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Control over brain activation and pain learned by using real-time functional MRI.

If an individual can learn to directly control activation of localized regions within the brain, this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease. Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain. Here, we found that by using real-time functional MRI (rtfMRI) to guide training, subjects were able to learn to control activation in the rostral anterior cingulate cortex (rACC), a region putatively involved in pain perception and regulation. When subjects deliberately induced increases or decreases in rACC fMRI activation, there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus. Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information, or using rtfMRI information derived from a different brain region, or sham rtfMRI information derived previously from a different subject. Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training. These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training, that voluntary control over activation in rACC leads to control over pain perception, and that these effects were powerful enough to impact severe, chronic clinical pain.

Adolescent↗

Texture segregation in the human visual cortex: A functional MRI study.

The segregation of visual scenes based on contour information is a fundamental process of early vision. Contours can be defined by simple cues, such as luminance, as well as by more complex cues, such as texture. Single-cell recording studies in monkeys suggest that the neural processing of complex contours starts as early as primary visual cortex. Additionally, lesion studies in monkeys indicate an important contribution of higher order areas to these processes. Using functional MRI, we have investigated the level at which neural correlates of texture segregation can be found in the human visual cortex. Activity evoked by line textures, with and without texture-defined boundaries, was compared in five healthy subjects. Areas V1, V2/VP, V4, TEO, and V3A were activated by both kinds of line textures as compared with blank presentations. Textures with boundaries forming a checkerboard pattern, relative to uniform textures, evoked significantly more activity in areas V4, TEO, less reliably in V3A, but not in V1 or V2/VP. These results provide evidence that higher order areas with large receptive fields play an important role in the segregation of visual scenes based on texture-defined boundaries.

Adult↗

Cortical reorganization associated lower extremity motor recovery as evidenced by functional MRI and diffusion tensor tractography in a stroke patient.

PURPOSE: Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. METHODS: Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygenation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0-60 degrees at 0.5 Hz. RESULTS: Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. CONCLUSIONS: Our results indicate that an ipsilateral motor pathway from the unaffected (right) motor cortex to the paretic (right) leg was present in this patient. This study raises the potential that the contralesional (ipsilateral) SM1 is involved in cortical reorganization associated lower extremity motor recovery in stroke. This study is the first neuroimaging evidence that the combined fMRI and DTI fiber tracing can significantly expand the explanatory power of probing cortical reorganization underlying motor recovery mechanism in stroke.

Adolescent↗

Functional MRI studies of spatial and nonspatial working memory.

Single-unit recordings in monkeys have revealed neurons in the lateral prefrontal cortex that increase their firing during a delay between the presentation of information and its later use in behavior. Based on monkey lesion and neurophysiology studies, it has been proposed that a dorsal region of lateral prefrontal cortex is necessary for temporary storage of spatial information whereas a more ventral region is necessary for the maintenance of nonspatial information. Functional neuroimaging studies, however, have not clearly demonstrated such a division in humans. We present here an analysis of all reported human functional neuroimaging studies plotted onto a standardized brain. This analysis did not find evidence for a dorsal/ventral subdivision of prefrontal cortex depending on the type of material held in working memory, but a hemispheric organization was suggested (i.e., left-nonspatial; right-spatial). We also performed functional MRI studies in 16 normal subjects during two tasks designed to probe either nonspatial or spatial working memory, respectively. A group and subgroup analysis revealed similarly located activation in right middle frontal gyrus (Brodmann's area 46) in both spatial and nonspatial [working memory-control] subtractions. Based on another model of prefrontal organization [M. Petrides, Frontal lobes and behavior, Cur. Opin. Neurobiol., 4 (1994) 207-211], a reconsideration of the previous imaging literature data suggested that a dorsal/ventral subdivision of prefrontal cortex may depend upon the type of processing performed upon the information held in working memory.

Adult↗

Inhibition of subliminally primed responses is mediated by the caudate and thalamus: evidence from functional MRI and Huntington's disease.

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless trigger the preactivation of a motor response. Automatic inhibitory control processes prevent such response tendencies from interfering with behaviour. The present study investigated the possibility that these inhibitory control processes are mediated by a cortico-striatal-pallidal-thalamic pathway by using a masked prime task with Huntington's disease patients (Experiment 1) and with healthy volunteers in a functional MRI (fMRI) study (Experiment 2). In the masked prime task, clearly visible left- or right-pointing target arrows are preceded by briefly presented and subsequently masked prime arrows. Participants respond quickly with a left or right key-press to each target. Trials are either compatible (prime and target pointing in the same direction) or incompatible (prime and target pointing in different directions). Prior behavioural and electrophysiological results show that automatic inhibition of the initially primed response tendency is reflected in a 'negative compatibility effect' (faster reaction times for incompatible trials than for compatible trials), and is shown to consist of three distinct processes (prime activation, response inhibition and response conflict) occurring within 300 ms. Experiment 1 tested the hypothesis that lesions of the striatum would interrupt automatic inhibitory control by studying early-stage Huntington's disease patients. Findings supported the hypothesis: there was a bimodal distribution for patients, with one-third (choreic) showing disinhibition, manifested as an absent negative compatibility effect, and two-thirds (non-choreic) showing excessive inhibition, manifested as a significantly greater negative compatibility effect than that in controls. Experiment 2 used fMRI and a region of interest (ROI) template-based method to further test the hypothesis that structures of the striatal-pallidal-thalamic pathway mediate one or more of the processes of automatic inhibitory control. Neither prime activation nor response conflict significantly engaged any ROIs, but the response inhibition process led to significant modulation of both the caudate and thalamus. Taken together, these experiments indicate a causal role for the caudate nucleus and thalamus in automatic inhibitory motor control, and the results are consistent with performance of the task requiring both direct and indirect striatal-pallidal-thalamic pathways. The finding that Huntington's disease patients with greater chorea were disinhibited is consistent with the theory that chorea arises from selective degeneration of striatal projections to the lateral globus pallidus, while the exaggerated inhibitory effect for patients with little or no chorea may be due to additional degeneration of projections to the medial globus pallidus.

Adult↗

The functional neuroanatomy of episodic and semantic autobiographical remembering: a prospective functional MRI study.

Autobiographical memory comprises episodic and semantic components mediated by dissociable states of consciousness, one promoting the experience of the self at a specific moment in the past, and the other involving self-knowledge that does not require ''mental time travel.'' These components can be difficult to dissociate using retrospective autobiographical stimuli collection. In this study, we manipulated the episodic/semantic distinction within prospectively collected autobiographical stimuli. Over several months, participants made recordings documenting specific episodes, repeated episodes, and world knowledge. These recordings were later played back to participants during scanning with functional MRI. The results indicated overlapping but distinct patterns of brain activity corresponding to episodic and semantic autobiographical memory. Both episodic and semantic autobiographical memory engaged the left anteromedial prefrontal cortex associated with self-reference, but the episodic condition did so to a greater degree. The episodic condition uniquely engaged the medial temporal, posterior cingulate, and diencephalic regions associated with remote memory recovery. Whereas the episodic condition engaged the right temporo-parietal cortex involved in reconstruction of spatial context and attentional orienting, the semantic condition engaged the left temporo-parietal and parieto-frontal systems involved in egocentric spatial processing and top-down attentional control. Episodic recollection was also associated with suppression of emotional paralimbic regions. These findings support a functional neuroanatomical dissociation between episodic and semantic autobiographical memory, providing concordance to amnesic syndromes with disproportionate impairment in one of these two forms of autobiographical memory.

Adult↗

Representations of faces and body parts in macaque temporal cortex: a functional MRI study.

Human neuroimaging studies suggest that areas in temporal cortex respond preferentially to certain biologically relevant stimulus categories such as faces and bodies. Single-cell studies in monkeys have reported cells in inferior temporal cortex that respond selectively to faces, hands, and bodies but provide little evidence of large clusters of category-specific cells that would form "areas." We probed the category selectivity of macaque temporal cortex for representations of monkey faces and monkey body parts relative to man-made objects using functional MRI in animals trained to fixate. Two face-selective areas were activated bilaterally in the posterior and anterior superior temporal sulcus exhibiting different degrees of category selectivity. The posterior face area was more extensively activated in the right hemisphere than in the left hemisphere. Immediately adjacent to the face areas, regions were activated bilaterally responding preferentially to body parts. Our findings suggest a category-selective organization for faces and body parts in macaque temporal cortex.

Animals↗

Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI.

Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals 'see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Adult↗

Behavioral and functional MRI study of attention shift in human verbal working memory.

The tripartite model of memory proposed the requirement of attentional switching when accessing different items in working memory [J. Exp. Psychol. Learn. Mem. Cogn. 27 (2001) 817]. This internal focus of attention is limited to just one item and the switching process is time-consuming [Mem. Cogn. 26 (1998) 263]. In the current study, given a three-digit list stored in working memory, we found that it took longer to shift attention in the direction of "Upstream" than "Downstream", and that each shift was a "single step" process. To investigate the neural basis of this type of attention switching, we performed a functional MRI study. The results revealed that at least three important brain areas are involved, including the left dorsal lateral prefrontal cortex, the cingulate gyrus, and the medial occipital cortex. These areas all showed greater activation in the attention shift condition compared to control conditions of no (or decreased) attention shift requirements. In addition, the hemodynamic activities in these areas are highly correlated, suggesting a strong functional connectivity between them. Taken together with evidence from several recent investigations, our results suggest that these areas each play an important and specific role in collaboratively supporting the function of attention shift in working memory.

Adolescent↗

Neural fate of seen and unseen faces in visuospatial neglect: a combined event-related functional MRI and event-related potential study.

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Aged↗

Segmentation analysis in functional MRI: activation sensitivity and gray-matter specificity of RARE and FLASH.

Brain activation is accompanied by local decreases in vascular deoxyhemoglobin. Theoretically, gradient-echo and spin-echo sequences show similar sensitivity to capillary deoxyhemoglobin, but spin-echo sequences should be less sensitive to venous deoxyhemoglobin. This is an important distinction in the context of cortical localization. We report herein a direct experimental comparison of a gradient-echo sequence (fast low-angle shot [FLASH]) with a spin-echo sequence (rapid acquisition with relaxation enhancement [RARE]) for functional MRI (fMRI) in seven subjects undergoing visual stimulation. A Student t test analysis was used to locate areas of significant activation, and then computerized image segmentation was performed to determine the type of activated tissue. Contrary to previous reports, both sequences proved equally sensitive to overall activation. RARE activation, however, was more specific for gray matter, as suggested by prior theoretical models.

Adult↗

A study of the cortical processing of ano-rectal sensation using functional MRI.

Investigation of human ano-rectal physiology has concentrated largely on understanding the motor control of defecation and continence mechanisms. However, little is known of the physiology of ano-rectal sensation. There are important differences in the afferent innervation and sensory perception between the rectum and anal canal. This suggests that there could also be differences in the brain's processing of sensation from these two areas; however, this possibility remains unexplored. The aim of our study was to identify the cerebral areas processing anal (somatic) and rectal (visceral) sensation in healthy adults, using functional MRI. Eight male subjects with an age range of 21-39 years were studied on two separate occasions, one for rectal and the other for anal stimulation studies. Single shot gradient echo planar imaging was performed using a 1.5 tesla Phillips MRI scanner. For each subject, a series of 40 image sets containing 24 slices of the brain was obtained during periods of rapid phasic non-painful distension of the rectum or anal canal, alternating with rest periods, without stimulation. After motion correction, the images were analysed using cross correlation to identify the cerebral areas activated by the stimulus. Rectal stimulation resulted in bilateral activation of the inferior primary somatosensory, secondary somatosensory, sensory association, insular, peri-orbital, anterior cingulate and prefrontal cortices. Anal canal stimulation resulted in activation of areas similar to rectal stimulation, but the primary somatosensory cortex was activated at a more superior level, and there was no anterior cingulate activation. In conclusion, anal and rectal sensation resulted in a similar pattern of cortical activation, including areas involved with spatial discrimination, attention and affect. The differences in sensory perception from these two regions can be explained by their different representation in the primary somatosensory cortex. The anterior cingulate cortex was only activated by rectal stimulation, suggesting that the viscera have a greater representation on the limbic cortex than somatic structures, and this explains the greater autonomic responses evoked by visceral sensation in comparison with somatic sensation.

Adult↗

A new vibrotactile stimulator for functional MRI.

Presenting various stimuli in an MRI scanner can be difficult due to the high magnetic field associated with the scanner. Mechanical vibration stimuli are difficult to deliver to subjects in the MRI environment because most vibration devices contain internal circuitry that can adversely interact with the high magnetic field. Piezoelectric ceramics can provide a solution to this problem since they do not require any internal circuitry to vibrate. Piezoceramics are nonmagnetic and they can be made to vibrate if supplied with an alternating current from a straight wire. We designed a piezoceramic vibrotactile stimulator that is safe and effective in functional MRI experiments. The stimulator was tested in an fMRI experiment at 35 and 150 Hz. The results yielded activation sites in the primary sensory cortex and Brodmann area 40 at both frequencies.

Adult↗

Accessibility of spoken, written, and sign language in Landau-Kleffner syndrome: a linguistic and functional MRI study.

Landau-Kleffner syndrome (LKS) is an acquired aphasia which begins in childhood and is thought to arise from an epileptic disorder within the auditory speech cortex. Although the epilepsy usually subsides at puberty, a severe communication impairment often persists. Here we report on a detailed study of a 26-year old, left-handed male, with onset of LKS at age 5 years, who is aphasic for English but who learned British Sign Language (BSL) at age 13. We have investigated his skills in different language modalities, recorded EEGs during wakefulness, sleep, and under conditions of auditory stimulation, measured brain stem auditory-evoked potentials (BAEP), and performed functional MRI (fMRI) during a range of linguistic tasks. Our investigation demonstrated severe restrictions in comprehension and production of spoken English as well as lip-reading, while reading was comparatively less impaired. BSL was by far the most efficient mode of communication. All EEG recordings were normal, while BAEP showed minor abnormalities. fMRI revealed: 1) powerful and extensive bilateral (R > L) activation of auditory cortices in response to heard speech, much stronger than when listening to music; 2) very little response to silent lip-reading; 3) strong activation in the temporo-parieto-occipital association cortex, exclusively in the right hemisphere (RH), when viewing BSL signs. Analysis of these findings provides novel insights into the disturbance of the auditory speech cortex which underlies LKS and its diagnostic evaluation by fMRI, and underpins a strategy of restoring communication abilities in LKS through a natural sign language of the deaf (with Video)

Adult↗

Human anterior intraparietal area subserves prehension: a combined lesion and functional MRI activation study.

It has been shown in nonhuman primates that the posterior parietal cortex is involved in coordination of arm and eye movements in space, whereas the anterior intraparietal area in the anterior lateral bank of the intraparietal sulcus plays a crucial role in fine finger movements, such as grasping. In this study we show by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed. Patients with parietal lesions sparing the cortex lining the anterior intraparietal sulcus showed intact grasping behavior. Complementary evidence was obtained from functional MRI in normal control subjects showing a specific activation of the anterior lateral bank of the intraparietal sulcus during grasping. In conclusion, this combined lesion and activation study suggests that the anterior lateral bank of the intraparietal sulcus, possibly including the human homologue of the anterior intraparietal area, mediates the processing of sensorimotor integration of precisely tuned finger movements in humans.

Adult↗

The effect of pacing of experimental stimuli on observed functional MRI activity.

Neuroimaging activation studies typically observe signals during two or more periods of differing cognitive activity which are then analyzed by a subtraction to test for localized neuroanatomical dissociations between cognitive tasks. Significant activity found between task conditions is frequently assumed to reflect a novel cognitive process present in one task and not the other. We present a conceptual framework that considers the neural mechanisms underlying such observed neuroimaging changes. We propose that neuroimaging experiments which present stimuli at a fixed pace (where each trial takes the same amount of time) will be sensitive to changes in both duration and intensity of neural processing. In contrast, the signal observed during a self-paced design is derived from neural processing averaged over the reaction time and hence could be less sensitive to differences in duration of neural processing. As an empirical demonstration of these ideas, we studied normal subjects using echoplanar functional MRI during two visuospatial tasks (matching of either ROTATED or NONROTATED stimuli) performed using FIXED and SELF-PACED designs. In both pacing designs, reaction times were greater in the ROTATED than NONROTATED task, interpreted as a greater duration of neural processing during the ROTATED compared to the NONROTATED task. In the FIXED-PACED design, significantly greater signal was present within a parieto-occipital cortical region during the ROTATED task compared to the NONROTATED task. This difference was not observed during the SELF-PACED design. This result illustrates the importance of considering trial pacing in the interpretation of functional neuroimaging activation studies.

Adult↗

Force of voluntary exercise does not affect sensorimotor cortex activation as detected by functional MRI at 1.5 T.

Echo-planar brain images (1.5 T, 1-shot GRE, TR/TE = 3000/45) were acquired during 30-60 s cycles of repetitive (1.3-1.7 Hz) finger flexion exercise against light (0.24) vs heavy (1.40 kg) weights. In protocols during which exercise was alternated with periods of rest, active voxels were identified in the contralateral motor and somatosensory areas by cross-correlation against an on-off waveform. However, there was no significant difference between the responses to light vs heavy weights. In a continuous repetitive exercise protocol, in which only the weights were cycled, no force-correlated voxels were identified. Inasmuch as force-correlated neurons are known to be present in the primate cortex, the results illustrate a potential limitation of functional MRI studies based on the BOLD effect.

Adult↗

Preliminary results of a functional MRI study of brain activation patterns in stuttering and nonstuttering speakers during a lexical access task.

UNLABELLED: An fMRI study examining lexical access and lexical generation in nine non-stuttering and seven stuttering speakers is presented. Lexical access was examined during a word description task that was presented auditorily while subjects "silently" thought of the target words. Participants alternated between four 30-s rest blocks and four 30-s "active" blocks. Activation patterns were assessed utilizing a standard subtraction paradigm, where the activation during the rest blocks was subtracted from the activation during the active blocks. High levels of variability characterized activation patterns within both speaker groups. Group comparisons using random effects statistical analyses did not identify significant differences between the groups when corrected for multiple comparisons. Analyses were subsequently conducted by comparing the trends in the group activation patterns between the speaker groups using fixed (corrected) and random effects (uncorrected) analyses. Non-stuttering control speakers activated primarily left hemisphere cortical speech and language areas while the stuttering speakers appeared to produce more bilateral activation. Discussion of these results focuses on the specific within- and between-hemispheric activation patterns and possible interpretations of these patterns. EDUCATIONAL OBJECTIVES: The reader will learn about: (1) issues related to interpreting brain activation findings in stuttering speakers; (2) the role and neurological substrates of lexical access during speech production in non-stuttering and stuttering speakers; (3) the basics of functional MRI; and (4) the brain activation areas involved during a silent lexical retrieval task in non-stuttering and stuttering speakers.

Adult↗