Amygdalofugal Pathway Research Articles

Collothalamic projections to the human amygdala: hemispheric asymmetry modulates trait anxiety.

In 19 people probabilistic DTI tractography was used to visualize the topographic relationships between three white matter components of a fascicle, the supraventricular temporal bundle, that traverses above the temporal horn of the lateral ventricle: collothalamic auditory and visual projections to the amygdala via the posterior thalamus, and the amygdalofugal stria terminalis. This bundle constitutes a subcortical, 'low road' pathway that transmits threat signals to the amygdala, and that projects signals that bias orienting toward visual threat to the bed nucleus of the stria terminalis. The course of the visual streamline passes below the brachium of the superior colliculus through the position two thalamic nuclei that have been shown to both receive afferents from the superficial layers of the superior colliculus and to also project to the amygdala: the suprageniculate nucleus and the inferior pulvinar. The visual streamline passes laterally dorsal to the auditory streamline and both collothalamic streamlines then traverse together above the temporal horn of the lateral ventricle, dorsal to the stria terminalis, with the auditory streamline dorsal to visual streamline, and entering the lateral amygdala dorsal and medial to it. Individual differences in the degree of hemispheric asymmetry of the fractional anisotropy of the visual streamline, but not the auditory streamline, predicted trait anxiety: weaker left hemisphere connectivity relative to those in the right hemisphere, was associated with higher trait anxiety. There was no correlation between individual differences in the microstructure of either the stria terminalis or the ventral amygdalofugal pathway and trait anxiety.

Topographical anatomy of the septum verum and its white matter connections

The human septum verum represents a small but clinically important region of the brain. Based on the results of animal experiments, the stimulation of its medial part was recently proposed with various indications like epilepsy or cognitive impairment after traumatic brain injury. The aim of our study was to present the anatomical relationships of the human septum verum using fiber dissection and histological analysis to support its research and provide essential information for future deep brain stimulation therapies. 16 human cadaveric brains were dissected according to Klingler’s method. To validate our macroscopical findings, 12 samples obtained from the dissected brains and 2 additional specimens from unfrozen brains were prepared for histological examinations. We identified the following white matter connections of the septum verum: (1) the precommissural fibers of the fornix; (2) the inferior fascicle of the septum pellucidum; (3) the cingulum; (4) the medial olfactory stria; (5) the ventral amygdalofugal pathway; (6) the stria medullaris of the thalamus and (7) the stria terminalis. Moreover, we could distinguish a less-known fiber bundle connecting the postcommissural column of the fornix to the stria medullaris of the thalamus and the anterior thalamic nuclei. In this study we present valuable anatomical information about this region to promote safe and effective deep brain stimulation therapies in the future.

Ventral amygdalofugal pathway as an integrated surgically important network: microsurgical anatomy and segmentation based on fiber dissection.

The ventral amygdalofugal pathway (VAFP) provides afferent and efferent connections to the amygdala and spans along some of the frequently traversed intra-axial surgical corridors as a dominant fiber bundle. This study aimed to reveal the frequently overlooked VAFP fibers by examining their courses and connections to the basal forebrain, septal region, hypothalamus, thalamus, tegmentum, and brainstem. Ten postmortem human brains were used to display the characteristics of the VAFP, and fiber dissection results were compared with those of tractography. From anterior to posterior, the VAFP was separated into 5 different portions: 1) amygdala-substantia innominata; 2) amygdaloseptal (diagonal band of Broca); 3) amygdalo-thalamic; 4) amygdalo-hypothalamic, intermingling with the medial forebrain bundle and extending to the bed nucleus of stria terminalis; and 5) amygdalotegmental. The results of fiber dissections were confirmed with findings obtained from diffusion tensor tractography. This study supports the concept that interconnected forebrain, diencephalic, mesencephalic, and brainstem connections of the VAFP form an integrated surgically important network. The fiber dissection findings also provide the neuroanatomical basis for VAFP segmentation, which may help neurosurgeons better appreciate the complex microsurgical anatomy of the amygdalar connections. Amygdala-substantia innominata and amygdalotegmental connections are demonstrated for the first time and clarified within the structure of the VAFP.

Study of electrical activity of subcortical structures of the brain after destruction of the dorsal amygdalofugal pathway

Study of electrical activity of subcortical structures of the brain after destruction of the dorsal amygdalofugal pathway

Microstructural properties within the amygdala and affiliated white matter tracts across adolescence

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8–22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Microsurgical anatomy of the amygdaloid body and its connections.

The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several neuropsychiatric disorders renewed the interest in the study of its functional Neuroanatomy. In this scenario,we felt that a morphological study focused on the amygdaloid body anditsconnections could improve the understanding of thepossible implications in functional neurosurgery. With this purpose we performed a morfological study using nine formalin-fixed human hemispheres dissected under microscopicmagnification by using the fiber dissection technique originally described by Klingler. In our results the amygdaloid body presents two divergent projection systems named dorsal and ventral amygdalofugal pathways connecting the nuclear complex with the septum and the hypothalamus. Furthermore, the amygdaloid body is connected with the hippocampus through the amygdalo-hippocampal bundle, with the anterolateral temporal cortex through the amygdalo-temporalis fascicle, the anterior commissure and the temporo-pulvinar bundle of Arnold, with the insular cortex through the lateral olfactory stria, with the ambiens gyrus, the para-hippocampal gyrus and the basal forebrain through the cingulum, and with the frontal cortex through the uncinate fascicle. Finally, the amygdaloid body is connected with the brainstem through the medial forebrain bundle. Our description of the topographic anatomy of the amygdaloid body and its connections, hopefully representsa useful tool for clinicians and scientists, both in the scope of application and speculation.

The ansa peduncularis in the human brain: A tractography and fiber dissection study

IntroductionThe ansa peduncularis is a composite of white matter fiber bundles closely packed together that sweeps around the cerebral peduncle. The exact components of the ansa peduncularis and their anatomical trajectories are still not established firmly in the literature. ObjectiveThe aim of this study was to examine the topographical anatomy of the ansa peduncularis and its subcomponents using the fiber dissection and tractography techniques. MethodsTen formalin-fixed brains were prepared according to Klingler’s method and dissected by the fiber dissection technique from the lateral, medial and inferior surfaces. The ansa peduncularis was also traced using high definition fiber tracking (HDFT) from the MRI data of twenty healthy adults and a 1021-subject template from the Human Connectome Project. ResultsThe ventral amygdalofugal pathway system includes white matter fiber bundles with a topographically close relation as they sweep around the cerebral peduncle and contribute to form the ansa peduncularis: amygdaloseptal fibers connect the amygdala and anterior temporal cortex to the septal region and amygdalohypothalamic fibers project from the amygdala to the hypothalamus. Additionally, from the amygdala and anterior temporal cortex, amygdalothalamic fibers project to the medial thalamic region. The ansa lenticularis, which connects the globus pallidus to the thalamus, was not shown in our study. ConclusionThe study demonstrated the trajectory of the ansa peduncularis and its subcomponents, based on fiber dissection and tractography, improving our understanding of human brain anatomical connectivity.

Study of the electrical activity of limbic brain structures after the destruction of the dorsal amygdalofugal pathway

Study of the electrical activity of limbic brain structures after the destruction of the dorsal amygdalofugal pathway

Tract-Specific White Matter Correlates of Age-Related Reward Devaluation Deficits in Macaque Monkeys.

Aim:Cognitive aging is known to alter reward-guided behaviors that require interactions between the orbitofrontal cortex (OFC) and amygdala. In macaques, OFC, but not amygdala volumes decline with age and correlate with performance on a reward devaluation (RD) task. The present study used diffusion magnetic resonance imaging (dMRI) methods to investigate whether the condition of the white matter associated with amygdala-OFC connectivity changes with age and relates to reward devaluation.Methods:Diffusion-, T1- and T2-weighted MRIs were acquired from adult and aged bonnet macaques. Using probabilistic tractography, fractional anisotropy (FA) estimates from two separate white matter tracts associated with amygdala-OFC connectivity, the uncinate fasciculus (UF) and amygdalofugal (AF) pathways, were obtained. Performance measures on RD and reversal learning (RL) tasks were also acquired and related to FA indices from each anatomical tract.Results:Aged monkeys were impaired on both the RD and RL tasks and had lower FA indices in the AF pathway. Higher FA indices from the right hemisphere UF pathway correlated with better performance on an object-based RD task, whereas higher FA indices from the right hemisphere AF were associated with better performance on an object-free version of the task. FA measures from neither tract correlated with RL performance.Conclusions:These results suggest that the condition of the white matter connecting the amygdala and OFC may impact reward devaluation behaviors. Furthermore, the observation that FA indices from the UF and AF differentially relate to reward devaluation suggests that the amygdala-OFC interactions that occur via these separate tracts are partially independent.

Intrinsic functional connectivity of the central extended amygdala.

The central extended amygdala (EAc)-including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)-plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordinated activity of distributed neural circuits, the functional architecture of the EAc network and the degree to which the BST and the Ce show distinct patterns of functional connectivity is unclear. Here, we used a novel combination of imaging approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community-dwelling adults. Multiband imaging, high-precision registration techniques, and spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and showcase image registration techniques that are likely to be useful for researchers working with "deidentified" neuroimaging data.

Elucidation of White Matter Tracts of the Human Amygdala by Detailed Comparison between High-Resolution Postmortem Magnetic Resonance Imaging and Histology.

The amygdala has attracted considerable research interest because of its potential involvement in various neuropsychiatric disorders. Recently, attempts have been made using magnetic resonance imaging (MRI) to evaluate the integrity of the axonal connections to and from the amygdala under pathological conditions. Although amygdalar pathways have been studied extensively in animal models, anatomical references for the human brain are limited to histology-based resources from a small number of slice locations, orientations and annotations. In the present study, we performed high-resolution (250 μm) MRI of postmortem human brains followed by serial histology sectioning. The histology data were used to identify amygdalar pathways, and the anatomical delineation of the assigned structures was extended into 3D using the MRI data. We were able to define the detailed anatomy of the stria terminalis and amygdalofugal pathway, as well as the anatomy of the nearby basal forebrain areas, including the substantia innominata. The present results will help us understand in detail the white matter structures associated with the amygdala, and will serve as an anatomical reference for the design of in vivo MRI studies and interpretation of their data.

Revealing the ventral amygdalofugal pathway of the human limbic system using high spatial resolution diffusion tensor tractography.

The amygdala is known to have a role in core processes regulated by the limbic system such as motivation, memory, emotion, social behavior, self-awareness as well as certain primitive instincts. Several functional studies have investigated some of these brain tasks of the human limbic system. However, the underlying neuronal fiber connectivity of the amygdalo-diencephalon, as part of the limbic system, has not been delineated separately by prior diffusion-weighted imaging studies. The ability to trace the underlying fiber connections individually will be helpful in understanding the neurophysiology of these tracts in different functions. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine connections of the amygdala, hypothalamus, septum or other adjacent limbic structures have yet to be elucidated by diffusion-weighted tractography studies. We therefore aimed to further investigate these fine neuronal connections using fiber tractography and high spatial resolution diffusion tensor imaging on 3T on 15 healthy right-handed male human subjects (age range 24-37years). The ventral amygdalofugal pathway, anterior commissure and stria terminalis are the three main efferent pathways of the amygdala. We delineated the detailed trajectories of the ventral amygdalofugal tract, anterior commissure and their connections bilaterally in 15 normal adult human brains. Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to demonstrate the trajectory of amygdalofugal tract and its connections to the hypothalamic and septal nuclei. We further revealed, for the first time, the close relationship of the amygdalofugal tract and anterior commissure with the fornix, stria terminalis and uncinate fasciculus bilaterally in 15 healthy adult human brains.

Alterations in brain structure and functional connectivity in prescription opioid-dependent patients

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Pathways from the ventral hippocampus and caudal amygdala to forebrain regions that regulate sensorimotor gating in the rat

The neural substrates regulating sensorimotor gating in rodents are studied in order to understand the basis for gating deficits in clinical disorders such as schizophrenia. N-methyl- d-aspartate (NMDA) infusion into the ventral temporal lobe, including caudal parts of the ventral hippocampal region and amygdala, has been shown to disrupt sensorimotor gating in rats, as measured by prepulse inhibition (PPI) of startle. One working model is that reduced PPI after infusion of NMDA into this region is mediated via its efferents to ventral forebrain structures, i.e. medial prefrontal cortex (mPFC) and nucleus accumbens. Yet, PPI-disruptive effects persist after lesions of the precommissural fornix, the principal output pathway of the hippocampal formation. Here, we aimed to characterize non-fornical forebrain projections from this region that might mediate the PPI-disruptive effects of the ventral temporal lobe. Electrolytic lesions of the precommissural fornix in male Sprague–Dawley rats were followed by infusions of fluorogold into the mPFC or by infusions of biotinylated dextan amine into the ventral temporal lobe. Projections from the ventral subiculum and CA1 regions of the ventral hippocampus to the mPFC and accumbens core and shell were interrupted by fornix lesions. Projections to the mPFC and accumbens from other regions of the ventral temporal lobe, particularly the lateral entorhinal cortex and the embedded olfactory and vomeronasal parts of the caudal amygdala, survived fornix lesions. These additional projections coursed rostrally through the amygdala and emerged via the stria terminalis, interstitial nuclei of the posterior limb of the anterior commissure, and the ventral amygdalofugal pathway. PPI-regulatory portions of the ventral temporal lobe innervate the accumbens and mPFC via multiple routes. It remains to be determined which of these non-fornical projections may be responsible for the persistent regulation of PPI after fornix lesions.

Efferent Projections of the Anterior and Posterodorsal Regions of the Medial Nucleus of the Amygdala in the Mouse

The efferent projections of the anterior and posterodorsal part of the medial nucleus (MePD) in the mouse were studied by means of anterograde axonal tracing using biotinylated dextran amine. The MePD axons ran mainly via the stria terminalis and to a lesser extent via the ventral amygdalofugal pathway. The projections to the forebrain were broadly distributed and varied from very strong to scant. The most significant connections were destined to the bed nucleus of the stria terminalis in which all parts of the medial division were innervated by MePD neurons. Moderate projections reached the limbic striatum (nucleus accumbens), olfactory tubercle and the lateral septal nucleus. The substantia innominata was also innervated by the MePD, and especially the projection to its ventral portion was substantial. The profuse innervation of the medial preoptic nucleus and medial preoptic area indicated significant involvement of the MePD in sexual behavior. Many hypothalamic nuclei were innervated but to a different extent. The very strong innervation of the ventral premammillary nucleus further indicated the involvement of the MePD in the neuronal circuitry for sexual behavior. Substantial projections also reached the anterior hypothalamus and tuber cinereum, while the connections to the lateral hypothalamus were widespread but showed moderate density. MePD strongly innervated the ventrolateral part of the ventromedial hypothalamic nucleus and moderately its remaining parts. The neurosecretory hypothalamic nuclei and the arcuate nucleus contained only a few MePD terminals. The thalamic innervation was very scant and reached the lateral habenular nucleus and the nuclei of the midline. The mesencephalic connections were moderate to sparse and projected to the mesolimbic dopaminergic groups in the ventral tegmental area, the pars lateralis and the dorsal tier of the substantia nigra pars compacta, the periaqueductal gray and the dorsal raphe nucleus. The present results principally resembled data known in other rodent species; however, the efferents of the MePD often differed in extent and/or topical distribution.

The bed nucleus of the stria terminalis in the Syrian hamster: Subnuclei and connections of the posterior division

The bed nucleus of the stria terminalis is a key part of a ring of cells extending between the centromedial amygdala and bed nucleus of the stria terminalis referred to as the extended amygdala. The present study describes the architecture of the bed nucleus of the stria terminalis and the connections of subnuclei in posterior bed nucleus of the stria terminalis. The hamster bed nucleus of the stria terminalis is readily allotted to anterior and posterior divisions separated by the fibers of the body of the anterior commissure. The anterior division has four subnuclei: anteromedial, anterointermediate, anterolateral, and anteroventral. Within the posterior division, there are three distinct regions: posteromedial, posterointermediate, and posterolateral. In hamsters, the posterior bed nucleus of the stria terminalis contributes to male sexual behavior, particularly chemoinvestigation. Moreover, the posterior bed nucleus of the stria terminalis is part of a neural circuit essential for mating, including the medial amygdaloid nucleus and medial preoptic area. The connections of bed nucleus of the stria terminalis, posteromedial part, bed nucleus of the stria terminalis, posterointermediate part and bed nucleus of the stria terminalis, posterolateral part were visualized by co-injection of anterograde ( Phaseolus vulgaris leucoagglutinin) and retrograde (cholera toxin B) tract tracers. The bed nucleus of the stria terminalis, posterointermediate part and bed nucleus of the stria terminalis, posteromedial part have dense bidirectional connections with medial amygdaloid nucleus and cortical amygdala via the stria terminalis and ventral amygdalofugal pathway. These subnuclei also maintain bidirectional connections with steroid-concentrating areas including lateral septum, medial preoptic area, hypothalamus, and periaqueductal gray. The bed nucleus of the stria terminalis, posterointermediate part and bed nucleus of the stria terminalis, posteromedial part receive projections from the subiculum and send projections to deep mesencephalic nuclei. By contrast, the bed nucleus of the stria terminalis, posterolateral part is connected with the central amygdala, lateral hypothalamus, subthalamic nucleus, nucleus accumbens, substantia innominata, substantia nigra and thalamus. Thus, the bed nucleus of the stria terminalis, posterointermediate part and bed nucleus of the stria terminalis, posteromedial part have similar connections with areas involved in social behaviors. The bed nucleus of the stria terminalis, posterolateral part maintains connections with areas involved in motivational circuits. This supports the concept of distinct circuits within the extended amygdala which differentially link the centromedial amygdala and bed nucleus of the stria terminalis.

Activation of ventrolateral medullary neurons projecting to spinal autonomic areas after chemical stimulation of the central nucleus of amygdala: a neuroanatomical study in the rat

Several studies have shown that the central nucleus of amygdala is involved in cardiovascular regulation. The control of this function may be mediated by activation of the ventrolateral medulla neurons that project to preganglionic neurons located in the intermediolateral nucleus of the spinal cord. The aim of the present study was to examine whether stimulation of the central nucleus of amygdala activated ventrolateral medulla neurons projecting to the intermediolateral nucleus. For this purpose, the injection of a retrograde tracer, the cholera toxin b subunit (CTb), into the intermediolateral nucleus of the T2 segment was combined with immunohistochemical detection of Fos protein following chemical stimulation of the central nucleus of amygdala. Results showed that retrogradely labeled neurons were found throughout the ventrolateral medulla. Moreover, chemical stimulation of the central nucleus of amygdala induced: (1) a decrease of arterial blood pressure; (2) an expression of Fos protein mainly in sub-populations of neurons located in the intermediate and caudal parts of the ventrolateral medulla; (3) a significantly higher number of double labeled neurons (CTb-immunoreactive/Fos-immunoreactive) in the rostral part of the ventrolateral medulla than in the other parts of this region. These results show that the central nucleus of amygdala influences the activity of brainstem neurons projecting to the intermediolateral nucleus. Data were discussed in terms of descending amygdalofugal pathways involved in the hypotension.

Blockade of Excitability of Hippocampal Neurons after Coagulation of the Dorsal Amygdalofugal Pathway

In chronic experiments on rabbits, we demonstrated that electrolytic destruction of the stria terminalis results in the intense depression of the integral electrical activity of the hippocampus. Characteristics of the responses induced by electrical and chemostimulation of the hippocampus under the above conditions allowed us to conclude that a significant drop in the excitability of hippocampal neurons themselves, but not changes in the structure and intensity of afferent impulsation from the extrahippocampal structures, underlies such a depression. Morphological changes in neurons and satellite glial cells, such as lysis of the Nissl substance, hyperchromatosis, and wrinkling of the cells after destruction of the stria terminalis, were proof of the correctness of our conclusion. It is postulated that one of the main factors underlying the generalized effects observed in our experiments is probably the disturbance of functional characteristics of the hypothalamo-hypophyseal neurosecretory system induced by destruction of the amygdalofugal connections; this disturbance results in significant pathological shifts of metabolism in the hippocampus.

Lidocaine blockade of amygdala output in fear-conditioned rats reduces Fos expression in the ventrolateral periaqueductal gray

We showed recently that conditioned fear to context induces Fos expression in the ventrolateral periaqueductal gray [ Neuroscience (1997) 78, 165–177]. Neurons in this region are thought to play an important role in the expression of freezing during conditioned fear. To test the possibility that this activation comes directly from the amygdala, we looked at changes in Fos expression after a unilateral blockade of the ventral amygdalofugal pathway with lidocaine. The pathway contains fibres originating from the central nucleus of the amygdala that project directly and mainly ipsilaterally to the ventrolateral periaqueductal gray. Conditioned fear was evoked by re-exposing rats to the same box in which they had previously received electric footshocks. The test re-exposure was preceded by a unilateral microinjection of lidocaine (2%, 0.5–1 μl; n=20) or saline ( n=14). Lidocaine was also tested in non-conditioned animals ( n=13). The results show that, when lidocaine was microinjected in the medial part of the central nucleus of the amygdala or along the ventral amygdalofugal pathway of conditioned rats, fear-induced Fos expression in the ventrolateral periaqueductal gray was reduced on the side ipsilateral to the injection (up to 37% reduction in comparison to the contralateral side). Ipsilateral reductions were also observed with saline, but they were weaker (maximum of 27% reduction). Fos expression remained low on both sides in the non-fear-conditioned animals injected with lidocaine. Finally, although freezing was only partly reduced in the conditioned animals unilaterally injected with lidocaine, it was significantly correlated to the ipsilateral reduction in Fos expression. This study provides direct evidence that the projection from the central nucleus of the amygdala to the ventrolateral periaqueductal gray is activated during fear and that it contributes to the Fos response of the ventrolateral periaqueductal gray.

Postictal Elevation of Prolactin Levels After Psychic Auras‐Evidence for Seizure Discharges Involving Mesolimbic Structures

Purpose: The postictal elevation of prolactin (PRL) levels results from the spread of ictal discharges involving mesolimbic structures (amygdala and hippocampus), via the ventral amygdalofugal pathway to the hypothalamus. To determine whether the mesolimbic structures are involved, we measured postictal PRL levels after simple partial seizures (SPSs) with psychic symptoms (psychic auras), and compared them with those after complex partial seizures (CPSs), 80% of which have been reported to show significant postictal elevations of PRL. Methods: Serum PRL levels were measured 15, 30, and 60 min after each ictus. Samples were obtained for the baseline values when patients had been seizure free for 12 h. We regarded motionless stares followed by automatisms as CPSs, and we depended on the patient's description for the occurrence of psychic auras. Results: Seven patients with temporal lobe epilepsy (four men and three women; mean age, 41.4 years; range, 25–70 years; laterality of focus, right: left: bilateral = 4:1:2) were studied. Six CPSs (in five patients) and six SPSs (in three patients) were detected. In one patient, both types of seizures were analyzed on separate occasions. The CPSs observed were either gestural or oral automatisms. The described psychic auras consisted of types such as complex visual hallucinations (n = 4), ictal fear (n = 4), deja vu (n = 2), depersonalization (n = 2), macropsia (n = 1), and distortion of sense of time (n = 1). The total number of psychic aura types was greater than six (the number of SPSs with psychic symptoms) because any single episode had multiple types of auras. That is, the sequences of psychic aura types were as follows: ictal fear→depersonalization→complex visual hallucination; ictal fear→depersonalization; ictal fear→deja vu; deja vu→complex visual hallucination; macropsia→complex visual hallucination→distortion of time sense; and ictal fear‐complen visual hallucination. Postictal PRL levels invariably reached their peaks at 15 min. Mean 15‐min postictal PRL levels (for CPSs and SPSs with psychic symptoms, 45.6 and 46.7 ng/ml, respectively) were significantly higher than the mean baselines (9.6 and 9.9 ng/ml, respectively; p < 0.02. paired t test). Conclusions: In this study, the mean 15–min postictal PRL levels for SPSs with psychic symptoms (4.9 times as high as the baseline) were significantly increased to the same extent as those for CPSs (4.6 times as high as the baseline). Although some investigators assert that ictal discharges confined to the temporal neocortical region can elicit psychic auras, our results are indicative of seizure discharges involving mesolimbic structures in the development of psychic auras.