Blood Oxygenation Level-dependent Brain Research Articles

Functional Brain Networks to Evaluate Treatment Responses in Parkinson's Disease

Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson's disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease networks can also be used to measure rates of progression in natural history studies and to assess treatment responses in individual subjects. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, specific treatment-induced networks have been described in association with novel interventions for PD such as subthalamic adeno-associated virus glutamic acid decarboxylase (AAV2-GAD) gene therapy, as well as sham surgery or oral placebo under blinded conditions. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. In aggregate, these attributes suggest a role for functional brain networks as biomarkers in future clinical trials.

Is There a Role for Combined EMG-fMRI in Exploring the Pathophysiology of Essential Tremor and Improving Functional Neurosurgery?

BackgroundFunctional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.ObjectiveAim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.MethodsSimultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.ResultsAnalysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.ConclusionEMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.

Mild Cognitive Impairment: Evaluation with 4-T Functional MR Imaging

To prospectively assess abnormalities in brain activation patterns during encoding and retrieval in subjects with mild cognitive impairment by using 4-T functional magnetic resonance (MR) imaging. The institutional review board approved this HIPAA-compliant study; all subjects gave written informed consent. Twenty patients with mild cognitive impairment (12 men, eight women; mean age, 75.0 years +/- 7.6 [standard deviation]) and 20 elderly control subjects (nine men, 11 women; mean age, 71.2 years +/- 4.5) underwent functional MR imaging at 4 T during a novel-versus-familiar face-name encoding-retrieval task. The magnitude of blood oxygen level-dependent brain responses across the entire brain were compared within and between subjects with mild cognitive impairment and control subjects by using a voxelwise random-effects model. A one-sample t test was used for within-group analysis; an analysis-of-covariance model (with age as a covariate) was used for between-group analysis. Brain regions activated by the task (prefrontal, medial temporal, and parietal regions) during encoding were similar to those activated during retrieval, with larger areas activated during retrieval. Subjects with mild cognitive impairment showed decreased magnitude of activation in bilateral frontal cortex regions (during encoding and retrieval), the left hippocampus (during retrieval), and the left cerebellum (during encoding) compared with magnitude of activation in control subjects (P < .001). Patients with mild cognitive impairment showed increased activation in the posterior frontal lobes (during retrieval) (P < .001). Lower hippocampal activation during retrieval was the most significant correlate of clinical severity of memory loss in mild cognitive impairment (P < .001). A difference exists in the response of brain regions underlying encoding and retrieval in mild cognitive impairment. Memory deficits in mild cognitive impairment may be linked to functional alterations in several specific brain regions both inside and outside the medial temporal lobe.

Identification of Alzheimer Disease Risk by Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials. To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults. Cross-sectional case-control study. University of California, San Diego, Alzheimer Disease Research Center participants and San Diego community volunteers. Twenty cognitively normal individuals (10 high risk and 10 low risk), aged 58 to 65 years, were divided into 2 groups based on the presence or absence of the apolipoprotein E epsilon4 allele and a positive family history of AD. Word pairs were presented in a blocked design alternating between conditions of novel pairs, repeated pairs, and fixation. Whole-brain differences in blood oxygenation level-dependent brain responses between conditions were compared across risk groups. Compared with the low-risk group, the high-risk group showed many areas of differential blood oxygenation level-dependent response in regions commonly associated with AD pathology (eg, the left medial temporal lobe). Furthermore, different patterns of association between left medial temporal lobe activity and memory performance were demonstrated. Results support a theory of up-regulation in neuronal memory systems in people at risk for AD many years before the typical age at disease onset. They further demonstrate that functional magnetic resonance imaging is a viable technique to identify persons at risk for AD.

Attenuated Brain Response to Auditory Word Stimulation with Sevoflurane

Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery. Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct). Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively. Sevoflurane induces dose-dependent suppression of auditory blood oxygenation level-dependent signals, which likely limits the ability of words to be processed during anesthesia and compromises memory.

Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study

Using event-related functional magnetic resonance imaging we investigated blood oxygen level dependent brain activation in spider phobic and non-phobic subjects while exposed to phobia-related pictures (spiders) and non-phobia-related pictures (snakes and mushrooms). In contrast to previous studies, we show significantly increased amygdala activation in spider phobics, but not in controls, during presentation of phobia-relevant visual stimuli. Furthermore, phobia-specific increased activation was also found in the insula, the orbitofrontal cortex and the uncus. Our study confirms the role of the amygdala in fear processing and provides insights into brain activation patterns when animal phobics are confronted with phobia-related stimuli.