Incidental Verbal Semantic Processing Recruits the Fronto-temporal Semantic Control Network.

The frontoparietal semantic network, encompassing the inferior frontal gyrus and the posterior middle temporal cortex, is considered to be involved in semantic control processes. The explicit versus implicit nature of these control processes remains however poorly understood. The present study examined this question by assessing regional brain responses to the semantic attributes of an unattended stream of auditory words while participants' top-down attentional control processes were absorbed by a demanding visual search task. Response selectivity to semantic aspects of verbal stimuli was assessed via a functional magnetic resonance imaging response adaptation paradigm. We observed that implicit semantic processing of an unattended verbal stream recruited not only unimodal and amodal cortices in posterior supporting semantic knowledge areas, but also inferior frontal and posterior middle temporal areas considered to be part of the semantic control network. These results indicate that frontotemporal semantic networks support incidental semantic (control) processes.

Spectral quality of light modulates emotional brain responses in humans.

Light therapy can be an effective treatment for mood disorders, suggesting that light is able to affect mood state in the long term. As a first step to understand this effect, we hypothesized that light might also acutely influence emotion and tested whether short exposures to light modulate emotional brain responses. During functional magnetic resonance imaging, 17 healthy volunteers listened to emotional and neutral vocal stimuli while being exposed to alternating 40-s periods of blue or green ambient light. Blue (relative to green) light increased responses to emotional stimuli in the voice area of the temporal cortex and in the hippocampus. During emotional processing, the functional connectivity between the voice area, the amygdala, and the hypothalamus was selectively enhanced in the context of blue illumination, which shows that responses to emotional stimulation in the hypothalamus and amygdala are influenced by both the decoding of vocal information in the voice area and the spectral quality of ambient light. These results demonstrate the acute influence of light and its spectral quality on emotional brain processing and identify a unique network merging affective and ambient light information.

Pain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation.

Granitic groundwater colloids sampling and characterisation: the strategy for artefact elimination.

Colloids were separated by submicro-filtration of granitic groundwater samples collected at-line under in-situ thermodynamic conditions after down-hole groundwater sampling and transfer at the well head. The methodology avoids the generation of artefacts produced by pH changes due to CO(2) exchange, yielding potential carbonate precipitation, or by O(2) contamination yielding oxidized insoluble phases. The enhanced pressure and the anoxic conditions are also maintained through the filtering procedure. This procedure was carried out after a period of regular sampling of groundwater pumped to the ground surface and continuous on-line long-term measurements (weeks, months) of chemical and physical parameters in the unbroken sample water both at the ground surface and at depth down-hole. Colloid samples were characterized on the submicro-filtration membrane by scanning electron microscopy. Under deep granite groundwater conditions, natural colloids occur sparsely. The colloid concentration was determined C(col) approximately 1 and approximately 50 microg L(-1) for sizes ranging from 50 to 200 nm or n(col) approximately 3.9 x 10(9) and 47 x 10(9) L(-1) for sizes larger than 50 nm for KFM11A, Forsmark, and KLX17A, Laxemar, Oskarshamn, respectively, Sweden. These colloids are expected to be clay particles with an average size smaller than 200 nm for the Na-Ca-Cl and Na-Cl groundwaters (pH 7.6 and 8.00, ionic strength approximately 10(-1) and approximately 10(-2) mol L(-1), respectively, for KFM11A and KLX17A), the colloid concentrations were comparable with values previously reported in the literature.

Experience-dependent changes in cerebral activation during human REM sleep.

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.

Relation between contractile reserve and positron emission tomographic patterns of perfusion and glucose utilization in chronic ischemic left ventricular dysfunction: implications for identification of myocardial viability.

OBJECTIVES: This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion-metabolism mismatch. METHODS: In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 microg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments. RESULTS: Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion-metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake > or = 50% supplied by vessels with > or = 75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels. CONCLUSIONS: Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly < 50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.

Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study.

PURPOSE: [(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. PROCEDURES: Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1-156.5 MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. RESULTS: The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10(-2) ± 6.84 × 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 × 10(-2) ± 2.32 × 10(-3) mGy/MBq. CONCLUSIONS: This first human dosimetry study of [(18)F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

Functional neuroanatomy of hypnotic state.

BACKGROUND: The aim of the present study was to describe the distribution of regional cerebral blood flow during the hypnotic state (HS) in humans, using positron-emission tomography (PET) and statistical parametric mapping. METHODS: The hypnotic state relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness." A group of 9 subjects under polygraphic monitoring received six H215O infusions and was scanned in the following order: alert-HS-HS-HS with color hallucination-HS with color hallucination-alert. PET data were analyzed using statistical parametric mapping (SPM95). RESULTS: The group analysis showed that hypnotic state is related to the activation of a widespread, mainly left-sided, set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal cortices and a few right-sided regions: occipital and anterior cingulate cortices. CONCLUSIONS: The pattern of activation during hypnotic state differs from those induced in normal subjects by the simple evocation of autobiographical memories. It shares many similarities with mental imagery, from which it differs by the relative deactivation of precuneus.

Combined study of cerebral glucose metabolism and [11C]methionine accumulation in probable Alzheimer's disease using positron emission tomography.

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measures with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.

Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

Neural and cognitive bases of upper limb apraxia in corticobasal degeneration.

OBJECTIVE: To investigate the neural and cognitive bases of upper limb apraxia in corticobasal degeneration (CBD). METHODS: Eighteen patients with CBD underwent a cognitive neuropsychological assessment of apraxia and resting [(18)F]-fluorodeoxyglucose PET scanning. Two complementary measures of apraxia were computed for each modality of gesture production. First, a performance score measured error frequency during gesture execution. Second, as a more stringent test of the integrity of the praxis system, the correction score measured the patient's ability to correct his or her errors on a second attempt. For each measure type, a cut-off score for the presence of apraxia was defined with regard to healthy controls. Using each cut-off score, the regional cerebral glucose metabolism of patients with CBD with apraxia (i.e., performing below cut-off score) was compared with that of patients with CBD without apraxia. RESULTS: Mean performance scores were below normal values in all modalities. Anterior cingulate hypometabolism predominated in patients with CBD who performed below the cut-off performance score. At variance, mean correction scores were below normal values for gesture imitation only. Hypometabolism in superior parietal lobule and supplementary motor area characterized patients with CBD who were unable to correct their errors at the same rate as control subjects did. CONCLUSIONS: Distinct neural networks underlie distinct aspects of the upper limb apraxic deficits in CBD. Extending previous findings of gesture production deficits in CBD, the use of complementary measures of apraxic behavior discloses a visuoimitative upper limb apraxia in CBD, underlain by a metabolic decrease in a parietofrontal neural network.

Effects of incidental and intentional feature binding on recognition: a behavioural and PET activation study.

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were tested: incidental and intentional word-to-colour binding. Word-only recognition was associated with brain activation in a lexico-semantic left middle temporal region and in the cerebellum following an incidental colour encoding, and with brain activation in the left posterior middle frontal gyrus, right anterior cingulate and right inferior frontal gyrus following an intentional encoding. Recognition of bound features was associated with activation in left prefrontal and superior parietal regions following an incidental colour encoding, and with preferential right prefrontal cortex activation following an intentional colour encoding. Our results are in line with the hypothesis of a parietal involvement in context processing, and prefrontal areas in monitoring retrieval processes. Our results also support the hypothesis of a 'cortical asymmetry for reflective activity' (CARA).

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep.

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal reactivations during post-training sleep in animals have been observed in hippocampal (Wilson and McNaughton, 1994) and cortical (Amzica et al., 1997) neuronal populations. At the systems level, using positron emission tomography, we have recently shown that some brain areas reactivated during rapid-eye-movement sleep in human subjects previously trained on an implicit learning task (a serial reaction time task) (Maquet et al., 2000). These cortical reactivations, located in the left premotor area and bilateral cuneus, were thought to reflect the reprocessing--possibly the consolidation--of memory traces during post-training rapid-eye-movement sleep. Here, the experience-dependent functional connectivity of these brain regions is examined. It is shown that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during rapid-eye-movement sleep of subjects previously trained to the reaction time task compared to rapid-eye-movement sleep of untrained subjects. The increase in functional connectivity during post-training rapid-eye-movement sleep suggests that the brain areas reactivated during post-training rapid-eye-movement sleep participate in the optimization of the network that subtends subject's visuo-motor response. The optimization of this visuo-motor network during sleep could explain the gain in performance observed during the following day.

Differential diagnosis of Alzheimer's disease with PET.

UNLABELLED: PET studies have demonstrated bilateral temporo-parietal hypoperfusion and hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other dementias. METHODS: To evaluate the diagnostic power of cerebral metabolic distribution patterns for "cortical" degenerative dementias, PET scans obtained from 129 patients referred for differential diagnosis of dementia were analyzed visually. RESULTS: Sixty-five patients had a final clinical diagnosis of probable AD. Ninety-seven percent (97%) of those had abnormal metabolic scans and 94% showed a suggestive pattern of bilateral or unilateral temporo-parietal hypometabolism (with or without frontal involvement). Hypometabolism was unilateral in 23% of patients. Five subjects with a neuropathologically proven diagnosis of Alzheimer's disease had a suggestive metabolic pattern. One of those was an early case with frontal hypometabolism exceeding temporo-parietal involvement. Two patients with Alzheimer's-type dementia had isolated bilateral frontal hypometabolism. CONCLUSIONS: This alternative metabolic pattern may correspond to a non-Alzheimer pathology occurring in 10%-20% of patients suffering from clinically probable Alzheimer's disease. Most of the patients with possible but atypical Alzheimer's-type dementia showed isolated bilateral frontal involvement. This metabolic pattern probably corresponds to different diseases, such as Pick's disease, frontal lobe dementia or progressive subcortical gliosis.

Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine.

UNLABELLED: This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.

Myocardial kinetics of potassium-38 in humans and comparison with copper-62-PTSM.

UNLABELLED: The aim of this study was to define the kinetics of 38K and its suitability to evaluate myocardial blood flow at rest and during pharmacological vasodilation in normal subjects. Potassium-38's kinetic characteristics were also compared to those of a 62Cu-pyruvaldehyde bis(n4-methyl-thio-semicarbazone) copper (II) (PTSM) flow tracer. METHODS: Potassium-38 and 62Cu-PTSM were injected at rest and after pharmacological vasodilation in six healthy volunteers. Dynamic PET acquisition was performed over 20 min and myocardial tracer retention calculated. Homogeneity of regional myocardial tracer distribution was also evaluated. RESULTS: High image quality of the heart was observed at rest and after dipyridamole with both tracers. Potassium-38 demonstrated prolonged myocardial retention with minimal lung and liver accumulation. In contrast to 38K, 62Cu-PTSM demonstrated high liver uptake which may hinder observation of the inferior wall of the myocardium. Copper-62-PTSM dipyridamole-to-rest retention ratio was 1.49. CONCLUSIONS: Potassium-38 and 62Cu-PTSM display suitable kinetics for the qualitative evaluation of blood flow and flow reserve in the human heart. Compared to 62Cu-PTSM, potassium-38, which does not show high liver uptake, may more accurately estimate blood flow in the inferior wall of the heart. However, accurate quantification of myocardial blood flow using 38K or 62Cu-PTSM retention appears to be limited to decreasing retention fraction at hyperhemic states.

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Fluorodopa uptake and glucose metabolism in early stages of corticobasal degeneration.

Fluorodopa (FDOPA) and fluorodeoxyglucose (FDG) PET was performed in six patients in early stages of corticobasal degeneration (CBD) and compared to Parkinson's disease (PD) patients with a similar degree of bradykinesia and rigidity and to healthy controls. Statistical parametric mapping analysis comparing CBD to controls showed metabolic decrease in premotor, primary motor, supplementary motor, primary sensory, prefrontal, and parietal associative cortices, and in caudate and thalamus contralateral to the side of clinical signs. Except for the prefrontal regions a similar metabolic pattern was observed when CBD was compared to PD. Putamen FDOPA uptake was decreased in both CBD and PD. Caudate FDOPA uptake in CBD patients was decreased contralateral to clinical signs when compared to controls, but was higher than in PD. In early stages of CBD, FDOPA and FDG PET patterns differed from those observed in PD. In CBD the asymmetry in FDOPA uptake was less pronounced than that of clinical signs or metabolic impairment.

Medial temporal lobe metabolic impairment in dementia associated with motor neuron disease.

In the course of their disease certain patients with frontotemporal dementia (FTD) develop clinical features compatible with a motor neuron disease (FTD-MND). Previous reports have suggested that the functional pattern is similar in FTD and FTD-MND. However, some neuropathological studies suggest greater involvement of medial temporal regions in FTD-MND than in FTD. Using statistical parametric mapping (SPM96), we compared the metabolic patterns obtained at rest with positron emission tomography in 10 FTD patients and three FTD-MND patients with those obtained from 46 healthy subjects (HS). Mean age, duration of illness and dementia stage did not differ statistically between the FTD and FTD-MND groups. In comparison with HS, both groups showed frontal and anterior temporal hypometabolism at P<0.001. When the FTD-MND group was compared to the FTD group, significant hypometabolism was only observed in bilateral amygdala, bilateral hippocampus, and bilateral enthorinal and parahippocampal regions (Brodmann's areas, BA 28/36) at P<0.005. We found no significant differences in regional glucose uptake when FTD patients were contrasted to FTD-MND patients. Our results suggest statistically comparable frontal and lateral temporal hypometabolism in both conditions but greater impairment of medial temporal lobe activity in FTD-MND. Our results and a review of the literature support the hypothesis that there is a functional continuum between classical motor neuron disease (cMND), FTD-MND, and FTD.