Activation detection in fMRI data via multi-scale singularity detection

Detection of active areas in the brain by functional magnetic resonance imaging (fMRI) is a challenging problem in medical imaging. Moreover, determining the onset and end of activation signal at specific locations in 3-space can determined networks of temporal relationships required for brain mapping. We introduce a method for activation detection in fMRI data via wavelet analysis of singular features. We pose the problem of determining activated areas as singularity detection in the temporal domain. Overcomplete wavelet expansion at integer scales are used to trace wavelet modulus maxima across scales to construct maxima lines. Form these maxima lines, singularities in the signal are located corresponding to the onset and end of an activation signal. We present result for simulated phantom waveforms and clinical fMRI dat from human finger tapping experiments. Different levels of noise were added to two waveforms of phantom data. No assumptions about specific frequency and amplitude of an activation signal were made prior to analysis. Detection was reliable for modest levels of random noise, but less precise at higher levels. For clinical fMRI data, activation maps were comparable to those of existing standard techniques

High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period

This paper describes an individual who was diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) at age 17 when education was discontinued. By age 19, he was housebound without social contacts except for parents. Adequate trials of three selective serotonin reuptake inhibitors, two with atypical neuroleptics, were ineffective. Major exacerbations following ear infections involving Group A β-hemolytic streptococcus at ages 19 and 20 led to intravenous immune globulin therapy, which was also ineffective. At age 22, another severe exacerbation followed antibiotic treatment for H. pylori. This led to a hypothesis that postulates deficient signal transduction by the N-methyl-D-aspartate receptor (NMDAR). Treatment with glycine, an NMDAR coagonist, over 5 years led to robust reduction of OCD/BDD signs and symptoms except for partial relapses during treatment cessation. Education and social life were resumed and evidence suggests improved cognition. Our findings motivate further study of glycine treatment of OCD and BDD

Differential Regional Dysfunction of the Hippocampal Formation among Elderly with Memory Decline and Alzheimer's Disease

The hippocampal formation is composed of separate anatomical regions interconnected to form a circuit, and investigating abnormal hippocampal function is most revealing at the level of these regions. Until recently, regional analysis of the hippocampal formation could be performed only in animals or in human postmortem tissue. Here, we report a method using functional magnetic resonance imaging that evaluates the hippocampal regions in vivo, and we use this method to study elderly with normal memory, with isolated memory decline, and with probable Alzheimer's disease (AD). Although age-related memory decline occurs commonly, the cause of this decline remains unknown, with disagreement as to whether this decline represents one or more etiologies. Analysis revealed two distinct patterns of regional dysfunction among elderly with isolated memory decline--one pattern similar to that found in elders with AD, involving all hippocampal regions, and a second pattern with dysfunction restricted to only one hippocampal region, the subiculum. These results offer direct evidence of hippocampal dysfunction associated with memory decline in the elderly, and implicate both predementia AD and non-AD processes as possible underlying cause

Exploring the Neural Basis of Cognitive Reserve

There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes

Identification and Differential Vulnerability of a Neural Network in Sleep Deprivation

The study aimed to identify task-related brain activation networks whose change in expression exhibits subject differences as a function of differential susceptibility to sleep deprivation. Brain activity during a non-verbal recognition memory task was investigated in an event-related functional MRI paradigm both prior to and after 48 h of sleep deprivation. Nineteen healthy subjects participated. Regional covariance analysis was applied to data. An activation network pattern was identified whose expression decreased from pre- to post-sleep deprivation in 15 out 19 subjects (P < 0.05). Differential decrease in expression correlated with worsening performance in recognition accuracy (P < 0.05). Sites of de-activation were found in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri; increased activation was found in the bilateral insula, claustrum and right putamen. A network whose expression decreased after sleep deprivation and correlated with memory performance was identified. We conclude that this activation network plays a role in cognitive function during sleep deprivation

The prevalence and determinants of subclinical brain infarction: the Northern Manhattan Study

OBJECTIVE: Risk factors for subclinical brain infarcts (SBI) have not been well studied, especially in Hispanics and blacks who may be at higher risk for vascular disease. We examined the prevalence and determinants of SBI in a multi-ethnic community cohort. METHODS: The Northern Manhattan Study (NOMAS) includes 892 stroke-free participants who underwent brain magnetic resonance imaging (MRI). Baseline demographic and vascular risk factor data were collected. The presence of SBI was determined from the size, location, and imaging characteristics of the lesion based on FLAIR, T1 and T2, and proton density MRI sequences. We calculated the prevalence of SBI and cross-sectional associations with socio-demographic and vascular risk factors, using logistic regression to adjust for relevant covariates. RESULTS: Among 892 subjects (mean age 71.3 years), 158 (17.7%) had SBI (13.5% had 1 lesion, 4.3% had > 1 lesion). Of the total 216 infarcts, most were small (< 1 cm, 82.4%) and subcortical (82.9). SBI prevalence increased with age (< 65: 9.7%; 65–75: 16.4%; > 75: 26.1%), was increased among men (21.3% vs. 15.2% in women) and blacks (24.0% vs. 18.1% in whites and 15.8% in Hispanics). The presence of SBI was independently associated with older age (per year: OR 1.06, 95% CI 1.04–1.09), male sex (OR 1.79, 95% CI 1.22–2.61), and hypertension (OR 2.08, 95% CI 1.35–3.22) adjusting for age, sex, race-ethnicity, and vascular risk factors. A significant interaction (P = 0.002) between race and age was observed such that younger blacks had greater odds of having SBI. CONCLUSIONS: SBI were detected in nearly 18% of subjects in a multi-ethnic community-based cohort. Age, male sex, and hypertension were independently associated with SBI. Subclinical cerebral infarcts are more prevalent than symptomatic infarcts and may increase the true public health burden of stroke