Faculty Bibliography

Piriform cortical circuits are hypothesized to form perceptions from responses to specific odorant features, but the anterior piriform cortex (aPCX) and posterior piriform cortex (pPCX) differ markedly in their anatomical organization, differences that could lead to distinct roles in odor encoding. Here, we tested whether experience with a complex odorant mixture would modify encoding of the mixture and its components in aPCX and pPCX. Rats were exposed to an odorant mixture and its components in a go/no-go rewarded odor discrimination task. After reaching behavioral performance criterion, single-unit recordings were made from the aPCX and pPCX in these rats and in odor-naive, control, urethane-anesthetized rats. After odor experience, aPCX neurons were more narrowly tuned to the test odorants, and there was a decorrelation in aPCX population responses to the mixture and its components, suggesting a more distinct encoding of the familiar mixture from its components. In contrast, pPCX neurons were more broadly tuned to the familiar odorants, and pPCX population responses to the mixture and its components became more highly correlated, suggesting a pPCX encoding of similarity between familiar stimuli. The results suggest aPCX and pPCX play different roles in the processing of familiar odors and are consistent with an experience-dependent encoding (perceptual learning) of synthetic odorant identity in aPCX and an experience-dependent encoding of odor similarity or odor quality in pPCX

Huntington's disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis. We report here that mutant huntingtin causes disruption of mitochondrial function by inhibiting expression of PGC-1alpha, a transcriptional coactivator that regulates several metabolic processes, including mitochondrial biogenesis and respiration. Mutant huntingtin represses PGC-1alpha gene transcription by associating with the promoter and interfering with the CREB/TAF4-dependent transcriptional pathway critical for the regulation of PGC-1alpha gene expression. Crossbreeding of PGC-1alpha knockout (KO) mice with HD knockin (KI) mice leads to increased neurodegeneration of striatal neurons and motor abnormalities in the HD mice. Importantly, expression of PGC-1alpha partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated delivery of PGC-1alpha in the striatum provides neuroprotection in the transgenic HD mice. These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis

A scalable adaptive optics (AO) control system architecture composed of asynchronous control clusters based on the stochastic parallel gradient descent (SPGD) optimization technique is discussed. It is shown that subdivision of the control channels into asynchronous SPGD clusters improves the AO system performance by better utilizing individual and/or group characteristics of adaptive system components. Results of numerical simulations are presented for two different adaptive receiver systems based on asynchronous SPGD clusters-one with a single deformable mirror with Zernike response functions and a second with tip-tilt and segmented wavefront correctors. We also discuss adaptive wavefront control based on asynchronous parallel optimization of several local performance metrics-a control architecture referred to as distributed adaptive optics (DAO). Analysis of the DAO system architecture demonstrated the potential for significant increase of the adaptation process convergence rate that occurs due to partial decoupling of the system control clusters optimizing individual performance metrics

Accuracy of shifting movements between two notes was examined in nine cellists (intermediate-professional skill levels). Three pairs of notes separated by different distances were tested under the same movement rate. Finger position on the string was measured by a circuit. Angular velocities of the left upper arm and forearm were measured by two angular velocity sensors; thus elbow angular velocity during shifts was estimated. Results showed that with increased elbow velocity and shifting distance endpoint variability stayed constant. The force of gravity assisted elbow extension during shifts toward higher pitched notes compared to flexion towards lower pitched notes, but faster movement velocity did not result in increased landing variability. Performance for note E on the A string was found to be less variable than other notes, suggesting that physical cue from the cello body geometry was used as a landmark for finger position. Cutaneous feedback from the thumb when hitting the body-neck junction enabled faster elbow extension velocity compared to shifts towards other notes. Cellists who showed higher performance accuracy also showed higher perceptual ability and performance proficiency. These results suggest that long-term over-training of fast and accurate movements enables musicians to maintain accuracy and variability across different movement distances and velocities. Higher perceptual ability and performance proficiency are correlated with increased accuracy but not lower variability, indicating although perceptual ability and performance proficiency are important for pitch accuracy, movement variability is still constrained by the capacity of the motor system, which is highly fine-tuned and different than non-musicians.

Diseases of the small airspaces represent an increasingly important health problem. Asthma is primarily a disease of airway dysfunction, while chronic obstructive pulmonary disease (COPD) is associated with abnormalities in both the small airways and the alveoli. Conventional diffusion magnetic resonance imaging (MRI) of hyperpolarized noble gases, because of the short T(2)* of the gas, is only capable of monitoring diffusion over short times and hence only short distances. Diffusion imaging is therefore only sensitive to changes in small structures of the lung (primarily the alveoli), and will not adequately interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In this communication we present a new method, termed diffusional kurtosis imaging (DKI), that is particularly sensitive to diffusion over longer distances. DKI may therefore be more sensitive to abnormalities in the bronchioles and bronchi than conventional diffusion imaging. Preliminary DKI measurements on healthy human subjects and one patient with symptoms suggestive of small airway disease are presented. Although the apparent diffusion coefficient (ADC) in the patient was similar to that in the normal controls, diffusional kurtosis was markedly reduced. This suggests that DKI measurements may be useful for assessing diseases of the small airways. Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent and commonly studied forms of psychopathology in children and adolescents. Causal models of ADHD have long implicated dysfunction in fronto-striatal and frontal-parietal networks supporting executive function, a hypothesis that can now be examined systematically using functional neuroimaging. The present work provides an objective, unbiased statistically-based meta-analysis of published functional neuroimaging studies of ADHD. METHODS: A recently developed voxel-wise quantitative meta-analytic technique known as activation likelihood estimation (ALE) was applied to 16 neuroimaging studies examining and contrasting patterns of neural activity in patients with ADHD and healthy controls. Voxel-wise results are reported using a statistical threshold of p < .05, corrected. Given the large number of studies examining response inhibition, additional meta-analyses focusing specifically on group differences in the neural correlates of inhibition were included. RESULTS: Across studies, significant patterns of frontal hypoactivity were detected in patients with ADHD, affecting anterior cingulate, dorsolateral prefrontal, and inferior prefrontal cortices, as well as related regions including basal ganglia, thalamus, and portions of parietal cortex. When focusing on studies of response inhibition alone, a more limited set of group differences were observed, including inferior prefrontal cortex, medial wall regions, and the precentral gyrus. In contrast, analyses focusing on studies of constructs other than response inhibition revealed a more extensive pattern of hypofunction in patients with ADHD than those of response inhibition. CONCLUSIONS: To date, the most consistent findings in the neuroimaging literature of ADHD are deficits in neural activity within fronto-striatal and fronto-parietal circuits. The distributed nature of these results fails to support models emphasizing dysfunction in any one frontal sub-region. While our findings are suggestive of the primacy of deficits in frontal-based neural circuitry underlying ADHD, we discuss potential biases in the literature that need to be addressed before such a conclusion can be fully embraced.

BACKGROUND: Because chronic kidney disease (CKD) may be associated with gastrointestinal bleeding from trivial mucosal lesions, we hypothesized that the predictive value of a positive fecal occult blood test (FOBT) result for clinically important colonic lesions would decrease as the stage of CKD worsened. METHODS: We prospectively identified 1,225 consecutive asymptomatic average-risk patients who were referred for colonoscopy to evaluate a positive FOBT result. Using the Modification of Diet in Renal Disease equation, we estimated glomerular filtration rate (GFR) and staged the severity of CKD by using standard criteria as follows: normal/stage 1 (GFR > or = 90 mL/min/1.73 m2 [> or = 1.50 mL/s]), stage 2/3 (GFR 30 to 89 mL/min/1.73 m2 [0.50 to 1.48 mL/s]), and stage 4/5 (GFR < 30 mL/min/1.73 m2 [< 0.50 mL/s] or dialysis). RESULTS: Clinically important lesions were identified in 23.9% of 531 individuals with none/stage 1 CKD, 32.8% of 497 subjects with stage 2/3 CKD, and 42.6% of 197 patients with stage 4/5 CKD (P < 0.001). Compared with patients with none/stage 1 CKD, adjusted odds of identifying a clinically important lesion were 1.61 (95% confidence interval, 1.21 to 2.15) in subjects with stage 2/3 CKD and 2.33 (95% confidence interval, 1.62 to 3.36) in patients with stage 4/5 CKD. Prevalences of adenomas of 1 cm or greater (15.1% versus 20.1% versus 22.8%; P = 0.007), carcinomas (5.1% versus 10.1% versus 13.2%; P < 0.001), and vascular ectasias (1.7% versus 2.4% versus 6.1%; P = 0.003) increased with the severity of CKD. CONCLUSION: Contrary to our initial hypothesis, we found that the predictive value of a positive FOBT result for clinically important colonic lesions increased as the severity of CKD worsened