Imaging Signal Changes Research Articles

Visual Information Processing of Faces in Body Dysmorphic Disorder

Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived appearance defects. Clinical observation suggests that patients with BDD focus on details of their appearance at the expense of configural elements. This study examines abnormalities in visual information processing in BDD that may underlie clinical symptoms. To determine whether patients with BDD have abnormal patterns of brain activation when visually processing others' faces with high, low, or normal spatial frequency information. Case-control study. University hospital. Twelve right-handed, medication-free subjects with BDD and 13 control subjects matched by age, sex, and educational achievement. Intervention Functional magnetic resonance imaging while performing matching tasks of face stimuli. Stimuli were neutral-expression photographs of others' faces that were unaltered, altered to include only high spatial frequency visual information, or altered to include only low spatial frequency visual information. Blood oxygen level-dependent functional magnetic resonance imaging signal changes in the BDD and control groups during tasks with each stimulus type. Subjects with BDD showed greater left hemisphere activity relative to controls, particularly in lateral prefrontal cortex and lateral temporal lobe regions for all face tasks (and dorsal anterior cingulate activity for the low spatial frequency task). Controls recruited left-sided prefrontal and dorsal anterior cingulate activity only for the high spatial frequency task. Subjects with BDD demonstrate fundamental differences from controls in visually processing others' faces. The predominance of left-sided activity for low spatial frequency and normal faces suggests detail encoding and analysis rather than holistic processing, a pattern evident in controls only for high spatial frequency faces. These abnormalities may be associated with apparent perceptual distortions in patients with BDD. The fact that these findings occurred while subjects viewed others' faces suggests differences in visual processing beyond distortions of their own appearance.

Discriminating brain activity from task-related artifacts in functional MRI: Fractal scaling analysis simulation and application

Functional magnetic resonance imaging (fMRI) signal changes can be separated from background noise by various processing algorithms, including the well-known deconvolution method. However, discriminating signal changes due to task-related brain activities from those due to task-related head motion or other artifacts correlated in time to the task has been little addressed. We examine whether three exploratory fractal scaling analyses correctly classify these possibilities by capturing temporal self-similarity; namely, fluctuation analysis, wavelet multi-resolution analysis, and detrended fluctuation analysis (DFA). We specifically evaluate whether these fractal analytic methods can be effective and reliable in discriminating activations from artifacts. DFA is indeed robust for such classification. Brain activation maps derived by DFA are similar, but not identical, to maps derived by deconvolution. Deconvolution explicitly utilizes task timing to extract the signals whereas DFA does not, so these methods reveal somewhat different information from the data. DFA is better than deconvolution for distinguishing fMRI activations from task-related artifacts, although a combination of these approaches is superior to either one taken alone. We also present a method for estimating noise levels in fMRI data, validated with numerical simulations suggesting that Birn's model is effective for simulating fMRI signals. Simulations further corroborate that DFA is excellent at discriminating signal changes due to task-related brain activities from those due to task-related artifacts, under a range of conditions.

Acute neurological deficit after minor trauma in an infant with achondroplasia and cervicomedullary compression

Cervicomedullary compression at the foramen magnum in patients with achondroplasia can be associated with apnea, neurological deficits, and sudden death. Decompressive operations are often performed in symptomatic patients. In asymptomatic patients, the indications for prophylactic decompression are controversial. The authors present the case of a previously neurologically intact 4-month-old girl with achondroplasia who presented with severe hemiparesis after a low-velocity motor vehicle accident. Imaging studies demonstrated osseous compression of the medulla and upper cervical spinal cord with associated parenchymal signal changes. To the authors' knowledge this is the first reported case of a new neurological deficit after a minor trauma in this patient population. The authors review the relevant literature, focusing on the indications for cervicomedullary decompression in infants with achondroplasia. They propose that asymptomatic patients with achondroplasia and osseous compression at the foramen magnum should be offered prophy-lactic surgery if T2-weighted magnetic resonance imaging signal changes in the spinal cord are observed. Prophylactic surgery can be considered an option in patients whose imaging studies do not show signal changes in the spinal cord but demonstrate significant osseous compression and absence of visible subarachnoid spaces.

Functional Responses in the Human Spinal Cord during Willed Motor Actions: Evidence for Side- and Rate-Dependent Activity

Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functional activity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handed volunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace (approximately 0.5 Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the side of the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signal fluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed using the dominant hand at two different rates (approximately 0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higher rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique, the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin and that as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on the activity of spinal circuits.

MRI CHARACTERISTICS AND HISTOLOGY OF BONE MARROW LESIONS IN DOGS WITH EXPERIMENTALLY INDUCED OSTEOARTHRITIS

Signal changes within the bone marrow adjacent to osteoarthritic joints are commonly seen on magnetic resonance (MR) images in humans and in dogs. The histological nature of these lesions is poorly known. In this study, we describe the MR imaging of bone marrow lesions adjacent to the stifle joints of dogs with experimental osteoarthritis over 13 months. Histology of the proximal tibia at the end of the study was compared with the last MR imaging findings. In five adult dogs, the left cranial cruciate ligament was transected. Post-operatively, MR imaging was performed at 1, 2, 3, 4, 6, 8, and 13 months. Dogs were euthanised after 13 months and histological specimen of the proximal tibia were evaluated. Bone marrow edema like MR imaging signal changes were seen in every MR examination of all dogs in one or more locations of the proximal tibia and the distal femur. Lesions varied in size and location throughout the whole study with the exception of constantly seen lesions in the epiphyseal and metaphyseal region at the level of the tibial eminence. On histology, hematopoiesis and myxomatous transformation of the bone marrow and/or intertrabecular fibrosis without signs of bone marrow edema were consistent findings in the areas corresponding to the MR imaging signal changes. We conclude that within the bone marrow, zones of increased signal intensity on fat suppressed MR images do not necessarily represent edema but can be due to cellular infiltration. Contrary to humans, hematopoiesis is seen in bone marrow edema-like lesions in this canine model of osteoarthritis.

Perception modulates auditory cortex activation

Event-related functional magnetic resonance imaging signal change in Heschl's gyrus and the planum temporale was found to reflect sensory decisions about target presence. In a dichotic listening task, activation was higher for target present responses, irrespective of actual target presence. In fact, activation was highest for false alarms, that is, 'present' responses in the absence of a target stimulus, and lowest for missed targets. This shows that activity at the earliest stage of cortical auditory processing reflects subjective perceptual decisions. Whether this activation is driven by bottom-up or top-down factors remains to be investigated.

Neural Correlates of Antinociception in Borderline Personality Disorder

A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. Case-control study. A university hospital. Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Clinical and prognostic analysis of ossified ligamentum flavum in a Chinese population

The authors performed a retrospective study of clinical and radiological data obtained in 27 Chinese patients with myelopathy induced by ossification of the ligamentum flavum (OLF) who underwent surgery between March 1990 and March 2002. The factors related to surgical outcome of thoracic OLF-induced myelopathy were also assessed. The preoperative clinical features and radiological findings were reviewed retrospectively. Preoperative and postoperative neurological status was assessed using the Japanese Orthopaedic Association (JOA) scoring system and the Nurick Scale. The ossified lesions were classified into five types (lateral, extended, enlarged, fused, and tuberous). Multiple linear regression and logistic regression analyses were performed to establish the factors affecting surgical outcome. The patients' chief complaints were lower-limb weakness and gait disturbance (93%), numbness and sensory deficit (89%), and low-back pain (48%). The coexisting pathological entities were disc herniation, canal stenosis, and ossification of posterior longitudinal ligament. The ossified ligamentum flavum was mainly located at the T10-12 (67%) and T1-3 (15%) levels. Symptoms in 26 patients improved but resolved completely in only 14 after surgery. The mean overall JOA score was 5.3 +/- 1.9 preoperatively and 7.9 +/- 2.3 postoperatively. There is a significant difference between the pre- and postoperative neurological status (p < 0.05) determined by the Student t-test. The recovery rate was 46.3 +/- 9.4%. Multiple regression analysis revealed negative correlation between the duration of preoperative symptoms and surgical outcome as well as a positive correlation between the preoperative JOA score and surgical outcome. Logistic regression analysis demonstrated that fecal and/or urinary incontinence, positive patellar and/or ankle clonus, and intramedullary high T2-weighted magnetic resonance (MR) imaging signal change had negative effects on the surgical outcome. The clinical and radiological features of OLF in the Chinese population are similar to those observed in the Japanese population. The duration of preoperative symptoms and JOA score are the most important predictors of the postoperative JOA score and recovery rate. The patients with fecal and/or urinary incontinence, positive patellar and/or ankle clonus, and intramedullary high T2-weighted MR imaging signal change were at higher risk of poor outcome after surgery.

Effects of oxygen saturation on BOLD and arterial spin labelling perfusion fMRI signals studied in a motor activation task

Effects of oxygen availability on blood oxygenation level dependent (BOLD) and arterial spin labelling (ASL) perfusion functional magnetic resonance imaging (fMRI) signal changes upon motor activation were studied. Mild hypoxic hypoxia was induced by reducing the inspired oxygen content (FIO 2) to 12%, decreasing blood oxygen saturation ( Y) from 0.99 ± 0.01 to 0.85 ± 0.03. The fMRI signal characteristics were determined during finger tapping. BOLD activation volume decreased as a function of declining Y in the brain structures involved in execution of the motor task, however, the BOLD signal increase in activated parenchyma was not influenced by Y. ASL fMRI showed that the baseline CBF of 61.8 ± 3.6 ml/100 g/min was not affected by hypoxic hypoxia. Similar to the BOLD fMRI, the volume of motor cortex areas displaying increase in perfusion by ASL fMRI decreased, but the signal change due to perfusion increase was not influenced in hypoxia. The present fMRI results show distinct patterns of haemodynamic and metabolic responses in the brain to motor task between normoxia and hypoxia. On one hand, neither BOLD nor ASL fMRI signal changes are influenced by hypoxia during motor activation. On the other hand, hypoxia attenuates increase in both BOLD and perfusion fMRI signals upon finger tapping from the levels determined in normoxia. These observations indicate that haemodynamic and metabolic responses may be heterogeneous in brain during execution of motor functions in mild hypoxia.

Long-term test–retest reliability of functional MRI in a classification learning task

Functional MRI is widely used for imaging the neural correlates of psychological processes and how these brain processes change with learning, development and neuropsychiatric disorder. In order to interpret changes in imaging signals over time, for example, in patient studies, the long-term reliability of fMRI must first be established. Here, eight healthy adult subjects were scanned on two sessions, 1 year apart, while performing a classification learning task known to activate frontostriatal circuitry. We show that behavioral performance and frontostriatal activation were highly concordant at a group level at both time-points. Furthermore, intra-class correlation coefficients (ICCs), which index the degree of correlation between subjects at different time-points, were high for behavior and for functional activation. ICC was significantly higher within the network recruited by learning than outside that network. We conclude that fMRI can have high long-term test–retest reliability, making it suitable as a biomarker for brain development and neurodegeneration.

Neurologic Spectrum of Chronic Liver Failure and Basal Ganglia T1 Hyperintensity on Magnetic Resonance Imaging

An atypical form of parkinsonism has been described in patients with chronic liver disease, associated with increased T1 signal in the basal ganglia on magnetic resonance imaging. The magnetic resonance imaging signal changes are characteristic of manganese accumulation, which has been neuropathologically confirmed. Manganese neurotoxicity may result in additional neurologic findings besides parkinsonism. To fully characterize patients with chronic central nervous system symptoms and chronic liver failure associated with basal ganglia T1 hyperintensity. Prospective and retrospective case study. Mayo Clinic, Rochester, Minn. Eight patients referred for neurologic evaluation and studied prospectively, and 7 additional retrospectively identified patients who had been examined by Mayo Clinic neurologists. Neurologic syndromes identified. Three syndromes were recognized in these 15 patients with liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: (1) isolated parkinsonism, (2) gait ataxia plus other neurologic findings (ataxia-plus), and (3) cognitive impairment with psychiatric features. All but 1 patient had elevated blood manganese levels. Ammonia levels were normal in most, and the neurologic syndromes did not appear to reflect the well-known toxic-metabolic encephalopathy of liver disease. Chronic liver failure may result in heterogeneous neurologic syndromes that cut across a variety of liver diseases. We selected cases on the basis of evidence of brain manganese accumulation, and this may be a crucial component of these syndromes. Further studies are necessary to explore this issue.

Functional imaging evidence of the relationship between recurrent psychotic episodes and neurodegenerative course in schizophrenia

It remains controversial as to what determines the neurodegenerative course in schizophrenia. This study administered a modified version of the Stroop task and investigated the relationship between functional magnetic resonance imaging (fMRI) signal changes in dysfunctioned task-related regions and clinical course variables. Functional MRI data during task performance were acquired from 10 right-handed schizophrenic patients (mean ± SD age = 29.2 ± 10.3 years, range of illness duration = 0.8–14 years, number of episodes = 1–5) and 10 healthy controls (mean ± SD age = 30.3 ± 6.4). Imaging data were investigated on a voxel-by-voxel basis for single group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM 99b). Correlation analysis with age as a covariate identified those brain regions whose fMRI signal changes were significantly related to clinical course variables in schizophrenia. The number of psychotic episodes was negatively correlated with the fMRI signal change in the right inferior frontal and the right frontal precentral gyri among the activated regions during the Stroop task in schizophrenia, whereas the length of illness was not so correlated. The number of psychotic episodes was also negatively correlated with the fMRI signal change in the left paracingulate in which functional activity was diminished in the patients relative to the controls. Our results indicate that recurrent psychotic episodes are related to the neurodegenerative course in some dysfunctional brain regions in schizophrenia.

Spontaneous low‐frequency BOLD signal fluctuations: An fMRI investigation of the resting‐state default mode of brain function hypothesis

Recent neuroimaging studies have lead to the proposal that rest is characterized by an organized, baseline level of activity, a default mode of brain function that is suspended during specific goal-oriented mental activity. Previous studies have shown that the primary function subserved by the default mode is that of an introspectively oriented, self-referential mode of mental activity. The default mode of brain function hypothesis is readdressed from the perspective of the presence of low-frequency blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal changes (0.012-0.1 Hz) in the resting brain. The results show that the brain during rest is not tonically active in a single mode of brain function. Rather, the findings presented here suggest that the brain recurrently toggles between an introspectively oriented mode (default mode) and a state-of-mind that tentatively might be interpreted as an extrospectively oriented mode that involves a readiness and alertness to changes in the external and internal environment.

Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes

Methylphenidate (MPH) is a dopamine and noradrenaline enhancing drug used to treat attentional deficits. Understanding of its cognition-enhancing effects and the neurobiological mechanisms involved, especially in elderly people, is currently incomplete. The aim of this study was to investigate the relationship between MPH plasma levels and brain activation during visuospatial attention and movement preparation. Twelve healthy elderly volunteers were scanned twice using functional magnetic resonance imaging (fMRI) after oral administration of MPH 20 mg or placebo in a within-subject design. The cognitive paradigm was a four-choice reaction time task presented at two levels of difficulty (with and without spatial cue). Plasma MPH levels were measured at six time points between 30 and 205 min after dosing. FMRI data were analysed using a linear model to estimate physiological response to the task and nonparametric permutation tests for inference. Lateral premotor and medial posterior parietal cortical activation was increased by MPH, on average, over both levels of task difficulty. There was considerable intersubject variability in the pharmacokinetics of MPH. Greater area under the plasma concentration-time curve was positively correlated with strength of activation in motor and premotor cortex, temporoparietal cortex and caudate nucleus during the difficult version of the task. This is the first pharmacokinetic/pharmacodynamic study to find an association between plasma levels of MPH and its modulatory effects on brain activation measured using fMRI. The results suggest that catecholaminergic mechanisms may be important in brain adaptivity to task difficulty and in task-specific recruitment of spatial attention systems.

Clinical Implications of Splenium Magnetic Resonance Imaging Signal Changes

Magnetic resonance imaging (MRI) may show discrete splenium abnormalities; however, the implications of this radiologic finding are unclear. To describe causes, clinical presentations, and prognoses of midline splenium changes evident on MRI. Retrospective case series. Teaching hospital. Medical records of 9 patients with MRI-noted splenium changes were studied; 60 additional published cases were accessed. Sixty-nine cases were reviewed. Clinical and imaging findings, causes, and prognosis. Confusion (35 patients), ataxia (25 patients), and recent seizure (23 patients) were common. Causes included alcohol use, infections, hypoglycemia, trauma, salt abnormalities, and seizure. Twenty-eight patients had complete resolution, 23 improved, and 1 died. Diffusion-weighted imaging showed splenium abnormalities the best. Eleven of 12 patients showed decrease in apparent diffusion coefficient. Most improved clinically, as did their subsequent MRI studies. Midline splenium changes are commonly seen on MRI diffusion-weighted imaging sequences. Multiple causes can result in splenium changes. Physicians should evaluate for glucose and electrolyte abnormalities, seizure risk, ongoing infectious or parainfectious process, and traumatic causes.

Evidence for a dysfunctional retrosplenial cortex in patients with schizophrenia: a functional magnetic resonance imaging study with a semantic—perceptual contrast

We investigated whether the retrosplenial and the posterior cingulate cortex (RS-PCC) is functionally impaired in schizophrenia patients. Therefore, we measured functional magnetic resonance imaging (fMRI) signal changes associated with a synonym-judgment task known to activate, among other areas, the RS-PCC. Compared to 12 matched control subjects, 12 schizophrenia patients exhibited reliably weaker activations in the RS-PCC, the dorsolateral prefrontal cortex and the left orbitofrontal cortex ( P < 0.05, corrected). Differences in frontal activations are in line with previous studies showing a structurally and functionally affected prefrontal cortex in schizophrenia. The impaired RS-PCC functionality in a semantic task may relate to verbal memory deficits frequently observed in schizophrenia patients, because this region is pivotal for gating information into the medial temporal lobe memory system.

Neural mechanisms of working memory in ecstasy (MDMA) users who continue or discontinue ecstasy and amphetamine use: Evidence from an 18-month longitudinal functional magnetic resonance imaging study

Working memory processing in ecstasy (3,4-methylenedioxymethamphetamine) users is associated with neural alterations as measured by functional magnetic resonance imaging. Here, we examined whether cortical activation patterns change after prolonged periods of continued use or abstinence from ecstasy and amphetamine. We used an n-back task and functional magnetic resonance imaging in 17 ecstasy users at baseline (t(1)) and after 18 months (t(2)). Based on the reported drug use at t(2) we separated subjects with continued ecstasy and amphetamine use from subjects reporting abstinence during the follow-up period (n = 9 and n = 8, respectively). At baseline both groups had similar task performance and similar cortical activation patterns. Task performance remained unchanged in both groups. Furthermore, there were no detectable functional magnetic resonance imaging signal changes from t(1) to t(2) in the follow-up abstinent group. However, the continuing users showed a dose-dependent increased parietal activation for the 2-back task after the follow-up period. Our data suggest that ecstasy use, particularly in high doses, is associated with greater parietal activation during working memory performance. An altered activation pattern might appear before changes in cognitive performance become apparent and, hence, may reflect an early stage of neuronal injury from the neurotoxic drug ecstasy.

Update on neuroimaging in infectious central nervous system disease.

Neuroimaging constitutes an important component in the diagnosis of the underlying infectious agents in central nervous system infection. This review summarizes progress in the neuroimaging of infectious central nervous system disease since January 2003. It focuses on imaging of viral encephalitis, including that caused by exotic and emerging viruses, and on imaging in immunodeficient patients. Diffusion-weighted imaging has been shown to be superior to conventional magnetic resonance imaging for the detection of early signal abnormalities in herpes simplex virus encephalitis but also in enterovirus 71 encephalitis and in West Nile encephalitis. Several studies defined the pattern of magnetic resonance imaging signal changes in endemic diseases such as West Nile encephalitis, Murray Valley encephalitis, enterovirus 71 encephalitis and Japanese encephalitis, but also in encephalitides due to ubiquitous viruses such as measles virus and Lyssavirus (rabies). In patients with HIV infection, apparent diffusion coefficient ratios obtained by diffusion-weighted imaging were significantly greater in lesions due to Toxoplasma encephalitis than in primary central nervous system lymphomas. The diagnosis of unclear infectious central nervous system diseases remains a challenge. More recent magnetic resonance imaging techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy, provide additional helpful information. However, the mainstay of diagnosis remains the detection of viral DNA or serological markers of specific infectious agents within the cerebrospinal fluid.

In vivo micro magnetic resonance imaging signal changes in scrapie infected mice

Signal abnormalities on magnetic resonance imaging (MRI) T2-weighted images (T2WI) have been described in patients with Creutzfeldt–Jakob disease; however, the pathology underlying these findings remains to be fully described. We investigated the time-course of signal alterations in a murine model of prion disease using in vivo 9.4 Tesla micro magnetic resonance imaging (μMRI). The topography of μMRI signal changes was correlated with the accumulation of proteinase resistant PrP Sc in corresponding brain sections. Increased signal intensity on T2WI was observed in the septum and in the hippocampus of presymptomatic mice 120 days post infection (dpi). Mildly symptomatic animals (150 dpi) and animals with apparent neurological deficit (180 dpi) had a greater increase of signal intensity on T2WI in the septum and the hippocampus; in addition, abnormalities in the cortex and in the thalamus were found. Neuropathological evaluation demonstrated accumulation of PrP Sc and astrogliosis but only minimal or no spongiform changes in structures where abnormal signal was detected. These observations suggest that early pathological changes related to the accumulation of PrP Sc may be detectable in presymptomatic subjects using MRI systems with higher magnetic field strength.

Functional magnetic resonance imaging of the human brain and spinal cord by means of signal enhancement by extravascular protons

AbstractA review of functional magnetic resonance imaging (fMRI) signal changes in spin–echo image data is presented. Spin–echo fMRI data from the human brain and spinal cord show a consistent departure from that expected with blood oxygen level dependent (BOLD) contrast. Studies to investigate this finding demonstrate fMRI signal changes of 2.5% in the spinal cord and 0.7% in the brain at 1.5 T, which is extrapolated to an echo time of zero. Consistent evidence of a non‐BOLD contrast mechanism arising from a proton‐density change at sites of neuronal activation is demonstrated. A mathematical model and physiological explanation for signal enhancement by extravascular protons is also presented. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 28–34, 2003