Spontaneous Low-frequency Oscillations Research Articles

Frequency-specific alternations in the amplitude of low-frequency fluctuations in chronic tinnitus.

Tinnitus, a phantom ringing, buzzing, or hissing sensation with potentially debilitating consequences, is thought to arise from aberrant spontaneous neural activity at one or more sites within the central nervous system; however, the location and specific features of these oscillations are poorly understood with respect to specific tinnitus features. Recent resting-state functional magnetic resonance imaging (fMRI) studies suggest that aberrant fluctuations in spontaneous low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal may be an important factor in chronic tinnitus; however, the role that frequency-specific components of LFO play in subjective tinnitus remains unclear. A total of 39 chronic tinnitus patients and 41 well-matched healthy controls participated in the resting-state fMRI scans. The LFO amplitudes were investigated using the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) in two different frequency bands (slow-4: 0.027–0.073 Hz and slow-5: 0.01–0.027 Hz). We observed significant differences between tinnitus patients and normal controls in ALFF/fALFF in the two bands (slow-4 and slow-5) in several brain regions including the superior frontal gyrus (SFG), inferior frontal gyrus, middle temporal gyrus, angular gyrus, supramarginal gyrus, and middle occipital gyrus. Across the entire subject pool, significant differences in ALFF/fALFF between the two bands were found in the midbrain, basal ganglia, hippocampus and cerebellum (Slow 4 > Slow 5), and in the middle frontal gyrus, supramarginal gyrus, posterior cingulate cortex, and precuneus (Slow 5 > Slow 4). We also observed significant interaction between frequency bands and patient groups in the orbitofrontal gyrus. Furthermore, tinnitus distress was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-4 band in left SFG, whereas tinnitus duration was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-5 band in left SFG. Resting-state fMRI provides an unbiased method for identifying aberrant spontaneous LFO occurring throughout the central nervous system. Chronic tinnitus patients have widespread abnormalities in ALFF and fALFF slow-4 and slow-5 band which are correlated with tinnitus distress and duration. These results provide new insights on the neuropathophysiology of chronic tinnitus; therapies capable of reversing these aberrant patterns may reduce tinnitus distress.

Stimulus-dependent modulation of spontaneous low-frequency oscillations in the rat visual cortex.

Research on spontaneous low-frequency oscillations is important to reveal underlying regulatory mechanisms in the brain. The mechanism for the stimulus modulation of low-frequency oscillations is not known. Here, we used the intrinsic optical imaging technique to examine stimulus-modulated low-frequency oscillation signals in the rat visual cortex. The stimulation was presented monocularly as a flashing light with different frequencies and intensities. The phases of low-frequency oscillations in different regions tended to be synchronized and the rhythms typically accelerated within a 30-s period after stimulation. These phenomena were confined to visual stimuli with specific flashing frequencies (12.5-17.5 Hz) and intensities (5-10 mA). The acceleration and synchronization induced by the flashing frequency were more marked than those induced by the intensity. These results show that spontaneous low-frequency oscillations can be modulated by parameter-dependent flashing lights and indicate the potential utility of the visual stimulus paradigm in exploring the origin and function of low-frequency oscillations.

Resting-State Functional Magnetic Resonance Imaging

Recent research in brain imaging has highlighted the role of different neural networks in the resting state (ie, no task) in which the brain displays spontaneous low-frequency neuronal oscillations. These can be indirectly measured with resting-state functional magnetic resonance imaging, and functional connectivity can be inferred as the spatiotemporal correlations of this signal. This technique has proliferated in recent years and has allowed the noninvasive investigation of large-scale, distributed functional networks. In this review, we give a brief overview of resting-state networks and examine the use of resting-state functional magnetic resonance imaging in neurosurgical contexts, specifically with respect to neurooncology, epilepsy surgery, and deep brain stimulation. We discuss the advantages and disadvantages compared with task-based functional magnetic resonance imaging, the limitations of resting-state functional magnetic resonance imaging, and the emerging directions of this relatively new technology.

Functional MRI Signal Fluctuations: A Preclinical Biomarker for Cognitive Impairment in Type 2 Diabetes?

Type 2 diabetes mellitus (T2DM) is associated with macrovascular and microvascular complications as well as an increased risk for cognitive impairment (CI), ranging from mild memory impairment to fully developed dementia (1). Both vascular dementia (VD) and Alzheimer disease (AD) dementia are increased in patients with T2DM. However, it is not clear if T2DM directly causes CI and dementia or if the two disorders share a common pathophysiological process (2). Insulin resistance, hyperglycemia, and hypoglycemia have all been implicated as risk factors for CI in T2DM (3). However, their relative importance remains uncertain. The possibility that altered brain insulin action plays a role is consistent with human data showing that AD is associated with decreased insulin receptor expression in the brain (4), impaired insulin signaling (5), and decreased insulin levels in the cerebrospinal fluid (CSF) (6). Furthermore, insulin delivery directly into the hippocampus enhances spatial memory in nondiabetic rats, whereas this response to intrahippocampal insulin is impaired in diet-induced obese rats (7). In small clinical trials, intranasal insulin delivery appears to improve memory function in patients with CI and AD (8). Functional MRI, based on the blood oxygenation level–dependent (BOLD) contrast mechanism, has become an important tool to investigate the brain’s neurophysiologic response to specific stimuli or cognitive tasks. In contrast, resting-state functional MRI (rs-fMRI) measures spontaneous low-frequency oscillations in the BOLD …

Spontaneous Low Frequency Oscillations in Acute Ischemic Stroke ? A Near Infrared Spectroscopy (NIRS) Study

Background and purpose: Continuous wave near infrared spectroscopy (NIRS) is a non-invasive bed-side optical method to detect changes in oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the outermost layers of the cerebral cortex. Cortical oxyHb low frequency oscillations (LFOs) in the 0.09-0.11 Hz range are affected by changes in cerebral autoregulation (CA), which is altered following stroke. We examined oxyHb LFOs at bed-side as a marker of CA in the subacute phase in stroke patients with or without recombinant tissue plasminogen activator thrombolytic therapy. Methods: We recruited 29 patients admitted to the stroke unit with symptoms of ischemic stroke. 11/29 patients received thrombolytic therapy. NIRS examination was conducted 2 days (median time) from stroke onset. NIRS optodes were placed on each side of the head with a 3 cm source-detector distance. Using transfer function analysis, inter-hemispheric phase shift and amplitude ratio of the oxyHb oscillations in the 0.09-0.11 Hz range were assessed. Results: The correlation between NIHSS scores at admission and oxyHb parameters revealed a significant positive correlation between stroke severity at admission and inter-hemispheric phase shift (P=0.028). The oxyHb absolute inter-hemispheric phase shift was significantly less in patients receiving thrombolytic therapy compared to non-thrombolytic therapy patients (3° vs. 23°, P=0.005). Conclusions: Stroke severity correlates with the degree of impaired cortical CA and stroke patients receiving thrombolytic therapy might have less severely impaired CA. NIRS detects alteration in cortical oxyHb LFOs between hemispheres in stroke patients in the subacute phase and may be a feasible method to explore changes at bed-side in a stroke unit.

The alteration of spontaneous low frequency oscillations caused by acute electromagnetic fields exposure

ObjectiveThe motivation of this study is to evaluate the possible alteration of regional resting state brain activity induced by the acute radiofrequency electromagnetic field (RF-EMF) exposure (30min) of Long Term Evolution (LTE) signal. MethodsWe designed a controllable near-field LTE RF-EMF exposure environment. Eighteen subjects participated in a double-blind, crossover, randomized and counterbalanced experiment including two sessions (real and sham exposure). The radiation source was close to the right ear. Then the resting state fMRI signals of human brain were collected before and after the exposure in both sessions. We measured the amplitude of low frequency fluctuation (ALFF) and fractional ALFF (fALFF) to characterize the spontaneous brain activity. ResultsWe found the decreased ALFF value around in left superior temporal gyrus, left middle temporal gyrus, right superior temporal gyrus, right medial frontal gyrus and right paracentral lobule after the real exposure. And the decreased fALFF value was also detected in right medial frontal gyrus and right paracentral lobule. ConclusionsThe study provided the evidences that 30min LTE RF-EMF exposure modulated the spontaneous low frequency fluctuations in some brain regions. SignificanceWith resting state fMRI, we found the alteration of spontaneous low frequency fluctuations induced by the acute LTE RF-EMF exposure.

Hemodynamic and electrophysiological spontaneous low-frequency oscillations in the cortex: Directional influences revealed by Granger causality

We used a combined electrophysiological/hemodynamic system to examine low-frequency oscillations (LFOs) in spontaneous neuronal activities (spike trains and local field potentials) and hemodynamic signals (cerebral blood flow) recorded from the anesthetized rat somatosensory and visual cortices. The laser Doppler flowmetry (LDF) probe was tilted slightly to approach the area in which a microelectrode array (MEA) was implanted for simultaneous recordings. Spike trains (STs) were converted into continuous-time rate functions (CRFs) using the ST instantaneous firing rates. LFOs were detected for all three of the components using the multi-taper method (MTM). The frequencies of these LFOs ranged from 0.052 to 0.167Hz (mean±SD, 0.10±0.026Hz) for cerebral blood flow (CBF), from 0.027 to 0.26Hz (mean±SD, 0.12±0.041Hz) for the CRFs of the STs and from 0.04 to 0.19Hz (mean±SD, 0.11±0.035Hz) for local field potentials (LFPs). We evaluated the Granger causal relationships of spontaneous LFOs among CBF, LFPs and CRFs using Granger causality (GC) analysis. Significant Granger causal relationships were observed from LFPs to CBF, from STs to CBF and from LFPs to STs at approximately 0.1Hz. The present results indicate that spontaneous LFOs exist not only in hemodynamic components but also in neuronal activities of the rat cortex. To the best of our knowledge, the present study is the first to identify Granger causal influences among CBF, LFPs and STs and show that spontaneous LFOs carry important Granger causal influences from neural activities to hemodynamic signals.

Structural and Functional Changes in Subcortical Vascular Mild Cognitive Impairment: A Combined Voxel-Based Morphometry and Resting-State fMRI Study

The present study aimed to investigate changes in structural gray matter (GM) volume and functional amplitude of spontaneous low-frequency oscillations (LFO) and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI). Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex) and temporal (the superior and inferior temporal gyri) brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate). Functionally, svMCI-related changes were predominantly found in the default mode network (DMN). Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex), whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus). As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus) consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.

Phase-amplitude investigation of spontaneous low-frequency oscillations of cerebral hemodynamics with near-infrared spectroscopy: A sleep study in human subjects

We have investigated the amplitude and phase of spontaneous low-frequency oscillations (LFOs) of the cerebral deoxy- and oxy-hemoglobin concentrations ([Hb] and [HbO]) in a human sleep study using near-infrared spectroscopy (NIRS). Amplitude and phase analysis was based on the analytic signal method, and phasor algebra was used to decompose measured [Hb] and [HbO] oscillations into cerebral blood volume (CBV) and flow velocity (CBFV) oscillations. We have found a greater phase lead of [Hb] vs. [HbO] LFOs during non-REM sleep with respect to the awake and REM sleep states (maximum increase in [Hb] phase lead: ~π/2). Furthermore, during non-REM sleep, the amplitudes of [Hb] and [HbO] LFOs are suppressed with respect to the awake and REM sleep states (maximum amplitude decrease: 87%). The associated cerebral blood volume and flow velocity oscillations are found to maintain their relative phase difference during sleep, whereas their amplitudes are attenuated during non-REM sleep. These results show the potential of phase-amplitude analysis of [Hb] and [HbO] oscillations measured by NIRS in the investigation of hemodynamics associated with cerebral physiology, activation, and pathological conditions.

Low-Frequency Spontaneous Oscillations of Cerebral Hemodynamics Investigated With Near-Infrared Spectroscopy: A Review

Hemodynamic low-frequency oscillations (LFOs), in the range 0.01-0.1 Hz, are intriguing, yet elusive phenomena, which occur spontaneously in the vascular system. More than 150 years have passed since their discovery, but the cellular mechanisms at their origin and their physiological implications have yet to be unraveled. The study of LF hemodynamic oscillations is considered to be relevant in areas of brain research such as cerebral autoregulation, functional and effective connectivity, and their related pathologies. These research areas have been traditionally investigated by transcranial Doppler (autoregulation) and functional MRI [functional connectivity (FC)]. The purpose of this paper is to review the work that has been done in this area using near-infrared spectroscopy (NIRS), which is a noninvasive technique used for monitoring and imaging tissue hemodynamics. NIRS has the advantage of being sensitive to both oxy- and deoxyhemoglobin concentration changes. Therefore, not only can it be used in autoregulation and FC studies (for broader populations of subjects), it can also help understand the local interplay between vascular and metabolic parameters. Finally, we present a novel approach to the study of LFOs and to the physiological interpretation of the amplitude and relative phase of oscillatory components of oxy- and deoxyhemoglobin concentrations.

Noninvasive optical evaluation of spontaneous low frequency oscillations in cerebral hemodynamics

Spontaneous low frequency oscillations (LFOs) around 0.1 Hz have been observed in mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV). Previous studies have shown that cerebral autoregulation in major arteries can be assessed by quantification of the phase shift between LFOs of MAP and CBFV. However, many cerebral diseases are associated with abnormal microvasculature and tissue dysfunction in brain, and quantification of these abnormalities requires direct measurement of cerebral tissue hemodynamics. This pilot study used a novel hybrid near-infrared diffuse optical instrument to noninvasively and simultaneously detect LFOs of cerebral blood flow (CBF) and cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: [HbO(2)]/[Hb]/THC) in human prefrontal cortex. Using the hybrid instrument and a finger plethysmograph, the dynamic changes of CBF, [HbO(2)], [Hb], THC and MAP were concurrently measured in 15 healthy subjects at rest, during 70° head-up-tilting (HUT) and during enforced breathing at 0.1 Hz. The LFOs were extracted from the measured variables using power spectral analysis, and the phase shifts and coherences of LFOs between MAP and each of the measured hemodynamic variables were calculated from the corresponding transfer functions. Levels of coherence (>0.4) were used to judge the success of LFO measurements. We found that CBF, [HbO(2)] and THC were reliable hemodynamic parameters in detecting LFOs and HUT was the most robust and stable protocol for quantifying phase shifts of hemodynamic LFOs. Comparing with other relevant studies, similar success rates for detecting cerebral LFOs have been achieved in our study. The phase shifts of LFOs in CBF were also close to those in CBFV reported by other groups, although the results in cerebral oxygenation measurements during enforced breathing varied across studies. Future study will investigate cerebral LFOs in patients with cerebral impairment and evaluate their cerebral autoregulation capabilities and neurocognitive functions via the quantification of LFO phase shifts.

Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain

Low-frequency oscillations in cerebral blood flow that are suggestive of resting-state brain activity have recently been reported, but no study on the development of resting-state brain activity in preterm infants has been performed. The objective of this study was to measure the cerebral blood flow oscillations, which are assumed to represent brain function in the resting state, in preterm and term infants of the same postconceptional age. The subjects were 9 preterm infants who had reached full term (gestational age (GA): 23–34weeks, postconceptional age: 37–46weeks) and 10 term infants (GA: 37–40weeks, postconceptional age: 37–41weeks). Their changes in concentration of oxyhemoglobin ([oxyHb]) and deoxyhemoglobin ([deoxyHb]) were measured in the parieto-temporal region during quiet sleep using multi-channel near-infrared spectroscopy, and the power spectral densities (PSD) of the oscillations in the concentrations of these molecules were analyzed and compared. The preterm infants displayed a higher proportion of 0.06–0.10Hz low frequency oscillations of [oxyHb] and [deoxyHb] than the term infants, and the gestational age and the proportion of low frequency oscillations were inversely correlated. These findings suggest that resting-state cerebral blood flow oscillations differ between preterm and term infants, and that the development of circulatory regulation and nerve activity in preterm infants are influenced by the extrauterine environment.

Abstract 2654: A prospective study of the effects of adjuvant chemotherapy (CT) on cognition and brain function in breast cancer patients

Abstract There is an accumulating body of literature reporting that cognitive deficits, possibly long lasting, including lack of concentration, short-term memory loss and difficulties in multitasking are observed in patients receiving chemotherapy (CT) (“chemobrain”). We have used functional magnetic resonance imaging (fMRI) to determine the nature of the changes in brain function that underlie the cognitive deficits that can result from CT. This research was carried out prospectively in women being treated with adjuvant CT for early-stage breast cancer (BC). Methods: Seven healthy aged-matched control subjects (No CT) and six subjects with BC took part in this study undergoing functional fMRI scanning on a 3.0T scanner prior to initiating CT and after receiving their fourth cycle of anthracycline-based CT. Task activation (n-back) and resting-state functional connectivity (fC) scans were carried out. The N-back letter task is a continuous performance task having 3 levels of increasing cognitive load designed to probe regions of the brain activated by attention and working memory. Resting-state fC measures spontaneous low frequency oscillations in MR signal in brain and is used to create maps of fC among brain regions. Results: There were no significant differences in n-back task performance between the CT group and controls. However, significant differences (p≤0.05) in task activation and fC between the two subjects groups were observed. N-back task activation was significantly greater in the BC group compared with controls in right inferior frontal gyrus and right cerebellum. There were significant interactions between subject group and cognitive load within right inferior parietal and left inferior occipital cortex. The default mode network consists of interconnected regions of the brain that are active while the subjects are at rest and reduce activity when subjects perform specific tasks. Within this network, the BC group has significantly less deactivation during task compared to controls. There were also differences between the groups in resting-state fC. Using the left amygdala as a seed region, changes in fC were seen in the pre-chemo scans of the BC group compared to the controls. The BC subjects showed a 185% increase in intraregional fC and increased fC with the superior temporal gyrus, an area along with the amygdala that is activated by emotional stimuli. These changes in fC may be due to increased stress response in BC subjects. After four sessions of CT the BC group showed significant decreases in fC between the amygdala and the parahippocampal gyrus, an area involved in encoding and retrieving memories. This decrease in functional connectivity along with alterations in brain activation by cognitive tasks may play a part in the memory and other cognitive complaints associated with cancer and CT and may inform the search for strategies to reduce CT associated cognitive dysfunction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2654. doi:1538-7445.AM2012-2654

Nitric Oxide Modulation of Low‐Frequency Oscillations in Cortical Vessels in FHM – a NIRS Study

The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before. To investigate changes in spontaneous low-frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near-infrared spectroscopy in FHM patients. Twenty-three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 µg/kg/minute over 20 minutes. Using near-infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion. GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post-hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695). FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM.

Physiological denoising of BOLD fMRI data using Regressor Interpolation at Progressive Time Delays (RIPTiDe) processing of concurrent fMRI and near-infrared spectroscopy (NIRS)

Confounding noise in BOLD fMRI data arises primarily from fluctuations in blood flow and oxygenation due to cardiac and respiratory effects, spontaneous low frequency oscillations (LFO) in arterial pressure, and non-task related neural activity. Cardiac noise is particularly problematic, as the low sampling frequency of BOLD fMRI ensures that these effects are aliased in recorded data. Various methods have been proposed to estimate the noise signal through measurement and transformation of the cardiac and respiratory waveforms (e.g. RETROICOR and respiration volume per time (RVT)) and model-free estimation of noise variance through examination of spatial and temporal patterns. We have previously demonstrated that by applying a voxel-specific time delay to concurrently acquired near infrared spectroscopy (NIRS) data, we can generate regressors that reflect systemic blood flow and oxygenation fluctuations effects. Here, we apply this method to the task of removing physiological noise from BOLD data. We compare the efficacy of noise removal using various sets of noise regressors generated from NIRS data, and also compare the noise removal to RETROICOR+RVT. We compare the results of resting state analyses using the original and noise filtered data, and we evaluate the bias for the different noise filtration methods by computing null distributions from the resting data and comparing them with the expected theoretical distributions. Using the best set of processing choices, six NIRS-generated regressors with voxel-specific time delays explain a median of 10.5% of the variance throughout the brain, with the highest reductions being seen in gray matter. By comparison, the nine RETROICOR+RVT regressors together explain a median of 6.8% of the variance in the BOLD data. Detection of resting state networks was enhanced with NIRS denoising, and there were no appreciable differences in the bias of the different techniques. Physiological noise regressors generated using Regressor Interpolation at Progressive Time Delays (RIPTiDe) offer an effective method for efficiently removing hemodynamic noise from BOLD data.

Low frequency oscillations of response time explain parent ratings of inattention and hyperactivity/impulsivity

Greater intra-subject variability (ISV) in response time is a heritable endophenotype of attention-deficit/hyperactivity disorder (ADHD). Spontaneous low frequency oscillations (LFO: 0.01-0.1 Hz) observed in brain functional magnetic resonance signals might account for such behavioral variability. Recently, we demonstrated that ISV in response time (RT) explained ratings of ADHD symptoms. Building on this finding, here we hypothesized that LFO in RT time series would explain these ratings, both independently and in addition to RT coefficient of variation (CV). To measure RT LFO, we applied Morlet wavelet transform to the previously collected RT data. Our community sample consisted of 98 children (including 66 boys, mean age 9.9 ± 1.4 years), who completed four computer Tasks of Executive Control. Conners' Parent Rating Scale ratings were obtained. RT LFO of three tasks significantly explained ratings of inattention, hyperactivity and three global Conners' subscales. In addition, RT LFO during two tasks that included an inhibitory component increased the proportions of variance explained in subscales of both inattention and hyperactivity/impulsivity, beyond the effects of RT-CV. Three specific low frequency bands (Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz; Slow-3: 0.073-0.20 Hz) were strongly related to the ADHD scales. We conclude that RT LFO predict dimensional ratings of ADHD symptoms both independently and in addition to RTCV. Results suggest that frequency analyses are a suitable methodology to link behavioral responses to putative underlying physiological processes.

L-DOPA changes spontaneous low-frequency BOLD signal oscillations in Parkinson's disease: a resting state fMRI study

Analysis of the amplitude of low frequency BOLD signal fluctuations (ALFF) in the resting state has recently been used to study the dynamics of intrinsic neural activity. Several studies have also suggested its potential as a biomarker for neuropsychiatric disease. In the current study, we quantified ALFF to determine changes in intrinsic neural oscillations in patients with Parkinson's disease (PD) on and off L-DOPA. Twenty-four PD patients and 24 healthy age-matched controls participated in the study. PD patients underwent two resting state fMRI sessions, either ON a controlled dose of L-DOPA or following a placebo pill (OFF). Control participants underwent one test session. We found that there was increased amplitude of low frequency BOLD signal oscillations for PD patients OFF L-DOPA in the primary and secondary motor areas, and in the middle and medial prefrontal cortices. L-DOPA significantly reduced the amplitude of low frequency oscillations within these regions. The degree of ALFF in the premotor cortex predicted patients' motor performance as measured by the Grooved Pegboard task, such that greater ALFF was associated with poorer performance. These results are in line with the pathophysiology of PD, which shows changes in neural oscillations. Thus, frequency domain analyses of resting state BOLD fMRI signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.

Partitioning of Physiological Noise Signals in the Brain with Concurrent Near-Infrared Spectroscopy and fMRI

The blood-oxygen level dependent (BOLD) signals measured by functional magnetic resonance imaging (fMRI) are contaminated with noise from various physiological processes, such as spontaneous low-frequency oscillations (LFOs), respiration, and cardiac pulsation. These processes are coupled to the BOLD signal by different mechanisms, and represent variations with very different frequency content; however, because of the low sampling rate of fMRI, these signals are generally not separable by frequency, as the cardiac and respiratory waveforms alias into the LFO band. In this study, we investigated the spatial and temporal characteristics of the individual noise processes by conducting concurrent near-infrared spectroscopy (NIRS) and fMRI studies on six subjects during a resting state acquisition. Three time series corresponding to LFO, respiration, and cardiac pulsation were extracted by frequency from the NIRS signal (which has sufficient temporal resolution to critically sample the cardiac waveform) and used as regressors in a BOLD fMRI analysis. Our results suggest that LFO and cardiac signals modulate the BOLD signal independently through the circulatory system. The spatiotemporal evolution of the LFO signal in the BOLD data correlates with the global cerebral blood flow. Near-infrared spectroscopy can be used to partition these contributing factors and independently determine their contribution to the BOLD signal.

Personality traits and the amplitude of spontaneous low-frequency oscillations during resting state

Recently, neural substrates of the Big Five personality model were investigated using neuroimaging. We examined the relationships between the amplitude of spontaneous low-frequency oscillations (LFO) and the Big Five traits using resting-state functional magnetic resonance imaging (R-fMRI). Twenty-four healthy right-handed undergraduates (23.13 ± 1.87 years, 9 males and 15 females) participated in 5-min R-fMRI and completed the NEO Five-Factor Inventory. We observed that Neuroticism correlated negatively with regional activity of the middle frontal gyrus and precuneus; Extraversion correlated positively with regional activity of the striatum, precuneus, and superior frontal gyrus; Openness correlated positively with the thalamus and amygdala, and negatively with the superior frontal gyrus; Conscientiousness correlated positively with regional activity of the middle frontal gyrus and correlated negatively with the cerebellum. Our results revealed the neural substrates of Extraversion, Neuroticism, Openness, and Conscientiousness in the amplitude of spontaneous LFO.

Spontaneous Low-Frequency Oscillations in Cerebral Vessels: Applications in Carotid Artery Disease and Ischemic Stroke

The etiology behind and physiological significance of spontaneous oscillations in the low-frequency spectrum in both systemic and cerebral vessels remain unknown. Experimental studies have proposed that spontaneous oscillations in cerebral blood flow reflect impaired cerebral autoregulation (CA). Analysis of CA by measurement of spontaneous oscillations in the low-frequency spectrum in cerebral vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease (CAD) and stroke. We reviewed studies exploring spontaneous oscillations in the low-frequency spectrum in patients with CAD and ischemic stroke, conditions known to involve impaired CA. Several studies have reported changes in oscillations after CAD and stroke after surgery and over time compared with healthy controls. Phase shift in the frequency domain and correlation coefficients in the time domain are the most frequently used parameters for analyzing spontaneous oscillations in systemic and cerebral vessels. At present, there is no gold standard for analyzing spontaneous oscillations in the low-frequency spectrum, and simplistic models of CA have failed to predict or explain the spontaneous oscillation changes found in CAD and stroke studies. Near-infrared spectroscopy is suggested as a future complementary tool for assessing changes affecting the cortical arterial system.