Try a new search

Format these results:

Searched for:

person:butlet01

in-biosketch:yes

Total Results:

62


Basal forebrain septal nuclei are enlarged in healthy subjects prior to the development of Alzheimer's disease

Butler, Tracy; Harvey, Patrick; Deshpande, Anup; Tanzi, Emily; Li, Yi; Tsui, Wai; Silver, Caroline; Fischer, Esther; Wang, Xiuyuan; Chen, Jingyun; Rusinek, Henry; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; de Leon, Mony J
Alzheimer's disease (AD) is known to be associated with loss of cholinergic neurons in the nucleus basalis of Meynert, located in the posterior basal forebrain. Structural changes of septal nuclei, located in the anterior basal forebrain, have not been well studied in AD. Using a validated algorithm, we manually traced septal nuclei on high-resolution coronal magnetic resonance imaging (MRI) in 40 subjects with mild cognitive impairment (MCI) or AD, 89 healthy controls, and 18 subjects who were cognitively normal at the time of MRI but went on to develop AD an average of 2.8 years later. We found that cognitively normal subjects destined to develop AD in the future had enlarged septal nuclei as compared to both healthy controls and patients with current MCI or AD. To our knowledge, this is the first time a brain structure has been found to be enlarged in association with risk of AD. Further research is needed to determine if septal enlargement reflects neuroplastic compensation, amyloid deposition, inflammation, or another process and to determine whether it can serve as an early MRI biomarker of AD.
PMID: 29499501
ISSN: 1558-1497
CID: 2966052

Not All Androgen Deprivation Therapies Are Created Equal: Leuprolide and the Decreased Risk of Developing Alzheimer's Disease [Letter]

Bowen, Richard L; Butler, Tracy; Atwood, Craig S
PMCID:5019750
PMID: 27298416
ISSN: 1527-7755
CID: 2145092

Comparison of human septal nuclei MRI measurements using automated segmentation and a new manual protocol based on histology

Butler, Tracy; Zaborszky, Laszlo; Pirraglia, Elizabeth; Li, Jinyu; Wang, Xiuyuan Hugh; Li, Yi; Tsui, Wai; Talos, Delia; Devinsky, Orrin; Kuchna, Izabela; Nowicki, Krzysztof; French, Jacqueline; Kuzniecky, Rubin; Wegiel, Jerzy; Glodzik, Lidia; Rusinek, Henry; Deleon, Mony J; Thesen, Thomas
Septal nuclei, located in basal forebrain, are strongly connected with hippocampi and important in learning and memory, but have received limited research attention in human MRI studies. While probabilistic maps for estimating septal volume on MRI are now available, they have not been independently validated against manual tracing of MRI, typically considered the gold standard for delineating brain structures. We developed a protocol for manual tracing of the human septal region on MRI based on examination of neuroanatomical specimens. We applied this tracing protocol to T1 MRI scans (n=86) from subjects with temporal epilepsy and healthy controls to measure septal volume. To assess the inter-rater reliability of the protocol, a second tracer used the same protocol on 20 scans that were randomly selected from the 72 healthy controls. In addition to measuring septal volume, maximum septal thickness between the ventricles was measured and recorded. The same scans (n=86) were also analysed using septal probabilistic maps and Dartel toolbox in SPM. Results show that our manual tracing algorithm is reliable, and that septal volume measurements obtained via manual and automated methods correlate significantly with each other (p<.001). Both manual and automated methods detected significantly enlarged septal nuclei in patients with temporal lobe epilepsy in accord with a proposed compensatory neuroplastic process related to the strong connections between septal nuclei and hippocampi. Septal thickness, which was simple to measure with excellent inter-rater reliability, correlated well with both manual and automated septal volume, suggesting it could serve as an easy-to-measure surrogate for septal volume in future studies. Our results call attention to the important though understudied human septal region, confirm its enlargement in temporal lobe epilepsy, and provide a reliable new manual delineation protocol that will facilitate continued study of this critical region.
PMCID:4180657
PMID: 24736183
ISSN: 1053-8119
CID: 908982

Septal nuclei enlargement in human temporal lobe epilepsy without mesial temporal sclerosis

Butler, Tracy; Zaborszky, Laszlo; Wang, Xiuyuan; McDonald, Carrie R; Blackmon, Karen; Quinn, Brian T; Dubois, Jonathan; Carlson, Chad; Barr, William B; French, Jacqueline; Kuzniecky, Ruben; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas
OBJECTIVE: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic. METHOD: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors. RESULTS: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. CONCLUSION: Septal nuclei are enlarged in patients with TLE without MTS. Further investigation of septal nuclei and antiepileptic septo-hippocampal neurocircuitry could be relevant to development of new therapeutic interventions such as septal stimulation for refractory TLE.
PMCID:3590047
PMID: 23303846
ISSN: 0028-3878
CID: 214042

Transient and chronic seizure-induced inflammation in human focal epilepsy

Butler, Tracy; Li, Yi; Tsui, Wai; Friedman, Daniel; Maoz, Anat; Wang, Xiuyuan; Harvey, Patrick; Tanzi, Emily; Morim, Simon; Kang, Yeona; Mosconi, Lisa; Talos, Delia; Kuzniecky, Ruben; Vallhabjosula, Shankar; Thesen, Thomas; Glodzik, Lidia; Ichise, Masanori; Silbersweig, David; Stern, Emily; de Leon, Mony J; French, Jacqueline
In animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure-free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy.
PMCID:5266563
PMID: 27381590
ISSN: 1528-1167
CID: 2237892

Hippocampal structural changes across the menstrual cycle

Protopopescu, Xenia; Butler, Tracy; Pan, Hong; Root, James; Altemus, Margaret; Polanecsky, Margaret; McEwen, Bruce; Silbersweig, David; Stern, Emily
Magnetic resonance imaging (MRI) in association with Jacobian-modulated voxel-based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1-weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late-follicular phase (Days 10-12 after onset of menses), and once during the premenstrual late-luteal phase (1-5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well-established animal findings of hormone-mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle
PMID: 18767068
ISSN: 1098-1063
CID: 106035

Why is mesial temporal lobe epilepsy with Ammon's horn sclerosis becoming less common? [Letter]

Butler, T A; Dugan, P; French, J
PMID: 25495399
ISSN: 1468-1331
CID: 1515162

Imaging Inflammation in a Patient with Epilepsy Due to Focal Cortical Dysplasia

Butler T; Ichise M; Teich AF; Gerard E; Osborne J; French J; Devinsky O; Kuzniecky R; Gilliam F; Pervez F; Provenzano F; Goldsmith S; Vallabhajosula S; Stern E; Silbersweig D
BACKGROUND AND PURPOSE: Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans. We hypothesize that in patients with active epilepsy, [C11]PK11195 PET (PK-PET) may be able to identify areas of focally increased inflammation corresponding to the seizure onset zone. METHODS: A young woman with intractable epilepsy underwent PK-PET as part of an approved research study. PK-PET results were compared with results from other clinical studies. RESULTS: PK-PET revealed an area of focally increased radiotracer uptake in the right frontal lobe corresponding to this patient's seizure focus as identified by ictal and interictal 18F-fluorodeoxyglucose (FDG)-PET and EEG. Routine brain magnetic resonance imaging (MRI) was initially considered normal, though high-resolution studies showed possible subtle dysplasia of the right frontal lobe. The patient underwent a right frontal lobe resection, and pathological evaluation showed focal cortical dysplasia with activated microglia. CONCLUSIONS: PK-PET can identify neuroinflammation associated with subtle focal cortical dysplasia, and may therefore have a clinical role in guiding epilepsy surgery for patients with difficult-to-localize seizure foci. J Neuroimaging 2011;XX:1-3
PMCID:5303618
PMID: 21223436
ISSN: 1552-6569
CID: 120738

Quadratic relationship between systolic blood pressure and white matter lesions in individuals with hypertension

Woldstad, Christopher; Rusinek, Henry; Sweeney, Elizabeth; Butler, Tracy; Li, Yi; Tanzi, Emily; Mardy, Christopher; Harvey, Patrick; de Leon, Mony J; Glodzik, Lidia
BACKGROUND:There is a well documented relationship between cardiovascular risk factors and the development of brain injury, which can lead to cognitive dysfunction. Hypertension (HTN) is a condition increasing the risk of silent and symptomatic ischemic brain lesions. Although benefits of hypertension treatment are indisputable, the target blood pressure value where the possibility of tissue damage is most reduced remains under debate. METHOD/METHODS:Our group performed a cross-sectional (n = 376) and longitudinal (n = 188) study of individuals without dementia or stroke (60% women n = 228, age 68.5 ± 7.4 years; men n = 148, age 70.7 ± 6.9 years). Participants were split into hypertensive (n = 169) and normotensive (n = 207) groups. MR images were obtained on a 3T system. Linear modeling was performed in hypertensive and normotensive cohorts to investigate the relationship between systolic (SBP) and diastolic (DBP) blood pressure, white matter lesion (WML), and brain volumes. RESULTS:Participants in the hypertensive cohort showed a quadratic relationship between SBP and WML, with the lowest amounts of WML being measured in participants with readings at approximately 124 mmHg. Additionally, the hypertensive cohort also exhibited a quadratic relationship between DBP and mean hippocampal volume; participants with readings at approximately 77 mmHg showing the largest volumes. Longitudinally, all groups experienced WML growth, despite different BP trajectories, further suggesting that WML expansion may occur despite or because of BP reduction in individuals with compromised vascular system. CONCLUSION/CONCLUSIONS:Overall, our study suggests that in the hypertensive group there is a valley of mid-range blood pressures displaying less pathology in the brain.
PMID: 36204999
ISSN: 1473-5598
CID: 5361812

Association between lower body temperature and increased tau pathology in cognitively normal older adults

Blessing, Esther M; Parekh, Ankit; Betensky, Rebecca A; Babb, James; Saba, Natalie; Debure, Ludovic; Varga, Andrew W; Ayappa, Indu; Rapoport, David M; Butler, Tracy A; de Leon, Mony J; Wisniewski, Thomas; Lopresti, Brian J; Osorio, Ricardo S
BACKGROUND:Preclinical studies suggest body temperature (Tb) and consequently brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD). Tau phosphorylation is substantially increased by small (<1 °C) decreases in temperature within the human physiological range, and thermoregulatory nuclei are affected by tau pathology early in the AD continuum. In this study we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults. METHODS:Tb was continuously measured with ingestible telemetry sensors for 48-h. This period also included two nights of nocturnal polysomnography to delineate whether Tb during waking vs sleep is differentially associated with tau pathology. Tau phosphorylation was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement. In addition, neurofibrillary tangle (NFT) burden in early Braak stage regions was imaged with PET-MR using the [18F]MK-6240 radiotracer on average one month later. RESULTS:Lower Tb was associated with increased NFT burden, as well as increased plasma and CSF P-tau levels (p < 0.05). NFT burden was associated with lower Tb during waking (p < 0.05) but not during sleep intervals. Plasma and CSF Ptau levels were highly correlated with each other (p < 0.05), and both variables were correlated with tau tangle radiotracer uptake (p < 0.05). CONCLUSIONS:These results, the first available for human, suggest that lower Tb in older adults may be associated with increased soluble and aggregated tau pathology. Our findings add to the substantial preclinical literature associating lower body and brain temperature with tau hyperphosphorylation. CLINICAL TRIAL NUMBER/BACKGROUND:NCT03053908.
PMID: 35550158
ISSN: 1095-953x
CID: 5214682