Two separate activation regions are seen within the corpus callosum for the group comparison using the 2<sup>nd</sup> level contrast NÏ€S0 - N0SÏ€, threshold p<.001, uncorrected for family-wise error (FWE)
<p>Because the activation maps have been smoothed at 8×8×8 mm FWHM, there may appear to be ... more <p>Because the activation maps have been smoothed at 8×8×8 mm FWHM, there may appear to be an overlap of the activation with the ventricle seen on the high resolution T1 image, which we did not attempt to mask. The statistics for this cluster is an indication that there exists at least one point of activation within the cluster with true significance (p<.01, FWE, cluster-wise for the larger region, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041263#pone-0041263-t004" target="_blank">Table 4</a>). Obviously, the true source of activation would be in the tissue region, as the region of significance would likely be near voxels with the highest t-scores, which are located within the corpus callosum. The large activation seen in the L. insula is also cluster-wise significant (p<.01). All conditions were presented using random permutation ordering to prevent possible cyclic responses or habituation effects being mix with the contrast of conditions. Furthermore, SPMd was used to prevent any possible influence of outliers or motion.</p
Abstract 3268: Ct Perfusion As A Tool To Predict The Risk Of Hemorrhagic Transformation In Ischemic Stroke Treated With Tissue Plasminogen Activator: A Single Center Experience
Stroke, 2012
Objective: To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admi... more Objective: To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume (CBV) and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis. Methods: Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 - 2011 within 3 hours after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates CBV and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow up CT head without contrast, done within 36 hours of the thrombolysis therapy. Clinical, demographic and CTP variab...
It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hype... more It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand 11 C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.
Neural Plasticity in Patients with Tinnitus and Sensorineural Hearing Loss
Acoustical Signal Processing in the Central Auditory System, 1997
Hearing loss and tinnitus and are two common problems that both increase in prevalence with advan... more Hearing loss and tinnitus and are two common problems that both increase in prevalence with advancing age. The self-reported incidence of hearing loss reaches 35% by age 75 (Nadol, Jr. 1993). This incidence may be low by a factor of two or more. Experience at the Rochester Institute of Technology suggests that 90% or more of adults in their 70’s have hearing loss when standard audiometric tests are used as the test measure (R. Frisina, personal communication). Public health survey data show that the incidence of severe, disabling tinnitus also rises with age and parallels the increase in the incidence of hearing loss (National Center for Health Statistics, 1968). These two problems account for a substantial amount of disability due to the impairments in communication and the attendant psychological impact of isolation, depression, and other symptoms (O’Connor et al. 1987; Hallametal. 1984).
In our previous study we investigated Masking Level Differences (MLD) using functional Magnetic R... more In our previous study we investigated Masking Level Differences (MLD) using functional Magnetic Resonance Imaging (fMRI), but were unable to confirm neural correlations for the MLD within the auditory cortex and inferior colliculus. Here we have duplicated conditions from our previous study, but have included more participants and changed the study site to a new location with a newer scanner and presentation system. Additionally, Diffusion Tensor Imaging (DTI) is included to allow investigation of fiber tracts that may be involved with MLDs. Twenty participants were included and underwent audiometric testing and MRI scanning. The current study revealed regions of increased and decreased activity within the auditory cortex when comparing the combined noise and signal of the dichotic MLD stimuli (N0SÏ€ and NÏ€S0) with N0S0. Furthermore, we found evidence of inferior colliculus involvement. Our DTI findings show strong correlations between DTI measures within the brainstem and signal det...
We tested the hypothesis that tinnitus was due to excessive spontaneous activity in the central a... more We tested the hypothesis that tinnitus was due to excessive spontaneous activity in the central auditory system by seeking cerebral blood flow (CBF) changes that paralleled changes in the loudness of tinnitus in patients able to alter the loudness of their tinnitus. We found CBF changes in the left temporal lobe in patients with right ear tinnitus, in contrast to bilateral temporal lobe activity associated with stimulation of the right ear. The tones activated more extensive portions of the brain in patients than controls. We conclude that tinnitus is not cochlear in origin and associated with plastic transformations of the central auditory system. We suggest that tinnitus arises as a consequence of these aberrant new pathways and may be the auditory system analog to phantom limb sensations in amputees.
E-071 CT perfusion as a tool to predict the risk of hemorrhagic transformation in ischemic stroke treated with tissue plasminogen activator: a single center experience
Journal of NeuroInterventional Surgery, 2012
Objective To use the CT Perfusion (CTP) parameters at the time of hospital admission, including C... more Objective To use the CT Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis. Methods Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 and 2011 within 3 h after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates Cerebral Blood Volume and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow-up CT head without contrast, done within 36 h of the thrombolysis therapy. Clinical, demographic and CTP variables were compared between the HT and non-HT groups using logistic regression analyses. Results HT developed in 8 (40%) patients. Patients with HT had lower ASPECT score (p=0.03), higher NIHSS on admission (p=0.01) and worse outcome (p=0.04) compared to patients who did not develop HT. Baseline blood flow defects were comparable between the two groups. The mean PS for the HT group was 0.53 ml/min/100 g brain tissue, which was significantly higher than that for the non-HT group of 0.04 ml/min/100 g brain tissue (p<0.0001). The mean area under the curve was 0.92 (95% CI). The PS threshold of 0.26 ml/min/100 g brain tissue had a sensitivity of 80% and a specificity of 92% for detecting patients with high risk of hemorrhagic transformation after intravenous thrombolysis. Conclusions Admission CTP measurements might be useful to predict patients who are at higher risk to develop hemorrhagic transformation after acute ischemic stroke therapy. Competing interests T Kass-Hout: Genentech. O Kass-Hout: None. M Al Masry: None. M Mokin: None. D Wack: None. E Nourollahzadeh: None. A Siddiqui: NINDS 1R01NS064592-01A1, University at Buffalo. Shurtleff, Inc, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra. Codman & Shurtleff, Inc, Genentech. Hotspur, Intratech Medical, StimSox, Valor Medical. Abbott Vascular, American Association of Neurological Surgeons, Neocure Group LLC, an Emergency Medicine Conference. E Levy: Codman & Shurtleff, Inc, ev3/Covidien Vascular Therapies, Boston Scientific. TheraSyn Sensors, Inc. Medical Ltd., Mynx/Access Closure. Boston Scientific. K Synder: Toshiba and ev3.
Individual images in dynamic molecular imaging studies are noisy because of short duration of fra... more Individual images in dynamic molecular imaging studies are noisy because of short duration of frames. To reduce noise in these studies we used a method that employed the Hilbert transform and Singular Value Decomposition (SVD) processing. Use of this method, which we call the Complex Singular Value Decomposition (CSVD), significantly reduces noise while preserving signal intensity of dynamic images. Further, we used simulations to examine the effect of CSVD processing on estimates of receptor kinetic parameters. We found a significant reduction in variance when CSVD processing was applied to images that had Gaussian noise added to the signal. The signals were preserved even after adding noise, thus the simulations revealed that noise reduction was not at the cost of relevant signal. It therefore appears that CSVD processing can be used in dynamic molecular imaging and other similar studies to reduce noise and improve signal quality.
Reports of memory impairment after cardiac surgery are controversial. To address this controversy... more Reports of memory impairment after cardiac surgery are controversial. To address this controversy, we used positron emission tomography to examine changes in regional cerebral blood flow (rCBF) during memory processing before and after elective coronary artery bypass grafting surgery. In postoperative scans we observed significantly reduced rCBF in two of the most important memory processing areas: the medial temporal lobe (p=0.023) and the prefrontal cortex (p=0.002). The results suggest postoperative attenuation of rCBF in brain areas involved in memory processing. These reductions could be used to evaluate severity of memory impairment after coronary artery bypass grafting surgery in patients at risk.
Duration of human MU opiate receptor blockade following naltrexone: Measurement by 11C-carfentanil pet
Clinical Pharmacology & Therapeutics, 2005
ABSTRACT Background Naltrexone is a mu opiate receptor antagonist approved for the treatment of a... more ABSTRACT Background Naltrexone is a mu opiate receptor antagonist approved for the treatment of alcohol dependency. Previous reports have suggested a duration of receptor occupancy of naltrexone that greatly exceeds that predicted by it&amp;#39;s 4 hour T1/2, or the 13 hour T1/2 of beta naltrexol, the predominant metabolite. We undertook a double blind, placebo controlled, randomized study of receptor occupancy using the highly selective mu opiate receptor ligand 11C-carfentanil.Methods Healthy volunteers underwent PET imaging with 11C-carfentanil at baseline, 3 24, 72 and 144 hours following a single dose of placebo, 12.5, 50 or 100mg of naltrexone. Regional analysis was undertaken using a statistical parametric mapping approach (SPM2).ResultsTo date, 15 of 24 subjects have completed all phases of the study. At interim analysis, regions of significantly (p&amp;lt;0.001) lower activity were mapped in all known regions of brain mu receptors 3 and 24 hours following all doses of naltrexone. This effect was measurable at 72 hours for the combined 50/100mg dose. At 144 hours, significant blockade remained in the left temporal lobe. (see Table)Conclusions Our findings provide tomographic evidence of a persistence of blockade of the mu opiate receptor for up to 144 hours following naltrexone, with no evidence of a receptor level placebo effect. Correlation with plasma naltrexone and beta naltrexone is planned.Clinical Pharmacology &amp;amp; Therapeutics (2005) 77, P26-P26; doi: 10.1016/j.clpt.2004.11.099Table 1. Placebo12.5 mg50/100 mgBaseline vsN = 6N = 4N = 53HNSP &amp;lt; 0.001P &amp;lt; 0.00124HNSP &amp;lt; 0.001P &amp;lt; 0.00172HNSNSP &amp;lt; 0.001144HNSNSP &amp;lt; 0.01
We used PET to map brain regions responding to changes in tinnitus loudness in four patients who ... more We used PET to map brain regions responding to changes in tinnitus loudness in four patients who could alter tinnitus loudness by performing voluntary oral facial movements (OFMs). Cerebral blood flow was measured in four patients and six controls at rest, during the OFM, and during stimulation with pure tones. OFM-induced loudness changes affected the auditory cortex contralateral to the ear in which tinnitus was perceived, whereas unilateral cochlear stimulation caused bilateral effects, suggesting a retrocochlear origin for their tinnitus. Patients, compared with controls, showed evidence for more widespread activation by the tones and aberrant links between the limbic and auditory systems. These abnormal patterns provide evidence for cortical plasticity that may account for tinnitus and associated symptoms. Although audiologic symptoms and examinations of these patients were typical, the unusual ability to modulate tinnitus loudness with an OFM suggests some caution may be warra...
To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that ma... more To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that may follow cerebellar-pontine angle surgery. Methods: The authors examined eight patients with GET and used PET to map the neural sites activated by lateral gaze in them and seven age-and sex-matched control subjects. Results: In patients with GET, tinnitus loudness and pitch increased with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural activity related to GET was seen in the auditory lateral pontine tegmentum or auditory cortex. GET-associated nystagmus appears to activate the cuneus and cerebellar vermis. These sites were found in addition to an extensive network that included frontal eye fields and other sites in frontal, parietal, and temporal cortex that were activated by lateral gaze in seven control subjects and the patients. The unilateral deafness in patients with GET was associated with expansion of auditory cortical areas responsive to tones delivered to the good ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial nerve dysfunction were common. Conclusions: Patients with GET have plastic changes in multiple neural systems that allow neural activity associated with eye movement, including those associated with the neural integrator, to stimulate the auditory system. Anomalous auditory activation is enhanced by the failure of cross-modal inhibition to suppress auditory cortical activity. The time course for the development of GET suggests that it may be due to multiple mechanisms.
Mapping the neural systems that mediate the Paced Auditory Serial Addition Task (PASAT)
Journal of the International Neuropsychological Society, 2004
The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add t... more The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions.
Purpose: To compare functional magnetic resonance imaging (fMRI) activation patterns during a cog... more Purpose: To compare functional magnetic resonance imaging (fMRI) activation patterns during a cognitive task, exercise capacity, and symptoms in postconcussion syndrome (PCS) patients who received exercise treatment (n = 4) with a PCS placebo stretching group (n = 4) and a healthy control group (n = 4). Methods: Subjects completed a math processing task during fMRI and an exercise treadmill test before (time 1) and after approximately 12 weeks (time 2). Exercise subjects performed aerobic exercise at 80% of the heart rate (HR) attained on the treadmill test, 20 minutes per day with an HR monitor at home, 6 days per week. The program was modified as the HR for symptom exacerbation increased. Results: At time 1, there was no difference in fMRI activation between the 2 PCS groups but healthy controls had significantly greater activation in the posterior cingulate gyrus, lingual gyrus, and cerebellum versus all PCS subjects (P < .05, corrected for multiple comparisons). At time 2, exercise PCS did not differ from healthy controls whereas placebo stretching PCS had significantly less activity in the cerebellum (P < .05 corrected) and in the anterior cingulate gyrus and thalamus (P < .001, uncorrected) versus healthy controls. At time 2, exercise PCS achieved a significantly greater exercise HR (P < .001) and had fewer symptoms (P < .0004) than placebo stretching PCS. Cognitive performance did not differ by group or time. Conclusions: Controlled aerobic exercise rehabilitation may help restore normal cerebral blood flow regulation, as indicated by fMRI activation, in PCS patients. The PCS symptoms may be related to abnormal cerebral blood flow regulation.
Cerebral 18 F-deoxyglucose positron emission tomography (FDG-PET) has shown altered auditory path... more Cerebral 18 F-deoxyglucose positron emission tomography (FDG-PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG-PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro-medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal-hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschl's gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left-sided overactivation was found independently from tinnitus laterality.
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