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Empirical validation of the triple-code model of numerical processing for complex math operations using functional MRI and group Independent Component Analysis of the mental addition and subtraction of fractions.

The suitability of a previously hypothesized triple-code model of numerical processing, involving analog magnitude, auditory verbal, and visual Arabic codes of representation, was investigated for the complex mathematical task of the mental addition and subtraction of fractions. Functional magnetic resonance imaging (fMRI) data from 15 normal adult subjects were processed using exploratory group Independent Component Analysis (ICA). Separate task-related components were found with activation in bilateral inferior parietal, left perisylvian, and ventral occipitotemporal areas. These results support the hypothesized triple-code model corresponding to the activated regions found in the individual components and indicate that the triple-code model may be a suitable framework for analyzing the neuropsychological bases of the performance of complex mathematical tasks.

Adult↗

Functional MRI reveals an interhemispheric dissociation of frontal and temporal language regions in a patient with focal epilepsy.

We report the case of a patient with frontal lobe epilepsy in whom the Wada test failed to lateralize representation of language (fluent speech was observed after amobarbital injection on both the right and left side). Functional magnetic resonance imaging (fMRI) during a lexical processing task revealed an atypical organization of language represented by an interhemispheric dissociation of language regions with a right frontal dominance and a left temporal dominance. Consistent with the fMRI results, the patient's ability to name pictures was not reliably impaired by electrocortical stimulation (ECS) of left frontal cortex. The findings from Wada, fMRI, and ECS were confirmed by a lack of language impairment after left frontal lobectomy for seizures. This case illustrates that fMRI can precisely map cortical language networks in epileptic patients and that fMRI may be used to help interpret laterality results provided by the Wada procedure.

Adult↗

Functional MRI studies of auditory comprehension.

The location of brain regions essential for auditory language comprehension is an important consideration in the planning of neurosurgical procedures that involve resections within the dominant temporal lobe. Language testing during intraoperative and extraoperative cortical stimulation has been the primary method for localizing these regions; however, noninvasive alternatives using functional neuroimaging have been sought. Here we report on a study of 14 subjects who listened passively to alternating sentences spoken in their native English language and in unfamiliar Turkish while functional magnetic resonance images were acquired. The English sentences produced strong activation within the left superior temporal sulcus in all subjects. Lesser activation was seen in homotopic right hemisphere locations in several subjects. In addition to these posterior temporal activations, 8 subjects also showed activation to English sentences in the left inferior frontal gyrus. Turkish sentences evoked no coherent region of activation in any subject. As both the Turkish and English sentences were read by the same speaker, and were matched for length, volume, and intonation, we conclude that the activation pattern evoked by the English sentences reflects auditory comprehension. This conclusion is further supported by additional control studies that have shown a markedly different pattern of activation by pure tone frequency glides.

Acoustic Stimulation↗

A functional MRI study of high-level cognition. II. The game of GO.

GO is a board game thought to be different from chess in many aspects, most significantly in that GO emphasizes global strategy more than local battle, a property very difficult for computer programs to emulate. To investigate the neural basis of GO, functional magnetic resonance imaging (fMRI) was used to measure brain activities of subjects engaged in playing GO. Enhanced activations were observed in many cortical areas, such as dorsal prefrontal, parietal, occipital, posterior temporal, and primary somatosensory and motor areas. Quantitative analysis indicated a modest degree of stronger activation in right parietal area than in left. This type of right hemisphere lateralization differs from the modest left hemisphere lateralization observed during chess playing.

Brain Mapping↗

Understanding neural system dynamics through task modulation and measurement of functional MRI amplitude, latency, and width.

Estimates of hemodynamic amplitude, delay, and width were combined to investigate system dynamics involved in lexical decision making. Subjects performed a lexical decision task using word and nonword stimuli rotated 0 degrees, 60 degrees, or 120 degrees. Averaged hemodynamic responses to repeated stimulation were fit to a Gamma-variate function convolved with a heavyside function of varying onset and duration to estimate each voxel's activation delay and width. Consistent with prolonged reaction times for the rotated stimuli and nonwords, the motor cortex showed delayed hemodynamic onset for both conditions. Language areas such as the lingual gyrus, middle temporal gyrus, fusiform gyrus, and precuneus all showed delayed hemodynamic onsets to rotated stimuli but not to nonword stimuli. The inferior frontal gyrus showed both increased onset latency for rotated stimuli and a wider hemodynamic response to nonwords, consistent with prolonged processing in this area during the lexical decision task. Phonological processing areas such as superior temporal and angular gyrus showed no delay or width difference for rotated stimuli. These results suggest that phonological routes but not semantic routes to the lexicon can proceed regardless of stimulus orientation. This study demonstrates the utility of estimating hemodynamic delay and width in addition to amplitude allowing for more quantitative measures of brain function such as mental chronometry.

Adult↗

Functional MRI of visual-spatial processing in neurofibromatosis, type I.

Visual-spatial impairment and neuroanatomical abnormalities are considered hallmark features of neurofibromatosis, type I (NF-I). Numerous studies have demonstrated visual-spatial deficits in children with NF-I, but few relations between these deficits and neuroanatomical abnormalities have been identified. We compared the functional neuroanatomy of cerebral regions involved in the spatial transformation of alphanumeric stimuli in individuals with NF-I and healthy control participants using functional magnetic resonance imaging (fMRI). Given the prevalence of visual pathway abnormalities and visual-spatial deficits in NF-I, we hypothesized that less neuronal hemodynamic activity would be found in occipital and parietal cortices in this group compared with controls. However, NF-I participants relied to a greater degree than controls on posterior cortex (including occipital, parietal, and middle temporal cortices) relative to lateral and inferior frontal regions during visual-spatial analysis. This pattern was significantly related to their behavioral performance on the fMRI task, which in turn was also positively correlated with reading scores. These findings support evidence of frontal cortical anomalies in NF-I and may provide a pathophysiological basis for cognitive deficits in NF-I.

Adolescent↗

Dopaminergic effects on electrophysiological and functional MRI measures of human cortical stimulus-response power laws.

Power laws have been widely used to formulate relationships between objective intensity of stimulation and subjective intensity of sensation. We investigated the effects of dopaminergic drug treatment (sulpiride) on the relationship between somatosensory stimulus intensity and cortical response measured electrophysiologically by somatosensory-evoked potentials (SEP) and functional magnetic resonance imaging (fMRI). The intensity of stimulation was related by a simple power law to both electrophysiological and fMRI measures of cortical response, with overlapping confidence intervals for both power law exponents. Sulpiride did not modulate the power law exponent, but significantly attenuated the "gain" of both stimulus-response functions. Using path analysis we decomposed dopaminergic effects on fMRI data into an indirect component (16%), predictable by drug effects on SEP, and a direct component (84%), not explained electrophysiologically. Results indicate that sulpiride has comparable effects on power law parameters estimated from SEP and fMRI, but fMRI has superior sensitivity to detect drug effects on somatosensory cortical recruitment by graded stimulation.

Adult↗

Impaired neural networks for approximate calculation in dyscalculic children: a functional MRI study.

BACKGROUND: Developmental dyscalculia (DD) is a specific learning disability affecting the acquisition of mathematical skills in children with otherwise normal general intelligence. The goal of the present study was to examine cerebral mechanisms underlying DD. METHODS: Eighteen children with DD aged 11.2 +/- 1.3 years and twenty age-matched typically achieving schoolchildren were investigated using functional magnetic resonance imaging (fMRI) during trials testing approximate and exact mathematical calculation, as well as magnitude comparison. RESULTS: Children with DD showed greater inter-individual variability and had weaker activation in almost the entire neuronal network for approximate calculation including the intraparietal sulcus, and the middle and inferior frontal gyrus of both hemispheres. In particular, the left intraparietal sulcus, the left inferior frontal gyrus and the right middle frontal gyrus seem to play crucial roles in correct approximate calculation, since brain activation correlated with accuracy rate in these regions. In contrast, no differences between groups could be found for exact calculation and magnitude comparison. In general, fMRI revealed similar parietal and prefrontal activation patterns in DD children compared to controls for all conditions. CONCLUSION: In conclusion, there is evidence for a deficient recruitment of neural resources in children with DD when processing analog magnitudes of numbers.

Journal Article↗

A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica.

Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations (r values ranging from -0.76 to -0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the 'classical' sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.

Adult↗

Unified structural equation modeling approach for the analysis of multisubject, multivariate functional MRI data.

The ultimate goal of brain connectivity studies is to propose, test, modify, and compare certain directional brain pathways. Path analysis or structural equation modeling (SEM) is an ideal statistical method for such studies. In this work, we propose a two-stage unified SEM plus GLM (General Linear Model) approach for the analysis of multisubject, multivariate functional magnetic resonance imaging (fMRI) time series data with subject-level covariates. In Stage 1, we analyze the fMRI multivariate time series for each subject individually via a unified SEM model by combining longitudinal pathways represented by a multivariate autoregressive (MAR) model, and contemporaneous pathways represented by a conventional SEM. In Stage 2, the resulting subject-level path coefficients are merged with subject-level covariates such as gender, age, IQ, etc., to examine the impact of these covariates on effective connectivity via a GLM. Our approach is exemplified via the analysis of an fMRI visual attention experiment. Furthermore, the significant path network from the unified SEM analysis is compared to that from a conventional SEM analysis without incorporating the longitudinal information as well as that from a Dynamic Causal Modeling (DCM) approach.

Attention↗

Functional MRI neuroanatomic correlates of the Hooper Visual Organization Test.

The Hooper Visual Organization Test (VOT), a commonly applied neuropsychological test of visual spatial ability, is used for assessing patients with suspected right hemisphere, or parietal lobe involvement. A controversy has developed over whether the inferences of this test metric can be assumed to involve global, lateralized, or regional functionality. In this study, the characteristic visual organization and object naming aspects of the VOT task presentation were adapted to a functional MR imaging (fMRI) paradigm to probe the neuroanatomic correlates of this neuropsychological test. Whole brain fMRI mapping results are reported on a cohort of normal subjects. Bilateral fMRI responses were found predominantly in the posterior brain, in regions of superior parietal lobules, ventral temporal-occipital cortex, and posterior visual association areas, and to a lesser extent, the frontal eye fields bilaterally, and left dorsolateral prefrontal cortex. The results indicate a general brain region or network in which VOT impairment, due to its visuospatial and object identification demands, is possible to be detected. Discussion is made of interpretive limitations when adapting neuropsychological tests to fMRI analysis.

Adult↗

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.

Acute Disease↗

Encoding novel face-name associations: a functional MRI study.

The process of forming new associations between previously unrelated items of information, such as a name and a face, likely requires the integration of activity within multiple brain regions. The hippocampus and related structures in the medial temporal lobe are thought to be particularly critical in binding together items of information. We studied eight healthy young subjects with functional magnetic resonance imaging (fMRI) during the encoding of novel face-name associations compared to viewing repeated face-name pairs. A consistent pattern of activation was observed in the hippocampus, pulvinar nucleus of the thalamus, fusiform and dorsolateral prefrontal cortices across individual subjects. The location of the activation within the hippocampus was more anterior than previously reported in studies using similar novel vs. repeated paradigms with stimuli that did not specifically require relational processing among unrelated items. These data suggest that the process of forming new face-name associations is supported by a distributed network of brain regions, and provide additional evidence for the essential role of the hippocampus in associative memory processes.

Adult↗

Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging.

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.

Adult↗

Activation of visuomotor systems during visually guided movements: a functional MRI study.

The dorsal stream is a dominant visuomotor pathway that connects the striate and extrastriate cortices to posterior parietal areas. In turn, the posterior parietal areas send projections to the frontal primary motor and premotor areas. This cortical pathway is hypothesized to be involved in the transformation of a visual input into the appropriate motor output. In this study we used functional magnetic resonance imaging (fMRI) of the entire brain to determine the patterns of activation that occurred while subjects performed a visually guided motor task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR system equipped with a head gradient coil and a birdcage RF coil using a T2*-weighted EPI sequence. Functional activation was determined for three different tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a joystick in relation to various targets, (2) a hand movement task consisting of moving the joystick without visual input, and (3) a eye movement task consisting of moving the eyes alone without visual input. Blood oxygenation level-dependent (BOLD) contrast-based activation maps of each subject were generated using period cross-correlation statistics. Subsequently, each subject's brain was normalized to Talairach coordinates, and the individual maps were compared on a pixel by pixel basis. Significantly activated pixels common to at least four out of six subjects were retained to construct the final functional image. The pattern of activation during visually guided movements was consistent with the flow of information from striate and extrastriate visual areas, to the posterior parietal complex, and then to frontal motor areas. The extensive activation of this network and the reproducibility among subjects is consistent with a role for the dorsal stream in transforming visual information into motor behavior. Also extensively activated were the medial and lateral cerebellar structures, implicating the cortico-pontocerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.

Animals↗

A functional MRI study of simple arithmetic--a comparison between children and adults.

The purpose of this study was to examine brain areas involved in simple arithmetic, and to compare these areas between adults and children. Eight children (four girls and four boys; age, 9-14 years) and eight adults (four women and four men; age, 40-49 years) were subjected to this study. Functional magnetic resonance imaging (fMRI) was performed during mental calculation of addition, subtraction, and multiplication of single digits. In each group, the left middle frontal, bilateral inferior temporal and bilateral lateral occipital cortices were activated during each task. The adult group showed activation of the right frontal cortex during addition and multiplication tasks, but the children group did not. Activation of the intraparietal cortex was observed in the adult group during each task. Although, activation patterns were slightly different among tasks, as well as between groups, only a small number of areas showed statistically significant differences. The results indicate that cortical networks involved in simple arithmetic are similar among arithmetic operations, and may not show significant changes in the structure during the second decade of life.

Adolescent↗

Functional MRI studies of human visual motion perception: texture, luminance, attention and after-effects.

Motion of an object is thought to be perceived independently of the object's surface properties. However, theoretical, neuropsychological and psychophysical observations have suggested that motion of textures, called 'second-order motion', may be processed by a separate system from luminance-based, or 'first-order', motion. Functional magnetic resonance imaging (fMRI) responses during passive viewing, attentional modulation and post-adaptation motion after-effects (MAE) of these stimuli were measured in seven retinotopic visual areas (labeled V1, V2, V3, VP, V4v, V3A and LO) and the motion-sensitive area MT/MST (V5). In all visual areas, responses were strikingly similar to motion of first- and second-order stimuli. These results differ from a prior investigation, because here the motion-specific responses were isolated. Directing attention towards and away from the motion elicited equivalent response modulation for the two types. Dramatic post-adaptation (MAE) differences in perception of the two stimuli were observed and fMRI activation mimicked perceptual changes, but did not reveal the processing differences. In fact, no visual area was found to respond selectively to the motion of second-order stimuli, suggesting that motion perception arises from a unified motion detection system.

Adolescent↗

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Basal Ganglia↗