Blood Oxygenation Level-dependent fMRI Response Research Articles

Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia

Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation – GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain.

Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss.

Some men who use finasteride for hair loss report persistent sexual and other symptoms after discontinuing finasteride therapy. To determine whether these persistent symptoms after discontinuation of finasteride use are due to androgen deficiency, decreased peripheral androgen action, or persistent inhibition of steroid 5α-reductase (SRD5A) enzymes. Finasteride users, who reported persistent sexual symptoms after discontinuing finasteride (group 1); age-matched finasteride users who did not report sexual symptoms (group 2); and healthy men who had never used finasteride (group 3). Sexual function, mood, affect, cognition, hormone levels, body composition, functional magnetic resonance imaging (fMRI) response to sexually and affectively valenced stimuli, nucleotide sequences of androgen receptor (AR), SRD5A1, and SRD5A2; expression levels of androgen-dependent genes in skin. Academic medical center. Symptomatic finasteride users were similar in body composition, strength, and nucleotide sequences of AR, SRD5A1, and SRD5A2 genes to asymptomatic finasteride users and nonusers. Symptomatic finasteride users had impaired sexual function, higher depression scores, a more negative affectivity balance, and more cognitive complaints than men in groups 2 and 3 but had normal objectively assessed cognitive function. Testosterone, dihydrotestosterone, 5α-androstane-3α,17β-diol-glucuronide, testosterone to dihydrotestosterone and androsterone glucuronide to etiocholanolone glucuronide ratios, and markers of peripheral androgen action and expression levels of AR-dependent genes in skin did not differ among groups. fMRI blood oxygen level-dependent responses to erotic and nonerotic stimuli revealed abnormal function in brain circuitry linked to sexual arousal and major depression. We found no evidence of androgen deficiency, decreased peripheral androgen action, or persistent peripheral inhibition of SRD5A in men with persistent sexual symptoms after finasteride use. Symptomatic finasteride users revealed depressed mood and fMRI findings consistent with those observed in depression.

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.

Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink. Male beer drinkers (n=28, age=24±2, drinks/wk=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables. Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.

Dependence of chromatic responses in V1 on visual field eccentricity and spatial frequency: an fMRI study

Psychophysical sensitivity to red-green chromatic modulation decreases with visual eccentricity, compared to sensitivity to luminance modulation, even after appropriate stimulus scaling. This is likely to occur at a central, rather than a retinal, site. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to stimuli designed to separately stimulate different afferent channels' [red-green, luminance, and short-wavelength (S)-cone] circular gratings were recorded as a function of visual eccentricity (±10 deg) and spatial frequency (SF) in human primary visual cortex (V1) and further visual areas (V2v, V3v). In V1, the SF tuning of BOLD fMRI responses became coarser with eccentricity. For red-green and luminance gratings, similar SF tuning curves were found at all eccentricities. The pattern for S-cone modulation differed, with SF tuning changing more slowly with eccentricity than for the other two modalities. This may be due to the different retinal distribution with eccentricity of this receptor type. A similar pattern held in V2v and V3v. This would suggest that transformation or spatial filtering of the chromatic (red-green) signal occurs beyond these areas.

The Ability of Functional Magnetic Resonance Imaging to Predict Heavy Drinking and Alcohol Problems 5 Years Later.

Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent (BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes (Paulus etal., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (fMRI) patterns. Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5years later at age 25. Correlations between baseline fMRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes. Baseline fMRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections. The data suggest that fMRI BOLD response contrasts predicted heavier drinking and alcohol problems 5years later, even after considering baseline low LRs. Future work will focus on whether fMRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates.

Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.

Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [(11) C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, 12 in the [(11) C]PHNO PET study, 8 of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. Using [(11) C]PHNO and PET brain imaging techniques we show that body mass index was positively associated with D2R/D3R availability in the dorsal striatum, but that functional MR BOLD response was unrelated to D2R/D3R availability. These results suggest the existence of a nonlinear relationship between D2R/D3R availability and body mass index and that the altered BOLD responses to food consumption seen in obesity are not directly related to D2R/D3R availability.

The long-term effects of prenatal nicotine exposure on verbal working memory: An fMRI study of young adults

BackgroundUsing functional magnetic resonance imaging (fMRI), the long-term effects of prenatal nicotine exposure on verbal working memory were investigated in young adults. Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood. This allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. MethodsTwelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a 2-Back working memory task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants with more prenatal nicotine exposure demonstrated significantly greater activity in several regions of the brain that typically subserve verbal working memory including the middle frontal gyrus, precentral gyrus, the inferior parietal lobe and the cingulate gyrus. ResultsThese results suggest that prenatal nicotine exposure contributes to altered neural functioning during verbal working memory that continues into adulthood. Working memory is critical for a wide range of cognitive skills such as language comprehension, learning and reasoning. ConclusionThus, these findings highlight the need for continued educational programs and public awareness campaigns to reduce tobacco use among pregnant women.

The effect of echo time and post-processing procedure on blood oxygenation level-dependent (BOLD) functional connectivity analysis

While spontaneous BOLD fMRI signal is a common tool to map functional connectivity, unexplained inter- and intra-subject variability frequently complicates interpretation. Similar to evoked BOLD fMRI responses, spontaneous BOLD signal is expected to vary with echo time (TE) and corresponding intra/extravascular sensitivity. This may contribute to discrepant conclusions even following identical post-processing pipelines. Here we applied commonly-utilized independent component analysis (ICA) as well as seed-based correlation analysis and investigated default mode network (DMN) and visual network (VN) detection from BOLD data acquired at three TEs (3T; TR=2500ms; TE=15ms, 35ms, and 55ms) and from quantitative R2* maps. Explained variance in ICA analysis was significantly higher (P<0.05) when R2*-derived maps were considered relative to single-TE data with no post-processing. While explained variance in the BOLD data increased with motion correction, R2* derived DMN and VN were minimally affected by motion correction. Explained variance increased in all data when physiological noise confounds were removed using CompCor. Notably, the R2*-derived connectivity patterns were least affected by motion and physiological noise confounds in a seed-based correlation analysis. Intermediate (35ms) and long (55ms) TE data provided similar spatial and temporal characteristics only after reducing motion and physiological noise contamination. Results provide an exemplar for how 3T spontaneous BOLD network detection varies with TE and post-processing procedure over the range of commonly acquired TE values.

Layer-dependent BOLD and CBV-weighted fMRI responses in the rat olfactory bulb

The olfactory bulb is a laminarized brain structure involved in odor sensation that has important implications to basic neuroscience research, like mechanisms for neurovascular coupling and early disease diagnosis. To investigate laminar-dependent responses to odor exposure, blood oxygenation level-dependent (BOLD) and cerebral blood volume weighted (CBVw) fMRI with iron oxide nanoparticle contrast agent were obtained with 110×110×500μm3 resolution in urethane-anesthetized rats at 9.4T. The baseline total CBV is the largest at the olfactory bulb surface and midline, and decreases in the deeper layers, while a band of increased microvasculature density is observed at the glomerular, external plexiform and mitral cell layers. With odor exposure, CBVw fMRI is more sensitive and reproducible than BOLD. BOLD fMRI had the greatest activation on the bulb surface, midline, olfactory nerve and glomerular layers, while CBVw activation peaked in glomerular and external plexiform layers, but was still significant in mitral cell layer. Negative BOLD responses were observed in the bulb midline and near large blood vessels. CBVw laminar profiles are similar to the layer-dependent metabolic changes to the same odor exposure reported by previous glucose metabolism studies. Unique activation patterns for two different odor conditions were also differentiated with CBVw fMRI. Our study suggests that CBVw activation better represents the spatial location of metabolic activity in the olfactory bulb than BOLD.

Poststimulus undershoots in cerebral blood flow and BOLD fMRI responses are modulated by poststimulus neuronal activity

fMRI is the foremost technique for noninvasive measurement of human brain function. However, its utility is limited by an incomplete understanding of the relationship between neuronal activity and the hemodynamic response. Though the primary peak of the hemodynamic response is modulated by neuronal activity, the origin of the typically negative poststimulus signal is poorly understood and its amplitude assumed to covary with the primary response. We use simultaneous recordings of EEG with blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI during unilateral median nerve stimulation to show that the poststimulus fMRI signal is neuronally modulated. We observe high spatial agreement between concurrent BOLD and CBF responses to median nerve stimulation, with primary signal increases in contralateral sensorimotor cortex and primary signal decreases in ipsilateral sensorimotor cortex. During the poststimulus period, the amplitude and directionality (positive/negative) of the BOLD signal in both contralateral and ipsilateral sensorimotor cortex depends on the poststimulus synchrony of 8-13 Hz EEG neuronal activity, which is often considered to reflect cortical inhibition, along with concordant changes in CBF and metabolism. Therefore we present conclusive evidence that the fMRI time course represents a hemodynamic signature of at least two distinct temporal phases of neuronal activity, substantially improving understanding of the origin of the BOLD response and increasing the potential measurements of brain function provided by fMRI. We suggest that the poststimulus EEG and fMRI responses may be required for the resetting of the entire sensory network to enable a return to resting-state activity levels.

Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.

The long-term effects of prenatal nicotine exposure on response inhibition: An fMRI study of young adults

The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical.

What secrets can functional MRI reveal about the developing infant brain?

Department of Neurobiology & Behavior, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, NY 10027, USA Functional MRI (fMRI) has provided unprecedented insights into the workings of the human brain since its inception over 20 years ago. However, one intractable complication in interpreting fMRI data is that its signal is derived from changes in the brain’s blood flow and blood oxygenation levels. fMRI is not a direct measure of neuronal activity. Moreover, contrary to popular belief, the fMRI blood oxygen level dependent (BOLD) signal is not dominated by the consumption of oxygen by activated neurons. A normal ‘positive’ fMRI BOLD response corresponds to a decrease in the local concentration of deoxyhemoglobin resulting from a strong overperfusion and hyperoxygenation of a particular region of the brain. While in many cases the relation between neuronal activity and localized blood flow increases is fairly robust [1,2], relatively little is understood about how the brain’s ‘blood flow response’ is initiated and controlled in relation to neuronal activity at a cellular level. As a result, interpretation of fMRI can be complicated in situations in which neurovascular coupling may be altered, for example in pathologies such as stroke, Alzheimer’s disease or brain cancer, and, according to a recent study, during postnatal brain development [3,4].

Genetic Variation in the Alpha Synuclein Gene (SNCA) Is Associated With BOLD Response to Alcohol Cues

Preclinical studies implicate the gene encoding the alpha synuclein protein (SNCA) in the pathophysiology of alcohol dependence and dopamine neuron function. Results from clinical studies are less conclusive. Using neurobiological phenotypes in genetic studies, rather than typical heterogeneous diagnostic categories derived from self-report, may improve reliability across studies. This study aimed to examine whether polymorphisms in the SNCA gene were associated with alcohol taste cue-elicited responses in the brain, one such intermediate phenotype. A total of 326 heavy drinkers who underwent an alcohol taste task during functional magnetic resonance imaging (fMRI) also were genotyped. Analyses focused on two previously identified SNCA variants (rs2583985 and rs356168) as well as 27 other single nucleotide polymorphisms from the Illumina Human1M BeadChip that were used in an exploratory analysis of the whole gene. Neurobiological phenotypes were defined as fMRI blood oxygenation level-dependent (BOLD) responses to alcohol taste cue (vs. a control cue) in seven regions of interest known to be involved in cue processing and rich in dopaminergic axon terminals. Polymorphisms in the SNCA gene were significantly correlated with BOLD activation. Specifically, the largest effect sizes and significance were seen for rs2583985 in paracingulate and caudate (focused analysis) and for rs1372522 in paracingulate (exploratory analysis). Activation in all regions of interest was correlated with alcohol-dependence severity. SNCA genotype was found to be associated with the degree of fMRI BOLD response during exposure to the taste of alcohol versus a control taste. This study also further validates the use of this alcohol taste task as an intermediate phenotype for alcohol-dependence severity.

High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses

The six cortical layers have distinct anatomical andphysiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, aswell as laminar differences in neurovascular coupling.

Effects of the α2‐adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex

This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

Shedding light on the BOLD fMRI response

Fluorescence recording of neural activity in the magnetic resonance scanner is a new strategy for examining the cellular underpinnings of blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI).

Aging effects on functional auditory and visual processing using fMRI with variable sensory loading

IntroductionTraditionally, studies investigating the functional implications of age-related structural brain alterations have focused on higher cognitive processes; by increasing stimulus load, these studies assess behavioral and neurophysiological performance. In order to understand age-related changes in these higher cognitive processes, it is crucial to examine changes in visual and auditory processes that are the gateways to higher cognitive functions. This study provides evidence for age-related functional decline in visual and auditory processing, and regional alterations in functional brain processing, using non-invasive neuroimaging. MethodsUsing functional magnetic resonance imaging (fMRI), younger (n = 11; mean age = 31) and older (n = 10; mean age = 68) adults were imaged while observing flashing checkerboard images (passive visual stimuli) and hearing word lists (passive auditory stimuli) across varying stimuli presentation rates. ResultsYounger adults showed greater overall levels of temporal and occipital cortical activation than older adults for both auditory and visual stimuli. The relative change in activity as a function of stimulus presentation rate showed differences between young and older participants. In visual cortex, the older group showed a decrease in fMRI blood oxygen level dependent (BOLD) signal magnitude as stimulus frequency increased, whereas the younger group showed a linear increase. In auditory cortex, the younger group showed a relative increase as a function of word presentation rate, while older participants showed a relatively stable magnitude of fMRI BOLD response across all rates. When analyzing participants across all ages, only the auditory cortical activation showed a continuous, monotonically decreasing BOLD signal magnitude as a function of age. ConclusionsOur preliminary findings show an age-related decline in demand-related, passive early sensory processing. As stimulus demand increases, visual and auditory cortex do not show increases in activity in older compared to younger people. This may negatively impact on the fidelity of information available to higher cognitive processing. Such evidence may inform future studies focused on cognitive decline in aging.

Gain control in the response of human visual cortex to plaids

A recent intrinsic signal optical imaging study in tree shrew showed, surprisingly, that the population response of V1 to plaid patterns comprising grating components of equal contrast is predicted by the average of the responses to the individual components (MacEvoy SP, Tucker TR, Fitzpatrick D. Nat Neurosci 12: 637-645, 2009). This prompted us to compare responses to plaids and gratings in human visual cortex as a function of contrast and orientation. We found that the functional MRI (fMRI) blood oxygenation level-dependent (BOLD) responses of areas V1-V3 to a plaid comprising superposed grating components of equal contrast are significantly higher than the responses to a single component. Furthermore, the orientation response profile of a plaid is poorly predicted from a linear combination of the responses to its components. Together, these results indicate that the model of MacEvoy et al. (2009) cannot, without modification, account for the fMRI BOLD response to plaids in human visual cortex.

Abstract 2762: Asymmetry of The Blood Oxygen Level-Dependent fMRI Response During Hypercapnia Is Reliable to Evaluate Cerebrovascular Reactivity in Patients with Severe Unilateral Carotid Stenosis

Background and Purpose: Previous transcranial Doppler studies have suggested that, in patients with severe carotid stenosis, the lack of cerebrovascular reactivity (CVR) is an independent predictor of ipsilateral stroke. The BOLD (Blood Oxygenation Level-Dependent) fMRI contrast can be used to assess the CVR during normal condition and during hemodynamic stress, like hypercapnia. The purpose of this study is to evaluate the BOLD signal parameters on the Middle Cerebral Artery (MCA) territory, induced by auditory stimulus, during different levels of hypercapnia in patients with severe unilateral carotid stenosis, comparing the ipsilateral hemisphere (IH) to the contralateral hemisphere (CH). Methods: The images were obtained from 16 patients with severe unilateral carotid stenosis. Patients were submitted to an auditory stimulus (3s) in three different conditions: normocapnia and at EtCO2 increase of 5 and 10mmHg. The images were acquired with a 3T Philips MR, preprocessed and analyzed using an autoregressive method. Results: The BOLD signal from the IH was different from the CH during the basal condition and at 5mmHg (p&lt;0.0001), but not at the 10mmHg ETCO2 increase. For each BOLD parameter, the major differences between the hemispheres were seen on the onset time (p&lt;0.0001) and amplitude of BOLD signal (p&lt;0.0001). The width difference was significant between the basal and 10mmhHg increase (p&lt;0.01). In these three parameters, the BOLD signal of the IH presented no significant variations with the CO2 increment. However, the BOLD signal for CH showed an increase on the time-to-onset and width and amplitude decrease. The time to peak parameters of the BOLD signal showed no differences between the hemispheres and at hypercapnic conditions. Conclusion: In our results the IH did not respond to the hypercapnic stress as the CH. Therefore, among patients with severe carotid stenosis, BOLD can reliably identify some that have an exhausted CVR, which cannot respond to a vasodilatory stress like hypercapnia. Future studies using this technique may help to select patients for recanalization procedures.