Adult attachment style is associated with cerebral μ‐opioid receptor availability in humans

Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ‐opioid system is linked to long‐term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ‐opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR‐specific ligand [¹¹C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships‐Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals’ social relationships and psychosocial well‐being. Hum Brain Mapp 36:3621–3628, 2015. © 2015 Wiley Periodicals, Inc.     

Aerobic exercise modulates anticipatory reward processing via the μ‐opioid receptor system

Physical exercise modulates food reward and helps control body weight. The endogenous µ‐opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise‐induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR‐selective radioligand [¹¹C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise‐induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise‐induced changes in MOR binding correlated negatively with the exercise‐induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise‐induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.     

Acute “binge” cocaine increases mu-opioid receptor mRNA levels in areas of the rat mesolimbic mesocortical dopamine system

Autoradiography studies demonstrated that chronic “binge” cocaine administration increased mu-opioid receptor density in dopaminergically innervated rat brain regions, including the cingulate cortex, the nucleus accumbens, and the basolateral amygdala. The present study investigated the effects of a single day of binge-pattern cocaine administration (3 × 15 mg/kg, intraperitoneally [i.p.] at hourly intervals) on mu-opioid receptor mRNA levels in selected brain regions. Rats were sacrificed 30 min after the third injection and mRNA levels were measured by a quantitative solution hybridization RNase protection assay. Acute binge cocaine administration significantly increased mu-opioid receptor mRNA levels in the frontal cortex, nucleus accumbens, and amygdala, but not in the caudate-putamen, thalamus, hippocampus, and hypothalamus. As has been suggested for other G-protein coupled receptors, the rapid increase of MOR mRNA reported in this study might represent an adaptive response to compensate for a decrease in number of receptors following cocaine-induced opioid peptide release.     

The cingulum and cingulate U‐fibers in children and adolescents with autism spectrum disorders

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U‐fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra‐cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U‐fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U‐fibers, an atypical age‐related decline in right posterior cingulate U‐fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U‐fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U‐fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.     

Activation likelihood estimation meta‐analysis of brain correlates of placebo analgesia in human experimental pain

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which areas consistently contribute to placebo analgesia‐related networks. In the present study, we used activation likelihood estimation (ALE) meta‐analysis, a state‐of‐the‐art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo‐related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anterior insula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid‐ and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulated in parallel with behavioral analgesia. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving.

BACKGROUND: Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [11C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. METHODS: Regional brain mOR binding potential (BP) was measured with [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. RESULTS: Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. CONCLUSIONS: These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.     

Functional connectivity corresponding to the tonotopic differentiation of the human auditory cortex

Recent research has demonstrated that resting‐state functional connectivity (RS‐FC) within the human auditory cortex (HAC) is frequency‐selective, but whether RS‐FC between the HAC and other brain areas is differentiated by frequency remains unclear. Three types of data were collected in this study, including resting‐state functional magnetic resonance imaging (fMRI) data, task‐based fMRI data using six pure tone stimuli (200, 400, 800, 1,600, 3,200, and 6,400 Hz), and structural imaging data. We first used task‐based fMRI to identify frequency‐selective cortical regions in the HAC. Six regions of interest (ROIs) were defined based on the responses of 50 participants to the six pure tone stimuli. Then, these ROIs were used as seeds to determine RS‐FC between the HAC and other brain regions. The results showed that there was RS‐FC between the HAC and brain regions that included the superior temporal gyrus, dorsolateral prefrontal cortex (DL‐PFC), parietal cortex, occipital lobe, and subcortical structures. Importantly, significant differences in FC were observed among most of the brain regions that showed RS‐FC with the HAC. Specifically, there was stronger RS‐FC between (1) low‐frequency (200 and 400 Hz) regions and brain regions including the premotor cortex, somatosensory/‐association cortex, and DL‐PFC; (2) intermediate‐frequency (800 and 1,600 Hz) regions and brain regions including the anterior/posterior superior temporal sulcus, supramarginal gyrus, and inferior frontal cortex; (3) intermediate/low‐frequency regions and vision‐related regions; (4) high‐frequency (3,200 and 6,400 Hz) regions and the anterior cingulate cortex or left DL‐PFC. These findings demonstrate that RS‐FC between the HAC and other brain areas is frequency selective.     

Changes in the circadian rhythm of mRNA expression for µ‐opioid receptors in the periaqueductal gray under a neuropathic pain‐like state

Variation in the production of opioid receptors over a 24‐h period is considered to contribute to circadian alterations in neuropathic pain. In this study, we investigated the possible changes in the circadian rhythm of mRNA expression for µ‐opioid receptor (MOR), κ‐opioid receptor (KOR), and adrenaline α2a receptor (α2a) in the periaqueductal gray, frontal cortex, thalamus, and spinal cord following sciatic nerve ligation in mice. In sham‐operated mice, the latencies of hind paw‐withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly greater than that at 8:00 and the latency at 2:00 was significantly less than those at 14:00 and 20:00, indicating a “rest” period‐dominant circadian rhythm for thermal pain‐thresholds. In sciatic nerve‐ligated mice, the latencies of hind paw‐withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly less than that at 8:00, and the latency at 2:00 was significantly greater than those at 14:00 and 20:00. A correlative tendency between the time‐variation of pain latency and the time‐variation of MOR mRNA expression was observed in the periaqueductal gray of sham‐operated and sciatic nerve‐ligated mice. In contrast, neither mouse showed a strong circadian rhythm for the expressions of KOR and α2a mRNAs in any region. The present data suggest that changes in MOR mRNA expression in the periaqueductal gray may be synchronized with the circadian rhythm for the pain threshold for noxious thermal stimuli. In contrast, neuropathic pain in mice exhibited a negative circadian pattern for the expression of MOR, KOR, and α2a receptors in the frontal cortex, thalamus, and spinal cord. Synapse 67:216–223, 2013. © 2012 Wiley Periodicals, Inc.     

Dopaminergic and GABA‐ergic markers of impulsivity in rats: evidence for anatomical localisation in ventral striatum and prefrontal cortex

Accumulating evidence indicates that impulsivity, in its multiple forms, involves cortical and subcortical mechanisms and abnormal dopamine (DA) transmission. Although decreased DA D2/D3 receptor availability in the nucleus accumbens (NAcb) predicts trait‐like impulsivity in rats it is unclear whether this neurochemical marker extends to both the NAcb core (NAcbC) and shell (NAcbS) and whether markers for other neurotransmitter systems implicated in impulsivity such as serotonin (5‐HT), endogenous opioids and γ‐amino‐butyric acid (GABA) are likewise altered in impulsive rats. We therefore used autoradiography to investigate DA transporter (DAT), 5‐HT transporter (5‐HTT) and D1, D2/D3, μ‐opioid and GABA(A) receptor binding in selected regions of the prefrontal cortex and striatum in rats expressing low and high impulsive behaviour on the five‐choice serial reaction‐time task. High‐impulsive (HI) rats exhibited significantly lower binding for DAT and D2/D3 receptors in the NAcbS and for D1 receptors in the NAcbC compared with low‐impulsive (LI) rats. HI rats also showed significantly lower GABA(A) receptor binding in the anterior cingulate cortex. For all regions where receptor binding was altered in HI rats, binding was inversely correlated with impulsive responding on task. There were no significant differences in binding for 5‐HTT or μ‐opioid receptors in any of the regions investigated. These results indicate that altered D2/D3 receptor binding is localised to the NAcbS of trait‐like impulsive rats and is accompanied by reduced binding for DAT. Alterations in binding for D1 receptors in the NAcbC and GABA(A) receptors in the anterior cingulate cortex demonstrate additional markers and putative mechanisms underlying the expression of behavioural impulsivity.     

Cortical deactivations during gastric fundus distension in health: visceral pain‐specific response or attenuation of ‘default mode’ brain function? A H215O‐PET study

Abstract Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H₂¹⁵O‐brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C₁) no distension (baseline); isobaric distension to individual thresholds for (C₂) first, (C₃) marked, (C₄) unpleasant sensation and (C₅) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P_{uncorrected_voxel_level} < 0.001 and P_{corrected_cluster_level} < 0.05. Baseline–maximal distension (C₁–C₄) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso‐ and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task‐independent suspension of ‘default mode’ activity (as described in various cognitive tasks) or an visceral pain/interoception‐specific process remains to be elucidated.     

Evoked potential study of hippocampal efferent projections in the human brain

Objective

To explore in human potential hippocampal projections within and outside the temporal lobe.

Methods

We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites.

Results

Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus.

Conclusion

Our results demonstrate a large distribution of direct or indirect hippocampal projections.

Significance

This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.     

Low frequency stimulation of the nucleus tegmenti pedunculopontini increases cortical metabolism in Parkinsonian patients

Background and purpose: To evaluate the effects of 25‐Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. Methods: Six patients with Parkinson’s disease (PD) who had bilateral stereotactic implantation of PPTg at least 12 months prior to evaluation were included in our study. All underwent, in separate sessions, 18‐FDG‐PET in core assessment programme for intra‐cerebral transplantation as well as motor evaluation [Unified Parkinson’s disease rating scale (UPDRS) – section III] and a battery of cognitive testing. Results: PPTg‐ON (low bipolar contacts, 25 Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito‐frontal cortex (BA47), anterior cingulate (BA 25–32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg‐ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg‐ON improved delayed recall (P < 0.05) and executive functions whilst the UPDRS revealed a modest (−21%) and variable treatment effect. Conclusions: Low frequency stimulation of PPTg, a sub‐region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono‐lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD.     

Identification of μ‐ and κ‐opioid receptors as potential targets to regulate parasympathetic,sympathetic, and sensory neurons within rat intracardiac ganglia

Recent interest has been focused on the opioid regulation of heart performance; however, specific allocation of opioid receptors to the parasympathetic, sympathetic, and sensory innervations of the heart is scarce. Therefore, the present study aimed to characterize such specific target sites for opioids in intracardiac ganglia, which act as a complex network for the integration of the heart's neuronal in‐ and output. Tissue samples from rat heart atria were subjected to RT‐PCR, Western blot, radioligand‐binding, and double immunofluorescence confocal analysis of μ (M)‐ and κ (K)‐opioid receptors (ORs) with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene‐related peptide (CGRP), and substance P (SP). Our results demonstrated MOR‐ and KOR‐specific mRNA, receptor protein, and selective membrane ligand binding. By using immunofluorescence confocal microscopy, MOR and KOR immunoreactivity were colocalized with VAChT in large‐diameter parasympathetic principal neurons, with TH‐immunoreactive small intensely fluorescent (SIF) cells, and on nearby TH‐IR varicose terminals. In addition, MOR and KOR immunoreactivity were identified on CGRP‐ and SP‐IR sensory neurons throughout intracardiac ganglia and atrial myocardium. Our findings show that MOR and KOR are expressed as mRNA and translated into specific receptor proteins on cardiac parasympathetic, sympathetic, and sensory neurons as potential binding sites for opioids. Thus, they may well play a role within the complex network for the integration of the heart's neuronal in‐ and output. J. Comp. Neurol. 518:3836–3847, 2010. © 2010 Wiley‐Liss, Inc.     

Uncertainty in visual and auditory series is coded by modality‐general and modality‐specific neural systems

Coding for the degree of disorder in a temporally unfolding sensory input allows for optimized encoding of these inputs via information compression and predictive processing. Prior neuroimaging work has examined sensitivity to statistical regularities within single sensory modalities and has associated this function with the hippocampus, anterior cingulate, and lateral temporal cortex. Here we investigated to what extent sensitivity to input disorder, quantified by Markov entropy, is subserved by modality‐general or modality‐specific neural systems when participants are not required to monitor the input. Participants were presented with rapid (3.3 Hz) auditory and visual series varying over four levels of entropy, while monitoring an infrequently changing fixation cross. For visual series, sensitivity to the magnitude of disorder was found in early visual cortex, the anterior cingulate, and the intraparietal sulcus. For auditory series, sensitivity was found in inferior frontal, lateral temporal, and supplementary motor regions implicated in speech perception and sequencing. Ventral premotor and central cingulate cortices were identified as possible candidates for modality‐general uncertainty processing, exhibiting marginal sensitivity to disorder in both modalities. The right temporal pole differentiated the highest and lowest levels of disorder in both modalities, but did not show general sensitivity to the parametric manipulation of disorder. Our results indicate that neural sensitivity to input disorder relies largely on modality‐specific systems embedded in extended sensory cortices, though uncertainty‐related processing in frontal regions may be driven by both input modalities. Hum Brain Mapp 35:1111–1128, 2014. © 2013 Wiley Periodicals, Inc.     

Evidence for modulation of opioidergic activity in central vestibular processing: A [18F] diprenorphine PET study

Animal and functional imaging studies had identified cortical structures such as the parieto‐insular vestibular cortex, the retro‐insular cortex, or the anterior cingulate cortex belonging to a vestibular cortical network. Basic animal studies revealed that endorphins might be important transmitters involved in cerebral vestibular processing. The aim of the present study was therefore to analyse whether the opioid system is involved in vestibular neurotransmission of humans or not. Changes in opioid receptor availability during caloric air stimulation of the right ear were studied with [¹⁸F] Fluoroethyl‐diprenorphine ([¹⁸F]FEDPN) PET scans in 10 right‐handed healthy volunteers and compared to a control condition. Decrease in receptor availability to [¹⁸F]FEDPN during vestibular stimulation in comparison to the control condition was significant at the right posterior insular cortex and the postcentral region indicating more endogenous opioidergic binding in these regions during stimulation. These data give evidence that the opioidergic system plays a role in the right hemispheric dominance of the vestibular cortical system in right‐handers. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Imaging of δ- and μ-opioid receptors in temporal lobe epilepsy by positron emission tomography

The involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies in patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation of the opioid-receptor subtypes. The present study extends our previous observations to δ-opioid receptors by using the δ-receptor-selective antagonist [¹¹C]methylnatrindole ([¹¹C]MeNTI). Paired measurements of δ- and μ-opioid receptor binding and metabolic activity were performed with PET using [¹¹C]MeNTI and [¹¹C]carfentanil ([¹¹C]CFN) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG), respectively. Binding of [¹¹C]MeNTI and [¹¹C]CFN increased and [¹⁸F]FDG uptake decreased in the temporal cortex (TC) ipsilateral to the focus. Decreases in [¹⁸F]FDG uptake were more widespread regionally than were increases in opioid receptors. Increases in the δ- and μ-receptor binding showed different regional patterns. Increases in δ-receptor binding were confined to the middle aspect of the inferior TC, whereas binding of δ receptors increased in the mid-inferior TC and anterior aspect of the middle and superior TC. The increase in δ receptors suggests their anticonvulsant action, as previously shown for the δ-receptor subtype, whereas the different regional pattern of receptor alterations suggest the distinct roles of different opioid-receptor subtypes in seizure phenomena.     

PET imaging of opiate receptor binding in human epilepsy using [18F]cyclofoxy.

We used [18F]cyclofoxy (CF), a potent opiate antagonist with affinity for mu and kappa receptors, and the Scanditronix PC1024-7B PET scanner to study 14 patients with complex partial seizures (CPS), and 14 normal controls. Epileptic foci were localized by prolonged EEG-video monitoring. EEG was recorded continuously during each scan. Immediately before CF administration, [15O]labeled water was used to measure cerebral blood flow, and showed hypoperfusion ipsilateral to the EEG focus. Blood samples (corrected for radiolabeled metabolites) and tissue time-activity data were acquired over 90 min following bolus CF injection. Anatomic regions were outlined directly on the PET images. A kinetic model was used to derive the total volume of distribution (Vt) in each brain region. Specific binding (Vs) was determined by substracting non-specific binding (Vt) measured in a receptor-poor brain region (occipital cortex). Regions with high Vs included mesial temporal lobes, thalamus, basal ganglia, and frontal cortex. Individual patients appeared to have higher binding in temporal lobe ipsilateral to the EEG focus, but there was no asymmetry for the patients as a group in mean Vt or Vs in anterior mesial, posterior mesial, anterior lateral, posterior lateral temporal cortex, thalamus, basal ganglia, or, for Vt, in regions of low specific binding: occipital lobe, parietal lobe, cerebellum.     

Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a probe into the pathophysiology and possible treatment of neuropsychiatric disorders. To explore its regional effects, we combined rTMS with positron emission tomography (PET). Fourteen healthy volunteers participated in a baseline 18-fluorodeoxyglucose (FDG) PET scan. During a second FDG infusion on the same day, seven subjects received 30 min of 1 Hz rTMS at 80% of motor threshold to left prefrontal cortex, and seven other subjects received sham rTMS under identical conditions. Global and normalized regional cerebral glucose metabolic rates (rCMRglu) from the active and sham conditions were compared to baseline and then to each other. Sham, but not active 1 Hz rTMS, was associated with significantly increased global CMRglu. Compared to baseline, active rTMS induced normalized decreases in rCMRglu in right prefrontal cortex, bilateral anterior cingulate, basal ganglia (L>R), hypothalamus, midbrain, and cerebellum. Increases in rCMRglu were seen in bilateral posterior temporal and occipital cortices. Sham rTMS compared to baseline resulted in isolated normalized decreases in rCMRglu in left dorsal anterior cingulate and left basal ganglia, and increases in posterior association and occiptal regions. Differences between the 1 Hz active versus sham changes from baseline revealed that active rTMS induced relative decrements in rCMRglu in the left superior frontal gyrus and increases in the cuneus (L>R). One Hertz rTMS at 80% motor threshold over the left prefrontal cortex in healthy subjects compared to sham rTMS in another group (each compared to baseline) induced an area of decreased normalized left prefrontal rCMRglu not directly under the stimulation site, as well as increases in occipital cortex. While these results are in the predicted direction, further studies using other designs and higher intensities and frequencies of rTMS are indicated to better describe the local and distant changes induced by rTMS.     

Regional brain activity when selecting a response despite interference: An H2 15O PET study of the stroop and an emotional stroop

The Stroop interference test requires a person to respond to specific elements of a stimulus while suppressing a competing response. Previous positron emission tomography (PET) work has shown increased activity in the right anterior cingulate gyrus during the Stroop test. It is unclear, however, whether the anterior cingulate participates more in the attentional rather than the response selection aspects of the task or whether different interference stimuli might activate different brain regions. We sought to determine (1) whether the Stroop interference task causes increased activation in the right anterior cingulate as previously reported, (2) whether this activation varied as a function of response time, (3) what brain regions were functionally linked to the cingulate during performance of the Stroop, and (4) whether a modified Stroop task involving emotionally distracting words would activate the cingulate and other limbic and paralimbic regions. Twenty-one healthy volunteers were scanned with H₂¹⁵O PET while they performed the Stroop interference test (standard Stroop), a modified Stroop task using distracting words with sad emotional content (sad Stroop), and a control task of naming colors. These were presented in a manner designed to maximize the response selection aspects of the task. Images were stereotactically normalized and analyzed using statistical parametric mapping (SPM). Predictably, subjects were significantly slower during the standard Stroop than the sad Stroop or the control task. The left mideingulate region robustly activated during the standard Stroop compared to the control task. The sad Stroop activated this same region, but to a less significant degree. Correlational regional network analysis revealed an inverse relationship between activation in the left mideingulate and the left insula and temporal lobe. Additionally, activity in different regions of the cingulate gyrus correlated with performance speed during the standard Stroop. These results suggest that the left midcingulate is likely to be part of a neural network activated when one attempts to override a competing verbal response. Finally, the left midcingulate region appears to be functionally coupled to the left insula, temporal, and frontal cortex during cognitive interference tasks involving language. These results underscore the important role of the cingulate gyrus in selecting appropriate and suppressing inappropriate verbal responses. © 1994 Wiley-Liss, Inc.     

~(11)C-PIBPET和~(18)F-FDGPET显像诊断阿尔茨海默病与遗忘型轻度认知损害的临床价值

目的应用11C-PIB PET和18F-FDG PET显像研究阿尔茨海默病和遗忘型轻度认知损害患者β-淀粉样蛋白(Aβ)沉积与葡萄糖代谢之间的关系,联合载脂蛋白E(ApoE)基因型进一步探讨遗忘型轻度认知损害与阿尔茨海默病的相关性。方法利用PET显像对阿尔茨海默病(14例)、遗忘型轻度认知损害(10例)和正常对照者(5例)脑组织Aβ沉积和葡萄糖代谢变化进行分析,采用聚合酶链反应-限制性片段长度多态性方法对ApoE基因型进行分析。结果阿尔茨海默病组患者11C-PIB标准化摄取比值在下顶叶、颞叶外侧、额叶、后扣带回皮质和楔前叶、枕叶和纹状体均高于正常对照组(P0.05);遗忘型轻度认知损害组患者脑组织11C-PIB结合水平呈双峰形。11C-PIB+aMCI亚组与阿尔茨海默病组、11C-PIB-aMCI亚组与正常对照组之间11C-PIB标准化摄取比值差异均无统计学意义(P0.05)。18F-FDG PET显像显示,3/5例11C-PIB+aMCI亚组患者双侧顶叶、颞叶和楔前叶代谢减低,其中2例ApoEε4等位基因携带者随访期间进展至阿尔茨海默病;3/5例11C-PIB-aMCI亚组患者双侧额叶和前扣带回代谢减低。结论11C-PIB PET显像是筛查具有阿尔茨海默病病理特点的遗忘型轻度认知损害患者的有效工具。具有阿尔茨海默病病理特征的遗忘型轻度认知损害患者可伴有顶叶、颞叶外侧皮质和楔前叶代谢减低,其中ApoEε4等位基因携带者更易进展至阿尔茨海默病痴呆。