Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change in blood flow versus change in cognitive state

No human fMRI studies have examined ketamine effects on the BOLD signal change associated with cognitive task performance. We wished to distinguish between effects on 1) cerebral blood flow, with resultant change in BOLD signal; and 2) cognition and neural mechanisms underlying BOLD signal change associated with task performance. Eight right-handed men (mean age 28.75 years) received ketamine or saline i.v. in a randomized, double-blind manner (bolus 0.23 mg/kg; 0.5 mg/kg over 45 min to a maximum 1 hr). Subjects viewed 10 alternating 30-sec blocks of faces with neutral expressions and a fixation cross and discriminated gender of faces. Gradient echo echoplanar images were acquired on a GE Signa 1.5 T Neurovascular system. One hundred T2-weighted images depicting BOLD contrast were acquired over 5 min (for each task) at each of 14 near-axial noncontiguous 7-mm thick planes. Ketamine significantly increased dissociative phenomena and negative symptoms, but did not affect performance of the gender discrimination task. Significant BOLD signal change was demonstrated predominantly in occipitotemporal cortex with both ketamine and placebo. Only two clusters in middle occipital gyrus (BA 18) and precentral gyrus (BA 4) showed significantly decreased BOLD signal change during ketamine compared to placebo. BOLD signal change was not significantly greater in any region during ketamine. Our findings demonstrate subtle rather than major differences between the effects of ketamine and placebo upon the BOLD signal change during perception of face-non face contrast. We suggest that they represent task-dependent effects of the drug/placebo, rather than task-independent effects of the drug per se, and indicate that the effects of ketamine on cerebral blood flow are predominantly focal and task-dependent, rather than global and task-independent.     

Projections of digit afferents to the cuneate nucleus in the raccoon before and after partial deafferentation

Within the cuneate nucleus of the raccoon, the representations of individual forepaw digits are anatomically separated by densely myelinated laminae. This unique arrangement was utilized to determine whether the terminations of cutaneous afferents from individual digits are precisely restricted to the appropriate region of the cuneate nucleus or overlap with afferents from adjacent digits. By using the transganglionic transport of horseradish peroxidase (HRP), it was found that, for each digit, the terminal labeling was restricted to the appropriate 150-250-micron-wide column that extended rostrocaudally throughout the nucleus. The topographical arrangement of digit input corresponded to the known electrophysiology, with the terminal column for the fifth digit located most medially within the nucleus and those for digits 4 to 1 successively more laterally. Within a column, the density of labeling was greater over cell clusters than between clusters. These results indicate that afferents from adjacent digits do not overlap in the cuneate nucleus. In six animals, the fifth digit was amputated, and 2-4 months later, HRP was injected into the nerves of the fourth digit to determine whether its afferents had sprouted into the denervated fifth-digit column. The projection pattern from the fourth digit in each of these animals was the same as in normal animals and the same as in the intact contralateral side. These results indicate that the reorganization seen in the cerebral cortex following peripheral deafferentation cannot be attributed to changes in the afferent fiber projections to the cuneate nucleus.     

Spatial attention modulates the cortical somatosensory representation of the digits in humans

The topographic organization of the primary somatosensory cortex adapts to alterations of afferent input. Here, electric source imaging was used to show that spatial attention modifies cortical somatosensory representations in humans. The cortical representation of the electrically stimulated digit 2 (resp. digits 2 and 3) of the right hand was more medial along the somatosensory area 3b in subjects who focused attention on digit 4 of the right hand, while it was more lateral when subjects attended digit 4 of the contralateral hand. This effect was very fast since the direction of attention was changed every 6 min. The results indicate that cortical somatosensory representations not only depend on afferent input but vary when spatial attention is directed towards different parts of the body.     

Brain stimulation revisited

The results of the following selected studies using magnetic coil (MC) stimulation are presented: (1) evidence for focality of MC stimulation, (2) MC stimulation of frontal areas related to speech, (3) transcallosal responses evoked by MC stimulation, and (4) suppression of visual perception with MC stimulation over occipital cortex. The authors served as subjects, and in most studies a standard Cadwell stimulator and round MC were used. Using a more vertical, rather than tangential, MC orientation and threshold stimulation, nearly isolated movements of individual digits were elicited implying focal cortical excitation. MC stimulation of frontal areas of either hemisphere elicited electromyography in contralateral laryngeal muscles. The shortest latency responses that were often accompanied by arm movement were thought to be elicited from intermediate areas of precentral gyrus and longer latency responses, from near Broca's area, extreme lateral precentral gyrus, and the supplementary motor area. MC stimulation over the occipital cortex resulted in suppression of visual perception of letters briefly flashed on a screen. The topography of suppression implicated the geniculocalcarine system as the site of MC effect. Focal MC stimulation of posterior frontal cerebral cortex elicited a transcallosal response from contralateral homologous cortex with a latency similar to that obtained with focal anodic stimulation but with considerably less excitation of cranial muscles.     

Cortical connections to single digit representations in area 3b of somatosensory cortex in squirrel monkeys and prosimian galagos

The ventral posterior nucleus of thalamus sends highly segregated inputs into each digit representation in area 3b of primary somatosensory cortex. However, the spatial organization of the connections that link digit representations of areas 3b with other somatosensory areas is less understood. Here we examined the cortical inputs to individual digit representations of area 3b in four squirrel monkeys and one prosimian galago. Retrograde tracers were injected into neurophysiologically defined representations of individual digits of area 3b. Cortical tissues were cut parallel to the surface in some cases and showed that feedback projections to individual digits overlapped extensively in the hand representations of areas 3b, 1, and parietal ventral (PV) and second somatosensory (S2) areas. Other regions with overlapping populations of labeled cells included area 3a and primary motor cortex (M1). The results were confirmed in other cases in which the cortical tissues were cut in the coronal plane. The same cases also showed that cells were primarily labeled in the infragranular and supragranular layers. Thus, feedback projections to individual digit representations in area 3b mainly originate from multiple digits and other portions of hand representations of areas 3b, 1, PV, and S2. This organization is in stark contrast to the segregated thalamocortical inputs, which originate in single digit representations and terminate in the matching digit representation in the cortex. The organization of feedback connections could provide a substrate for the integration of information across the representations of adjacent digits in area 3b. J. Comp. Neurol. 521:3768–3790, 2013. © 2013 Wiley Periodicals, Inc.     

Functional somatotopy of finger representations in human primary motor cortex

To assess the degree of fine-scale somatotopy within the hand area of the human primary motor cortex (M1), functional mapping of individual movements of all fingers was performed in healthy young subjects (n = 7) using MRI at 0.8 x 0.8 mm2 resolution and 4 mm section thickness. The experimental design comprised both a direct paradigm contrasting single digit movements vs. motor rest and multiple differential paradigms contrasting single digit movements vs. the movement of another digit. Direct mapping resulted in largely overlapping activations. A somatotopic arrangement was only recognizable when considering the mean center-of-mass coordinates of individual digit representations averaged across subjects. In contrast, differential paradigms revealed more segregated and somatotopically ordered activations in single subjects. The use of center-of-mass coordinates yielded inter-digit distances ranging from 2.0 to 16.8 mm, which reached statistical significance for pairs of more distant digits. For the middle fingers, the functional somatotopy obtained by differential mapping was dependent on the choice of the digit used for control. These results confirm previous concepts that finger somatotopy in the human M1 hand area emerges as a functional predominance of individual digit representations sharing common areas in a distributed though ordered network.     

Projection of the digit and wrist area of precentral gyrus to the putamen: Relation between topography and physiological properties of neurons in the putamen

The autoradiographic technique was used to examine the projection from the digit and wrist area of the precentral gyrus to the putamen in two macaque monkeys. Motor responses elicited by intracortical microstimulation were mapped to guide selection of the site of injection of isotope. Additionally, an electrophysiological study of the activity of putamen neurons during voluntary movements of the distal arm in an awake monkey was performed prior to the anatomical study in one of the animals. Two major findings resulted from this study. Firstly, the area of representation of the digits and wrist in area 4 gives rise to a substantial projection to the putamen. The distribution of terminals consisted of a simple pattern of clusters at anterior levels of the putamen. At caudal levels in the putamen, the clusters merged into a single diagonal band of label. This basic pattern was found to be virtually identical in the two monkeys. Secondly, the location of neurons in the putamen which were activated during voluntary movements of the distal arm was closely associated with the terminal distribution of fibers from the digit and wrist zone of area 4. These data provide strong evidence to support the idea that the putamen is concerned with motor function of distal muscles of the arm, and that the topographic characteristics of the corticoputamen projection are closely related to the physiological properties of individual neurons in the putamen.     

Functional neuroimaging studies of human somatosensory cortex

Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly.These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.     

Interference of concomitant tasks on simple reaction time: Attentional and motor factors

Simple reaction times to lateralized unstructured visual stimuli were measured in normal subjects while they were carrying out concomitant left hemisphere tasks. Three tasks were used. In the first task the subjects had to pay attention to strings of digits, acoustically presented, and detect letters randomly interspersed among the digits; in the second task the subjects had to memorize strings of acoustically presented digits; inthe third task they had to repeat each digit of a string as soon as they heard it. In spite of the greater difficulty of the first two tasks with respect to the third one, only this last task, the only one requiring a verbo-motor response, produced a significant disadvantage for the left hemisphere responses to light. It is argued that in RT experiments a specific left hemisphere interference takes place when the secondary task requires the organization of a motor response.     

Distinct fine‐scale fMRI activation patterns of contra‐ and ipsilateral somatosensory areas 3b and 1 in humans

Inter‐areal and ipsilateral cortical responses to tactile stimulation have not been well described in human S1 cortex. By taking advantage of the high signal‐to‐noise ratio at 7 T, we quantified blood oxygenation level dependent (BOLD) response patterns and time courses to tactile stimuli on individual distal finger pads at a fine spatial scale, and examined whether there are inter‐areal (area 3b versus area 1) and interhemispheric response differences to unilateral tactile stimulation in healthy human subjects. We found that 2‐Hz tactile stimulation of individual fingertips evoked detectable BOLD signal changes in both contralateral and ipsilateral area 3b and area 1. Contralateral digit activations were organized in an orderly somatotopic manner, and BOLD responses in area 3b were more digit selective than those in area 1. However, the area of cortex that was responsive to stimulation of a single digit (stimulus–response field) was similar across areas. In the ipsilateral hemisphere, response magnitudes in both areas 3b and 1 were significantly weaker than those of the contralateral hemisphere. Digit activations exhibited no clear somatotopic organizational pattern in either area 3b or area 1, yet digit selectivity was retained in area 1 but not in area 3b. The observation of distinct digit‐selective responses of contralateral area 3b versus area 1 supports a higher order function of contralateral area 1 in spatial integration. In contrast, ipsilateral cortices may play a less discriminative role in the perception of unilateral tactile sensation in humans. Hum Brain Mapp 35:4841–4857, 2014. © 2014 Wiley Periodicals, Inc.     

Réorganisation du cortex sensorimoteur dans le cadre de la paralysie cérébrale unilatérale : apports des neurosciences

Cerebral palsy (CP) is a non-progressive injury to the developing central nervous system and defines as permanent disorders of the development of movement and posture, causing activity limitation. This neurodevelopmental disorder may lead to spastic unilateral cerebral palsy after early unilateral brain lesions. Physical and rehabilitation medicine has a particular interest in the study of organization and reorganization of the sensorimotor cortex following early brain injury. From neuroscience standpoint, early brain lesions have been shown to induce substantial neural reorganization owing to the higher plasticity in the developing brain. Unilateral injuries either to the motor cortex or the corticospinal tract can lead to different patterns of reorganization of the sensorimotor cortex. Many patients develop ipsilateral corticospinal pathways to control the paretic hand with the non-lesioned hemisphere. This type of reorganization is often observed following unilateral periventricular brain lesions, which damage the corticospinal tracts in the periventricular white matter. In this group of patients, the primary motor cortex has been found to be represented in the non-lesioned precentral gyrus ipsilateral to the paretic side. Inversely, in patients with perinatal unilateral middle cerebral artery stroke, primary motor cortex remains organised in the lesioned precentral gyrus contralateral to the paretic hand. However, regardless of these inter- or intrahemispheric motor representations, the primary somatosensory cortex representation remains in the lesioned hemisphere in both groups. These two types of corticospinal reorganization could influence the efficacy of rehabilitation.     

正常人手运动功能脑皮质定位的研究

目的 研究正常人手复杂运动时脑皮质的功能定位。方法 采用SIEMENS成像系统的EPI-Bolding程序，采集7例受试运动和静止状态的T1W图像共6个时相，应用相应软件分析得到差异信号图像，在T1W结构图像融合，并进行三维重建。结果 7例受试在执行握拳运动时，对侧皮质中央前回的第一运动区（Broadman 4区）均可见明显激活信号，对侧或双侧的补充运动区均有激活信号，2例运动前区激活，3例可见同侧中央前回运动皮质的激活信号。三维重建显示第一运动区的激活信号主要位于对侧中央沟的中外侧，补充运动区的激活信号位于运动前区（Broadman 6区）近正中的内侧面。结论 正常人手复杂运动时脑皮质运动网络被广泛激活，功能核磁共振的激活信号反映了脑的高级功能活动。     

Long-Evans rats have a larger cortical topographic representation of movement than Fischer-344 rats: a microstimulation study of motor cortex in naïve and skilled reaching-trained rats

Intracortical microstimulation of the frontal cortex evokes movements in the contralateral limbs, paws, and digits of placental mammals including the laboratory rat. The topographic representation of movement in the rat consists of a rostral forelimb area (RFA), a caudal forelimb area (CFA), and a hind limb area (HLA). The size of these representations can vary between individual animals and the proportional representation of the body parts within regions can also change as a function of experience. To date, there have been no investigations of strain differences in the cortical map of rats, and this was the objective of the present investigation. The effect of cortical stimulation was compared in young male Long-Evans rats and Fischer-344 rats. The overall size of the motor cortex representation was greater in Long-Evans rats compared to Fischer-344 rats and the threshold required to elicit a movement was higher in the Fischer-344 rats. An additional set of animals were trained in a skilled reaching task to rule out the possibility that experiential differences in the groups could account for the result and to examine the relationship between the differences in topography of cortical movement representations and motor performance. The Long-Evans rats were quantitatively and qualitatively better in skilled reaching than the Fischer-344 rats. Also, Long-Evans rats exhibited a relatively larger area of the topographic representation and lower thresholds for eliciting movement in the contralateral forelimb. This is the first study to describe pronounced strain-related differences in the microstimulation-topographic map of the motor cortex. The results are discussed in relation to using strain differences as a way of examining the behavioral, the physiological, and the anatomical organization of the motor system.     

Functional MRI activation of primary and secondary motor areas in healthy subjects☆

BACKGROUND： Functional MRI （fMRI） demonstrates the localization of hand representation in the motor cortex, thereby providing feasible noninvasive mapping of functional activities in the human brain.
OBJECTIVE： To observe cortical activation within different cortical motor regions during repetitive hand movements in healthy subjects through the use of fMRI.
DESIGN： An observational study, with each subject acting as his own control.
SETTING： Department of Radiology, the First Affiliated Hospital of Nanchang University.
PARTICIPANTS： Seven healthy volunteers, 4 males and 3 females, aged 19 to 38 years, participated in the study. All subjects were right-handed, with no neurological or psychological disorders. Informed written consent was obtained from all subjects, and the study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University.
METHODS： The study was performed at the Department of Radiology between June-August 2005. A 1.5 Tesla Siemens MRI scanner （Symphony, Germany） was used to acquire T1-weighted structural images, which were oriented parallel to the line running through the anterior and the posterior commissures. Subjects were instructed on a task and were allowed to practice briefly prior to the imaging procedure. The motor activation task consisted of the right hand performing a clenching movement. The T1-W images were acquired from six alternating epochs of rest and activation from all seven healthy subjects. Data were collected with echoplanar imaging of brain oxygen level dependent （BOLD） sequence. Each series comprised six cycles of task performance （30 seconds）, alternating with rest （30 seconds） periods, and 3-second time intervals. The differences between active and baseline fMRI imaging were calculated using the student t-test. Differential maps were overlaid on the high resolution TI-W structural image for neuroanatomical correlation of activation areas.
MAIN OUTCOME MEASURES： The omega-shaped hand knob     

Cortical gamma‐oscillations modulated by auditory–motor tasks‐intracranial recording in patients with epilepsy

Human activities often involve hand‐motor responses following external auditory–verbal commands. It has been believed that hand movements are predominantly driven by the contralateral primary sensorimotor cortex, whereas auditory–verbal information is processed in both superior temporal gyri. It remains unknown whether cortical activation in the superior temporal gyrus during an auditory–motor task is affected by laterality of hand‐motor responses. Here, event‐related γ‐oscillations were intracranially recorded as quantitative measures of cortical activation; we determined how cortical structures were activated by auditory‐cued movement using each hand in 15 patients with focal epilepsy. Auditory–verbal stimuli elicited augmentation of γ‐oscillations in a posterior portion of the superior temporal gyrus, whereas hand‐motor responses elicited γ‐augmentation in the pre‐ and postcentral gyri. The magnitudes of such γ‐augmentation in the superior temporal, precentral, and postcentral gyri were significantly larger when the hand contralateral to the recorded hemisphere was required to be used for motor responses, compared with when the ipsilateral hand was. The superior temporal gyrus in each hemisphere might play a greater pivotal role when the contralateral hand needs to be used for motor responses, compared with when the ipsilateral hand does. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Attentional shifts induced by uninformative number symbols modulate neural activity in human occipital cortex

Number processing interacts with space encoding in a wide variety of experimental paradigms. Most intriguingly, the passive viewing of uninformative number symbols can shift visuo-spatial attention to different target locations according to the number magnitude, i.e., small/large numbers facilitate processing of left/right targets, respectively. The brain architecture dedicated to these attention shifts associated with numbers remains unknown. Evoked potential recordings indicate that both early and late stages are involved in this spatio-numerical interaction, but the neuro-functional anatomy needs to be specified. Here we use, for the first time, functional magnetic resonance imaging (fMRI) to investigate attentional orienting following uninformative Arabic digits. We show that BOLD response in occipital visual regions is modulated by the congruency between digit magnitude (small/large) and target side (left/right). Additionally, we report higher BOLD responses following large (8, 9) compared to small (1, 2) digits in two bilateral parietal regions, yielding a significant effect of digit magnitude. We propose and discuss the view that encoding of semantic representations related to number symbols in parietal cortex leads to shifts in visuo-spatial attention and enhances visual processing in the occipital cortex according to number-space congruency rules.     

Do children with a specific reading disability have a general serial-ordering deficit?

Two experiments are described in which reading disabled subjects and their normal controls were tested for their ability to abstract sequential regularities from a noisy background. Subjects were presented with an adaptation of the repeated digits task of Hebb (1961) and its spatial analogue the Corsi Blocks (Milner, B. Br. Med. Bull. 27, 272-277, 1971). Normal subjects had a digit span significantly better than their block span and also significantly better than that of the disabled readers. This suggested that normal subjects have better defined "storage filters" for digits or a specific advantage in the construction of 'transitory filters' for verbal material. There were no differences between groups on block span. On the repeated digit sequences normal readers abstracted a relatively stable "storage filter" in the first five recurrent trials whereas the disabled readers showed no discrimination until the last five recurrent trials. On the repeated blocks task the disabled group performed as well as normal readers. Taken together this date gives strong evidence for a specific deficit in verbal serial organization in disabled readers but does not support a general deficit in serial organization.     

The relationship of corpus callosum connections to electrical stimulation maps of motor, supplementary motor, and the frontal eye fields in owl monkeys

Microstimulation and anatomical techniques were combined to reveal the organization and interhemispheric connections of motor cortex in owl monkeys. Movements of body parts were elicited with low levels of electrical stimulation delivered with microelectrodes over a large region of precentral cortex. Movements were produced from three physiologically defined cortical regions. The largest region, the primary motor field, M-I, occupied a 4-6-mm strip of cortex immediately rostral to area 3a. M-I represented body movements from tail to mouth in a grossly somatotopic mediolateral cortical sequence. Specific movements were usually represented at more than one location, and often at as many as six or seven separate locations within M-I. Although movements related to adjoining joints typically were elicited from adjacent cortical sites, movements of nonadjacent joints also were produced by stimulation of adjacent sites. Thus, both sites producing wrist movements and sites producing shoulder movements were found next to sites producing digit movements. Movements of digits of the forepaw were evoked at several locations including a location rostral to or within cortex representing the face. Overall, the somatotopic organization did not completely correspond to previous concepts of M-I in that it was neither a single topographic representation, nor two serial or mirror symmetric representations, nor a "nesting about joints" representation. Instead, M-I is more adequately described as a mosaic of regions, each representing movements of a restricted part of the body, with multiple representations of movements that tend to be somatotopically related. A second pattern of representation of body movements, the supplementary motor area (SMA), adjoined the rostromedial border of M-I. SMA represented the body from tail to face in a caudorostral cortical sequence, with the most rostral portion related to eye movements. Movements elicited by near-threshold levels of current were often restricted to a single muscle or joint, as in M-I, and the same movement was sometimes multiply represented. Typically, more intense stimulating currents were required for evoking movements in SMA than in M-I. A third motor region, the frontal eye field (FEF), bordered the representation of eyelids and face in M-I. Eye movements elicited from this cortex consisted of rapid horizontal and downward deviation of gaze into the contralateral visual hemifield.     

Bereitschaftspotential in a simple movement or in a motor sequence starting with the same simple movement.

The Bereitschaftspotential (BP) recorded from 3 derivations (vertex, left and right precentral areas) in 20 right-handed, normal young subjects was compared in 2 kinds of motor task: a simple movement (task A) and a motor sequence (task B) starting with the simple movement (A). Differences in the onset time and amplitude of the BP were observed: the onset was earlier and the amplitude was larger in the sequential motor task (B) than in the simple one (A). These differences were more important at the vertex (Cz) and in the right precentral area (C4) than in the left contralateral precentral area (C3). These results suggest that the preparatory processes involved in a motor sequence do not exclusively concern the initial movement but also the remainder of the motor task and that the BP is dependent upon the duration or the complexity of the motor task to be executed. The BP seems on temporal grounds to be a global and not a partial expression of a motor task. The changes in the onset time and amplitude of the BP are maximal at the vertex and this could be related to a greater and perhaps earlier activation of SMA in complex sequential motor tasks.     

Localization of the hand motor area by arterial spin labeling and blood oxygen level‐dependent functional magnetic resonance imaging

The new clinically available arterial spin labeling (ASL) perfusion imaging sequences present some advantages relatively to the commonly used blood oxygen level‐dependent (BOLD) method for functional brain studies using magnetic resonance imaging (MRI). In particular, regional cerebral blood flow (CBF) changes are thought to be more directly related with neuronal activation. In this study, we aimed to investigate the accuracy of the functional localization of the hand motor area obtained by simultaneous CBF and BOLD contrasts provided by ASL functional MRI (fMRI) and compare it with a standard BOLD fMRI protocol. For this purpose, we measured the distance between the center of gravity of the activation clusters obtained with each contrast (CBF, BOLD_ASL, and Standard BOLD) and 11 positions defined on a well‐established anatomical landmark of the hand motor area (the omega in the axial plane of the precentral gyrus). We found that CBF measurements were significantly closer to the anatomical landmark than the ones obtained using either simultaneous BOLD_ASL or standard BOLD contrasts. Moreover, we also observed reduced intersubject variability of the functional localization, as well as percent signal change, for CBF relative to both BOLD contrast measurements. In conclusion, our results add further evidence in support to the notion that CBF provides a more accurate localization of motor activation than BOLD contrast, indicating that ASL may be an appropriate technique for clinical fMRI studies. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.