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Binding crossmodal object features in perirhinal cortex.

Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.

Adolescent↗

Movement quantity and frequency coding in human motor areas.

Studies of movement coding have indicated a relationship between functional MRI signals and increasing frequency of movement in primary motor cortex and other motor-related structures. However, prior work has typically used block-designs and fixed-time intervals across the varying movements frequencies that may prevent ready distinction of brain mechanisms related to movement quantity and, especially, movement frequency. Here, we obtained functional MRI signals from humans working in an event-related design to extract independent activation related to movement quantity or movement frequency. Participants tapped once, twice, or thrice at 1, 2, or 3 Hz, and the tapping evoked activation related to movement quantity in the precentral and postcentral gyri, supplementary motor area, cerebellum, putamen, and thalamus. Increasing movement frequency failed to yield activation in these motor-related areas, although linear movement frequency affects occurred in nonmotor regions of cortex and subcortex. Our results do not replicate prior data suggesting movement frequency encoding in motor-related areas; instead we observed movement quantity coding in motor-related brain areas. The discrepancy between prior studies and this study likely relates to methodology concerns. We suggest that the movement quantity relationships in human motor areas and encoding of movement frequency in nonmotor areas may reflect a functional anatomical substrate for mediating distinct movement parameters.

Adult↗

Maturation of widely distributed brain function subserves cognitive development.

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.

Adolescent↗

Competition and representation during memory retrieval: roles of the prefrontal cortex and the posterior parietal cortex.

In this functional-MRI study we examined the hypothesis that the prefrontal cortex responds differently to the extent of competition during retrieval, whereas the parietal cortex is responsible for problem representation that should not be directly related to the competition. Participants mastered arbitrary person-location pairs, and their recognition memory was tested in a functional-MRI session. The pairs were constructed such that a person was associated with one, two, or three different locations and vice versa. The recognition time increased with the number of associations, reflecting increased competition. A confirmatory analysis of imaging data with prespecified prefrontal and parietal regions showed that, although both regions were highly involved during memory retrieval, only the prefrontal region responded to the levels of competition. This result was consistent with predictions of an information-processing model as well as with an exploratory identification of regions of interest.

Adult↗

Activity in the peri-infarct rim in relation to recovery from stroke.

BACKGROUND AND PURPOSE: In the rim of tissue surrounding a cortical infarct, animal studies have described an increase in a number of growth-related processes that likely contribute to behavioral recovery. The current study hypothesized that in patients with good outcome after stroke, brain activation in peri-infarct tissue would be greater than normal. METHODS: In 15 patients with good recovery chronically after ischemic cortical stroke, activation within peri-infarct brain tissue was directly compared with activation within the same brain tissue of 13 control subjects. RESULTS: Although most patients did show activation within peri-infarct tissues, their activation compared with controls was reduced rather than increased. Evaluation of the T2*-weighted images underlying functional MRI mapping disclosed a significant gradient of increased T2* signal in peri-infarct tissues, likely attributable to tissue changes such as gliosis. CONCLUSIONS: Among well-recovered stroke patients, cortical activation is present in the area surrounding a cortical infarct but is smaller than normal. A baseline derangement of the T2*-weighted signal underlying functional MRI (fMRI) is also present in this area, which might influence interpretation of fMRI findings. The relationship between increased tissue T2* signal and fMRI activation is not known and requires further study.

Aged↗

Preliminary experience in glioma surgery with intraoperative high-field MRI.

OBJECTIVE: To apply a new setup, combining the benefits of high-field magnetic resonance imaging (MRI) with microscope-based neuronavigation, providing anatomical and functional guidance, in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 1.5 T scanner, located in a radiofrequency-shielded operating theatre. The patient is lying on a rotating operating table, which is locked at the 160 degree position for surgery at the 5 G zone and turned into the scanner for imaging. The microscope, placed in the 5 G zone, in combination with a ceiling mounted navigation system enables microscope-based neuronavigation; integrated data from magnetoencephalography and functional MRI provide functional guidance. RESULTS: 126 patients were investigated with intraoperative high-field MRI, among them were 37 patients with gliomas. In the biopsy/catheter group (n = 8) MRI reliably depicted the needle position or the location of catheter placement. In the group with glioma resection (n = 29) intraoperative MRI revealed that the surgical objective was not achieved in 28%, leading to further tumour removal. We did not observe complications attributable to intraoperative high-field MRI. Image quality was not diminished by the operating room equipment, so that there was nearly no noticeable difference between pre- and intraoperative image quality. Neuronavigational guidance was applied in 31 patients: the integrated use of functional data prevented an increased morbidity despite extended resections. CONCLUSION: Intraoperative high-field MRI allows a reliable delineation of the extent of resection in glioma surgery. If the surgical objective was not met, a modification of the surgical strategy during the same operation is possible, thus leading to more radical resections. Furthermore, high-field MRI offers increased image quality and a much broader spectrum of different imaging modalities, compared to previous intraoperative low-field systems.

Adolescent↗

Magnetic resonance spectroscopy guided brain tumor resection: differentiation between recurrent glioma and radiation change in two diagnostically difficult cases.

BACKGROUND: It is often difficult to differentiate a recurrent glioma from the effects of post-operative radiotherapy by means of conventional neurodiagnostic imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows in vivo measurements of the concentration of brain metabolites such as choline-containing phospholipids (Cho), may provide in vivo biochemical information helpful in distinguishing areas of tumor recurrence from areas of radiation effect. PATIENTS AND METHODS: Two patients who had undergone resection and post-operative radiotherapy for a cerebral glioma became newly symptomatic. Computed tomographic (CT) and magnetic resonance imaging (MRI) performed after the intravenous infusion of contrast material, and in one case, [18F]fluorodeoxyglucose positron emission tomography (PET), could not differentiate between the possibilities of recurrent glioma and radiation effect. The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were compared to histological findings originating from the same locations. RESULTS: A high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven dense tumor recurrence, while low Cho signal was present where radiation changes predominated. CONCLUSIONS: The differentiation between the recurrence of a cerebral glioma and the effects of post-operative irradiation was achieved using 1H-MRSI in these two patients whose conventional neurodiagnostic imaging was equivocal for such a distinction. Where these two conditions are present, metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered with other imaging modalities such as MRI and may also be integrated with functional MRI or functional PET within a multimodal imaging-guided surgical navigation system to assure maximal resection of recurrent tumor while minimizing the risk of added neurological damage.

Adult↗

Dorsal anterior cingulate cortex: a role in reward-based decision making.

Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > or = FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.

Adult↗

Neurocircuitry in alcoholism: a substrate of disruption and repair.

The chronic, excessive consumption of alcohol results in significant modification of selective neural systems of the brain structure, physiology, and function. Quantitative MR structural imaging, diffusion tensor imaging (DTI), and functional MRI (fMRI), together with neuropsychological challenges, have enabled rigorous in vivo characterization of the results of alcoholism on the brain in the human condition. Neuroimaging has also enabled longitudinal study for the examination of alcoholism's dynamic course through periods of drinking and sobriety. Controlled studies have revealed compelling evidence for alcohol-related brain structural and functional modification--some longstanding, some transient, and some compensatory. Patterns of circuitry disruption identified through structural and functional MRI studies suggest a central role for degradation of frontocerebellar neuronal nodes and connecting circuitry affecting widespread brain regions and contributing to alcoholism's salient, enduring, and debilitating cognitive and motor deficits--executive dysfunction, visuospatial impairment, and ataxia.

Aging↗

[Functional neuroimaging in children].

In pharmacoresistant partial epilepsy (PRPE) in children, functional cerebral imaging helps localizing the epileptogenic zone using SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) and the functional motor and language cortex using functional MRI. Regarding SPECT, only ictal SPECT exhibits an acceptable sensitivity (80 p. 100), together with interictal SPECT and subtraction image processing. Regarding PET, sensitivity has not been validated yet compared with intracranial EEG, neither using 18FDG, nor using more recent tracers such as 11C-flumazénil or 11C-alpha-méthyl-tryptophane. However, both techniques are useful to decide the placement of the intracranial electrodes, particularly in cryptogenic cases or when preoperative data are discordant. Functional MRI for language is going to be validated compared with WADA test and to provide a very useful and non invasive alternative method to lateralize the language networks in children able to cooperate. FMRI also provides a unique opportunity to follow the post-lesional or post-surgery plasticity of these networks using repeated examinations in a same patient. Functional imaging techniques therefore provide a useful additional contribution in the presurgery work-up of PRPE in children.

Adolescent↗

Functional magnetic resonance imaging during hypotension in the developing animal.

Hypotension in adult animals recruits brain sites extending from cerebellar cortex to the midbrain and forebrain, suggesting a range of motor and endocrine reactions to maintain perfusion. We hypothesized that comparable neural actions during development rely more extensively on localized medullary processes. We used functional MRI to assess neural responses during sodium nitroprusside challenges in 14 isoflurane-anesthetized kittens, aged 14-25 days, and seven adult cats. Baseline arterial pressure increased with age in kittens, and basal heart rates were higher. The magnitude of depressor responses increased with age, while baroreceptor reflex sensitivity initially increased over those of adults. In contrast to a decline in adult cats, functional MRI signal intensity increased significantly in dorsal and ventrolateral medullary regions and the midline raphe in the kittens during the hypotensive challenges. In addition, significant signal intensity differences emerged in cerebellar cortex and deep nuclei, dorsolateral pons, midbrain tectum, hippocampus, thalamus, and insular cortex. The altered neural responses in medullary baroreceptor reflex sites may have resulted from disinhibitory or facilitatory influences from cerebellar and more rostral structures as a result of inadequately developed myelination or other neural processes. A comparable immaturity of blood pressure control mechanisms in humans would have significant clinical implications.

Age Factors↗

Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics.

A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.

Animals↗

The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Adult↗

Ghost artifact reduction for echo planar imaging using image phase correction.

An algorithm is described for reducing ghost artifacts in echo planar imaging (EPI) using phase corrections derived from images reconstructed using only even or odd k-space lines. The N/2 ghost, that arises principally from time-reversal of alternate k-space lines, was significantly reduced by this algorithm without the need for a calibration scan. In images obtained in eight subjects undergoing EPI for auditory functional MRI (fMRI) experiments, N/2 ghost intensity was reduced from 10.3% +/- 2.1% (range: 7.9-14.1%) to 4.5% +/- 0.2% (range: 4.1-4.9%) of parent image intensity, corresponding to a percent reduction in ghost intensity of 54% +/- 9% (range: 43-65%), and the algorithm restored this intensity to the parent image. It provided a significant improvement in image appearance, and increased the correlation coefficients related to neural activation in functional MRI studies. The algorithm provided reduction of artifacts from all polynomial orders of spatial phase errors in both spatial directions. The algorithm did not eliminate N/2 ghost intensity contributed by field inhomogeneities, susceptibility, or chemical shift.

Algorithms↗

Somatosensory gating and recovery from stroke involving the thalamus.

BACKGROUND AND PURPOSE: In the undamaged brain, sensory input to the cortex is intricately controlled via sensory gating mechanisms. Given the role of corticothalamic pathways in this control, it was hypothesized that in patients recovering from thalamic stroke there would be evidence of disrupted sensory gating and that efficient control of cortical sensory inputs would emerge during recovery. METHODS: Four patients were tested serially after stroke from 1 to 24 weeks after injury. Perceptual thresholds, somatosensory evoked potential amplitudes, and functional MRI activations under specific somatosensory stimulation conditions were measured. RESULTS: All patients demonstrated comparable results, revealing disrupted threshold detection to vibrotactile stimuli in the presence of a concurrent competing, contralateral input. In contrast, threshold detection was comparable between the affected and unaffected sides when there were no competing stimuli. This compromised capacity to inhibit competing sensory inputs was paralleled by a reduction in the measured activation of cortical representation in the stroke-affected hemisphere (functional MRI and somatosensory evoked potential) during bilateral stimulation. After recovery, perceptual detection improvements during bilateral stimulation were paralleled by enhancements of primary somatosensory cortical activation in the stroke-affected hemisphere. CONCLUSIONS: These results provide insight into potential mechanisms that contribute to sensory gating and suggest that the ability to control sensory input through effective gating mechanisms, in addition to primary somatosensory representation, may be important for poststroke sensory recovery.

Aged↗

The spread of attention across modalities and space in a multisensory object.

Attending to a stimulus is known to enhance the neural responses to that stimulus. Recent experiments on visual attention have shown that this modulation can have object-based characteristics, such that, when certain parts of a visual object are attended, other parts automatically also receive enhanced processing. Here, we investigated whether visual attention can modulate neural responses to other components of a multisensory object defined by synchronous, but spatially disparate, auditory and visual stimuli. The audiovisual integration of such multisensory stimuli typically leads to mislocalization of the sound toward the visual stimulus (ventriloquism illusion). Using event-related potentials and functional MRI, we found that the brain's response to task-irrelevant sounds occurring synchronously with a visual stimulus from a different location was larger when that accompanying visual stimulus was attended versus unattended. The event-related potential effect consisted of sustained, frontally distributed, brain activity that emerged relatively late in processing, an effect resembling attention-related enhancements seen at earlier latencies during intramodal auditory attention. Moreover, the functional MRI data confirmed that the effect included specific enhancement of activity in auditory cortex. These findings indicate that attention to one sensory modality can spread to encompass simultaneous signals from another modality, even when they are task-irrelevant and from a different location. This cross-modal attentional spread appears to reflect an object-based, late selection process wherein spatially discrepant auditory stimulation is grouped with synchronous attended visual input into a multisensory object, resulting in the auditory information being pulled into the attentional spotlight and bestowed with enhanced processing.

Acoustic Stimulation↗

Functional MRI-BOLD of visually triggered headache in patients with migraine.

BACKGROUND: Spreading depression of Leao has been hypothesized as the basis for the visual aura of the migraine attack, supported by cerebral blood flow measurements of spreading hypoperfusion. The early depolarizing or activation phase of experimental spreading depression, however, is associated with a transient but pronounced cerebral blood flow increase that precedes spreading hypoperfusion. OBJECTIVE: To study this early phase of the migraine attack, we investigated visually triggered attacks of headache and visual symptoms using a red-green checkerboard stimulus in patients with migraine. INTERVENTIONS: We studied occipital cortex activation during visual stimulation by measuring occipital cortex perfusion with functional magnetic resonance imaging-blood oxygenation level-dependent contrast in 10 patients with migraine with aura and 2 patients with migraine without aura and 6 healthy subjects. RESULTS: In 6 patients with migraine with aura and 2 patients with migraine without aura, their typical headache with (n = 2) or without visual change was visually triggered at 7.3 minutes (mean time) after visual stimulation began. In 5 of these patients, the onset of headache or visual change, or both, was preceded by suppression of initial activation (mean onset time, 4.3 minutes; P<.001) The suppression slowly propagated into contiguous occipital cortex at a rate ranging from 3 to 6 mm/ min. This neuronal suppression was accompanied by baseline contrast intensity increases that indicated vasodilatation and tissue hyperoxygenation. CONCLUSIONS: We conclude that visually triggered headache and visual change in patients with migraine is accompanied by spreading suppression of initial neuronal activation and increased occipital cortex oxygenation. We postulate that this spreading suppression may be associated with initial activation of a migraine attack, independent of whether there are associated aura symptoms. We further postulate that there may be an association between vasodilation accompanying the initial stage of suppression and the induction of headache.

Adult↗

Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.

Adult↗