Although there is increasing evidence for microglial activation after an ischaemic stroke in the infarct core and the peri-infarct region, the "evolution" of the process in stroke patients is poorly known. Using PET and [((11))C]vinpocetine, we measured the regional changes of TSPO in the brain of nine ischaemic stroke patients up to 14weeks after the insult. Already a week after stroke there was an increased radioligand uptake, indicating the up-regulation of TSPO and the presence of activated microglia, in both the ischaemic core and the peri-infarct zone. This increased activation showed a steady decrease with post stroke time. The proportion between %SUV values in the peri-infarct zone and the ischaemic core increased with time. There were no time-dependent TSPO activity changes in other regions, not affected directly by the stroke. The present observations demonstrate that increased regional microglia activation, as a consequence of stroke, can be visualised with PET, using the TSPO molecular imaging biomarker [((11))C]vinpocetine. The evolution of this microglial activation shows a time dependent decrease the gradient of which is different between the peri-infarct zone and the ischaemic core. The findings indicate an increased microglial activation in the peri-stroke region for several weeks after the insult.

Peter Coles (1) claims that the statistical analyses in our study (2) are “strongly undermined by an inappropriate choice of variables.” This rather harsh statement is surprising and inappropriate especially because Coles seems to generalize his criticism although two completely different statistical methods were used for the data analysis; the connectivity analysis was carried out by using …

Cerebral responses to putative pheromones and objects of sexual attraction were recently found to differ between homo- and heterosexual subjects. Although this observation may merely mirror perceptional differences, it raises the intriguing question as to whether certain sexually dimorphic features in the brain may differ between individuals of the same sex but different sexual orientation. We addressed this issue by studying hemispheric asymmetry and functional connectivity, two parameters that in previous publications have shown specific sex differences. Ninety subjects [25 heterosexual men (HeM) and women (HeW), and 20 homosexual men (HoM) and women (HoW)] were investigated with magnetic resonance volumetry of cerebral and cerebellar hemispheres. Fifty of them also participated in PET measurements of cerebral blood flow, used for analyses of functional connections from the right and left amygdalae. HeM and HoW showed a rightward cerebral asymmetry, whereas volumes of the cerebral hemispheres were symmetrical in HoM and HeW. No cerebellar asymmetries were found. Homosexual subjects also showed sex-atypical amygdala connections. In HoM, as in HeW, the connections were more widespread from the left amygdala; in HoW and HeM, on the other hand, from the right amygdala. Furthermore, in HoM and HeW the connections were primarily displayed with the contralateral amygdala and the anterior cingulate, in HeM and HoW with the caudate, putamen, and the prefrontal cortex. The present study shows sex-atypical cerebral asymmetry and functional connections in homosexual subjects. The results cannot be primarily ascribed to learned effects, and they suggest a linkage to neurobiological entities.

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala + piriform + insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

The testosterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. AND is detected primarily in male sweat, whereas EST has been found in female urine. In a previous positron emission tomography study, we found that smelling AND and EST activated regions covering sexually dimorphic nuclei of the anterior hypothalamus, and that this activation was differentiated with respect to sex and compound. In the present study, the pattern of activation induced by AND and EST was compared among homosexual men, heterosexual men, and heterosexual women. In contrast to heterosexual men, and in congruence with heterosexual women, homosexual men displayed hypothalamic activation in response to AND. Maximal activation was observed in the medial preoptic area/anterior hypothalamus, which, according to animal studies, is highly involved in sexual behavior. As opposed to putative pheromones, common odors were processed similarly in all three groups of subjects and engaged only the olfactory brain (amygdala, piriform, orbitofrontal, and insular cortex). These findings show that our brain reacts differently to the two putative pheromones compared with common odors, and suggest a link between sexual orientation and hypothalamic neuronal processes.

The progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. In previous positron emission tomography studies, we found that smelling AND and EST activated regions primarily incorporating the sexually dimorphic nuclei of the anterior hypothalamus, that this activation was differentiated with respect to sex and compound, and that homosexual men processed AND congruently with heterosexual women rather than heterosexual men. These observations indicate involvement of the anterior hypothalamus in physiological processes related to sexual orientation in humans. We expand the information on this issue in the present study by performing identical positron emission tomography experiments on 12 lesbian women. In contrast to heterosexual women, lesbian women processed AND stimuli by the olfactory networks and not the anterior hypothalamus. Furthermore, when smelling EST, they partly shared activation of the anterior hypothalamus with heterosexual men. These data support our previous results about differentiated processing of pheromone-like stimuli in humans and further strengthen the notion of a coupling between hypothalamic neuronal circuits and sexual preferences.

BACKGROUNDJuvenile myoclonic epilepsy (JME) is classified as primarily generalized epilepsy and as such is assumed to lack an anatomic substrate. Although neurochemical abnormalities are probable, few studies have investigated whether they exist in JME. Animal data and the high incidence of myoclonic seizures in serotonin-intoxicated patients suggest that the serotonin system may be disturbed in JME.OBJECTIVETo test the hypothesis that JME is associated with a disturbed serotonin system and that this disturbance could be reflected in altered serotonin 1A receptor binding.DESIGNThe serotonin 1A receptor binding potential (BP) was measured with positron emission tomography and serotonin 1A receptor antagonist carbonyl-carbon 11-WAY-100635. The BP was calculated using a reference tissue model in several limbic and neocortical regions and the raphe nuclei.SETTINGEpilepsy clinics of the Karolinska University Hospital, Stockholm, Sweden.PATIENTSEleven patients with JME and 11 controls were studied.MAIN OUTCOME MEASURESerotonin 1A receptor BP calculated in a set of volumes of interest.RESULTSThe patients with JME showed a reduced BP in the dorsolateral prefrontal cortex, raphe nuclei, and hippocampus.CONCLUSIONSThe observed reductions in serotonin 1A receptor BP suggest that the serotonin system is affected in JME. Although the data give no definitive information about underlying mechanisms, they provide a strong argument for the view that not all brain regions are homogeneously involved in this condition, further questioning the current classification of primarily generalized epilepsy.

Objective: To test the hypothesis that in mesial temporal lobe epilepsy (MTLE) there is involvement outside of mesial structures and that this involvement affects serotonin systems, thus suggesting a mechanism for affective symptoms in this population. Methods: Serotonin 5-HT1A receptor binding was studied with PET and [Carbonyl-11C]WAY-100 635 in 14 patients (6 with left-, 8 with right-sided mesial temporal lobe focus) and 14 controls. The 5-HT1A receptor binding potential was calculated for hippocampus, amygdala, orbitofrontal, insular, lateral temporal, and anterior cingulate cortex, in raphe nuclei, and in two regions presumably uninvolved in the epileptogenic process (parietal, and dorsolateral frontal neocortex). Results: The binding potential was reduced in the epileptogenic hippocampus (p = 0.0001) and amygdala (p = 0.0001) in all patients, including the six with normal [18F]FDG PET and MRI. It was also reduced in the anterior cingulate (p = 0.002), insular (p = 0.015), and lateral temporal cortex (p = 0.029) ipsilaterally to the focus, in contralateral hippocampus (p = 0.025), and in the raphe nuclei (p = 0.016). Conclusion: Patients with severe MTLE show reduced 5-HT1A receptor binding potential in the EEG-focus, and its limbic connections. [11C]WAY-100 635 PET may provide additional information to EEG, [18F]FDG PET, and MRI when evaluating patients with intractable seizures. Reductions in 5-HT1A binding in the insula and cingulate suggest a mechanism by which affective symptoms in MTLE may result.

A sentence φ \varphi is Γ \Gamma -conservative over T T if T + φ ⊢ ψ T + \varphi \vdash \psi implies T ⊢ ψ T \vdash \psi for every ψ ∈ Γ \psi \in \Gamma . In §1 this concept for Γ = ∑ n + 1 0 \Gamma = \sum _{n + 1}^0 and ∏ n + 1 0 \prod _{n + 1}^0 is investigated. In §2 results from §1 are applied to interpretability in theories containing arithmetic.

This paper is an appendix to Keisler's papers [3], [4]. We assume that the reader is fully acquainted with these papers and use their terminology without further explanation. One of the main tools in a number of proofs in [4] is the following result which is all but stated explicitly in [4].