Action and object processing in aphasia: from nouns and verbs to the effect of manipulability.

The processing of words and pictures representing actions and objects was tested in 21 aphasic patients and 20 healthy controls across three word production tasks: picture-naming (PN), single word reading (WR) and word repetition (WRP). Analysis 1 targeted task and lexical category (noun-verb), revealing worse performance on PN and verb items for both patients and control participants. For Analysis 2 we used data collected in a concurrent gesture norming study to re-categorize the noun-verb items along hand imagery parameters (i.e., objects that can/cannot be manipulated and actions which do/do not involve fine hand movements). Here, patients displayed relative difficulty with the 'manipulable' items, while controls displayed the opposite pattern. Therefore, whereas the noun-verb distinction resulted simply in lower verb accuracy across groups, the 'manipulability' distinction revealed a 'double-dissociation' between patients and control participants. These results carry implications for theories of embodiment, lexico-semantic dissociations, and the organization of meaning in the brain.

Brain activity during intra- and cross-modal priming: new empirical data and review of the literature.

A positron emission tomography (PET) study was conducted to investigate the neurofunctional correlate of auditory within-modality and auditory-to-visual cross-modality stem completion priming. Compared to the auditory-to-auditory priming condition, cross-modality priming was associated with a significantly larger regional cerebral blood flow (rCBF) decrease at the boundary between left inferior temporal and fusiform gyri, brain regions previously associated with modality independent lexical retrieval and reading. Instead, within-modality auditory priming was associated with a bilateral pattern of prefrontal rCBF increase. This was likely the expression of more efficient access to output lexical representations and involuntary retrieval of the recent episode during which the just generated word had been encountered.

Bilateral paramedian thalamic syndrome: abnormal circadian wake-sleep and autonomic functions.

OBJECTIVES: To describe wake-sleep and body core temperature (t degrees ) rhythm abnormalities in two patients with bilateral paramedian thalamic calcifications. METHODS: Patients underwent (18F)FDG PET scans and 24 hour polygraphic recordings of wake-sleep and t degrees. RESULTS: PET showed bilateral thalamic hypometabolism in both patients with additional basal ganglia or mesiolateral frontal and cingular hypometabolism. Wake-sleep studies showed abnormal sleep organisation and in the case with frontal and limbic PET hypometabolism, pre-sleep behaviour associated with "subwakefulness" EEG activities, lack of EEG spindles and K complexes, and features of status dissociatus. The t degrees rhythms showed increased mesor in both (37.4 degrees C and 37.75 degrees C) and inverted rhythm in one patient. CONCLUSIONS: Paramedian thalamic structures and interconnected, especially frontal and cingular, areas play a part in the organisation of the wake-sleep cycle and attendant autonomic functions.

Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks.

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies.

Word and picture matching: a PET study of semantic category effects.

We report two positron emission tomography (PET) studies of cerebral activation during picture and word matching tasks, in which we compared directly the processing of stimuli belonging to different semantic categories (animate and inanimate) in the visual (pictures) and verbal (words) modality. In the first experiment, brain activation was measured in eleven healthy adults during a same/different matching task for textures, meaningless shapes and pictures of animals and artefacts (tools). Activations for meaningless shapes when compared to visual texture discrimination were localized in the left occipital and inferior temporal cortex. Animal picture identification, either in the comparison with meaningless shapes and in the direct comparison with non-living pictures, involved primarily activation of occipital regions, namely the lingual gyrus bilaterally and the left fusiform gyrus. For artefact picture identification, in the same comparison with meaningless shape-baseline and in the direct comparison with living pictures, all activations were left hemispheric, through the dorsolateral frontal (Ba 44/6 and 45) and temporal (Ba 21, 20) cortex. In the second experiment, brain activation was measured in eight healthy adults during a same/different matching task for visually presented words referring to animals and manipulable objects (tools); the baseline was a pseudoword discrimination task. When compared with the tool condition, the animal condition activated posterior left hemispheric areas, namely the fusiform (Ba 37) and the inferior occipital gyrus (Ba 18). The right superior parietal lobule (Ba 7) and the left thalamus were also activated. The reverse comparison (tools vs animals) showed left hemispheric activations in the middle temporal gyrus (Ba 21) and precuneus (Ba 7), as well as bilateral activation in the occipital regions. These results are compatible with different brain networks subserving the identification of living and non-living entities; in particular, they indicate a crucial role of the left fusiform gyrus in the processing of animate entities and of the left middle temporal gyrus for tools, both from words and pictures. The activation of other areas, such as the dorsolateral frontal cortex, appears to be specific for the semantic access of tools only from pictures.

Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis.

UNLABELLED: The basal ganglia are thought to be involved in the primary dystonias, largely because of the repeated demonstration of neuropathological changes in these nuclei in the secondary dystonias. A hyperactivity of a network involving basal ganglia has been suggested in experimental animal dystonia. To test this hypothesis in humans, we studied the functional correlates of primary cervical dystonia using [18F]FDG and PET. MATERIAL AND METHODS: Regional cerebral glucose metabolism (rCMRglc) was measured in 10 patients with idiopathic torticollis (6 drug-free and 4 drug-naive) and in 15 normal controls, using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). RESULTS: A significant hypermetabolism in the basal ganglia, thalamus, premotor-motor cortex and cerebellum in the patients compared with normal controls was found. The patients were correctly assigned to their clinical category by a discriminant function analysis with a total accuracy of 96%. CONCLUSION: The results support the hypothesis that a dysfunction of a subcortical-cortical motor network may play a role in the pathogenesis of focal dystonia, in agreement with the experimental dystonia models.

High-resolution SPECT study of regional cerebral blood flow in drug-free and drug-naive schizophrenic patients.

OBJECTIVE: The purpose of the study was to compare regional cerebral blood flow (CBF) in schizophrenic patients never treated with psychotropic drugs (drug-naive) and in schizophrenic patients free from drugs for various amounts of time. METHOD: Seventeen schizophrenic patients (nine who were drug naive and eight who had been drug free for at least 3 weeks) and 12 healthy volunteers were included in the study. Regional cerebral perfusion was studied with the use of a head-dedicated, high-resolution single photon emission computed tomography (SPECT) system. Cerebral SPECT scans were performed with technetium-99m-hexamethyl-propyleneamine oxime as a tracer. Regional CBF was measured as a ratio of regional tracer uptake to either cerebellar or whole brain tracer uptake. RESULTS: When the cerebellum was taken as the reference region, the drug-naive patients showed a significant bilateral reduction of perfusion in the mesial, dorsolateral, and basal prefrontal cortex, in the temporal cortex, and in the subcortical gray structures: thalamus, caudate nucleus, and putamen/pallidum complex. No significant differences emerged in the comparison between the drug-free patients and the healthy subjects. With correction for whole brain activity, some of the differences that had been found disappeared, but a significant hypoperfusion persisted in the basal ganglia and thalamus of the drug-naive, but not the drug-free, patients. Few correlations between symptom presentation and regional CBF perfusion were observed in the schizophrenic patients. CONCLUSIONS: These results suggest a pattern of cerebral hypoperfusion in schizophrenic patients never treated with neuroleptics that was not detectable in patients who had undergone various periods of pharmacological washout.

[18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment.

BACKGROUND: We used [18F]FDG and PET in patients with obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement before and after treatment with serotonin-specific reuptake inhibitors. METHOD: In 11 untreated, drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was compared with that of 15 age-matched normal controls. RESULTS: rCMRglu values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen complex. After treatment a significant improvement in obsessive-compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P < 0.01). CONCLUSIONS: These findings indicate that OCD is associated with functional hyperactivity of a selected neuronal network and that treatment to reduce symptoms may have a selective neuromodulatory effect on cingulate cortex.

Primary amnesia of insidious onset with subsequent stabilisation.

A patient had a slowly developing amnesic syndrome that remained substantially unchanged during the two and a half years of observation. Intellectual skills were excellent and there was no language, perception, praxis, or calculation deficit. The memory impairment involved verbal and visual learning, sparing spatial learning and, to a large extent, retrograde memory. Magnetic resonance imaging was normal, but PET showed a hypometabolism of the left temporal mesial region and thalamus. This case extends the spectrum of monosymptomatic cognitive disorders, previously reported in the area of language, praxis, and visual recognition, to amnesia.

Mapping motor representations with positron emission tomography.

Brain activity was mapped in normal subjects during passive observation of the movements of an 'alien' hand and while imagining grasping objects with their own hand. None of the tasks required actual movement. Shifting from one mental task to the other greatly changed the pattern of brain activation. During observation of hand movements, activation was mainly found in visual cortical areas, but also in subcortical areas involved in motor behaviour, such as the basal ganglia and the cerebellum. During motor imagery, cortical and subcortical areas related to motor preparation and programming were strongly activated. These data support the notion that motor learning during observation of movements and mental practice involves rehearsal of neural pathways related to cognitive stages of motor control.

[18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.

We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.

Metabolic impairment in human amnesia: a PET study of memory networks.

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its "pure" form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papez's circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with "pure" amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy.

We have studied 5 patients with unilateral, severe chronic pain due to cancer before and after percutaneous, ventrolateral cervical cordotomy to investigate the central effects of the procedure. The aim was to identify the functional anatomical correlates of abolishing unilateral nociceptive input to the brain. Patients were investigated by positron emission tomography using C15O2 to evaluate cerebral blood flow. Comparisons were made between the patients with unilateral pain before cordotomy and normal volunteers. These demonstrated significantly less blood flow in 3 out of 4 of the individual quadrants of the hemithalamus contralateral to the side of pain (P less than 0.01-0.05). These differences were abolished by cordotomy. Comparison of the patients before and after cordotomy showed a significant decrease in blood flow in the dorsal anterior quadrant of the thalamus contralateral to the side of pain (P less than 0.05) which was normalised after cordotomy. There were no significant changes in the prefrontal or primary somatosensory cortex. We conclude that chronic pain results in a decrease of synaptic activity at thalamic level either from decreased activity in neurones projecting to that region and/or attenuated local neuronal firing. We have demonstrated no secondary remote effects in cortex, indicating the importance of subcortical mechanisms in central responses to chronic pain.

The anatomy of unilateral neglect after right-hemisphere stroke lesions. A clinical/CT-scan correlation study in man.

The anatomical correlates of extrapersonal visual neglect were investigated in 110 right-handed stroke patients with lesions confined to the right hemisphere. Neglect is much more frequently associated with retrorolandic damage, as compared with frontal lesions. The inferior parietal lobule appears to be the area most frequently involved in patients with cortical lesions showing signs of neglect. When the cerebral lesion is confined to deep structures, neglect occurs much more frequently when grey nuclei such as the thalamus and the basal ganglia are damaged; a remarkable number of negative cases were, however, found. Conversely, lesions limited to the subcortical white matter are rarely associated with neglect. The relevance of these results to anatomophysiological models of directed attention and neglect is discussed.