Recruitment and stabilization of brain activation within a working memory task; an FMRI study.

Seventeen subjects underwent functional magnetic resonance imaging (fMRI) performing a 2-Back verbal working memory (VWM) task alternating with a control task to characterize the temporal dynamics of the specific brain regions involved in VWM. Serial sampling of 2-Back sub-blocks revealed many small areas of activation that grew and merged over time. Significant temporal effects for volume recruitment were seen in specific brain regions known to be involved in VWM, including the bilateral dorsolateral prefrontal (DLPFC), medial frontal (MFC), posterior parietal (PPC) cortices and also some extra-cortical and subcortical regions of interest (ROIs). Signal intensity increased over time in most ROIs recruited early in the task, including the DLPFC, MFC, and PPC but excluding dorsal premotor areas. MFC intensity increased rapidly then stabilized with time. The uniqueness of the MFC response raises the possibility that it drives the recruitment process. Increases in intensity and volume were associated with worsening VWM performance over time, suggesting that recruitment of brain resources is necessary in attempting to sustain difficult tasks. Worsening of performance over sub-blocks despite stable task demands reinforces this temporal "load effect".

Imaging phonological similarity effects on verbal working memory.

Studies of verbal working memory (VWM) report that performance declines as the phonemic similarity of stimuli increases. To determine how phonological similarity affects brain function during VWM, "standard" and "similarity" versions of the 2-Back task were presented to 34 healthy participants during functional magnetic resonance imaging (FMRI). Letter consonants presented during similarity blocks rhymed, while consonants did not rhyme during standard blocks. Empirical ROIs were identified from significant 2-Back-related activity observed during either condition. A priori ROIs were selected from functional neuroimaging literature on phonological processing. Although VWM-related activity was not modulated by similarity in any of four regions recruited (dorsolateral prefrontal, posterior parietal, anterior insular, and supplementary motor cortices), four of five regions of deactivation exhibited significantly greater deactivation during the similarity compared to the standard condition (posterior cingulate, paracentral lobule, posterior insula, and parahippocampal gyrus). In a priori phonological processing-related ROIs, similarity did not affect observed increases in activity (supplementary motor area, Broca's area, and cerebellum), while two of the three regions exhibiting decreased activity (near Wernicke's area and Heschel's Gyrus) also exhibited more deactivation during similarity. Accuracy was lower during the similarity 2-Back, positively related to activity within recruited VWM-related ROIs, and inversely related to activity in regions of VWM-related deactivation. Based on known functions of these ROIs, we conclude that language, audition, and self-reflection processes may disengage during phonological interference, while activity levels are maintained in regions recruited during VWM processing. Similarity effects likely include suspension of attention to unrelated and distracting processes to improve concentration.

Clock drawing and frontal lobe behavioral effects of memantine in Alzheimer's disease: a rater-blinded study.

Caregivers of Alzheimer's disease patients treated with memantine have reported improved frontal lobe behaviors. The present study examined these possible improvements in executive functioning using rater-blinded scoring of a clock-drawing test. Fifty-one Alzheimer's disease patients were treated with open-label memantine for 10 weeks. Clock drawing and Mini-Mental State Examination data were collected before and after treatment. Clock drawing improved significantly with treatment, whereas Mini-Mental State Examination data did not. Twenty-seven patients judged as improved in frontal lobe behaviors by caregivers demonstrated a statistically significant improvement in clock drawing to command, whereas 24 patients judged to be unchanged or worse with memantine in their frontal lobe behaviors had no change in their clock drawing and had worsening on their Mini-Mental State Examination. The current findings suggest that memantine improves frontal lobe behavior in some Alzheimer's disease patients and that clock drawing to command may be sensitive to these improvements.

FMRI correlates of the WAIS-III symbol search subtest.

Functional magnetic resonance imaging (FMRI) experiments frequently administer substantially adapted cognitive tests. This study was designed to identify FMRI correlates of a well-standardized clinical measure presented with minor adaptations. We administered the WAIS-III Symbol Search (SS) and a visuospatial control task to fifteen adults during FMRI. SS-related brain activity was identified, followed by analyses of activity related to performance level. Compared to the control task, SS was associated with greater activity in bilateral medial occipital, occipitoparietal, occipitotemporal, parietal, and dorsolateral prefrontal cortices (DLPFC). Across both tasks, slower processing speed was also related to greater activity in these areas, except right DLPFC. Greater activity in left DLPFC was specifically related to slower processing speed during SS. Performance was consistent with education levels. Findings suggest that SS performance involves regions associated with executive and visual processing. Furthermore, slower SS performance was related to greater recruitment of left hemisphere regions associated with executive function in other studies.