Circulating levels of Locusta diuretic hormone: the effects of feeding

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flow-sensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an interleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes can be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 +/- 11 SD ml/100 g tissue/min and 43 +/- 16 SD % (n = 12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previous results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.     

Spatial and temporal differentiation of fMRI BOLD response in primary visual cortex of human brain during sustained visual simulation

The blood oxygenation level dependent (BOLD) response during sustained visual stimulation has been studied by several groups using fMRI with controversial conclusions. This issue was investigated for the human brain at high (4 Tesla) magnetic field strength using a flashing goggle at 8 Hz. The results demonstrate that the overall BOLD response in the primary visual cortex has an initial overshoot after the onset of visual stimulation and an undershoot after the termination of visual stimulation. A significant and positive BOLD response, however, remains constant between the initial and terminal transient responses. The temporal BOLD responses in the primary visual cortex were spatially dependent. The regions identified as draining veins in images displayed proportionately larger initial and terminal transient responses, whereas regions devoid of such vessels and associated mainly with parenchyma exhibited a more time-independent BOLD response. These results reveal that the BOLD effect and, presumably, the uncoupling between cerebral blood flow and cerebral metabolic rate of oxygen consumption, are maintained in the primary visual cortex during sustained visual stimulation, and the temporal characteristics of the BOLD effect are spatially dependent.     

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.     

Imaging motor-to-sensory discharges in the human brain: an experimental tool for the assessment of functional connectivity

We present a new approach to studying functional connectivity in the human brain. This approach is based on the observation that when we engage in motor activity, a discharge corollary to the motor command is sent from motor to sensory structures. Thus, as long as movement-related sensory input is either prevented or masked, modulation of neuronal activity in sensory structures would indicate the presence of functional connectivity between the motor and the sensory regions. Using positron emission tomography, such a central interaction between motor and sensory regions can be assessed by measuring regional changes in cerebral blood flow (CBF) in sensory regions. In this paper, we describe the experimental design and the results of two studies of corollary discharges, namely those generated during eye movements and speech. In these studies, a graded approach was used to establish the relationship between the number of eye movements or utterances and CBF in visual or auditory regions, respectively. Significant covariations between the number of movements and CBF in sensory regions were found, thus indicating the presence of functional connectivity between motor and sensory regions. In addition, interregional CBF covariations were computed and the effect of removing the intersubject variance on these covariations was evaluated. The corollary-discharge-based approach to studying functional connectivity is discussed in the context of more traditional computational approaches to network analysis in functional brain imaging.     

Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.     

Adult age differences in regional cerebral blood flow during visual world identification: evidence from H215O PET

We used H215O PET to investigate adult age differences in regional cerebral blood flow (rCBF) during the performance of a visual word identification task. The study participants were 20 healthy, right-handed men: 10 young adults between 18 and 27 years of age, and 10 older adults between 63 and 75 years of age. The word identification task comprised six blocks of test trials representing four task conditions; subjects responded manually. The task conditions varied with regard to whether semantic retrieval was required (e.g., word/nonword discrimination vs simple response to each stimulus) and with regard to the difficulty of visual encoding (e.g., words presented normally vs words with asterisks inserted between adjacent letters). Each subject performed all six trial blocks, concurrently with each of six H215O PET scans. Analyses of quantitative CBF data obtained from the arterial time-activity curve demonstrated a significant age-related decline in global CBF rate. Analyses of the changes in rCBF between task conditions indicated that retrieval of semantic information sufficient to distinguish words from nonwords is mediated by a ventral occipitotemporal cortical pathway. Specific areas within this pathway were also associated with visual encoding processes. Several rCBF activations were significantly greater for young adults than for older adults, indicating an age-related decline in processing efficiency within this ventral occipitotemporal pathway. Although the performance data demonstrated a greater age-related slowing for visual encoding than for semantic retrieval, these age-related performance changes were not associated with corresponding changes in rCBF activation.     

Anxiety and the variability of word associates.

15 Ss who scored high on the Taylor MA scale and 15 Ss who scored low on the MA scale were given a word associate task. The highly anxious Ss tended to have sets of word associates lower in intersubject variability than the nonanxious Ss for stimulus words that elicited sets of word associates that are low in variability. Highly anxious Ss tended to give sets of word associates higher in intersubject variability than nonanxious Ss for stimulus words that elicited sets of word associates that are high in intersubject variability. A 2nd experiment reports data indicating a relationship between inter- and intrasubject variability of word associates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Secretoneurin and chemoattractant receptor interactions

Regional alterations in cerebral blood flow (CBF) are widely used as a surrogate for neuronal function based on an intact coupling between changes in regional CBF and metabolism, activation-flow coupling (AFC). To further investigate parameters affecting AFC, we have implemented a rat model with electrical forepaw stimulation under alpha-chloralose anesthesia using laser Doppler (LD) measurements of flow parameters through thinned skull over contralateral somatosensory cortex. Signal averaging of the LD response was used to improve reproducibility. A characteristic flow response to electrical forepaw stimulation was reliably recorded from the somatosensory cortex using signal averaging. Stimulation at 5 Hz maximized the LD response, and constant current stimulation up to 1 mA did not induce changes in systemic blood pressure. The shape of the flow response consisted of an initial peak followed by a steady state plateau phase which was observed for stimulation durations longer than 4 s. When individual LD parameters of velocity, red blood cell concentration (CRBC), and cerebral blood flow (CBF) were compared, changes in LDCBF were primarily attributable to changes in LDvelocity rather than LDCRBC. This finding was also observed during hypercapnia. Characterization of AFC in the model provides a background for future studies of the effects of pharmacological manipulation or pathophysiological states.     

Follow-up of long-time treatment with intravesical oxybutynin for neurogenic bladder in children

Functional imaging of a language task using positron emission tomography was performed as part of the preoperative assessment of a patient with a left supplementary motor area (SMA) tumor. Positron emission tomography scans were obtained during language tasks (verb generation and word reading of visually presented nouns) that normally lead to increased blood flow in the SMA relative to a control condition (visual fixation). In the patient, the normal SMA response was an order of magnitude larger in the region of the tumor. Other regions, such as left inferior frontal cortex and right cerebellum, showed equivalent activation in the patient and normal subjects. Histopathologic study revealed an anaplastic astrocytoma. Thus, this exaggerated vascular response to local neuronal activation occurred in the setting of a proliferation of glial cells. This is consistent with models of coupling of regional CBF and neuronal activity that implicate glia as the mediator between neurons and vasculature. The concept that tumoral disruption of normal vascular responses could, in some cases, potentially enhance rather than dampen the response is proposed.     

Characterization of stability of performance in patients with traumatic brain injury: Variability and consistency on reaction time tests.

The stability of performance of reaction times (RTs) on 3 visual discrimination tasks was assessed in patients with varying severity of traumatic brain injury (TBI) and in matched control Ss. Results were analyzed for group and individual variability and consistency of performance over time. There was significantly greater intersubject (group) variability in the TBI group. Individual patients (intrasubject) tended to be more variable in performance and less consistent over time than control Ss, but this occurred only with specific measures, which suggests that increased lack of stability in performance is not a general impairment after brain damage but requires specific analyses for identification of performance differences. This intrasubject variability was indepedent of test–retest and split-half test reliability. No obvious factors such as severity of brain injury were related to the variability and inconsistency of performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular pathophysiology of cystic fibrosis based on the rescued knockout mouse model

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.     

Reproducibility of shear rate and shear stress assessment by means of ultrasound in the common carotid artery of young human males and females

In the present study, the reliability of an ultrasonic shear rate estimating system, in terms of intrasubject intrasession, intersubject intrasession and intersubject intersession variability coefficients for the assessment of wall shear rate (WSR) in the common carotid artery (CCA) was determined in eight presumed healthy volunteers. Measurements were performed on consecutive days (day 1, day 2 and day 7). To investigate whether there were differences in WSR due to gender, dynamic WSR in the CCA was assessed in 11 presumed healthy males (mean age 24 y) and 11 presumed healthy females (mean age 25 y). Wall shear stress (WSS) was estimated from WSR and calculated whole blood viscosity. The average intrasubject intrasession variability was about 15% for peak WSR and about 12% for mean WSR. The intersubject intrasession variability for peak WSR decreased from 19% on day 1 to 16% on day 7 and for mean WSR from 17% on day 1 to 11% on day 7. The intersubject intersession variability is on the order of 5% for peak WSR and about 4% for mean WSR. No significant differences could be detected between peak and mean WSR values on day 1, day 2 and day 7, indicating good short- and medium-term intersubject intersession reproducibilities. No differences in peak and mean WSR were found between the left and the right CCA in the male group as well as in the female group. Mean WSS was similar in males (1.3 +/- 0.3 Pa) and in females (1.2 +/- 0.2 Pa), but peak WSS was slightly, but significantly, higher in males (4.3 +/- 1.3 Pa) than in females (3.3 +/- 0.7 Pa). It can be concluded that peak and mean WSR can be reliably determined noninvasively using ultrasound.     

A comparison of discrimination and reversal learning for olfactory and visual stimuli in aged rats.

The present study investigated age-related differences in discrimination and reversal learning for olfactory and visual stimuli in 6-month and 24-month-old rats. Rats were trained to discriminate between two pseudo-randomly selected odors or objects. Once each animal reached a criterion on discrimination trials, the reward contingencies were reversed. Young and aged rats acquired the olfactory and visual discrimination tasks at similar rates. However, on reversal trials, aged rats required significantly more trials to reach the learning criterion on both the olfactory and visual reversal tasks than young rats. The deficit in reversal learning was comparable for odors and objects. Furthermore, the results showed that rats acquired the olfactory task more readily than the visual task. The present study represents the first examination of age-related differences in reversal learning using the same paradigm for odors and objects to facilitate cross-modal comparisons. The results may have important implications for the selection of memory paradigms for future research studies on aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A spreadsheet program for simulation of bioequivalence and bioavailability studies

This paper presents a spreadsheet for Excel for Windows, which simulates bioequivalence (BE) trials. The program incorporates intersubject and intrasubject variability in drug absorption and disposition as well as assay precision and the uniformity of the administered dose. The output provides confidence intervals and a pass/fail code for each study. This program is useful for simulating BE trials using widely available and simple-to-use spreadsheet programs. An example of the application of the program in assessing the influence of intrasubject variability on the outcome of BE testing of two identical formulations is also presented.     

Changes in fMRI Following Cognitive Rehabilitation in Severe Traumatic Brain Injury: A Case Study.

Objective: To illustrate the relationship between changes in neuropsychological testing and changes in functional magnetic resonance imaging (fMRI) before and after cognitive rehabilitation therapy (CRT). Study Design: Single case study. Setting: Outpatient treatment center. Participant: A woman with history of severe traumatic brain injury (TBI) 16 years before study. Intervention: Individualized CRT using a developmental metacognitive model. Main Outcome Measures: Neuropsychological tests and fMRI imaging performed during an eye movement task and a reading comprehension task. Results: Improvements on some neuropsychological test scores (>1 SD) and changes in the magnitude and distribution of the blood oxygen level dependent (BOLD) response as a function of task performance on both fMRI tasks. Conclusions: Individuals with severe TBI many years postinjury can demonstrate improvements in neuropsychological testing following CRT. Behavioral improvements can be related to changes in brain activity using fMRI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attentional systems and the allocation of cerebral resources in reading and grammatical tasks

To evaluate the possible role of attentional centers as modulators of neural networks that mediate visual tasks involving reading and grammatical manipulations of verbs, we measured cerebral blood flow (CBF) using positron emission tomography (PET), and reaction times as subjects read verbs, "nonce verbs" such as jelt or brep, and formed past tenses of regular, irregular and nonce verbs after viewing their stems. Statistical parametric maps (SPMs) showed significant activation of the pulvinar in the read verb irregular, and generate nonce past tense tasks, compared to rest. This was confirmed by a post hoc ANOVA of CBF values from a discrete locus in the pulvinar (p = .0000417). Functional links between the pulvinar and other brain regions were shown by high correlations of CBF in the pulvinar with CBF in brain regions known to have anatomical connections to the pulvinar, particularly those mediating vision. There was also a significant relationship between task-specific reaction times and rest minus task CBF differences in a multiple regression analysis that included CBF values from the pulvinar, superior colliculus plus reticular formation, and the anterior cingulate, known attentional centers (p = .021, r2 = 0.99). Regression analyses relating reaction time to the amount of brain activated (pixels in the SPMs) and the degree of activation of the pixels (mean Z score) yielded p values of .078 and .074, respectively. Our data provide direct experimental evidence to support the hypothesis that attentional centers are activated in proportion to the complexity of visually mediated language tasks and that the centers that mediate attention modulate the activity of task-specific neural networks.     

The stabilization of cortical evoked potentials during selective visual attention

The event-related potentials (ERP) to lateralized moving visual stimuli (administered to the right and to the left of the subject) were recorded in six derivations in eight healthy subjects during passive viewing and selective attention to one of the stimuli (the relevant one), which demanded precise and rapid motor reaction. It was shown that during the selective voluntary attention correlation between successive ERP was substantially higher than that under conditions of passive (involuntary) attention, i.e. the ERP in the occipital, parietal, and frontal derivations during voluntary attention were more stable. The less was correlation between the ERP at passive viewing, the greater was the difference between the values of correlation coefficients during selective and passive attention. It is suggested that role of selected attention consists in stabilization of activity of the cortical structures, which are involved in solving the behavioral task.     

Distortion product otoacoustic emission delay measurement in human ears

The measurement of distortion product otoacoustic emission (DPOAE) delay using the phase gradient method is discussed. A short f2 sweep paradigm is described. Its merits are discussed and comparisons made with other methods. Using sweeps of less than 4%, consistent and reliable measurements were obtained from 12 normal ears, except for a few isolated measurements. Investigation of these apparent anomalies indicated that the short f2 sweep method was sensitive to the localized effects of narrow distortion product intensity notches and spontaneous emissions. It is possible that middle ear pressure instability or some local change in the cochlea sometimes compounded the situation. The intersubject range (63% of the mean) of DPOAE delay values was greater than the range of values observed due to measurement variability (5.6% of the mean) or intrasubject variability (8.5% of the mean) demonstrating that the method can detect real differences between ears. However, comparison with previous work shows that caution is needed in interpreting these data, as all DPOAE phase methods provide only partial latency values. The physical interpretation depends on both the stimulus sweep used and the origin of DPOAES. Our data shows that f1 sweep derived latency is lower than f2 sweep data by more than 20%. Caution also needs to be exercised when comparing cochlear traveling wave delay, as inferred from electrophysiological data, with that obtained from DPOAE delay measurements.     

The time course of learning a visual skill

Several examples of experience-dependent perceptual improvement (perceptual learning) suggest that plasticity in specific neuronal loci could underlie the learning process. For a basic visual discrimination task (using an optimal stimulus for 'automatic' pre-attentive texture segregation), discrete retinal input-dependent changes within a very early stage in the stream of visual processing were indicated as the locus of a large and consistent learning effect. When do these changes occur? Here we report that except for a fast, rapidly saturating improvement early in the first practice session, performance was very stable within sessions. Indeed, observers showed little or no improvement until up to 8 hours after their last training session (latent phase). But large improvements occurred thereafter. Finally, there was almost no forgetting; what was gained was retained for at least 2-3 years. We conjecture that some types of perceptual experience trigger permanent neural changes in early processing stages of the adult visual system. These may take many hours to become functional.