PET Activation Study Research Articles

Reading the dyslexic brain: multiple dysfunctional routes revealed by a new meta-analysis of PET and fMRI activation studies.

Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimation methods. The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved spatially significant. Following binomial tests on the clusters, we found left hemispheric network specific for normal controls (i.e., of reduced involvement in dyslexics) including the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform regions: these were preferentially associated with reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task, nor cerebellar clusters showed a reduced association with dyslexics. We conclude that the examined literature demonstrates a specific lack of activation of the left occipito-temporal cortex in dyslexia particularly for reading and reading-like behaviors and for visuo-phonological tasks. Additional deficits of motor and attentional systems relevant for reading may be associated with altered functionality of dorsal left fronto-parietal cortex.

Stroke induced reorganization of the neural networks for sentence comprehension, and relationship to perilesional dysfunction revealed by MEG and ASL

Stroke induced reorganization of the neural networks for sentence comprehension, and relationship to perilesional dysfunction revealed by MEG and ASL

TH‐C‐BRB‐08: Treatment Verification Using Post‐Treatment PET Imaging and Monte Carlo Simulation

Purpose: Investigate the feasibility of using post proton therapy PET and Monte Carlo simulation as a treatment verification system for pediatric patients with localized brain tumors. Method: Under a prospective IRB approved protocol, twelve patients received proton therapy followed by a PET activation study. All patients were under the age of 3 and were under general anesthesia during treatment and post PET imaging. On the day of the PET evaluation, the patient was treated with a single beam corresponding to the activation beam under study. A separate plan was developed to ensure that using a single beam did not compromise the treatment plan. The duration between end of treatment and start of PET imaging for each of the single field treatments was recorded. The PET activation study was acquired for 30 minutes. The patient was fully immobilized for the PET in the same manner as during treatment. The Monte Carlo simulation utilized a previously verified proton dose distribution system modified to report a weighted count of positrons. Comparisons between the treatment planning dose and acquired PET image and between the acquired PET image and Monte Carlos simulated image were made. Results: On average, there were 3 treatment fields per plan and 2 per plan that met the criteria for the PET activation study. The average time between end of irradiation and start of PET acquisition was 14.5+/−1.3 minutes. Based on preliminary data, setup errors are detectable and, utilizing Monte Carlo, distal edge errors may be detectable. Conclusion: The potential exists to detect setup errors and it may be possible to determine if there is a discrepancy between the planned and delivered distal edge of a field. Out of room PET verification has limited clinical usefulness; however, in room PET may be of benefit.

Cerebral glucose metabolism change was detected by SPM in F-18 FDG PET activation study with whisker stimulation in rats

Cerebral glucose metabolism change was detected by SPM in F-18 FDG PET activation study with whisker stimulation in rats

Anatomic substrate of analgesia produced by long-term peripheral nerve stimulation in patients with neuropathic pain: a PET activation study

Anatomic substrate of analgesia produced by long-term peripheral nerve stimulation in patients with neuropathic pain: a PET activation study

Evolution of Brain Activation with Good and Poor Motor Recovery after Stroke

Objective. To characterize the evolution of brain activation in stroke patients with variable motor recovery and quantify changes relative to healthy controls. Methods. Serial PET activation studies, using a simple finger-tapping task, and quantitative measures of motor performance were obtained in 9 patients (2-7 weeks poststroke and 6 months later) and compared with serial healthy volunteer data. Results. Patients with moderate impairment and good recovery (n = 5) activated the primary sensorimotor cortex (SM1) contralateral to the paretic hand moved, bilateral supplementary motor area (SMA), contralateral cingulate gyrus, and ipsilateral lateral premotor cortex. Activation in the bilateral SMA was greater at the initial study but reduced over time compared to healthy controls and poor recoverers. Patients with severe impairment and poor recovery (n =4) showed limited activation of contralateral SM1 and SMA at both studies and no significant change over time. A posterior shift in SM1 activation was evident in good and poor recoverers. Conclusions. Activation of typical motor regions and recruitment of additional sites occur subacutely poststroke, with evolution to normal patterns in moderately impaired patients who recover well. In comparison, severely impaired, poor-recovery patients show persistent, reduced activation. Dynamic changes in SMA, differentially observed in good recoverers over 6 months, highlight its importance in recovery.

A PET activation study of brush-evoked allodynia in patientswith nerve injury pain

Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. PET data were analyzed for the whole group and for single subjects. Allodynic stimulation activated the contralateral orbitofrontal cortex (BA 11) in every patient. Whereas normal brushing activated most strongly the contralateral insular cortex, allodynic brushing produced an ipsilateral activation in this area. Another important difference between normal and allodynic brushing was the absence of a contralateral primary somatosensory cortex (SI) activation during allodynic brushing. No thalamic activation was observed during allodynic or control brushing. Although no anterior cingulate cortex (ACC) activation could be demonstrated in the group analysis, single subject analysis revealed that four patients activated this region during brush-evoked allodynia. A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.

Force level independent representations of predictive grip force–load force coupling: A PET activation study

The existence of forward internal models is a fundamental principle in theories of predictive motor control. There are indications that internal models are represented in the cerebellum. So far, no conclusive data exist on automated procedures involving predictive motor behavior. In particular, it is unknown whether single or multiple task-specific internal models handle the broad range of behavioral situations in which they occur. Using H 2 15O PET in eight subjects, we examined predictive motor control in an automated grip force–load force coupling task at three differing load force levels. In the experimental condition, subjects pulled a grasped object against an isometric resistance while simultaneously producing anticipatory grip forces. There were three control conditions (pull force isolated; grip force isolated; motor rest). A 2 × 2 factorial design was chosen to reveal the interaction effect of grip force–pull force coupling. The factors were pull force (with/without) and grip force (with/without). Grip and load forces were well matched between experimental and control conditions. Conjunction inference and interaction analyses identified force coupling related activity in the ipsilateral posterior cerebellum that was independent of force levels. Interaction effects were also identified in the anterior cingulate and frontal association regions, the right caudate nucleus, and the left lingual gyrus. These data demonstrate the existence of modular representations for predictive force coupling, with the ipsilateral cerebellum playing a major role. Moreover, the data implicate that the representations for predictive force control are applicable to a range of different environmental affordances.

Circuits neuronaux de la lecture et de récriture dans la langue japonaise (le kanji et la kana)

Japanese writing system consists of two different types of letters, kana (phonogram) and kanji (morphogram). Various types of alexia with or without agraphia in the Japanese language cause specific type of kanji/kanja dissociation. Upon the neuropsychological analysis of these dissociations, we have proposed a hypothesis of dual neuronal circuits of reading and writing process. Subsequent PET activation studies upon normal subjects confirmed the hypothesis; semantic reading pathway via area 37 on the inferior border of the left temporal lobe and phonological reading pathway via middle portion of the left lateral occipital lobe.

The parahippocampal gyrus in the baboon: anatomical, cytoarchitectonic and magnetic resonance imaging (MRI) studies.

The parahippocampal gyrus, located at the medial temporal lobe, is a key structure in declarative memory processing. We have analyzed the general organization of the parahippocampal gyrus in the baboon, a nonhuman primate species relatively close to human. This region is rostrocaudally made up of the temporopolar, perirhinal, entorhinal (divided into seven subfields) and posterior parahippocampal (areas TH and TF) cortices. The basic analysis has been performed in three brains, serially sectioned and stained with thionin, myelin stain, acetylcholinesterase and parvalbumin, to determine cytoarchitectonic boundaries. Borders of all subfields were charted onto camera lucida drawings, and two-dimensional maps of the surface and topography of the parahippocampal gyrus were made. Finally, the limits of each parahippocampal area were then transposed on corresponding MR images (commonly used for in vivo PET or functional MRI activation studies) of two animals for precise identification. The general cytoarchitectonic features of the baboon parahippocampal gyrus are similar to macaques, but the size of temporopolar cortex and the laminar organization of perirhinal and posterior parahippocampal cortices resemble humans more than macaque species. In conclusion, the size and structure of the baboon parahippocampal cortex makes this species very appropriate for experimental studies on memory function.

Network for auditory intrinsic alertness: a PET study

Intrinsic alertness designates the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time (RT) measurements without preceding warning stimuli. Until now, cerebral networks subserving alertness after visual and somatosensory stimulation have been reported. Studies concerning other intensity aspects of alertness like sustained attention and vigilance, on the other hand, have been performed in the auditory modality, too. In a 15 O -butanol PET-activation study in 10 right-handed young healthy male volunteers an intrinsic alertness network was studied for the auditory modality. In contrast with a sensorimotor control condition we found an extended predominantly right-hemisphere network similar to those reported for other sensory modalities including frontal, cingular, inferior parietal, temporal and thalamic structures, when subjects waited for and rapidly responded to a 1000 Hz tone signal by pressing a response key with the right-hand thumb. There were, however, some differences in the topography of the frontal, temporal and thalamic activations between auditory and visual stimulation which are discussed with respect to similar results for auditory vigilance and auditory selective attention tasks reported in the literature.

Semantic decision making in early probable AD: a PET activation study

We studied the neural correlates of semantic decision making in early probable Alzheimer disease patients and age-matched controls by measuring changes in relative cerebral blood flow by PET (oxygen-15) while they performed a category-specific word-matching task with either animal or artefact names. In comparison to a baseline (matching words by physical identity), semantic decision making elicited increased blood flow in the left frontal lobe (BA 6, 11, 47) and in the contralateral cerebellum in the controls. The only category-specific difference in controls was activation of the left supplementary motor area (BA 6) when making decisions on artefacts. In contrast, the patients recruited more extensive brain regions, encompassing areas in the left frontal lobe (BA 44, 45, 47), right occipital cortex (BA 18), midbrain, and the cerebellum bilaterally. Behaviorally, the patients performed the tasks with equal success albeit more slowly. No animal–artefact differences emerged in the patients' activation patterns, indicating that their activation increases reflected a generalized, presumably compensatory reaction to higher task demands in the face of a progressive neurological disease.

Interindividual variability in the hemispheric organization for speech

A PET activation study was designed to investigate hemispheric specialization during speech comprehension and production in right- and left-handed subjects. Normalized regional cerebral blood flow (NrCBF) was repeatedly monitored while subjects either listened to factual stories (Story) or covertly generated verbs semantically related to heard nouns (Gener), using silent resting (Rest) as a common control condition. NrCBF variations in each task, as compared to Rest, as well as functional asymmetry indices (FAI = right minus left NrCBF variations), were computed in anatomical regions of interest (AROIs) defined on the single-subject MNI template. FAIs were predominantly leftward in all regions during both tasks, although larger FAIs were observed during Gener. Subjects were declared “typical” for language hemispheric specialization based on the presence of significant leftward asymmetries (FAI < 0) in the pars triangularis and opercularis of the inferior frontal gyrus during Gener, and in the middle and inferior temporal AROIs during Story. Six subjects (including five LH) showed an atypical language representation. Among them, one presented a right hemisphere specialization during both tasks, another a shift in hemispheric specialization from production to comprehension (left during Gener, right during Story). The group of 14 typical subjects showed significant positive correlation between homologous left and right AROIs NrCBF variations in temporal areas during Story, and in temporal and inferior frontal areas during Gener, almost all regions presenting a leftward FAI. Such correlations were also present in deactivated areas with strong leftward asymmetry (supramarginalis gyrus, inferior parietal region). These results suggest that entry into a language task translates into a hemispheric reconfiguration of lateral cortical areas with global NrCBF increase in the dominant hemisphere and decrease in the minor hemisphere. This can be considered as the setting up of a “language mode”, under the control of a mechanism that operates at a perisylvian level. On top of this global organization, regional variations carry on the performance of the cognitive operations specific to the language task to be performed. Hemispheric relationships could be different in atypical subjects, with either between task hemispheric regulation differences or differences in regional specialization.

Disturbance and recovery of language function: correlates in PET activation studies

Disturbance of neurologic function in disorders of the central nervous system is expressed as an altered activation pattern in functional networks employed by specific tasks and can be studied by functional imaging modalities, e.g., positron emission tomography. Language, a complex brain function, is based on the interplay of a distributed network in which partial functions are executed in various centers, the primary language areas. These areas are hierarchically organized and activated according to the complexity of the specific language task. The specialization of different centers and the lateralization of integrative functions into the dominant (usually left) hemisphere are achieved by collateral and transcallosal inhibition of secondary language areas which normally are not employed for performance of a specific language task.

Reflections on the application of 13C‐MRS to research on brain metabolism

The power of (13)C-MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Examples from animal studies, by examination of tissue extracts from the whole brain, brain slices and cultured cells, include observation of intermediates such as citrate and triose phosphates which have yielded novel information on neuronal/glial relationships. The use of (13)C-labelled acetate as a specific precursor for glial metabolism provided evidence in support of the view that some of the GABA produced in the brain is derived from glial glutamine. Such studies have also provided direct evidence on the contribution of anaplerotic pathways to intermediary metabolism. Analogous studies are now being performed on the human brain, where (13)C-acetate is used to quantitate the overall contribution of glial cells to intermediary metabolism, and use of (13)C-glucose enables direct calculation of rates of flux through the TCA (F(TCA)) and of the glutamate-glutamine cycle (F(CYC)), leading to the conclusion that the rate of glial recycling of glutamate accounts for some 50% of F(TCA). The rate of 0.74 micromol min(-1) g(-1) for F(TCA) is compatible with PET rates of CMRglc of 0.3-0.4 micromol min(-1) g(-1) (since each glucose molecule yields two molecules of pyruvate entering the TCA). Our brain activation studies showed a 60% increase in F(TCA), which is very similar to the increases in CBF and in CMRglc observed in PET activation studies.

Effects of attenuation correction and reconstruction method on PET activation studies

The outcome of Statistical Parametric Mapping (SPM) analyses of PET activation studies depends among others, on the quality of reconstructed data. In general, filtered back-projection (FBP) is used for reconstruction in PET activation studies. There is, however, increasing interest in iterative reconstruction algorithms such as ordered subset expectation maximization (OSEM) algorithms. The aim of the present study was to investigate the effects of reconstruction techniques and attenuation correction (AC) on the detection of activation foci following statistical analysis with SPM. First, a replicate study was performed to assess the effects of the reconstruction method on pixel variance. Second, a phantom study was performed to evaluate the influence of both locations of an activated area and applied reconstruction method on SPM outcome. A volumetric method was used to compute the number of false positive voxels for all reconstructions. In addition, average t values within activation foci and for false positive voxels were calculated. For the assessment of the effects of reconstruction on clinical data, a group of 11 patients was studied. For all reconstructions SPM maps were created and compared. Both the clinical and the phantom data showed that use of iterative reconstruction methods reduced false positive results, while showing similar SPM results within activated areas as FBP. Reconstruction of data without attenuation correction reduced noise for FBP only, but did not affect the quality of SPM results for OSEM. It is concluded that OSEM is a good alternative for FBP reconstructions providing SPM results with less noise.

Attenuation correction of PET activation studies in the presenceof task-related motion

Motion-induced misalignment between transmission and emission scans can result in erroneous estimation of regional tissue activity concentrations. If this motion is of a random nature, mismatch between transmission and emission scans is likely to result in diminished signal-to-noise ratios. In the case of task-related motion, however, corresponding systematic reconstruction artefacts may lead to false-positive or false-negative results. The purpose of the present study was to investigate whether implementation of an image registration (IR) method, which allows for motion-corrected attenuation correction, would improve accuracy of H 2 15O PET activation studies. To evaluate the performance of this method, phantom studies as well as studies in human subjects were performed. Results were compared with three alternative methods: standard attenuation correction without motion correction, calculated attenuation correction, and no attenuation correction. The phantom measurements showed that, for quantitative assessment of regional activity concentrations, the IR method was superior to the other attenuation correction methods. In a single-subject study with intentional task-related motion during a visual stimulation paradigm, false-positive results, obtained with the standard attenuation correction method, disappeared after attenuation correction using the IR method. Finally, a group analysis of 11 patients indicated that an increase in signal-to-noise ratio was obtained with the IR method. Therefore, in our view, the IR method should be considered as a first choice for attenuation correction in PET activation studies.

Experimental evaluation of iterative reconstruction versus filtered back projection for 3D [ 15O]water PET activation studies using statistical parametric mapping analysis

Iterative reconstructions are increasingly used for clinical PET studies owing to the better noise properties compared with filtered backprojection (FBP). The purpose of the present study was to compare ordered subsets expectation maximization (OSEM) iterative reconstruction with FBP as input for statistical parametric mapping (SPM) analysis of PET activation studies. Two phantom studies were performed simulating both motor and cognitive tasks and acquiring data with both high and low statistics. In contrast to clinical studies, where no a priori information is known, phantom studies allow for an accurate and detailed comparison between different reconstruction techniques. The significance of “activations” during “tasks” was determined using SPM99 software. Using region of interest analysis of SPM results, it was found that the maximum and average t values within each hot spot of the phantom were higher for OSEM than for FBP. In addition, OSEM4 × 16 (4 iterations, 16 subsets) produced fewer false-positive voxels than FBP, OSEM1 × 16 and OSEM2 × 16. In conclusion, for PET activation studies use of OSEM4 × 16 seems to give the best tradeoff between signal detection and noise reduction.

Residual naming after damage to the left temporal pole: a PET activation study

Normal subjects activate the left temporal polar cortex when they name persons, and subjects with damage to the left temporal pole due to left anterior temporal lobectomy are impaired in the retrieval of the proper names of persons. Eight such subjects were studied in a PET activation experiment to address the neural systems supporting their residual naming. We hypothesized that there would be increased activity, relative to normal controls, in the surround of the damaged region, the homologous right temporal pole, or both. Neither the group nor individual target subjects showed significantly increased activity in the lesion surround or in the right temporal pole. Several other regions that are activated by normals during the retrieval of the proper names of persons and which were undamaged in the target subjects (left anterior superior temporal sulcus, mesial frontal cortex, and anterior cingulate) were nevertheless significantly less activated by the target subjects, a finding that suggests that damage to the left temporal pole alters the function of a large-scale system needed for the retrieval of proper nouns. There was increased activity in early visual cortices, suggesting intensification of visual processing to compensate for the defective preferred name retrieval processing.

PET activation studies comparing two speech tasks widely used in surgical mapping

“Automatic” speech, especially counting, is frequently preserved in aphasia, even when word production is severely impaired. Although brain sites and processes for automatic speech are not well understood, counting is frequently used to elicit fluent speech during preoperative and intraoperative cortical mapping for language. Obtaining both behavioral and functional brain imaging measures, this study compared counting with a word production task (generation of animal names), including non-verbal vocalizations and quiet rest as control states, in normal and aphasic subjects. Behavioral data indicated that normal and aphasic groups did not differ in counting or non-verbal vocalizations, but did differ significantly in word production (“naming” animals). Functional brain imaging results on normal subjects using partial least squares analysis of PET rCBF images revealed three significant latent variables (LVs): one for naming and vocalizing, identifying bilateral anterior areas, with left predominating over right; a second LV for naming, identifying left and right frontal and temporal areas. For the third, only marginally significant LV, which was associated with automatic speech alone (counting), right and subcortical sites predominated. For patients, two LVs emerged, identified with naming and vocalization, and corresponding to a variety of cerebral sites; the analysis failed to find a specific latent variable for counting. A comparison between group data for normal subjects and patients suggested that the naming, counting, and vocalization tasks were performed differently by the two groups. These results suggest that word generation as a verbal task is more likely to elicit activity in classical language areas than counting. Further studies are suggested to better understand differences between neurological substrates for non-propositional and automatic speech.