study was to describe BOLD-fMRI responses during 2 separate working memory tasks and a finger tapping task in men with OSA. A secondary aim was to explore the possible relation between OSA severity (apnea/hypopnea index) and BOLD-fMRI signal patterns. METHODS: Nine treatment-naïve men (mean age [+/- SD] of 45.7 [+/- 6.6] years) with OSA underwent BOLD fMRI testing on a research-dedicated university-based MRI scanner. During BOLD-fMRI subjects performed a Paced Auditory Serial Addition task (PASAT), an auditory N-Back task (2-BACK) task, and an alternating finger tapping. RESULTS: PASAT and 2-BACK tasks produced similar patterns of increased bilateral activation in posterior parietal, prefrontal and cerebellar regions. BOLD signal deactivations were observed within posterior cingulate, retrosplenial and inferior frontal regions during PASAT and 2-BACK, but not during tapping. With increased disease severity, BOLD activation patterns were increased in the right parietal lobe, but decreased in the cerebellar vermis. CONCLUSIONS: These preliminary findings suggest that the severity of OSA may correlate with neural activation during tasks of working memory, potentially reflecting compensatory neural responses in severe disease.

A twin study of cognitive function in chronic fatigue syndrome: the effects of sudden illness onset.

Variable reports of neuropsychological deficits in individuals with chronic fatigue syndrome (CFS) may, in part, be attributable to methodological limitations. In this study, these limitations were addressed by controlling for genetic and environmental influences and by assessing the effects of comorbid depression and mode of illness onset. Specifically, the researchers conducted a co-twin control study of 22 pairs of monozygotic twins, in which 1 twin met strict criteria for CFS and the co-twin was healthy. Twins underwent a structured psychiatric interview and comprehensive neuropsychological assessment evaluating 6 cognitive domains. Results indicated that twin groups had similar intellectual and visual memory functioning, but fatigued twins exhibited decreases in motor functions (p = .05), speed of information processing (p = .02), verbal memory (p = .02), and executive functioning (p = .01). Major depression did not affect neuropsychological functioning among fatigued twins, although twins with sudden illness onset demonstrated slowed information processing compared with those with gradual onset (p = .01). Sudden onset CFS was associated with reduced speed of information processing. If confirmed, these findings suggest the need to distinguish illness onset in future CFS studies and may have implications for treatment, cognitive rehabilitation, and disability determination.

Trail making test errors and executive function in schizophrenia and depression.

The Trail Making Test (TMT) frequently is used as a measure of executive cognitive function. However, traditional use of test completion time as the primary outcome score does not give the more detailed information on cognitive processes that analysis of test-taking errors may provide. The present study compared TMT performance of three groups: patients with schizophrenia, patients with major depression, and healthy control participants (n = 30 for each group). Three operationally defined error types were examined: (a) tracking, (b) perseverative, and (c) proximity. Although both patient groups were slower than the healthy control group, only the schizophrenia group made significantly more errors, particularly tracking errors, suggesting a greater degree of cognitive disorganization. Within-group analysis of a larger group of schizophrenia patients (n = 84) revealed that TMT time was most strongly associated with the Withdrawal-Retardation factor of the Brief Psychiatric Rating scale. In contrast, TMT errors were most strongly associated with the Conceptual Disorganization factor. Comparisons of TMT scores and other cognitive tests showed moderate to high associations with tests of working memory, psychomotor speed, and executive function. Stepwise regression analysis revealed an independent association between Digit Cancellation and Part B Time, indicating a unique contribution of visuomotor scanning to performance. In contrast, Part B errors were uniquely associated with the Verbal Series Attention Test and the Token Test, tests of mental tracking and executive-mediated working memory, respectively. These findings demonstrate the utility of TMT error analysis in revealing cognitive deficits not traditionally captured using completion time as the sole outcome variable.

Cerebral and cerebellar motor activation abnormalities in a subject with Joubert syndrome: functional magnetic resonance imaging (MRI) study.

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, and a distinctive hindbrain malformation involving the cerebellum and brain stem, visualized radiographically on magnetic resonance imaging (MRI) as the "molar tooth sign." In postmortem brains from subjects with Joubert syndrome, there is an apparent absence of decussation of both corticospinal and superior cerebellar tracts, although the functional significance has not been elucidated. We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI. In contrast to the typical highly lateralized activation seen in our control subject, the subject with Joubert syndrome demonstrated striking bilateral activation of the sensorimotor and cerebellar cortex. Although our functional MRI data do not indicate a clear absence of decussation, the abnormal activation pattern observed suggests altered brain functional organization in relation to anatomic differences. Malformation of the hindbrain could result in recruitment of alternative pathways, similar to what has been observed following ischemic injury to the developing or mature central nervous system.

Cognitive processing in monozygotic twins discordant for chronic fatigue syndrome.

Twenty-one pairs of monozygotic twins discordant for chronic fatigue syndrome (CFS) and 21 matched healthy control (HC) subjects were assessed with 5 untimed tests and 5 timed tests from the computer-based NeuroCognitive Assessment Battery (R. K. Mahurin, 1993). Random effects regression showed no difference between CFS and healthy twins on any of the cognitive tests. Further, the twin groups did not differ from the HC group on any content-dependent measure. In contrast, both sets of twins performed worse than the HC group on all speed-dependent tests except Finger Tapping. Self-rated fatigue and dysphoric mood were only weakly correlated with cognitive performance. These data point toward a shared genetic trait related to information processing that is manifest in the CFS context. The findings have implications for differentiating genetic and acquired vulnerability in the symptomatic expression of the disorder. ((c) 2004 APA, all rights reserved)

Age and features of movement influence motor overflow.

OBJECTIVES: To measure the magnitude and prevalence of motor overflow to the arm at rest during attempted unilateral arm movements. DESIGN: Cross-sectional assessment. SETTING: Motor physiology laboratory. PARTICIPANTS: Healthy young (n=20) and elderly (n=20) adult subjects. MEASUREMENTS: Surface electromyography (EMG) was obtained from bilateral forearm muscles during performance of 12 different unilateral finger-tapping tasks. RESULTS: For all subjects, faster movement rate (F=2.56-3.30, P<.05), cognitive distraction (F=4.09, P<.05), and fatigue (F=15.15, P<.001) were each associated with a significant increase in the magnitude of EMG in the arm intended to be at rest. In elderly subjects, tapping at maximum rate and fatigue were each associated with a further increase in motor overflow across the midline. In addition, better left hand dexterity correlated with greater motor overflow to the right hand during rapid left hand tapping (r=0.63, P<.005). Prevalence of motor overflow was also higher in older subjects for some tasks, for example during 1 Hz tapping by the right index finger (motor overflow present in 45%, vs 15% young subjects, P<.05). CONCLUSION: Several behavioral variables increase motor overflow across the midline in young and elderly adults. Motor overflow was even greater in elderly subjects with the most demanding tasks and was greater in those with better motor status, suggesting that this form of motor system change is a compensatory event of normal aging rather than age-related dysfunction. The results support the hypotheses that healthy aging is associated with an increase in the degree to which brain function is bilaterally organized.

The functional neuroanatomy of the placebo effect.

OBJECTIVE: Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. METHOD: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial. RESULTS: Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents. CONCLUSIONS: The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.