Decreased 67-gallium plasma protein binding in senile dementia of the Alzheimer type

We examined the plasma-protein-binding of 67-gallium in 10 patients with probable dementia of the Alzheimer-type (DAT), diagnosed according to NINCDS-ADRDA-criteria, and in 10 healthy controls matched for age (mean: 82 and 83 years) and sex (2m:8f). In comparison to the control group, the percentage of 67-gallium bound in the plasma of DAT-patients was significantly decreased (10.6% vs 15.5%; p less than 0.05). As gallium and aluminum show corresponding biochemical characteristics, these results may indicate a potential contribution of a disturbed peripheral transport in DAT, leading to the intracerebral deposition of neurotoxic aluminum levels.     

Latency as a region contrast: Measuring ERP latency differences with Dynamic Time Warping

Methods for measuring onset latency contrasts are evaluated against a new method utilizing the dynamic time warping (DTW) algorithm. This new method allows latency to be measured across a region instead of single point. We use computer simulations to compare the methods’ power and Type I error rates under different scenarios. We perform per‐participant analysis for different signal‐to‐noise ratios and two sizes of window (broad vs. narrow). In addition, the methods are tested in combination with single‐participant and jackknife average waveforms for different effect sizes, at the group level. DTW performs better than the other methods, being less sensitive to noise as well as to placement and width of the window selected.     

Lexical retrieval during fluent speech production: an fMRI study

We investigated the neural correlates of lexical retrieval during fluent speech production using fMRI. Blood oxygenation level dependent (BOLD) contrast was measured while subjects spoke about 7 Rorschach inkblots for 3 min each. Varying degrees of speech rate were elicited during each run. In a within-subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each subject that showed the highest variance of speech output. The rate of articulation was positively correlated with activation in the left superior temporal (BA 22) and supramarginal (BA 39/ 40) gyri. The main negative correlations were in the fusiform gyri bilaterally (BA 19), the posterior cingulate (BA 30) and superior occipital gyrus (BA 19). Lexical retrieval during continuous language production engages areas in the left temporal and inferior parietal cortex. This pattern of activation differs from that evident during the generation of single words (verbal fluency), which is more associated with left prefrontal activation.     

A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction

OBJECTIVES: Even when euthymic bipolar disorder patients can have persistent deficits in working memory, but the neural basis of this deficit remains unclear. We undertook an functional magnetic resonance imaging investigation of euthymic bipolar disorder patients performing two working memory paradigms; the two-back and Sternberg tasks, selected to examine the central executive and the phonological loop respectively. We hypothesized that neuronal dysfunction would be specific to the network underlying the executive rather than the phonological loop component of working memory. METHODS: Twelve right-handed euthymic bipolar I males receiving lithium carbonate monotherapy were matched with 12 controls. The two-back task comprised a single working memory load contrasted with baseline vigilance condition. The Sternberg paradigm used a parametric design incorporating variable working memory load with fixed delay between presentation of an array of items to be remembered and a target item. Functional activation data were acquired during performance of the tasks and were analysed to produce brain activation maps representing significant group differences in activation (ANOVA). Load-response curves were derived from the Sternberg task data set. RESULTS: There were no significant between-group differences (t-test) in performance of the two-back task, or in 2 x 5 group by memory load ANOVA for the performance data from Sternberg task. In the two-back task, compared with controls bipolar disorder patients showed reductions in bilateral frontal, temporal and parietal activation, and increased activations with the left precentral, right medial frontal and left supramarginal gyri. No between-group differences were observed in the Sternberg task at any working memory load. CONCLUSIONS: Our findings support the notion that, in euthymic bipolar disorder, failure to engage fronto-executive function underpins the core neuropsychological deficits.     

Statistical methods of estimation and inference for functional MR image analysis

Two questions arising In the analysis of functional magnetic resonance imaging (fMRI) data acquired during periodic sensory stimulation are: i) how to measure the experimentally determined effect in fMRI time series; and ii) how to decide whether an apparent effect is significant Our approach is first to fit a time series regression model, including sine and cosine terms at the (fundamental) frequency of experimental stimulation, by pseudogeneralized least squares (PGLS) at each pixel of an image. Sinusoidal modeling takes account of locally variable hemodynamic delay and dispersion, and PGLS fitting corrects for residual or endogenous autocorrelation in fMRI time series, to yield best unbiased estimates of the amplitudes of the sine and cosine terms at fundamental frequency; from these parameters the authors derive estimates of experimentally determined power and its standard error. Randomization testing is then used to create inferential brain activation maps (BAMs) of pixels significantly activated by the experimental stimulus. The methods are illustrated by application to data acquired from normal human subjects during periodic visual and auditory stimulation.     

Prefrontal involvement in temporal bridging and timing movement

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.