Mechanisms of Selective Attention during Competitive Discrimination of Visual and Auditory Verbal Information: Positron Emission Tomography and Cortical Evoked Potential Studies

The mechanisms of selective verbal attention were studied under conditions of simultaneous delivery of speech signals via the visual and auditory channels. The investigation was based on the comparison and synthesis of data obtained by two methods: positron emission tomography (PET) and brain evoked potentials (EPs). A new approach was developed: complementary tasks were constructed in such a way that, despite principal methodological problems, the same phenomenon could be investigated in one paradigm in EP and PET studies. The results obtained by the two methods are in rather good agreement with respect to topography: the secondary and tertiary areas, as well as the associative brain areas, are involved in attention concentration, that is, selection of verbal information occurs at the level of cognitive processes. The combination of two complementary methods, PET and EP, allowed the processes of processing of sensory information and brain mechanisms of selective attention to be investigated much more completely. The PET studies contributed to further understanding of brain mechanisms evidencing where processing occurs and the EP method provided insight into the mechanism of how this information is processed inside the corresponding cortical areas. The finding that the activation of primary areas of the visual cortex is accompanied by the inhibition of visual information deserves attention. This conclusion can be considered highly significant because of the concordance of the two independent methods. How to interpret it is not yet clear. It is possible that, in the case of primary importance of verbal information and priority of the visual channel for the repression from consciousness of artificially irrelevant information, a safety mechanism is activated: the amplified signal enters the brain cortex, where it is retained in the short-term iconic memory. This enables a reaction to this stimulus (if necessary), in the presence of any additional sign involving selective attention.     

An fMRI Study of Audiovisual Speech Perception Reveals Multisensory Interactions in Auditory Cortex

Research on the neural basis of speech-reading implicates a network of auditory language regions involving inferior frontal cortex, premotor cortex and sites along superior temporal cortex. In audiovisual speech studies, neural activity is consistently reported in posterior superior temporal Sulcus (pSTS) and this site has been implicated in multimodal integration. Traditionally, multisensory interactions are considered high-level processing that engages heteromodal association cortices (such as STS). Recent work, however, challenges this notion and suggests that multisensory interactions may occur in low-level unimodal sensory cortices. While previous audiovisual speech studies demonstrate that high-level multisensory interactions occur in pSTS, what remains unclear is how early in the processing hierarchy these multisensory interactions may occur. The goal of the present fMRI experiment is to investigate how visual speech can influence activity in auditory cortex above and beyond its response to auditory speech. In an audiovisual speech experiment, subjects were presented with auditory speech with and without congruent visual input. Holding the auditory stimulus constant across the experiment, we investigated how the addition of visual speech influences activity in auditory cortex. We demonstrate that congruent visual speech increases the activity in auditory cortex.     

Detection of Cancer Metastases with a Dual-labeled Near-Infrared/Positron Emission Tomography Imaging Agent

By dual labeling a targeting moiety with both nuclear and optical probes, the ability for noninvasive imaging and intraoperative guidance may be possible. Herein, the ability to detect metastasis in an immunocompetent animal model of human epidermal growth factor receptor 2 (HER-2)-positive cancer metastases using positron emission tomography (PET) and near-infrared (NIR) fluorescence imaging is demonstrated. METHODS: (⁶⁴Cu-DOTA)_n-trastuzumab-(IRDye800)_m was synthesized, characterized, and administered to female Balb/c mice subcutaneously inoculated with highly metastatic 4T1.2neu/R breast cancer cells. (⁶⁴Cu-DOTA)_n-trastuzumab-(IRDye800)_m (150 µg, 150 µCi, m = 2, n = 2) was administered through the tail vein at weeks 2 and 6 after implantation, and PET/computed tomography and NIR fluorescence imaging were performed 24 hours later. Results were compared with the detection capabilities of F-18 fluorodeoxyglucose (¹⁸FDG-PET). RESULTS: Primary tumors were visualized with ¹⁸FDG and (⁶⁴Cu-DOTA)_n-trastuzumab-(IRDye800)_m, but resulting metastases were identified only with the dual-labeled imaging agent. ⁶⁴Cu-PET imaging detected lung metastases, whereas ex vivo NIR fluorescence showed uptake in regions of lung, skin, skeletal muscle, and lymph nodes, which corresponded with the presence of cancer cells as confirmed by histologic hematoxylin and eosin stains. In addition to detecting the agent in lymph nodes, the high signal-to-noise ratio from NIR fluorescence imaging enabled visualization of channels between the primary tumor and the axillary lymph nodes, suggesting a lymphatic route for trafficking cancer cells. Because antibody clearance occurs through the liver, we could not distinguish between nonspecific uptake and liver metastases. CONCLUSION: (⁶⁴Cu-DOTA)_n-trastuzumab-(IRDye800)_m may be an effective diagnostic imaging agent for staging HER-2-positive breast cancer patients and intraoperative resection.     

Alcohol ADME in Primates Studied with Positron Emission Tomography

Background and Purpose

The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol''s absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol''s brain bioavailability, however, is not well understood.

Experimental Approach

The ADME of C-11 labeled alcohol, CH₃ ¹¹CH₂OH, 1 and C-11 and deuterium dual labeled alcohol, CH₃ ¹¹CD₂OH, 2 in baboons was compared based on the principle that C–D bond is stronger than C–H bond, thus the reaction is slower if C–D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (C_max); peak uptake time (T_max), half-life of peak uptake (T_1/2), the area under the curve (AUC_60min), and the residue uptake (C_60min).

Key Results

For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol''s brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol.

Conclusion and Implications

The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol''s brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol''s ADME and its relationship to intoxication and medical consequences.     

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Stroke is the third leading cause of death among Americans 65 years of age or older¹. The quality of life for patients who suffer from a stroke fails to return to normal in a large majority of patients², which is mainly due to current lack of clinical treatment for acute stroke. This necessitates understanding the physiological effects of cerebral ischemia on brain tissue over time and is a major area of active research. Towards this end, experimental progress has been made using rats as a preclinical model for stroke, particularly, using non-invasive methods such as ¹⁸F-fluorodeoxyglucose (FDG) coupled with Positron Emission Tomography (PET) imaging^3,10,17. Here we present a strategy for inducing cerebral ischemia in rats by middle cerebral artery occlusion (MCAO) that mimics focal cerebral ischemia in humans, and imaging its effects over 24 hr using FDG-PET coupled with X-ray computed tomography (CT) with an Albira PET-CT instrument. A VOI template atlas was subsequently fused to the cerebral rat data to enable a unbiased analysis of the brain and its sub-regions⁴. In addition, a method for 3D visualization of the FDG-PET-CT time course is presented. In summary, we present a detailed protocol for initiating, quantifying, and visualizing an induced ischemic stroke event in a living Sprague-Dawley rat in three dimensions using FDG-PET.     

A Psychophysical Imaging Method Evidencing Auditory Cue Extraction during Speech Perception: A Group Analysis of Auditory Classification Images

Although there is a large consensus regarding the involvement of specific acoustic cues in speech perception, the precise mechanisms underlying the transformation from continuous acoustical properties into discrete perceptual units remains undetermined. This gap in knowledge is partially due to the lack of a turnkey solution for isolating critical speech cues from natural stimuli. In this paper, we describe a psychoacoustic imaging method known as the Auditory Classification Image technique that allows experimenters to estimate the relative importance of time-frequency regions in categorizing natural speech utterances in noise. Importantly, this technique enables the testing of hypotheses on the listening strategies of participants at the group level. We exemplify this approach by identifying the acoustic cues involved in da/ga categorization with two phonetic contexts, Al- or Ar-. The application of Auditory Classification Images to our group of 16 participants revealed significant critical regions on the second and third formant onsets, as predicted by the literature, as well as an unexpected temporal cue on the first formant. Finally, through a cluster-based nonparametric test, we demonstrate that this method is sufficiently sensitive to detect fine modifications of the classification strategies between different utterances of the same phoneme.     

Association between Striatal Subregions and Extrastriatal Regions in Dopamine D1 Receptor Expression: A Positron Emission Tomography Study

The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D₁ receptor (D₁R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [¹¹C]{"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 to measure D₁R expression. Parametric images of binding potentials (BP _ND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BP _ND using statistical parametric mapping 5. The BP _ND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BP _ND as well. The relationships in BP _ND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D₁R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D₁R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D₁R expression pattern throughout the whole brain.     

Radiolabeling Human Peripheral Blood Stem Cells for Positron Emission Tomography (PET) Imaging in Young Rhesus Monkeys

These studies focused on a new radiolabeling technique with copper (⁶⁴Cu) and zirconium (⁸⁹Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of ⁶⁴Cu-CD45 and ⁸⁹Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of ⁶⁴Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of ⁶⁴Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For ⁸⁹Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of ⁸⁹Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0–40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of ⁸⁹Zr-Df-CD45 labeling efficiency was observed when compared to ⁶⁴Cu-TETA-CD45. Similar to ⁶⁴Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10⁶ hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of ⁸⁹Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that ⁸⁹Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.     

Application of Dual Phase Imaging of 11C-Acetate Positron Emission Tomography on Differential Diagnosis of Small Hepatic Lesions

Objective

Previously we observed that dual phase ¹¹C-acetate positron emission tomography (AC-PET) could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1–3 cm in size.

Methods

33 patients having primary hepatic lesions with size of 1–3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11–18 min. The standardized uptake value (SUV) was calculated for tumor (SUVT) and normal tissue (SUVB), from which ¹¹C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB) in early imaging (R1), conventional imaging (R2), and variance between R2 and R1 (ΔR) were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0.

Results

20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC) for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r² = 0.55, P<0.001).

Conclusions

Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of ¹¹C-acetate uptake in dual phase imaging provided key information for final diagnosis.     

Localized Fetomaternal Hyperglycemia: Spatial and Kinetic Definition by Positron Emission Tomography

Background

Complex but common maternal diseases such as diabetes and obesity contribute to adverse fetal outcomes. Understanding of the mechanisms involved is hampered by difficulty in isolating individual elements of complex maternal states in vivo. We approached this problem in the context of maternal diabetes and sought an approach to expose the developing fetus in vivo to isolated hyperglycemia in the pregnant rat.

Methodology and Principal Findings

We hypothesized that glucose infused into the arterial supply of one uterine horn would more highly expose fetuses in the ipsilateral versus contralateral uterine horn. To test this, the glucose tracer [¹⁸F]fluorodeoxyglucose (FDG) was infused via the left uterine artery. Regional glucose uptake into maternal tissues and fetuses was quantified using positron emission tomography (PET). Upon infusion, FDG accumulation began in the left-sided placentae, subsequently spreading to the fetuses. Over two hours after completion of the infusion, FDG accumulation was significantly greater in left compared to right uterine horn fetuses, favoring the left by 1.9±0.1 and 2.8±0.3 fold under fasted and hyperinsulinemic conditions (p<10⁻¹¹ n = 32-35 and p<10⁻¹² n = 27–45) respectively. By contrast, centrally administered [³H]-2-deoxyglucose accumulated equally between the fetuses of the two uterine horns. Induction of significant hyperglycemia (10³ mg/dL) localized to the left uterine artery was sustained for at least 48 hours while maternal euglycemia was maintained.

Conclusions and Significance

This approach exposes selected fetuses to localized hyperglycemia in vivo, minimizing exposure of the mother and thus secondary effects. Additionally, a set of less exposed internal control fetuses are maintained for comparison, allowing direct study of the in vivo fetal effects of isolated hyperglycemia. Broadly, this approach can be extended to study a variety of maternal-sided perturbations suspected to directly affect fetal health.     

Relation between Dopamine Synthesis Capacity and Cell-Level Structure in Human Striatum: A Multi-Modal Study with Positron Emission Tomography and Diffusion Tensor Imaging

Positron emission tomography (PET) study has shown that dopamine synthesis capacity varied among healthy individuals. This interindividual difference might be due to a difference in the cell-level structure of presynaptic dopaminergic neurons, i.e., cellular density and/or number. In this study, the relations between the dopamine synthesis capacity measured by PET and the parameter estimates in diffusion tensor imaging (DTI) in striatal subregions were investigated in healthy human subjects. DTI and PET studies with carbon-11 labeled L-DOPA were performed in ten healthy subjects. Age-related changes in the above parameters were also considered. Fractional anisotropy showed a significant positive correlation with age in the posterior caudate. There was significant negative correlation between dopamine synthesis capacity and mean diffusivity in the posterior caudate and putamen. Assuming that mean diffusivity reflects the density of wide-spreading axonal terminals in the striatum, the result suggests that dopamine synthesis may be related to the density of dopaminergic neuronal fibers. It is evident that PET/DTI combined measurements can contribute to investigations of the pathophysiology of neuropsychiatric diseases involving malfunction of dopaminergic neurons.     

In Vivo Imaging of Schistosomes to Assess Disease Burden Using Positron Emission Tomography (PET)

Background

Schistosomes are chronic intravascular helminth parasites of humans causing a heavy burden of disease worldwide. Diagnosis of schistosomiasis currently requires the detection of schistosome eggs in the feces and urine of infected individuals. This method unreliably measures disease burden due to poor sensitivity and wide variances in egg shedding. In vivo imaging of schistosome parasites could potentially better assess disease burden, improve management of schistosomiasis, facilitate vaccine development, and enhance study of the parasite''s biology. Schistosoma mansoni (S. mansoni) have a high metabolic demand for glucose. In this work we investigated whether the parasite burden in mice could be assessed by positron emission tomography (PET) imaging with 2-deoxy-2[¹⁸F]fluoro-D-glucose (FDG).

Methodology/Principal Findings

Live adult S. mansoni worms FDG uptake in vitro increased with the number of worms. Athymic nude mice infected with S. mansoni 5–6 weeks earlier were used in the imaging studies. Fluorescence molecular tomography (FMT) imaging with Prosense 680 was first performed. Accumulation of the imaging probe in the lower abdomen correlated with the number of worms in mice with low infection burden. The total FDG uptake in the common portal vein and/or regions of elevated FDG uptake in the liver linearly correlated to the number of worms recovered from infected animals (R² = 0.58, P<0.001, n = 40). FDG uptake showed a stronger correlation with the worm burden in mice with more than 50 worms (R² = 0.85, P<0.001, n = 17). Cryomicrotome imaging confirmed that most of the worms in a mouse with a high infection burden were in the portal vein, but not in a mouse with a low infection burden. FDG uptake in recovered worms measured by well counting closely correlated with worm number (R² = 0.85, P<0.001, n = 21). Infected mice showed a 32% average decrease in total FDG uptake after three days of praziquantel treatment (P = 0.12). The total FDG uptake in untreated mice increased on average by 36% over the same period (P = 0.052).

Conclusion

FDG PET may be useful to non-invasively quantify the worm burden in schistosomiasis-infected animals. Future investigations aiming at minimizing non-specific FDG uptake and to improve the recovery of signal from worms located in the lower abdomen will include the development of more specific radiotracers.     

Speech Perception and Localisation with SCORE Bimodal: A Loudness Normalisation Strategy for Combined Cochlear Implant and Hearing Aid Stimulation

A significant fraction of newly implanted cochlear implant recipients use a hearing aid in their non-implanted ear. SCORE bimodal is a sound processing strategy developed for this configuration, aimed at normalising loudness perception and improving binaural loudness balance. Speech perception performance in quiet and noise and sound localisation ability of six bimodal listeners were measured with and without application of SCORE. Speech perception in quiet was measured either with only acoustic, only electric, or bimodal stimulation, at soft and normal conversational levels. For speech in quiet there was a significant improvement with application of SCORE. Speech perception in noise was measured for either steady-state noise, fluctuating noise, or a competing talker, at conversational levels with bimodal stimulation. For speech in noise there was no significant effect of application of SCORE. Modelling of interaural loudness differences in a long-term-average-speech-spectrum-weighted click train indicated that left-right discrimination of sound sources can improve with application of SCORE. As SCORE was found to leave speech perception unaffected or to improve it, it seems suitable for implementation in clinical devices.     

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses ¹⁸F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 °C) or cold-activated (CA) (17 °C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.     

Prognostic Value of SUVmax Measured by Pretreatment Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ewing Sarcoma

AimThe aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma.MethodsWe retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox’s proportional hazards regression model.ResultsThe median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2–18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63–508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34–54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21–43.95; HR, 7.3) were associated with worse overall survival.ConclusionsSUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma.     

18F-Fluorodeoxyglucose Positron Emission Tomography in Elderly Patients with an Elevated Erythrocyte Sedimentation Rate of Unknown Origin

Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of≥50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.     

Neural Adaptation and Behavioral Measures of Temporal Processing and Speech Perception in Cochlear Implant Recipients

The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.     

Positron Emission Tomography of the Human Brain in Relation to Psychological Defense Mechanisms in Patients with Multiple Sclerosis

Neurophysiological correlates of psychological defense mechanisms (PDMs) were studied in patients with multiple sclerosis. PDM scores (the Lifestyle Index test) were compared with the relative glucose metabolic rate (GMR) estimated by positron emission tomography. The results testified that the combined metabolic activity of the limbic system and the frontal and temporal brain areas of the right hemisphere plays a predominant role in the functioning of the PDM system. An increase or decrease in PDM activity was associated with changes in GMR in several brain structures of the parietal and frontal regions.     

Tactile-Vibration-Activated Foci in Insular and Parietal-Opercular Cortex Studied with Positron Emission Tomography: Mapping the Second Somatosensory Area in Humans

Positron emission tomographic measurements were used to study the distribution of focal changes in cerebral blood flow (CBF) induced by vibrotactile stimulation of the hands and feet in 22 normal humans. Subjects received bolus intravenous saline injections containing ～ 60 mCi ¹⁵O-labeled water. Active regions during stimulation were defined relative to resting, nonstimulated states. Scan data from different subjects were averaged after stereotactic standardization. The results identified previously described foci of increased CBF in postrolandic sensory cortex (primary somatosensory cortex) and supplementary motor cortex. New statistical testing procedures provided independent demonstrations of two additional increases in regional CBF, bilaterally, within the sylvian fissure. One site along the parietal operculum corresponded to previous conjectures about a second somatosensory cortical area (SII) in humans. Another site also was found on the insula. No topographic organization was found in either location. The discussion considers these responsive areas to innocuous tactile stimuli in reference to suggestions about a role for SII in the perception of pain.