Patterns of relative cerebral blood flow in minor cognitive motor disorder in human immunodeficiency virus infection.

Individuals infected with HIV are at risk to develop cognitive impairment during the course of their disease. Although many patients develop an HIV-associated dementia, others may develop the less severe minor cognitive motor disorder (MCMD). In this study, relative cerebral blood flow was measured with PET imaging in HIV+ MCMD patients, HIV+ control subjects, and HIV- control subjects; analyses were performed by using statistical parametric mapping. Comparing a short-term memory task versus a rest state yielded activation in superior temporal cortex, postcentral gyrus, and cerebellum in all three subject groups. Comparing long- and short-term memory tasks yielded activation throughout the frontal cortex, including BA46. Activation in this area was reduced in the HIV+ control subjects and further reduced in the MCMD+ patients. Thus, brain activation associated with lower-level, automatic processing appears normal in HIV+ MCMD+ subjects, but activation associated with effortful retrieval and organizational processes is abnormal.

Functional connectivity in auditory-verbal short-term memory in Alzheimer's disease.

Alzheimer's disease (AD) patients show normal patterns of regional cerebral blood flow during performance of subspan verbal memory tasks, but appear to allocate new brain regions when performing supraspan recall tasks. To understand the relationships among these interconnected brain regions, their functional connectivity was considered using principal components analysis (PCA). AD patients and controls were scanned in four conditions: visual fixation only and visual fixation with one-word recall, three-word recall, and eight-word recall. When applied to the data from the three recall task conditions (i.e., eliminating fixation), PCA revealed a significant first component accounting for 75.8% of the variance in the control data and 66.8% of the variance in the patient data. The one-word recall condition had a high positive component score, and the eight-word condition a high negative score. The correlations of individual voxels on this factor (i.e., spatial modes) were very similar between the patients and the controls. The overall similarity in the results of the PCAs between the patients and the controls suggests that they have similar functional connectivity. This would suggest that, at least in the early course of the dementia, the functional CNS organization of verbal memory systems remains normal.

Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease.

Conscious recall of past events that have specific temporal and spatial contexts, termed episodic memory, is mediated by a system of interrelated brain regions. In Alzheimer's disease (AD) this system breaks down, resulting in an inability to recall events from the immediate past. Using subtraction techniques with PET-acquired images of regional cerebral blood flow, we demonstrate that AD patients show a greater activation of regions of cerebral cortex normally involved in auditory-verbal memory, as well as activation of cortical areas not activated by normal elderly subjects. These results provide clear evidence of functional plasticity in the AD patient's brain even if those changes do not result in normal memory function, and provide insights into the mechanism by which the AD brain attempts to compensate for neurodegeneration.

Alterations in functional neuroanatomical connectivity in Alzheimer's disease. Positron emission tomography of auditory verbal short-term memory.

Conscious recall of past events which have specific temporal and spatial contexts, termed episodic memory, is mediated by a system of interrelated brain regions. In Alzheimer's disease (AD) this system breaks down, resulting in an inability to recall events from the immediate past. Studies of normal human auditory-verbal short-term memory suggest that the brain system underlying these processes has distinct components, and the present study utilized the methods of functional brain mapping to determine the nature and extent of the breakdown that occurs in AD. Using subtraction techniques of PET-acquired images of regional cerebral blood flow we demonstrate that AD patients show a compensatory hyperactivation of various regions of cerebral cortex normally involved in these tasks, as well as activation of cortical areas not activated by normal elderly subjects. These results provide clear evidence of functional plasticity in the AD patient's brain even if those changes do not result in normal memory function.

Positron emission tomography study of voluntary saccadic eye movements and spatial working memory.

1. The purpose of this study is to define the cortical regions that subserve voluntary saccadic eye movements and spatial working memory in humans. 2. Regional cerebral blood flow (rCBF) during performance of oculomotor tasks was measured with [15O]-H2O positron emission tomography (PET). Eleven well-trained, healthy young adults performed the following tasks: visual fixation, visually guided saccades, antisaccades (a task in which subjects made saccades away from rather than toward peripheral targets), and either an oculomotor delayed response (ODR, a task requiring memory-guided saccades after a delay period) or a conditional antisaccade task (a task in which the color of the peripheral target determined whether a saccade toward or away from the target was required). An additional six subjects performed a sequential hand movement task to compare localization of hand-related motor cortex and the frontal eye fields (FEFs) and of the hand- and eye-movement-related regions of the supplementary motor area (SMA). 3. Friston's statistical parametric mapping (SPM) method was used to identify significant changes in rCBF associated with task performance. Because SPM does not take advantage of the anatomic information available in magnetic resonance (MR) scans, each subject's PET scan was registered to that individual's MR scan, after which all PET and MR studies were transformed to conform to a standard reference MR image set. Subtraction images were visually inspected while overlayed on the reference MR scan to which PET images had been aligned, in order to confirm anatomic localization of significant rCBF changes. 4. Compared with visual fixation, performing visually guided saccades led to a significant bilateral activation in FEF, cerebellum, striate cortex, and posterior temporal cortex. Right posterior thalamus activation was also observed. 5. The visually guided saccade task served as the comparison task for the ODR, antisaccade, and conditional antisaccade tasks for identification of task-related changes in rCBF beyond those associated with saccade execution. Performance on the ODR task was associated with a bilateral increase of rCBF in FEFs, SMA, dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex. The cortical regions of increased regional blood flow during the ODR task also showed increased rCBF during the antisaccade task; however, FEF and SMA activations were significant only in the right hemisphere. These findings closely parallel those of single-cell recording studies with behaving monkeys in indicating that FEF, DLPFC, SMA, and posterior parietal cortex perform computational activity for voluntary purposive saccades. 6. Comparison of PET scans obtained during performance of eye movement and hand movement tasks indicated that peak activations in FEF were located approximately 2 cm lateral and 1 cm anterior to those of hand-related motor cortex. The oculomotor area of SMA, the supplementary eye field (SEF), was located approximately 7-8 mm anterior and superior to the hand-related area of SMA. 7. During performance of antisaccade and ODR tasks, rCBF was significantly lower in ventromedial prefrontal cortex (PFC), along the rectus gyrus, and in ventral anterior cingulate cortex than during the visually guided saccade and fixation tasks. During the antisaccade task, the ventral region of lower rCBF involved medial structures including left ventral striatum and bilateral medial temporal-limbic cortex. During the ODR task, the ventral aspect of the region of lower rCBF extended laterally, rather than medially, to include the temporal poles. The lower blood flow observed in ventromedial PFC during both the antisaccade and ODR tasks, relative to the visually guided saccade and fixation tasks, suggests that modulation of output from ventromedial PFC to limbic cortex and the striatum may play a role in the voluntary control of saccadic eye movements, possibly in the suppression of responses that would interrupt