Dynamic pattern of brain activation during sequencing of word strings evaluated by fMRI

An impaired ability to recite highly automated word strings (e.g., the names of the months of the year) in reverse order concomitant with preserved production of the conventional sequence has been considered a salient sign of frontal lobe dysfunction. Using functional magnetic resonance imaging (fMRI), the spatial and temporal pattern of brain activation during covert performance of these tasks was evaluated in healthy subjects. As compared to the response obtained during forward recitation, re-sequencing of the word string yielded additional activation of the bilateral middle and inferior frontal gyri, the posterior parietal cortex and the left anterior cingulate gyrus. The prefrontal responses are in accordance with the clinical findings referred to. However, the set of activated areas, as a whole, presumably reflects contribution of the various components of the working memory system to the sequencing of word strings. During successive periods of task administration, subjects showed a linear increase of production speed. Analysis of corresponding dynamic changes of regional hemodynamic responses revealed a significant increase at the level of the left inferior parietal cortex and a decrease within the mesial aspect of the left superior frontal gyrus. Presumably, the former finding reflects increasing demands on the phonological short-term memory store, due to faster updating of its content under increased word production rate. Decreasing activation within the superior frontal gyrus might indicate contribution of this area to the initiation of the cognitive processes subserving the sequencing of verbal items. These findings demonstrate the capability of fMRI as a powerful tool for the analysis of dynamic brain activation.     

Sensorimotor cerebral activation during optokinetic nystagmus. A functional MRI study

Self-motion or object motion can elicit optokinetic nystagmus (OKN), which is an integral part of dynamic spatial orientation. We used functional MR imaging during horizontal OKN to study cerebral activation patterns in sensory and ocular motor areas in 10 subjects. We found activation bilaterally in the primary visual cortex, the motion-sensitive areas in the occipitotemporal cortex (the middle temporal and medial superior temporal areas), and in areas known to control several types of saccades such as the precentral and posterior median frontal gyrus, the posterior parietal cortex, and the medial part of the superior frontal gyrus (frontal, parietal, and supplementary eye fields). Additionally, we observed cortical activation in the anterior and posterior parts of the insula and in the prefrontal cortex. Bilateral activation of subcortical structures such as the putamen, globus pallidus, caudate nucleus, and the thalamus traced the efferent pathways of OKN down to the brainstem. Functional MRI during OKN revealed a complex cerebral network of sensorimotor cortical and subcortical activation.     

Neural correlates of semantic and episodic memory retrieval

To investigate the functional neuroanatomy associated with retrieving semantic and episodic memories, we measured changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) while subjects generated single word responses to achromatic line drawings of objects. During separate scans, subjects either named each object, retrieved a commonly associated color of each object (semantic condition), or recalled a previously studied uncommon color of each object (episodic condition). Subjects were also scanned while staring at visual noise patterns to provide a low level perceptual baseline. Relative to the low level baseline, all three conditions revealed bilateral activations of posterior regions of the temporal lobes, cerebellum, and left lateralized activations in frontal regions. Retrieving semantic information, as compared to object naming, activated left inferior temporal, left superior parietal, and left frontal cortices. In addition, small regions of right frontal cortex were activated. Retrieving episodic information, as compared to object naming, activated bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal cortex, thalamus, and cerebellum. Direct comparison of the semantic and episodic conditions revealed bilateral activation in temporal and frontal lobes in the semantic task (left greater than right), and activation in medial parietal cortex, retrosplenial cortex, thalamus, and cerebellum (but not right frontal regions) in the episodic task. These results support the assertion that distinct neural structures mediate semantic and episodic memory retrieval. However, they also raise questions regarding the specific roles of left temporal and right frontal cortices during episodic memory retrieval, in particular.     

Effects of m-chlorophenylpiperazine on regional brain glucose utilization: a positron emission tomographic comparison of alcoholic and control subjects

m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[18F]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method. Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics.     

Procedural learning in first episode schizophrenia investigated with functional magnetic resonance imaging.

Objective: The present investigation assessed the severity, course, and cerebral implications of serial reaction time (SRT) procedural learning deficits in schizophrenia. Method: Hemodynamic changes on fMRI were assessed during an SRT task in 17 unmedicated first episode psychosis (FEP) patients and matched healthy controls. Results: The groups demonstrated comparable procedural learning and associated activation of anterior cingulate cortex, subcortical structures, and many left frontal structures. The groups also demonstrated comparable increased activation of right parietal structures on trials with demands for spatial localization without procedural memory. Relative to healthy controls, the schizophrenia sample showed less activation of one region of the left middle frontal cortex and more activation of left superior temporal cortex on procedural trials, but more activation of right medial frontal cortex on localization trials. Conclusions: Intact SRT procedural learning and normal or enhanced hemodynamic response in subcortical and right cortical structures diverges from prior results with medicated samples, suggesting a more focal cerebral dysfunction in the left middle frontal cortex before the onset of treatment. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Activation of multi-modal cortical areas underlies short-term memory

We wanted to examine whether there are cortical fields active in short-term retention of sensory information, independent of the sensory modality. To control for selective attention, response selection and motor output, the cortical activity during short-term memory (STM) tasks was compared with that during detection (DT) tasks. Using positron emission tomography and [15O]-butanol as a tracer, we measured the regional cerebral blood flow in ten subjects during three STM tasks in which the subjects had to keep in mind: (i) the pitch of tones; (ii) frequencies of a vibrating stylus; and (iii) luminance levels of a monochrome light. Another group of ten subjects undertook three tasks in which subjects detected changes in similar stimuli. Six cortical fields were significantly more activated during STM than during DT. These fields were activated irrespective of sensory modality, and were located in the left inferior frontal gyrus, right superior frontal gyrus, right inferior parietal cortex, anterior cingulate, left frontal operculum and right ventromedial prefrontal cortex. Since the DT tasks and the STM tasks differed only with respect to the STM component, we conclude that the neuronal activity specifically related to retention of the stimuli during the delays was located in these six multi-modal cortical areas. Since no differences were observed in the sensory-specific association cortices, the results indicate further that the activity in the sensory-specific association cortices due to selective attention is not different from the activity underlying short-term retention of sensory information.     

PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern

Using H2(15)O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self-paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.     

Neural effects of visualizing and perceiving aversive stimuli: a PET investigation

Cerebral blood flow was recorded (using positron emission tomography) while middle-aged subjects viewed or visualized pictures of neutral or aversive stimuli, and then determined whether auditorily presented statements correctly described the stimuli. Visualizing aversive stimuli enhanced cerebral blood flow, relative to visualizing neutral stimuli, in areas 17 (right) and 18 (bilateral), as well as the anterior insula (bilateral) and middle frontal cortex (left). Areas 17 and 18 have been identified as supporting the representations that underlie the experience of imagery, and the anterior insula is a major cortical recipient of input from the autonomic nervous system. Perceiving aversive stimuli enhanced cerebral blood flow, relative to neutral stimuli, in area 46, the angular gyrus and area 19, area 47, and the middle temporal gyrus (all in the left hemisphere). All of these areas have previously been implicated in visual object identification. It is striking that negative emotion did not modulate activation in any areas in the same way during imagery and perception.     

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.     

Cortical networks implicated in semantic and episodic memory: common or unique?

While previous functional neuroimaging studies have shown that semantic and episodic memory tasks activate different cortical regions, they never compared regional cerebral blood flow (rCBF) patterns associated with semantic and episodic memory within the same experimental design. In this study, we used H2(15)O PET to study subjects in the course of semantic and episodic memory tasks. rCBF was measured in 9 normal volunteers during a resting baseline condition and two cognitive tasks. In the semantic categorisation task subjects heard a list of concrete words and had to respond to words belonging to the "animals" or "food" category. In the episodic recognition task subjects heard a list of concrete words, half "old", i.e. belonging to the list of the semantic categorisation task, and half "new", i.e. presented for the first time. Subjects had to respond to the "old" words. Both tasks were compared to a resting condition. Statistical analysis was performed with Statistical Parametric Mapping (SPM). Compared to the resting condition, the semantic tasks, activated the superior temporal gyri bilaterally, the left frontal cortex, and right premotor cortex. The episodic tasks activated the left superior temporal gyrus, the frontal cortex bilaterally, and the right inferior parietal cortex. Compared to the episodic memory tasks, the semantic memory tasks activated the superior temporal/insular cortex bilaterally and the right premotor cortex. Compared to the semantic memory tasks, the episodic memory tasks activated the right frontal cortex. These results suggest that cortical networks implicated in semantic and episodic memory show both common and unique regions, with the right prefrontal cortex being the neural correlate specific of episodic remembering.     

Relative changes in regional cerebral blood flow during spinal cord stimulation in patients with refractory angina pectoris

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H(2)(15)O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at T1 modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.     

Visual form discrimination from texture cues: a PET study

With the purpose of localising the cerebral cortical areas participating in the discrimination of visual form generated exclusively by texture cues, we measured changes in regional cerebral blood flow (rCBF) with positron emissions tomography (PET) and 15O-butanol as the tracer. The subjects performed two odd-one-out discrimination tasks: a form-from-texture discrimination task (in which a visual form was defined by differences in texture) and its reference task, the discrimination of texture. During task performance, activated fields were present bilaterally in the primary visual cortex and its immediate extrastriate cortex, the right lateral occipital gyrus, bilaterally in the fusiform and superior temporal gyri and posterior parts of the superior parietal lobules, along the medial bank of the right intraparietal sulcus, and in the right supramarginal gyrus. Other fields were found in the cingulate and prefrontal cortex. The findings demonstrate that the discrimination of visual form as defined by texture engages cortical fields that are widely distributed ion the human brain. In the visual cortex, the activated fields are present in both the occipito-temporal and occipito-parietal visual areas. These results suggest that the perception and discrimination of forms in the visual system requires the joint-activation of neuronal populations in the visual cortex.     

Class II correction with magnets and superelastic coils followed by straight-wire mechanotherapy. Occlusal changes during and after dental therapy

We investigated facial recognition memory (for previously unfamiliar faces) and facial expression perception with functional magnetic resonance imaging (fMRI). Eight healthy, right-handed volunteers participated. For the facial recognition task, subjects made a decision as to the familiarity of each of 50 faces (25 previously viewed; 25 novel). We detected signal increase in the right middle temporal gyrus and left prefrontal cortex during presentation of familiar faces, and in several brain regions, including bilateral posterior cingulate gyri, bilateral insulae and right middle occipital cortex during presentation of unfamiliar faces. Standard facial expressions of emotion were used as stimuli in two further tasks of facial expression perception. In the first task, subjects were presented with alternating happy and neutral faces; in the second task, subjects were presented with alternating sad and neutral faces. During presentation of happy facial expressions, we detected a signal increase predominantly in the left anterior cingulate gyrus, bilateral posterior cingulate gyri, medial frontal cortex and right supramarginal gyrus, brain regions previously implicated in visuospatial and emotion processing tasks. No brain regions showed increased signal intensity during presentation of sad facial expressions. These results provide evidence for a distinction between the neural correlates of facial recognition memory and perception of facial expression but, whilst highlighting the role of limbic structures in perception of happy facial expressions, do not allow the mapping of a distinct neural substrate for perception of sad facial expressions.     

Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease

Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMRglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15 AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorso lateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions results in "positive" delusion formation.     

Multiwell 14CO2-capture assay for evaluation of substrate oxidation rates of cells in culture

The functional anatomy of the interactions between spoken language and visual mental imagery was investigated with PET in eight normal volunteers during a series of three conditions: listening to concrete word definitions and generating their mental images (CONC), listening to abstract word definitions (ABST) and silent REST. The CONC task specifically elicited activations of the bilateral inferior temporal gyri, of the left premotor and left prefrontal regions, while activations in the bilateral superior temporal gyri were smaller than during the ABST task, during which an additional activation of the anterior part of the right middle temporal gyrus was observed. No activation of the occipital areas was observed during the CONC task when compared either to the REST or to the ABST task. The present study demonstrates that a network including part of the bilateral ventral stream and the frontal working memory areas is recruited when mental imagery of concrete words is performed on the basis of continuous spoken language.     

Characterization of two rice MADS box genes that control flowering time

This study utilised positron emission tomography (PET) to identify the cortical areas involved in verbal initiation and suppression in normal subjects whilst performing a sentence completion test (the Hayling Test). In the first condition (response initiation) subjects were required to complete a sentence from which the last word was omitted, whereas in the second condition (response suppression) subjects were asked to complete a sentence with a word which made no sense in the context of the sentence. Subjects were also required to perform a control task in which they had to read out the last word of given sentences. Compared to the control task, response initiation was associated with left-sided activation of the frontal operculum, inferior frontal gyrus, middle temporal gyrus and the right anterior cingulate gyrus, whereas response suppression was associated with left frontal operculum, inferior frontal gyrus and right anterior cingulate gyrus activation. The difference in activation between the two conditions of the Hayling Test lay in the increased activation of the left middle temporal gyrus and the left inferior frontal gyrus during response initiation.     

Distributed neural systems underlying the timing of movements

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).     

Functional MRI activation in children with and without dyslexia during pseudoword aural repeat and visual decode: Before and after treatment.

Children without dyslexia (n=10) received nonphonological treatment, and those with dyslexia received phonological (n=11) or nonphonological (n=9) treatment. Before and after treatment they performed aural repeat, visual decode, and aural match pseudoword tasks during functional MRI scanning that separated stimulus input from response production. Group map analysis indicated that children with dyslexia overactivated compared with good readers during the aural-repeat/aural-match contrast in bilateral frontal (Brodmann's area [BA] 3, 4, 5, 6, 9), left parietal (BA 2, 3), left temporal (BA 38), and right temporal (BA 20, 21, 37) regions (stimulus input) and underactivated in right frontal (BA 24, 32) and right insula (BA 48) regions (response production); they underactivated in BA 19/V5 during the visual-decode/aural-match contrast (response production). Individual brain analysis for children with dyslexia revealed that during the aural-repeat/aural-match contrast (stimulus input), phonological treatment decreased and normalized activation in left supramarginal gyrus and postcentral gyrus. Nonphonological treatment increased and normalized activation during the visual-decode/aural-match contrast (response production) in BA19/V5 and changed activation in the same direction as good readers during aural-repeat/aural-match contrast (stimulus input) in left postcentral gyrus. The significance of the findings for competing theories of dyslexia is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On-line brain potential correlates of right parietal patients' attentional deficit

EEG potentials evoked by cues and targets were recorded in Posner's visual cueing task from 10 patients with lesions of the right parietal cortex and from age-matched healthy subjects. The patients' N1 component evoked by left-side cues was reduced at the right-parietal recording site, suggesting a general impairment in processing left-side visual input. As usual, patients' keypress responses were delayed when left targets were preceded by right cues. There were two correlates of this delay in the patients' EEG potentials evoked by the critical combination of right cue/left target: their mean amplitude 160-280 ms after target onset ('Nd') was less negative than with other combinations of cue and target, and the following frontal P300 was enhanced. The Nd reduction seems to be an on-line measure of patients' momentary decrease of attention for the left hemifield, while the frontal P300 might reflect the patients' attempts at reorienting. In conclusion, different components were sensitive to different aspects of the patients' disorder, suggesting the utility of this approach for developing detailed hypotheses on the mechanisms of attentional deficits involved in visual extinction and neglect.     

Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma

BACKGROUND: An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. OBJECTIVE: To characterize functional brain organization in apraxia. DESIGN AND METHODS: The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. RESULTS: Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. CONCLUSIONS: Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.