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Biomedical subjects

F M Mottaghy

Publications and source records attributed to F M Mottaghy.

At least 19 recordsLinked to original sources

Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours.

BACKGROUND: Integrated positron emission tomography (PET)/computed tomography (CT) scanners have been recently introduced in the diagnostic work-up of suspected pulmonary malignancy and demonstrate encouraging results in the staging of nonsmall-cell lung cancer. OBJECTIVE: To evaluate the usefulness of integrated FDG PET/CT in pulmonary carcinoid tumours. SETTING: University hospital. METHODS: We studied 13 patients (mean age +/- 1 SD, 57 +/- 11 years) with pulmonary carcinoid tumours. All patients demonstrated a single pulmonary lesion. Integrated PET/CT scan and surgical resection were performed in all patients. RESULTS: The pulmonary lesion size ranged from 1.1 to 5.0 cm. Final histological diagnosis confirmed 12 typical and one atypical pulmonary carcinoid. Mean proliferation rate of the typical carcinoids was 1.7 +/- 1.4%. None of the patients had recurrent carcinoid disease or died during follow-up (864 +/- 218 days). Mean standardized uptake value (SUV) of (18)F-fluorodeoxyglucose (FDG) in typical carcinoids was 3.0 +/- 1.5 (range 1.2 - 6.6); SUV in the atypical carcinoid was remarkably high with a value of 8.5. The SUV was lower than 2.5 in 6 of 12 patients (50%). Mediastinal lymph node metastases or extrathoracic metastases were not detected in any patient. CONCLUSIONS: (18)F-fluorodeoxyglucose PET/CT imaging improves accurate localization of metabolic activity and thus the interpretation of pulmonary lesions on CT. FDG uptake in pulmonary carcinoid tumours is often lower than expected for malignant tumours. Therefore, surgical resection or biopsy of lesions suspected to be carcinoids should be mandatory, even if they show no hypermetabolism on FDG PET images.

Adult↗

Internal radionuclide therapy: software for treatment planning using tomographic data.

AIM: Accurate dosimetry must be performed for each patient before therapy with unsealed radionuclides. Recently, the software tool ULMDOS was developed to facilitate planar dosimetric calculations and to support traceability and documentation as a prerequisite for good clinical practice. Here, the extended version of ULMDOS for processing of tomographic data is presented. METHODS: ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. Serial tomographic data can be loaded in an ECAT7 or DICOM format, and presented as maximum intensity projection. The definition of volumes of interest is supported by various tools (e.g., freehand, isocontour, polygon), region growing, and cluster analysis. Residence times are calculated from fits of the time activity data to exponential functions. RESULTS, DISCUSSION: Quantitative 3-dimensional data allow performing a more individualized dosimetry, as problems due to organ overlay, insufficient attenuation and scatter correction in the planar approach can be avoided. For traceability, documentation, retrospective examination and later processing all data can be saved in binary or ASCII format. Dosimetric calculations can be conducted within a single environment, thus it spares the time-consuming transfer of data between different software tools.

Humans↗

Interfering with working memory in humans.

The interference method transcranial magnetic stimulation has to be seen as a complimentary tool to the other noninvasive correlational techniques such as positron emission tomography, functional magnetic resonance imaging or electroencephalography in cognitive neuroscience. However, the combination of two methods e.g. transcranial magnetic stimulation and positron emission tomography seems to be the strongest approach to validate or postulate new hypotheses. In this review several studies using transcranial magnetic stimulation to disentangle working memory functions are presented. The conclusion is drawn that there exists a superordinated amodal central executive within the dorsolateral prefrontal cortex strongly connected with modality specific areas mainly within the prefrontal cortex.

Humans↗

Modulatory effects on human sensorimotor cortex by whole-hand afferent electrical stimulation.

OBJECTIVE: To investigate the effect of electrical stimulation of the nerve afferents of the hand on cortical activity elicited by whole-hand subthreshold stimulation for sensation in healthy human subjects. METHODS: Ten healthy volunteers were studied using BOLD-fMRI with 1) a test motor-task with finger-to-thumb tapping of the left hand, 2) a whole-hand afferent electrical stimulation of the left hand below the sensory level for sensation for 30 minutes, 3) a second fMRI run with the same paradigm as in the test motor-task immediately after electrical stimulation, and 4) a final identical fMRI run 2 hours post-stimulation to test the cortical changes induced by electrical stimulation. Experiments were carried out on a 1.5 T MR scanner and for fMRI echoplanar sequences were used. Data analysis was performed with SPM99. RESULTS: An increase of movement-related responses was seen within the primary motor and primary somatosensory areas of both hemispheres when comparing the test motor-task with the motor-task after electrical stimulation relative to the baseline or sham stimulation. Two hours post-stimulation the modulatory effects of mesh-glove stimulation diminished to baseline level except within the contralateral primary motor region. CONCLUSIONS: The increased BOLD response spatially localized within the sensorimotor cortex reflects an increase in neuronal activity that may provide augmented neuronal excitability.

Adult↗

[Significance of PET for ENT-tumors].

Significance for ENT-tumors. Molecular imaging with PET is based on the use of specific radioactive molecules as source of image contrast. In ENT-tumors mostly glucose and occasionally amino acid/protein metabolism were assessed with PET for tumor diagnosis. Thymidine salvage pathway and proliferation as well as tissue hypoxia are tested already in clinical studies and bear considerable potential for modulation of radiation ports and therapeutic response of cytoreductive regimens. This short review summarises actual clinical indications and potential of PET in ENT-tumors. For both nodal staging as well as detection of recurrent disease, sensitivity and specifity of FDG-PET were 80 - 100 %. FDG-PET proved to be superior to conventional imaging in most published studies. In CUP-syndrome the primary could be detected in 25 - 50 % of patients. Acquisition of PET and CT images in a combined scanner allow versatile PET based metabolic imaging in combination with high resolution and anatomical precise CT-based morphological imaging and thus combines advantages of both imaging modalities. Clinical as well as scientific potential of this functional metabolic and high resolution morphological imaging approach is high.

Amino Acids↗

Repetitive TMS temporarily alters brain diffusion.

The authors investigated whether repetitive transcranial magnetic stimulation (rTMS) at 1 Hz (12 minutes; 90% of motor threshold) to the primary motor cortex (M1) leads to changes in diffusion-weighted imaging (DWI). After the rTMS train, there was a temporary small restriction in diffusion within the targeted left M1 that disappeared after 5 minutes. These findings provide a physiologic correlate to the reported behavioral consequences of off-line 1-Hz rTMS and reveal the transitory nature of the effects.

Adult↗

Chronometry of parietal and prefrontal activations in verbal working memory revealed by transcranial magnetic stimulation.

We explored the temporal dynamics of parietal and prefrontal cortex involvement in verbal working memory employing single-pulse transcranial magnetic stimulation (TMS). In six healthy volunteers the left or right inferior parietal and prefrontal cortex was stimulated with the aid of a frameless stereotactic system. TMS was applied at 10 different time points 140-500 ms into the delay period of a two-back verbal working memory task. A choice reaction task was used as a control task. Interference with task accuracy was induced by TMS earlier in the parietal cortex than in the prefrontal cortex and earlier over the right than the left hemisphere. This suggests a propagation of information flow from posterior to anterior cortical sites converging in the left prefrontal cortex. Significant interference with reaction time was observed after 180 ms with left prefrontal cortex stimulation. These effects were not observed in the control task, underlining the task specificity of our results. We propose that the interference with right-sided prefrontal cortex stimulation leads to impaired performance due to disturbed input into the left prefrontal cortex, whereas left-sided TMS interferes directly with the final information processing. Left- and right-sided brain areas might be involved in parallel processing of semantic and object features of the stimuli, respectively.

Adult↗

[Neurocognition and PET. Strategies for data analysis in activation studies on working memory].

AIM: In cognitive neuroscience regional cerebral blood flow (rCBF) imaging with positron-emission-tomography (PET) is a powerful tool to characterize different aspects of cognitive processes by using different data analysis approaches. By use of an n-back verbal working memory task (varied from 0- to 3-back) we present cognitive subtraction analysis as basic strategy as well as parametric and covariance analyses and discuss the results. METHODS: Correlation analyses were performed using the individual performance rate as an external covariate, computing inter-regional correlations, and as network analysis applying structural equation modelling to evaluate the effective connectivity between the involved brain regions. RESULTS: Subtraction analyses revealed a fronto-parietal neuronal network also including the anterior cingulate cortex and the cerebellum. With higher memory load the parametric analysis evidenced linear rCBF increases in prefrontal, pre-motor and inferior parietal areas including the precuneus as well as in the anterior cingulate cortex. The rCBF correlation with the individual performance as external covariate depicted negative correlations in bilateral prefrontal and inferior parietal regions, in the precuneus and the anterior cingulate cortex. The network analysis demonstrated mainly occipito-frontally directed interactions which were predominantly left-hemispheric. Additionally, strong linkages were found between extrastriate and parietal regions as well as within the parietal cortex. CONCLUSION: The data analysis approaches presented here contribute to an extended and more elaborated understanding of cognitive processes and their different sub-aspects.

Brain↗

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans.

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Adult↗

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Adult↗

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS.

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.

Adult↗

Grammatical distinctions in the left frontal cortex.

Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.

Adolescent↗

Phase-specific modulation of cortical motor output during movement observation.

The effects of different phases of an observed movement on the modulation of cortical motor output were studied by means of transcranial magnetic stimulation (TMS). A video-clip of a reaching-grasping action was shown and single TMS pulses were delivered during its passive observation. Times of cortical stimulation were related to the phases of the shown movement, locking them to the appearance of specific kinematic landmarks. The amplitude of the motor evoked potentials (MEPs) induced by TMS in the first dorsal interosseus (FDI) muscle was modulated by the amount of the observed finger aperture. The presence of such an effect is consistent with the notion of a mirror neuron system in premotor areas that couples action execution and action observation also in terms of temporal coding.

Acoustic Stimulation↗

Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study.

OBJECTIVE: Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. METHODS: Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. RESULTS: TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. CONCLUSIONS: Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.

Adult↗

Intracortical inhibition and facilitation in human facial motor area: difference between upper and lower facial area.

OBJECTIVE: To investigate the intracortical inhibitory and excitatory systems in the motor cortical representation of upper and lower facial muscles. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied to 7 healthy volunteers, with the interstimulus interval (ISI) between the conditioning stimulus (CS) and test stimulus, varied from 1 to 20 ms. CS was set at 90% of motor threshold. Muscle evoked potentials (MEPs) were recorded from first dorsal interosseus (FDI), orbicularis oculi (o. oculi) and mentalis muscles. RESULT: TMS evoked MEPs in o. oculi on both ipsi- and contralateral sides in all subjects. In the paired-pulse study, MEP amplitude in the mentalis decreased at short ISIs of 1-3 ms, followed by increases at 12-20 ms. These effects were similar to those in the FDI. O. oculi did not show a distinct inhibitory period at short ISIs and facilitation at long ISIs was detected but was significantly less than in FDI and mentalis. In o. oculi, there was no significant difference between the effects of ipsilateral and contralateral CS on the MEPs. CONCLUSION: The bi-hemispheric control of volitional movement and the modulation from brainstem projections appear to markedly influence intracortical inhibitory and excitatory systems in the motor cortical representation of o. oculi.

Adult↗

Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters.

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.

Adult↗

RTMS induces brief events of muscle atonia in patients with narcolepsy.

STUDY OBJECTIVES: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) in patients with narcolepsy. DESIGN: Using rTMS, three patients with narcolepsy and cataplexy were investigated with and without their anticataplectic medication. rTMS of the motor cortex was performed at an intensity of 110% of resting motor threshold, a frequency of 20 Hz, and a duration of 2s. EMG activity was recorded for both the right and left first dorsal interosseous muscle (FDI). Eight healthy controls were also investigated under the same conditions. SETTING: The study was carried out in the sleep laboratory of the Neurology Department (University of Aachen). PATIENTS: One female and two male patients with narcolepsy/cataplexy. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In three narcoleptic patients, after three days of not taking their usual anticataplectic medication, rTMS of the motorcortex induced an interruption of voluntary EMG activity in the FDI. EMG reduction lasted from 0.6 to 3.5s and was more pronounced in the hand contralateral to the stimulated hemisphere. This result was not observed in these patients when taking their regular medication nor in the normal controls. Stimulation of other cortical areas, as well as stimulation of the peripheral nervous system, did not induce muscle weakness episodes. CONCLUSIONS: We postulate that rTMS of the descending voluntary motor pathway triggers muscle atonia similar to cataplexy by indirectly activating the mechanisms responsible for the generation of muscle atonia during REM sleep and cataplexy. We conclude that rTMS, in the future, might prove to be a useful addition to the diagnostic repertoire for narcolepsy.

Adult↗

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation.

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Adult↗