High-field fMRI unveils orientation columns in humans

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90° (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.     

Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity

Accurate interpretation of functional MRI (fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRI data.     

Transients may occur in functional magnetic resonance imaging without physiological basis

Functional magnetic resonance imaging (fMRI) has revolutionized the study of human brain activity, in both basic and clinical research. The commonly used blood oxygen level dependent (BOLD) signal in fMRI derives from changes in oxygen saturation of cerebral blood flow as a result of brain activity. Beyond the traditional spatial mapping of stimulus–activation correspondences, the detailed waveforms of BOLD responses are of high interest. Especially intriguing are the transient overshoots and undershoots, often, although inconclusively, attributed to the interplay between changes in cerebral blood flow and volume after neuronal activation. While physically simulating the BOLD response in fMRI phantoms, we encountered prominent transient deflections, although the magnetic field inside the phantom varied in a square-wave manner. Detailed analysis and modeling indicated that the transients arise from activation-related partial misalignment of the imaging slices and depend heavily on measurement parameters, such as the time between successive excitations. The results suggest that some transients encountered in normal fMRI recordings may be spurious, potentially compromising the physiological interpretation of BOLD signal overshoots and undershoots.     

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.     

Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology.     

Ultrafast two-photon fluorescence imaging of cerebral blood circulation in the mouse brain in vivo

Characterizing blood flow dynamics in vivo is critical to understanding the function of the vascular network under physiological and pathological conditions. Existing methods for hemodynamic imaging have insufficient spatial and temporal resolution to monitor blood flow at the cellular level in large blood vessels. By using an ultrafast line-scanning module based on free-space angular chirped enhanced delay, we achieved two-photon fluorescence imaging of cortical blood flow at 1,000 two-dimensional (2D) frames and 1,000,000 one-dimensional line scans per second in the awake mouse. This orders-of-magnitude increase in temporal resolution allowed us to measure cerebral blood flow at up to 49 mm/s and observe pulsatile blood flow at harmonics of heart rate. Directly visualizing red blood cell (RBC) flow through vessels down to >800 µm in depth, we characterized cortical layer–dependent flow velocity distributions of capillaries, obtained radial velocity profiles and kilohertz 2D velocity mapping of multifile blood flow, and performed RBC flux measurements from penetrating blood vessels.

The brain is nourished with a rich vascular network through which blood flow delivers nutrients and removes metabolic waste. The dynamics of blood flow (hemodynamics) are closely coupled with neural function and local metabolism, with many diseases of the brain having associated pathology in its hemodynamic characteristics (1–3). Ideal methods for characterizing blood flow in vivo should have sufficient spatiotemporal resolution to resolve capillaries and track red blood cell (RBC) motion. They should also be able to probe flow dynamics from blood vessels deep within the mammalian brain regardless of their orientation and should be capable of dealing with sample motion–induced artifacts.Despite its importance, many existing methods for hemodynamic imaging fail to meet all the above requirements. For example, functional MRI (4) probes hemodynamics throughout the brain but is lacking in spatiotemporal resolution. Ultrafast ultrasound imaging can achieve capillary resolution millimeters below the skull but lacks sensitivity toward the smallest capillaries and individual RBCs (5–7). Laser Doppler and laser speckle imaging (8) have high temporal resolution but poor spatial resolution. Photoacoustic microscopy (9) can measure hemodynamic responses from individual vessels but also lacks single-RBC sensitivity and is limited in maximal detectable flow speed. Techniques based on optical coherence tomography (10, 11) have high spatiotemporal resolution, but their complex signal dynamics make them qualitative rather than quantitative tools for hemodynamic imaging (12).Considered the gold standard for hemodynamics imaging when it comes to spatial resolution, two-photon fluorescence microscope (2PFM) scans tightly focused laser pulses across fluorescently labeled samples and record the two-photon–excited fluorescence signal at each focal position (13). With subcellular spatial resolution, 2PFM can monitor RBC movement in capillaries millimeters into the opaque rodent brain (14, 15) and has been extensively applied to study cortical blood flow (16).The temporal resolution of 2PFM depends on the focus-scanning speed. With two-dimensional (2D) scanning, conventional 2PFM using a resonant galvanometer can achieve tens of frames per second (17). To increase temporal resolution, one-dimensional (1D) line trajectory scans along the vessels at up to thousands of lines per second have been used (14, 16, 18, 19). However, 1D scanning does not track vessel morphology and is susceptible to motion-induced artifacts. Consequently, most previous 2PFM hemodynamic imaging was performed in anesthetized animals with little sample-induced motion (14, 16, 18, 20, 21).Here, we report ultrafast two-photon fluorescence imaging of cortical blood flow at a 1,000-Hz 2D frame rate and 1,000,000-Hz 1D line-scanning rate in the awake mouse cortex by using an ultrafast all-optical scanning method based on free-space angular chirp enhanced delay (FACED) (22, 23). With an orders-of-magnitude increase in temporal resolution, our system successfully measured cerebral blood flow up to 49 mm/s and revealed ultrafast flow dynamics at harmonics of the heart rate from cortical arterioles. With kilohertz 2D imaging and post hoc motion correction, we concurrently visualized RBC flow and vessel morphology at >800 µm in depth. The kilohertz frame rate also enabled us to characterize radial flow velocity profiles and achieve kilohertz 2D velocity mapping from venules and arterioles as well as RBC flux measurements from penetrating blood vessels.     

Vascular imprints of neuronal activity: Relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.     

Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain

The adult brain exhibits a local increase in cortical blood flow in response to external stimulus. However, broadly varying hemodynamic responses in the brains of newborn and young infants have been reported. Particular controversy exists over whether the “true” neonatal response to stimulation consists of a decrease or an increase in local deoxyhemoglobin, corresponding to a positive (adult-like) or negative blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI), respectively. A major difficulty with previous studies has been the variability in human subjects and measurement paradigms. Here, we present a systematic study in neonatal rats that charts the evolution of the cortical blood flow response during postnatal development using exposed-cortex multispectral optical imaging. We demonstrate that postnatal-day-12–13 rats (equivalent to human newborns) exhibit an “inverted” hemodynamic response (increasing deoxyhemoglobin, negative BOLD) with early signs of oxygen consumption followed by delayed, active constriction of pial arteries. We observed that the hemodynamic response then matures via development of an initial hyperemic (positive BOLD) phase that eventually masks oxygen consumption and balances vasoconstriction toward adulthood. We also observed that neonatal responses are particularly susceptible to stimulus-evoked systemic blood pressure increases, leading to cortical hyperemia that resembles adult positive BOLD responses. We propose that this confound may account for much of the variability in prior studies of neonatal cortical hemodynamics. Our results suggest that functional magnetic resonance imaging studies of infant and child development may be profoundly influenced by the maturing neurovascular and autoregulatory systems of the neonatal brain.     

脑梗死患者脑血流动力学的多层螺旋CT灌注成像研究

目的 探讨CT灌注成像(CTPI)在老年性脑梗死脑血流动力学研究中的价值.方法 48例临床拟诊脑梗死的患者,发病24 h内行CT 16层平扫及CTPI检查,测定兴趣区的脑血流量(CBF)、对比剂平均通过时间(MTT)和对比剂峰值时间(TTP),并与对侧相应脑组织灌注参数比较;所有病例3～10 d后行MRI随访.结果 本组中40.9%的患者CT平扫显示缺血灶,93.2%的患者CTPI显示异常灌注.CTPI发现异常灌注的敏感性为93.2%,特异性为100%;缺血区CBF减低,MTT、TTP延长,与对照区域比较差异有统计学意义(P＜0.01).结论 CTPI能够敏感地反映缺血脑组织的血流动力学状态,为老年性脑梗死的早期诊断、早期治疗提供重要信息.

Abstract：

Objective To study the value of CT perfusion imaging(CTPI)on brain hemodynamic of the aged with cerebral infarction. Methods The 48 patients who were doubted with cerebral infarction underwent 16-slice CT plain scanning and CTPI within 24 hours of onset. The cerebral blood flow(CBF), mean transit time(MTT)and time to peak(TTP)of contrast-medium in region of interest(FOV)were used as brain hemodynamic parameters in comparation with contralateral regions. All cases were followed up with MRI after 3-10 days. Results Ischemia lesion was found on CT plain scanning in 40.9% of patients, while 93.2% of patients showed abnormal perfusion on CTPI. The sensibility of CTPI in identifying ischemia area was 93.2%, and the specificity was 100%. CBF in research area was significantly reduced, MTT and TTP were remarkably increased in contrast to counterparts(P＜0.01). Conclusions CT perfusion imaging can sensitively reveal the hemodynamic condition of cerebral ischemia, which could provide the important information for early diagnosis and treatment of the elderly with brain infarction.     

From the Cover: Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [¹¹C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.     

Cerebral cortical registration of subliminal visceral stimulation

BACKGROUND & AIMS: Although brain registration of subliminal somatic stimulations such as masked visual stimuli and their influence on electrical and hemodynamic measures of cerebral activity have been reported previously, there have been no reports on cerebral cortical registration of subliminal visceral stimulation. Because studies evaluating the consequences of subliminal somatic stimulation have shown that subliminal stimulation can effect behavior, it is conceivable that such subliminal messages from the intestine could potentially influence intestinal sensory/motor function or effect the perception/interpretation of sensory signals originating from the gut. METHODS: We studied the cerebral cortical functional magnetic resonance imaging (fMRI) response to subliminal, liminal, and supraliminal rectal distention in healthy volunteers. RESULTS: Study findings indicate that subliminal afferent signals originating from the gut are registered in the cerebral cortex without reaching the level of awareness. Locations of cortical activity caused by intestinal subliminal stimulation are similar to those of liminal and supraliminal stimulation but their intensity and volume are significantly lower (P < 0.05). CONCLUSIONS: Subliminal afferent signals originating from the gut are registered in the cerebral cortex and induce changes in measures of brain activity, such as hemodynamic changes detectable by fMRI.     

氙CT指导脑血运重建术治疗症状性前循环动脉狭窄及闭塞

目的 探讨氙CT脑血流灌注成像技术在脑血运重建术前及疗效评估中的作用。方法 回顾性分析15例症状性前循环供血动脉粥样硬化性狭窄或闭塞患者的临床资料,其中行血管内支架置入术8例、颈内动脉内膜切除术1例和颞浅动脉-大脑中动脉旁路移植术6例,对比术前与术后2周内氙CT检测的局部脑血流量(r CBF)及术后6个月改良Rankin量表(mRS)评分。结果 (1)12例术前靶血管远端血流灌注异常患者平均r CBF值为(30±10)ml/(100 g·min),术后为(32±14)ml/(100 g·min),与术前比较差异有统计学意义(P=0.044);3例术前靶血管远端血流灌注正常患者平均r CBF值为(48±6)ml/(100 g·min),术后平均r CBF值为(50±7)ml/(100 g·min),与术前比较差异无统计学意义(P0.05)。(2)术后mRS评分改善8例,稳定7例。15例患者术后mRS评分为[1(0,3)]分,与术前[3(1,3)]分比较,差异有统计学意义(P0.05)。随访期间无一例新发神经功能障碍。结论 血运重建术可改善术前存在血流动力学障碍的症状性前循环供血动脉狭窄或闭塞患者的靶血管远端局部脑血流灌注及神经功能缺损症状,而术前氙CT脑血流灌注成像灌注异常可能较灌注正常患者获益更多。     

椎基底动脉迂曲扩张症的计算流体力学分析

目的 基于磁共振血管造影(MRA)的椎基底动脉迂曲扩张症(VBD)计算机流体力学分析。方法 选取2018年1月至2022年1月牡丹江医学院附属红旗医院诊断为VBD的40例患者,经MRI检查正常的40例患者图像。以椎基底动脉MRA图像构建椎基底动脉三维几何模型,分为VBD组与对照组,分析血流速度(V)、壁面剪切应力(WSS)及震荡剪切系数(OSI)。结果 VBD组V、WSS及OSI均高于对照组,差异有统计学意义(P <0.05)。在血流速度方面,高速血流集中于基底动脉及右侧大脑后动脉处。在WSS方面,VBD组高WSS位于右侧椎动脉、基底动脉、双侧大脑后动脉等大部分血管区域,以血管分叉处显著。在OSI方面,VBD组高OSI值以基底动脉末端至双侧大脑后动脉发出处明显,其余血管区域为波动性高OSI分布。结论 基于真实磁共振患者图像可建立三维个体化血管模型及进行血流动力学分析,获取VBD血流速度图、血管剪切应力云图及震荡剪切系数云图。建立VBD组及对照组模型,分析血流动力学发现,VBD组的基底动脉段具有高速血流、高WSS及高OSI,以末端显著,临床上应着重关注此区域。     

血压水平对脑血管和颈部血管血液动力学检测指标的影响

目的 应用超声技术,探讨不同血压水平对脑血管和颈部血管血液动力学检测指标的影响.方法 对225例伴颈动脉粥样硬化斑块的高血压患者,根据血压控制水平分为轻度高血压组(n=30)、中度高血压组(n=61)和重度高血压组(n=129).选择同期检测的无高血糖、高血脂及无颈动脉粥样硬化斑块且血压正常的患者94例作为对照组.经颅多普勒超声检测大脑中动脉、大脑前动脉、大脑后动脉以及椎动脉的平均血流速度和搏动指数的变化特征.采用颈部B超检测颈总动脉、颈内动脉以及椎动脉的平均血流速度和搏动指数的变化特征.结果 (1)各高血压组24 h动态血压水平与对照组比较均显著增高(P<0.05).(2)各高血压组脑部血管的平均血流速度和搏动指数与对照组比较差异均有统计学意义(P<0.05);各高血压组之间比较,随着血压水平的增加,脑部血管的平均血流速度降低,搏动指数增大(P<0.05).(3)各高血压组颈部血管的平均血流速度和搏动指数与对照组比较差异均有统计学意义(P<0.05);各高血压组之间比较,随着血压水平的增加,颈部血管的平均血流速度降低,搏动指数增大.结论 血压水平对脑部和颈部血管血液动力学均有影响,随着血压水平的增高,血流动力学指标的异常程度呈现渐进加重的趋势.从脑血管和颈部血管的血液动力学角度看,理想的血压水平应不超过140/90 mmHg.经颅多普勒超声结合颈动脉超声可对高血压痛患者颅内外动脉血流动力学的变化进行客观评价,为临床诊治提供依据.     

Effects of circulatory arrest and rewarming on regional blood flow during surface-induced hypothermia

Regional blood flow and distribution of cardiac output (CO) were evaluated by the radioactive microsphere technique in rhesus monkeys during surface rewarming following the induction of deep hypothermia (20° C.) under deep ether anesthesia. A comparison of animals subjected to 30 minutes of circulatory arrest and those not arrested revealed cerebral, coronary, and renal vascular resistance and flow patterns consistent with a hyperemic response to circulatory arrest at 20° C. Throughout rewarming cerebral and coronary absolute flows tended to be at or above the flows noted at comparable cooling temperatures in a previous study. Renal flow fraction (% Qt) were well preserved during rewarming to 30° C., but a decrease was observed thereafter. Carcass (muscle, skin, bone) %Qt was also reduced following rewarming, especially in arrested animals. CO appeared to be similar to those noted at comparable cooling temperatures until 30° C. during rewarming; thereafter, CO did not fully recover to awake control levels. These data suggest that regional flow is redistributed from the carcass and renal circulations to cerebral and coronary circulations in response to hemodynamic alterations during surface rewarming. It was concluded that autoregulative responses to both circulatory arrest and hemodynamic factors are elicited during surface rewarming from deep hypothermia to 20° C. with the method described.     

Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI

Functional MRI (fMRI) is widely assumed to measure neuronal activity, but no satisfactory mechanism for this linkage has been identified. Here we derived the changes in the energetic component from the blood oxygenation level-dependent (BOLD) fMRI signal and related it to changes in the neuronal spiking frequency in the activated voxels. Extracellular recordings were used to measure changes in cerebral spiking frequency (Deltanu/nu) of a neuronal ensemble during forepaw stimulation in the alpha-chloralose anesthetized rat. Under the same conditions localized changes in brain energy metabolism (DeltaCMR(O2)/CMR(O2)) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (DeltaCBF/CBF), cerebral blood volume (DeltaCBV/CBV), and transverse relaxation rates of tissue water (T(2)(*) and T(2)) by MRI methods at 7T. On stimulation from two different depths of anesthesia DeltaCMR(O2)/CMR(O2) approximately Deltanu/nu. Previous (13)C magnetic resonance spectroscopy studies, under similar conditions, had shown that DeltaCMR(O2)/CMR(O2) was proportional to changes in glutamatergic neurotransmitter flux (DeltaV(cyc)/V(cyc)). These combined results show that DeltaCMR(O2)/CMR(O2) approximately DeltaV(cyc)/V(cyc) approximately Deltanu/nu, thereby relating the energetic basis of brain activity to neuronal spiking frequency and neurotransmitter flux. Because DeltaCMR(O2)/CMR(O2) had the same high spatial and temporal resolutions of the fMRI signal, these results show how BOLD imaging, when converted to DeltaCMR(O2)/CMR(O2), responds to localized changes in neuronal spike frequency.     

Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates

In functional brain imaging there is controversy over which hemodynamic signal best represents neural activity. Intrinsic signal optical imaging (ISOI) suggests that the best signal is the early darkening observed at wavelengths absorbed preferentially by deoxyhemoglobin (HbR). It is assumed that this darkening or “initial dip” reports local conversion of oxyhemoglobin (HbO) to HbR, i.e., oxygen consumption caused by local neural activity, thus giving the most specific measure of such activity. The blood volume signal, by contrast, is believed to be more delayed and less specific. Here, we used multiwavelength ISOI to simultaneously map oxygenation and blood volume [i.e., total hemoglobin (HbT)] in primary visual cortex (V1) of the alert macaque. We found that the hemodynamic “point spread,” i.e., impulse response to a minimal visual stimulus, was as rapid and retinotopically specific when imaged by using blood volume as when using the initial dip. Quantitative separation of the imaged signal into HbR, HbO, and HbT showed, moreover, that the initial dip was dominated by a fast local increase in HbT, with no increase in HbR. We found only a delayed HbR decrease that was broader in retinotopic spread than HbO or HbT. Further, we show that the multiphasic time course of typical ISOI signals and the strength of the initial dip may reflect the temporal interplay of monophasic HbO, HbR, and HbT signals. Characterizing the hemodynamic response is important for understanding neurovascular coupling and elucidating the physiological basis of imaging techniques such as fMRI.     

Effect of phosphodiesterase-5 inhibitors on cerebral blood flow in human beings: a systematic review

Background

Phosphodiesterase-5 inhibitors (PDE5i) are established in the treatment of erectile dysfunction and pulmonary hypertension. Agents that augment cerebral blood flow could be a potential treatment for vascular cognitive impairment. The aim of this review was to assess the published effects of PDE5i on cerebral blood flow in human beings.

Mental chronometry using latency-resolved functional MRI

Vascular responses to neural activity are exploited as the basis of a number of brain imaging techniques. The vascular response is thought to be too slow to resolve the temporal sequence of events involved in cognitive tasks, and hence, imaging studies of mental chronometry have relied on techniques such as the evoked potential. Using rapid functional MRI (fMRI) of single trials of two simple behavioral tasks, we demonstrate that while the microvascular response to the onset of neural activity is delayed consistently by several seconds, the relative timing between the onset of the fMRI responses in different brain areas appears preserved. We examined a number of parameters that characterize the fMRI response and determined that its onset time is best defined by the inflection point from the resting baseline. We have found that fMRI onset latencies determined in this manner correlate well with independently measurable parameters of the tasks such as reaction time or stimulus presentation time and can be used to determine the origin of processing delays during cognitive or perceptual tasks with a temporal accuracy of tens of milliseconds and spatial resolution of millimeters.