Biomedical subjects

P T Fox

Publications and source records attributed to P T Fox.

At least 19 recordsLinked to original sources

PubMed2006

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder.

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age+/-s.d.=34.3+/-11.5 years) and 15 healthy comparison subjects (37.7+/-12.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P<0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

Adult↗

PubMed2003

Hypophonia in Parkinson's disease: neural correlates of voice treatment revealed by PET.

OBJECTIVE: To investigate the neural correlates of hypophonia in individuals with idiopathic PD (IPD) before and after voice treatment with the Lee Silverman Voice Treatment method (VT) using (15)O-H(2)O PET. METHODS: Regional cerebral blood flow (rCBF) changes associated with overt speech-motor tasks relative to the resting state were measured in the IPD subjects before and after VT, and in a group of healthy control volunteers. RESULTS: Behavioral measures of voice loudness significantly improved following treatment. Before VT, patients had strong speech-related activations in motor and premotor cortex (M1-mouth, supplementary motor cortex [SMA], and inferior lateral premotor cortex [ILPm]), which were significantly reduced post-VT. Similar to the post-treatment session, premotor activations were absent (SMA) or below statistical threshold (M1-mouth) in the healthy control group. In addition, following VT treatment, significant right-sided activations were present in anterior insular cortex, caudate head, putamen, and dorsolateral prefrontal cortex (DLPFC). Finally, the VT-induced neural changes were not present with transient experimenter-cued increases of loudness in VT-untreated patients. CONCLUSIONS: Effective improvement of IPD hypophonia following voice treatment with VT was accompanied by a reduction of cortical motor-premotor activations, resembling the functional pattern observed in healthy volunteers and suggesting normalization, and additional recruitment of right anterior insula, caudate head, putamen, and DLPFC. This treatment-dependent functional reorganization suggests a shift from an abnormally effortful (premotor cortex) to a more automatic (basal ganglia, anterior insula) implementation of speech-motor actions.

Aged↗

PubMed2002

The temporal dynamics of the effects in occipital cortex of visual-spatial selective attention.

The temporal dynamics of the effects of lateralized visual selective attention within the lower visual field were studied with the combined application of event-related potentials (ERPs) and positron emission tomography (15O PET). Bilateral stimuli were rapidly presented to the lower visual field while subjects either passively viewed them or covertly attended to a designated side to detect occasional targets. Lateralized attention resulted in strongly enhanced PET activity in contralateral dorsal occipital cortex, while ERPs showed an enhanced positivity (P1 effect, 80-160 ms) for all stimuli (both non-targets and targets) over contralateral occipital scalp. Dipole modeling seeded by the dorsal occipital PET foci yielded an excellent fit for the peak P1 attention effect. However, more detailed ERP modeling throughout the P1 latency window (90-160 ms) suggested a spatial-temporal movement of the attention-related enhancement that roughly paralleled the shape of the dorsal occipital PET attention-related activations-likely reflecting the sequential attention-related enhancement of early visual cortical areas. Lateralized spatial attention also resulted in a longer-latency contralateral enhanced negativity (N2 effect, 230-280 ms) with a highly similar distribution to the earlier P1 effect. Dipole modeling seeded by the same dorsal occipital PET foci also yielded an excellent fit. This pattern of results provides evidence for re-entrance of attention-enhanced activation to the same retinotopically organized region of dorsal extrastriate cortex. Finally, target stimuli in the attended location elicited an additional prolonged enhancement of the longer-latency negativity over contralateral occipital cortex. The combination of PET activation and dipole modeling suggested contribution from a ventral-occipital generator to this target-related activity.

Adolescent↗

PubMed2001

Neural correlates of response inhibition for behavioral regulation in humans assessed by functional magnetic resonance imaging.

To identify the specific frontal and cingulate regions involved in response inhibition, five Chinese right-handed male volunteers with an attention span reaching or exceeding a 7-digit level participated in this blocked design functional magnetic resonance imaging study. Each block represented one of the two experimental conditions, the Correct Matching or the Incorrect Matching condition. In the Correct Matching condition, the subjects were required to make correct judgement of whether the two 3-digit numbers presented in succession were the same or not; whereas in the Incorrect Matching condition, the participants were instructed to inhibit the correct responses. Bilateral activations of the prefrontal and anterior cingulate as well as the left posterior cingulated cortex were observed while the subjects were exercising response inhibition. The roles of these activations in response inhibition were discussed.

Adult↗

PubMed2001

Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air.

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO(2) inhalation. Comparisons were made with inhalation of a N(2)/O(2) gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.

Adult↗

PubMed2001

Brain responses associated with consciousness of breathlessness (air hunger).

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO(2) was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO(2-) was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].

Adult↗

PubMed2001

Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air.

Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO(2). Ventilation changes follow arterial blood partial pressure CO(2) changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO(2)-induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air; it provides predictive internal models about the consequences of CO(2) inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO(2) concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO(2), and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.

Adult↗

PubMed2001

An fMRI study with written Chinese.

Event-related functional magnetic resonance imaging (ER-fMRI) was used to investigate how the human brain processes phonology and transforms a word's visual form (orthography) into phonological form during reading in logographic Chinese, a writing system that differs markedly from alphabetic languages. We found that reading aloud of irregular words produced larger MR signal intensity changes over extensive regions involving left infero-middle frontal cortex, left motor cortex, right infero-frontal gyri, bilateral anterior superior temporal areas, and anterior cingulate cortex. Right superior parietal lobule, the cuneus in bilateral visual cortex, and thalamus participated in the processing of irregular, but not regular, words. These findings were discussed in comparison to neuroimaging findings from alphabetic languages, as well as in relation to models of reading.

Adult↗

PubMed2001

Comparison of navigator echo and centroid corrections of image displacement induced by static magnetic field drift on echo planar functional MRI.

Image displacement caused by static magnetic field drift may result in serious edge artifacts in echo-planar functional magnetic resonance imaging (MRI). We compared navigator echo and centroid methods for correcting the artifacts for phantom and in vivo studies. A motor-stimulation fMRI study was performed to demonstrate the possible effects due to the displacement. The navigator echo method was shown to be the superior technique for the correction of image displacement by effectively eliminating edge artifacts, resulting in improved functional maps.

Artifacts↗

PubMed2001

Perfusion-weighted imaging of interictal hypoperfusion in temporal lobe epilepsy using FAIR-HASTE: comparison with H(2)(15)O PET measurements.

To detect perfusion abnormalities in areas of high magnetic susceptibility in the brain, an arterial spin-labeling MRI technique utilizing flow-sensitive alternating inversion recovery (FAIR) and half-Fourier single shot turbo spin-echo (HASTE) for spin preparation and image acquisition, respectively, was developed. It was initially tested in a functional study involving visual stimulation, and was able to detect significant activation with an increase (approximately 70%) in relative cerebral blood flow. Subsequently, it was applied in a clinical situation in eight patients with temporal lobe epilepsy (TLE). The perfusion-weighted images obtained showed no susceptibility artifacts even in the region of the inferior temporal lobe and were able to detect interictal hypoperfusion in TLE. The results were compared with those derived from H(2)(15)O PET perfusion imaging in each patient. A statistically significant correlation (r = 0.75, P < 0.05) was found between results acquired from these two modalities. Magn Reson Med 45:431-435, 2001.

Artifacts↗

PubMed2001

Location-probability profiles for the mouth region of human primary motor-sensory cortex: model and validation.

The mouth representation of the human, primary motor cortex (M1) is not reliably identified by surface anatomy but may be reliably localized by means of spatial coordinates. For this report, three quantitative metanalyses were performed which jointly described the mean location, location variability and location-probability profiles of the human M1-mouth representation. First, a literature metanalysis of intersubject functional-area variability was performed using eleven, per-subject studies, each of which reported a coordinate-referenced measure of intersubject variability for one or more brain areas. From these data, a weighted-mean value for intersubject variability was computed, which proved to be small (5.6 mm, standard deviation), consistent across coordinate axes (x, y, z), and consistent across brain areas. Second, a literature metanalysis of the location of M1-mouth was performed using seven, coordinate-referenced, group-mean studies (71 subjects in all), each of which reported a grand-average location for M1-mouth. From this, a weighted-mean location and weighted values for total variability (interlaboratory plus interindividual) were determined. Using these two literature metanalyses as input data, location-probability profiles were computed for the cardinal axes (x, y, and z) of the reference space, using the functional volumes modeling (FVM) statistical model. Third, an original-data metanalysis was performed on in-house PET data from 30 normal subjects performing overt-speech tasks. M1-mouth's mean location, location variability, and location-probability profiles were consistent with those conjointly modeled by FVM from the two literature metanalyses. Collectively, these observations provide a detailed, consensus probabilistic description of the location of the human M1-mouth representation in standardized coordinates.

Adult↗

PubMed2001

A tool for comparison of PET and fMRI methods: calculation of the uncertainty in the location of an activation site in a PET image.

A technique for calculating the uncertainty in the location of an activation site in a PET image, without performing repeated measures, is presented. With the development of new fMRI methods for measuring cerebral hemodynamics, demonstration of the efficacy of these techniques will be critical to establish clinical utility. Comparisons with PET are a powerful tool for validating these new fMRI techniques. In addition to the fact that PET techniques are well-established methods for making physiological measurements in vivo, PET methods are also free of the geometric distortions and nonuniform signal-to-noise artifacts (due to signal dropout) common in fMRI techniques. Comparisons reported previously have been limited by the large number of trials acquired in single-subject fMRI studies and the small number of trials in a PET study (due to the radiation dose to the patient or the interscan delays for tracer decay). Our method calculates both the center of mass (CM) of a predefined region of interest and the uncertainty in the location of the CM using the preimage PET data (sinograms). Results of phantom studies demonstrate that our method is an unbiased measurement equivalent to that of repeated measures with a large number of images. Extension of this technique to estimate the uncertainty in the location of an activation site in a PET statistical parametric map will permit precise rigorous comparisons of PET and fMRI methods in single subjects without the constraints imposed by the relatively small number of PET measurements.

Brain Mapping↗

PubMed2001

The neural system underlying Chinese logograph reading.

Written Chinese as logographic script differs notably from alphabets such as English in visual form, orthography, phonology, and semantics. Thus, research on the Chinese language is important to advance our understanding of the universality and particularity of the organization of language systems in the brain. In this study, we examine the neural systems associated with logographic reading using functional magnetic resonance imaging. Two experimental tasks were devised, one based on semantic decision and the other on homophone decision. Compared to the fixation baseline, peak activations resulting from semantic as well as homophony decisions were localized in the left middle frontal gyrus (BA 9). Left inferior frontal cortex also mediated Chinese processing. In addition, more right hemisphere cortical regions (i.e., BAs 47/45, 7, 40/39, and the right visual system) were involved in reading Chinese relative to reading English. This is attributed to the square shape of the logograph which requires an elaborated analysis of the spatial information and locations of various strokes comprising the logographic character. We suggest that the left middle frontal area (BA 9) coordinates and integrates the intensive visuospatial analysis demanded by logographs' square configuration and the semantic (or phonological) analysis required by the present experimental tasks. Our study has implicated brain regions common to both logographic and alphabetic languages as well as brain regions specialized in processing logographs.

Adult↗

PubMed2001

Rate dependence of human visual cortical response due to brief stimulation: an event-related fMRI study.

The human brain response to a wide range of visual stimulus rates presented over a prolonged time period has been investigated by various neuroimaging techniques. However, to date, no imaging study has been performed to study the dynamic human brain response to various stimulus rates when presented in a short time. This report describes activation in the human brain due to brief visual stimulus presentation (1 s) for stimulus rates varying from 1 to 20 Hz using event-related functional MRI (fMRI). Our results show that the amplitude of the fMRI response increases with the stimulus frequency and plateaus at 6 Hz. This finding differs slightly from the results of previous blocked task paradigm experiments (with a longer time of stimulus presentation), in which the response peaks at approximately 8 Hz and then decreases. Our results are in close agreement with previously published psychophysical studies, suggesting that the fMRI signal in this experiment is indicative of cortical activity related to visual processing.

Evoked Potentials↗

PubMed2001

Cerebral hemodynamic response in Chinese (first) and English (second) language processing revealed by event-related functional MRI.

Comparative functional neuroimaging studies using the block design paradigm have previously demonstrated that there are no significant differences in the location of areas of cerebral activation when native Chinese speakers independently process single words or sentences in both the Chinese (first) and English (second) languages. While it has also been documented that significant domains of brain response include the inferior to middle left frontal lobe, the latency, amplitude and duration of the associated hemodynamic changes during isolated neural processing of Chinese and English languages still remain unknown. The aim of this study, therefore, was to examine the characteristics of the hemodynamic alterations in the above-mentioned regions with event-related functional MRI (ER-fMRI) when native Chinese speakers performed verb generation tasks in both the Chinese (first) and English (second) languages. Our results demonstrate the presence of a similar neural activity-induced hemodynamic response in the inferior to middle left frontal lobe during both tasks. Further, there were also no statistically significant differences among the variables that described the hemodynamic response curves. These findings strongly imply that the underlying neural mechanism for Chinese (first) and English (second) language processing may be similar in native Chinese speakers.

Adult↗

PubMed2001

Structure--function spatial covariance in the human visual cortex.

The value of sulcal landmarks for predicting functional areas was quantitatively examined. Medial occipital sulci were identified using anatomical magnetic resonance images to create individual cortical-surface models. Functional visual areas were identified using retinotopically organized visual stimuli, and positron emission tomography subtraction imaging with intra-subject averaging. Functional areas were assigned labels by placement along the cortical surface from V1. Structure-function spatial covariances between sulci and functional areas, and spatial covariances among functional areas, were determined by projecting sulcal landmarks and functional areas into a standardized stereotaxic space and computing the 'r' statistics. A functional area was considered to spatially covary with a sulcus or another functional area if their geometric centers correlated significantly (P < 0.05) in two or more axes. Statistically significant spatial covariances were found for some, but not all comparisons. The finding of significant spatial covariances within a standardized stereotaxic space indicates that nine-parameter spatial normalization does not account for all the predictive value of structural or functional locations, and may be improved upon by using selected sulcal and functional landmarks. The present findings quantify for the first time the strength of structure--function spatial covariance and comment directly on developmental theories addressing the etiology of structure--function correspondence.

Adolescent↗

PubMed2000

Detection of the brain response during a cognitive task using perfusion-based event-related functional MRI.

Event-related (ER) fMRI has evoked great interest due to the ability to depict the dynamic features of human brain function during various cognitive tasks. Thus far, all cognitive ER-fMRI studies have been based on blood oxygenation level-dependent (BOLD) contrast techniques. Compared with BOLD-based fMRI techniques, perfusion-based fMRI is able to localize the region of neuronal activity more accurately. This report demonstrates, for the first time, the detection of the brain response to a cognitive task using high temporal resolution perfusion-based ER-fMRI. An English verb generation task was used in this study. Results show that perfusion-based ER-fMRI accurately depicts the activation in Broca's area. Average changes in regional relative cerebral blood flow reached a maximum value of 30.7% at approximately 6.5 s after the start of stimulation and returned to 10% of the maximum value at approximately 12.8 s. Our results show that perfusion-based ER-fMRI is a useful tool for cognitive neuroscience studies, providing comparable temporal resolution and better localization of brain function than BOLD ER-fMRI.

Adult↗

PubMed2000

Differential limbic--cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders.

BACKGROUND: Affective disorders are associated with comorbidity of depression and anxiety symptoms. Positron emission tomography resting-state studies in affective disorders have generally failed to isolate specific symptom effects. Emotion provocation studies in healthy volunteers have produced variable results, due to differences in experimental paradigm and instructions. METHODS: To better delineate the neural correlates of sad mood and anxiety, this study used autobiographical memory scripts in eight healthy women to generate sadness, anxiety, or a neutral relaxed state in a within-subject design. RESULTS: Sadness and anxiety, when contrasted to a neutral emotional state, engaged a set of distinct paralimbic-cortical regions, with a limited number of common effects. Sadness was accompanied by specific activations of the subgenual cingulate area (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7. Anxiety was associated with specific activations of the ventral insula, the orbitofrontal and anterior temporal cortices, specific deactivation of parahippocampal gyri, and more prominent deactivation of the inferior temporal cortex BAs 20/37. CONCLUSIONS: These findings are interpreted within a model in which sadness and anxiety are represented by segregated corticolimbic pathways, where a major role is played by selective dorsal cortical deactivations during sadness, and ventral cortical deactivations in anxiety.

Adult↗