Increased amygdala fMRI activation after secretin administration.

It has recently been reported that secretin activates gene expression in the central nucleus of the amygdala in rats. To examine the neurophysiological effects of secretin on amygdalar activation in humans, the authors measured Blood Oxygen Level Dependent functional magnetic resonance imaging signal change during facial affect processing in a placebo-controlled double-blind study. The authors studied 12 healthy male subjects who were presented with three stimulus conditions: viewing happy, fearful, and neutral faces, before and after infusion with either secretin or placebo. To test whether treatment was associated with distinct patterns of activation, the two conditions (Pre and Post) were subjected to a subtraction analyses in SPM99 and hypotheses regarding the activation of the left and right amygdala were tested using a region-of-interest approach. Subtraction of treatment minus baseline activation during the fear condition yielded significant (p=.001) activation in the right amygdala and a nonsignificant increase in activation in the left amygdala. No significant differences were seen between the treatment conditions for the amygdala when viewing happy or neutral faces. These preliminary findings indicate that secretin may alter responsivity to affective stimuli. The presence of increased activation of the amygdala during the viewing of fearful faces is consistent with findings from animal studies and suggests a mechanism by which secretin may modulate social behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones

The regulation of central mu-opioid receptors in women during the menstrual cycle was explored with positron emission tomography and the selective radiotracer [11C]carfentanil. Ten healthy women were studied twice, during their follicular and luteal phases. Plasma concentrations of estradiol, progesterone, testosterone, and beta-endorphin were determined immediately before scanning. LH pulsatility was measured over the 9 h preceding each of the two positron emission tomography scans. No significant differences in the binding potential of mu-opioid receptors (binding capacity/Kd) were observed between phases of the menstrual cycle. However, significant negative correlations were observed between circulating levels of estradiol during the follicular phase and mu-receptor binding measures in the amygdala and hypothalamus, two regions thought to be involved in the regulation of GnRH pulsatility. LH pulse amplitude was positively correlated with mu binding in the amygdala, whereas LH pulse number was negatively correlated with binding in this same region. No significant associations were noted between LH pulse measures and the hypothalamus for this sample. These results suggest that amygdalar mu-opioid receptors exert a modulatory effect on GnRH pulsatility, and that circulating levels of estradiol also regulate central mu-opioid function.     

Amygdalar Lateralization in Fear Conditioning: Evidence for Greater Involvement of the Right Amygdala.

The relative contribution of left and right amygdalae in the acquisition and retention of fear conditioning was investigated in rats. Pretraining bilateral electrolytic lesions blocked the acquisition of conditioned fear to tone and context, whereas unilateral lesions induced partial impairments with no left-right amygdala differences. In contrast, posttraining bilateral and unilateral lesions produced significant deficits in the retention of conditioned fear to tone and context. Although no left-right difference was observed to tone, the right amygdala lesions generated greater deficits in contextual fear than the left amygdala lesions. These results indicate that fear conditioning is partially disrupted with unilateral amygdalar lesions, but that the right amygdala has greater involvement than the left amygdala when conditioning occurs under a normal brain state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diversity of capsular polysaccharide synthesis gene clusters in Streptococcus pneumoniae

Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS-). CS+ and CS- trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat (Quirk et al., 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.     

Impaired fear memories are correlated with subregion-specific deficits in hippocampal and amygdalar LTP.

Inbred mouse strains have different genetic backgrounds that likely influence memory and long-term potentiation (LTP). LTP, a form of synaptic plasticity, is a candidate cellular mechanism for some forms of learning and memory. Strains with impaired fear memory may have selective LTP deficits in different hippocampal subregions or in the amygdala. The authors assessed fear memory in 4 inbred strains: C57BL/6NCrlBR (B6), 129S1/SvImJ (129), C3H/HeJ (C3H), and DBA/2J (D2). The authors also measured LTP in the hippocampal Schaeffer collateral (SC) and medial perforant pathways (MPP) and in the basolateral amygdala. Contextual and cued fear memory, and SC and amygdalar LTP, were intact in B6 and 129, but all were impaired in C3H and D2. MPP LTP was similar in all 4 strains. Thus, SC, but not MPP, LTP correlates with hippocampus-dependent contextual memory expression, and amygdalar LTP correlates with amygdala-dependent cued memory expression, in these inbred strains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.     

Medial geniculate lesions block amygdalar and cingulothalamic learning-related neuronal activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.     

Asymmetries in the Hippocampus and Amygdala of Chimpanzees (Pan troglodytes).

Magnetic resonance imaging was used to measure the hippocampal and amygdalar volumes of 60 chimpanzees (Pan troglodytes). An asymmetry quotient (AQ) was then used to calculate the asymmetry for each of the structures. A one-sample t test indicated that there was a population-level right hemisphere asymmetry for the hippocampus. There was no significant population-level asymmetry for the amygdala. An analysis of variance using sex and rearing history as between-group variables showed no significant main effects or interaction effects on the AQ scores; however, males were more strongly lateralized than females. Several of these findings are consistent with results found in the human literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interneuronal frontal-amygdala interactions in cats trained for the quality of the reinforcement

In eight cats the appetitive instrumental conditioned reflexes to light were elaborated by the method of "active choice" of reinforcement quality: the short-latency bar-pressing responses were reinforced with bread-meat mixture and the delayed responses were reinforced with meat. The animals differed in behavior strategy: six cats preferred the delayed pressings (the so-called "self-control" group), and two cats preferred the pressings with short delay (the so-called "impulsive" group). The multiunit activity in the basolateral amygdala and frontal cortex was recorded by chronically implanted nichrome semimicroelectrodes. The interactions of the neighboring neurons in the basolateral amygdala and the frontal cortex (within the local neuronal networks) and between the amygdalar and cortical neurons (distributed neuronal networks of amygdalar-frontal and fronto-amygdalar directions) were estimated by means of statistical crosscorrelation analysis of spike trains. The interneuronal cross-correlations were studied with delays in the range of 0-100 ms. The number of cross-correlations between the neuronal discharges both in the local and distributed networks was significantly higher in "impulsive" cats, mainly, with delays in the range of 0-30 ms. In both groups of animals the number of correlations was the highest during omissions of conditioned pressings, i.e., in cases of difficult choice of reinforcement. We suggest that the basolateral amygdala, frontal cortex, and amygdalar-frontal distributed neuronal networks are involved in the system of brain structures, which determine the individual features of animal behavior.     

Associative fear conditioning of enkephalin mRNA levels in central amygdalar neurons.

The central nucleus of the amygdala (CEA) is required for the expression of learned fear responses. This study used in situ hybridization to show that mRNA levels of the neuropeptide enkephalin are increased in CEA neurons after rats are placed in an environment that they associate with an unpleasant experience. In contrast, mRNA levels of another neuropeptide, corticotropin releasing hormone, do not change under the same conditions in the CEA of the same rats. Conditioned neuropeptide levels in amygdalar circuits may act as a reversible "gain control" for long-term modulation of subsequent fear responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The amygdala is critical for seizure propagation from brainstem to forebrain

Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.     

Amygdala inactivation reverses fear's ability to impair divided attention and make time stand still.

The cognitive and emotional effects of amygdala or frontal cortex lesions were compared in rats trained to time both a 50-s visual signal paired with food and an embedded 10- or 20-s auditory signal that was paired with either appetitive (food) or aversive (footshock) outcomes. When both auditory and visual signals were paired with food, control and amygdalar-lesioned rats were able to divide attention and to time both signals simultaneously, whereas when the embedded auditory signal was paired with footshock, control rats were impaired in their ability to divide attention and were able to time only one signal at a time. In contrast, amygdalar inactivation blocked this fear-related impairment and allowed rats to time both signals simultaneously, whereas rats with frontal cortex lesions demonstrated sequential processing under all conditions. These results support the proposal that the frontal cortex exerts executive control over the allocation of attentional resources, but that under stressful conditions the amygdala is crucial for the emergence of fear-evoked increments in selective attention leading to deficits in the ability to time 2 or more signals simultaneously. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of Different States of Anxiety-Like Behavior by Chronic Stress.

Recent studies have identified putative cellular correlates of stress-induced amygdalar plasticity underlying anxiety-like behavior. Chronic immobilization stress (CIS), but not chronic unpredictable stress (CUS), has been reported to induce dendritic remodeling in the basolateral amygdala (BLA). The BLA is also important for consolidation of anxiety in the elevated plus-maze, which is manifested as increased open-arm avoidance on reexposure to the maze. The authors found that CIS, unlike CUS, facilitated anxiety-like behavior in the plus-maze, and this occluded further increase in anxiety when CIS rats were reexposed to the maze 72 hr after the first trial. However, both CUS and control rats exhibited consolidation between trials. Thus, consolidation of anxiety may share common cellular mechanisms that also underlie chronic stress-induced structural plasticity in the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential modulation of changes in hippocampal-septal synaptic excitability by the amygdala as a function of either elemental or contextual fear conditioning in mice

Recent data obtained using a classic fear conditioning paradigm showed a dissociation between the retention of associations relative to contextual information (dependent on the hippocampal formation) and the retention of elemental associations (dependent on the amygdala). Furthermore, it was reported that conditioned emotional responses (CERs) could be dissociated from the recollection of the learning experience (declarative memory) in humans and from modifications of the hippocampal-septal excitability in animals. Our aim was to determine whether these two systems ("behavioral expression" system and "factual memory" system) interact by examining the consequences of amygdalar lesions (1) on the modifications of hippocampal-septal excitability and (2) on the behavioral expression of fear (freezing) resulting from an aversive conditioning during reexposure to conditional stimuli (CSs). During conditioning, to modulate the predictive nature of the context and of a discrete stimulus (tone) on the unconditional stimulus (US) occurrence, the phasic discrete CS was paired with the US or randomly distributed with regard to the US. After the lesion, the CER was dramatically reduced during reexposure to the CSs, whatever the type of acquisition. However, the changes in hippocampal-septal excitability persisted but were altered. For controls, a decrease in septal excitability was observed during reexposure to the conditioning context only for the "unpaired group" (predictive context case). Conversely, among lesioned subjects this decrease was observed in the "paired group" (predictive discrete CS case), whereas this decrease was significantly reduced in the unpaired group with respect to the matched control group. The amplitude and the direction of these modifications suggest a differential modulation of hippocampal-septal excitability by the amygdala to amplify the contribution of the more predictive association signaling the occurrence of the aversive event.     

High blood cadmium levels are not associated with consumption of traditional food among the Inuit of Nunavik

The most reliable stereotactic methods in primates resort to ventricular as opposed to bony landmarks. The usual CA-CP system did not appear satisfactory for stereotaxy of the amygdala and anterior hippocampus. Variation studies on ventriculograms and reconstructions from histological material were done to find more reliable systems. The most precise system of coordinates for cartography and stereotaxy of the amygdala is based on the 'amygdalar notch', a ventricular diverticulum forming the angle between the inferior and anterior borders of the temporal horn of the lateral ventricle, located beneath the inferior border of the amygdala. The AN point, the vertex of the notch in the sagittal direction, is a reliable ventricular landmark in the antero-posterior and infero-superior directions. The medial vertex of the diverticulum, ANm, is a ventricular landmark in the medio-lateral direction. The 'AN system of coordinates' is a reliable system for amygdalar stereotaxy. Stereotaxy of the anterior hippocampus would benefit from other ventricular landmarks. The most lateral point of the main body (HiL) is a landmark for the medio-lateral dimension. Ventriculography and ventricular landmarks should always be used for stereotaxy in primate species.     

Functional MRI reveals left amygdala activation during emotion

The potential of functional magnetic resonance imaging (fMRI) for experimental studies of the brain and behavior considerable given its superior time and spatial resolution, but few studies have attempted to validate them against established methods for measuring cerebral activation. In a previous study absolute regional cerebral blood flow was measured in 16 healthy individuals using quantitative H215O-PET during standardized happy and sad mood induction and during two non-emotional control conditions. During sad mood, blood flow increased in the left amygdala and these changes correlated with shifts towards a negative affect. In the present study blood oxygenation level dependent (BOLD) changes were measured with fMRI during the same experimentally controlled mood states and control tasks. Twelve right-handed normal subjects were examined with a T2*-weighted FLASH sequence. A significant increase in signal intensity was found during sad as well as happy mood induction in the left amygdala. This converging evidence supports the potential of fMRI for advancing the understanding of neural substrates for emotional experience in humans.     

A differential neural response in the human amygdala to fearful and happy facial expressions

The amygdala is thought to play a crucial role in emotional and social behaviour. Animal studies implicate the amygdala in both fear conditioning and face perception. In humans, lesions of the amygdala can lead to selective deficits in the recognition of fearful facial expressions and impaired fear conditioning, and direct electrical stimulation evokes fearful emotional responses. Here we report direct in vivo evidence of a differential neural response in the human amygdala to facial expressions of fear and happiness. Positron-emission tomography (PET) measures of neural activity were acquired while subjects viewed photographs of fearful or happy faces, varying systematically in emotional intensity. The neuronal response in the left amygdala was significantly greater to fearful as opposed to happy expressions. Furthermore, this response showed a significant interaction with the intensity of emotion (increasing with increasing fearfulness, decreasing with increasing happiness). The findings provide direct evidence that the human amygdala is engaged in processing the emotional salience of faces, with a specificity of response to fearful facial expressions.     

Valence dependent asymmetric release of norepinephrine in the basolateral amygdala.

Emerging evidence from literature on humans suggests the valence of emotionally laden environmental stimuli may dictate whether amygdala activation is greater in one hemisphere relative to the contralateral side. However, only a paucity of animal studies attempt to unravel the mechanisms underlying the selective, valence-dependent initiation of activity in the amygdala of opposing hemispheres. The present studies assessed whether exposure to positive or negative appetitive conditions in an operant learning task differentially impacts norepinephrine activation of the left versus right amygdala, respectively. Dialysate samples of norepinephrine were collected from the basolateral nucleus of male Sprague–Dawley rats. Fluctuations in norepinephrine activity were sampled during training conditions involving an abrupt shift (i.e., increase or decrease) in the magnitude of food rewards normally provided for bar press responses. In a subsequent study, dialysate samples of norepinephrine were collected before, during, and after presentation of a negatively valenced stimulus involving footshock delivery during Pavlovian fear conditioning. Norepinephrine concentrations in the left but not right basolateral amygdala were elevated in groups presented with a positive experience of an unexpected increase in food reward after bar pressing (p     

Conditioning of a flavor aversion in rats by amygdala kindling.

Rats received 30 stimulations and 30 sham stimulations (the lead was attached to the subjects but no current was delivered) to the left basolateral amygdala in a quasirandom sequence. Stimulations were preceded by the presentation of 1 flavored solution conditional stimulus (CS+); sham stimulations were preceded by the presentation of another flavored solution, CS-. As kindled motor seizures developed, the rats began to consume significantly less of the CS+ than the CS- Moreover, at the end of the experiment, the rats consumed significantly less of the CS+ than the CS- during a 20-min conditioned flavor preference test in which both solutions were available simultaneously. These findings confirm and extend the recent report that interictal changes in defensive behavior can be conditioned by amygdalar kindling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Appetitive conditioning-induced plasticity is expressed during paradoxical sleep in the medial geniculate, but not in the lateral amygdala.

This study examined whether neurons in the medial division of the medial geniculate (MGm) and the dorsal part of the lateral amygdala (LAd) express learning-induced plasticity in paradoxical sleep (PS) after appetitive conditioning, as they do in PS after fear conditioning. Rats received tone-food pairings in 3 sessions. After each session, the tone was presented at a nonawakening intensity during PS. Multiunit activity was simultaneously recorded in MGm and LAd. During waking, increases in tone-evoked discharges developed in MGm and LAd; however, as training continued, they lessened in LAd, but not in MGm. During PS, conditioned tone responses were expressed in MGm, but not in LAd. Thus, these results demonstrate dissociation of MGm and LAd plasticity. Moreover, compared with fear conditioning results, they suggest that expression of amygdalar plasticity in PS depends on the emotional salience of the stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)