PubMed Health⌕ Search

Biomedical subjects

Joseph L Price

Publications and source records attributed to Joseph L Price.

At least 19 recordsLinked to original sources
PubMed2007

Cytoarchitectonic and chemoarchitectonic subdivisions of the perirhinal and parahippocampal cortices in macaque monkeys.

Although the perirhinal and parahippocampal cortices have been shown to be critically involved in memory processing, the boundaries and extent of these areas have been controversial. To produce a more objective and reproducible description, the architectonic boundaries and structure of the perirhinal (areas 35 and 36) and parahippocampal (areas TF and TH) cortices were analyzed in three macaque species, with four different staining methods [Nissl and immunohistochemistry for parvalbumin, nonphosphorylated neurofilaments (with SMI-32), and the m2 muscarinic acetylcholine receptor]. We further correlated the architectonic boundary of the parahippocampal cortex with connections to and from different subregions of anterior area TE and with previously published connections with the prefrontal cortex and temporal pole (Kondo et al. [2005] J. Comp. Neurol. 493:479-509). Together, these data provided a clear delineation of the perirhinal and parahippocampal areas, although it differs from previous descriptions. In particular, we did not extend the perirhinal cortex into the temporal pole, and the lateral boundaries of areas 36 and TF with area TE were placed more medially than in other studies. The lateral boundary of area TF in Macaca fuscata was located more laterally than in Macaca fascicularis or Macaca mulatta, although there was no difference in architectonic structure. We recognized a caudal, granular part of the parahippocampal cortex that we termed "area TFO." This area closely resembles the laterally adjacent area TE and the caudally adjacent area V4 but is clearly different from the more rostral area TF. These areas are likely to have distinct functions.

Animals↗
PubMed2005

Differential connections of the perirhinal and parahippocampal cortex with the orbital and medial prefrontal networks in macaque monkeys.

Previous anatomical studies indicate that the orbital and medial prefrontal cortex (OMPFC) of monkeys is organized into an "orbital" network, which appears to be related to feeding and reward, and a "medial" network, related to visceral control and emotion. In this study, we examined the connections of the orbital and medial prefrontal networks with the perirhinal (areas 35 and 36) and parahippocampal (areas TF and TH) cortex with anterograde and retrograde axonal tracers. The perirhinal cortex is reciprocally connected with orbital network areas Iapm, Iam, Ial, 13m, 13l, 12r, and 11l. In contrast, the parahippocampal cortex is reciprocally connected with the medial network, especially areas around the corpus callosum (areas 24a/b, caudal 32, and 25), and with area 11m. Projections from the parahippocampal cortex also extend to areas 10m, 10o, Iai, and rostral area 32, as well as to dorsolateral areas 9 and 46. In addition, both the perirhinal and parahippocampal cortex are reciprocally connected with areas that are intermediate between the orbital and medial networks (areas 13a, 13b, and 14c) and with the supracallosal area 24a'/b'. Outside the frontal cortex, the perirhinal cortex and the orbital prefrontal network are both interconnected with the ventral part of the temporal pole (TG), area TE and the ventral bank and fundus of the superior temporal sulcus (STS), and the dysgranular insula. In contrast, the parahippocampal cortex and the medial prefrontal network are connected with the dorsal TG, the rostral superior temporal gyrus (STG) and dorsal bank of STS, and the retrosplenial cortex.

Animals↗
PubMed2005

Free will versus survival: brain systems that underlie intrinsic constraints on behavior.

This article discusses the neuroanatomical systems involved in the related functions of fear and discernment of the consequences of one's actions, two internal constraints on free will and action. Both mechanisms are related to a system for control and modulation of visceral function stretching from the spinal cord to the ventromedial prefrontal cortex, including the ventral striatum, ventral pallidum, and mediodorsal thalamus, the amygdala, the hypothalamus, the periaqueductal gray (PAG), and the brainstem reticular formation and autonomic nuclei. Reflexes at the lower levels provide rapid visceral and somatic reactions to threatening stimuli, while the PAG and hypothalamus coordinate these to produce more concerted responses. The amygdala interacts with the cortical sensory systems in the assessment of fear-related stimuli and modulates the reflex responses through projections to the hypothalamus and brainstem. The ventromedial prefrontal cortex, especially the "medial prefrontal network," is connected to the amygdala, hypothalamus, and PAG, and allows cortical control over the system in relation to a wider set of emotions. This cortical region is involved both in the assessment of reward and in mood disorders and it plays a central role in the ability to discern the consequences of one's actions and make appropriate behavioral choices. It also forms an interconnected circuit with specific cortical areas in the rostral superior temporal cortex, posterior parahippocampal cortex, and retrosplenial/posterior cingulate cortex. The overall function of this circuit is unclear, but may be involved in introspective monitoring of the individual.

Amygdala↗
PubMed2005

Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry.

Bipolar disorder (BD) has been associated with abnormalities of brain structure. Specifically, in vivo volumetric MRI and/or post mortem studies of BD have reported abnormalities of gray matter (GM) volume in the medial prefrontal cortex (PFC), amygdala, hippocampal subiculum and ventral striatum. These structures share anatomical connections with each other and form part of a "visceromotor" network modulating emotional behavior. Areas of the lateral orbital, superior temporal and posterior cingulate cortices project to this network, but morphometric abnormalities in these areas have not been established in BD. The current study assessed tissue volumes within these areas in BD using MRI and voxel-based morphometry (VBM). MRI images were obtained from 36 BD subjects and 65 healthy controls. To account for possible neurotrophic and neuroprotective effects of psychotropic medications, BD subjects were divided into medicated and unmedicated groups. Images were segmented into tissue compartments, which were examined on a voxel-wise basis to determine the location and extent of morphometric changes. The GM was reduced in the posterior cingulate/retrosplenial cortex and superior temporal gyrus of unmedicated BD subjects relative to medicated BD subjects and in the lateral orbital cortex of medicated BD subjects relative to controls. White matter (WM) was increased in the orbital and posterior cingulate cortices, which most likely reflected alterations in gyral morphology resulting from the reductions in the associated GM. The morphometric abnormalities in the posterior cingulate, superior temporal and lateral orbital cortices in BD support the hypothesis that the extended network of neuroanatomical structures subserving visceromotor regulation contains structural alterations in BD. Additionally, localization of morphometric abnormalities to areas known to exhibit increased metabolism in depression supports the hypothesis that repeated stress and elevated glucocorticoid secretion may result in neuroplastic changes in BD.

Adult↗
PubMed2004

Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and gamma-aminobutyric acidergic cortical cells in the prelimbic cortex of the rat.

Although the reciprocal interconnections between the prefrontal cortex and the mediodorsal nucleus of the thalamus (MD) are well known, the involvement of inhibitory cortical interneurons in the neural circuit has not been fully defined. To address this issue, we conducted three combined neuroanatomical studies on the rat brain. First, the frequency and the spatial distribution of synapses made by reconstructed dendrites of nonpyramidal neurons were identified by impregnation of cortical cells with the Golgi method and identification of thalamocortical terminals by degeneration following thalamic lesions. Terminals from MD were found to make synaptic contacts with small dendritic shafts or spines of Golgi-impregnated nonpyramidal cells with very sparse dendritic spines. Second, a combined study that used anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and postembedding gamma-aminobutyric acid (GABA) immunocytochemistry indicated that PHA-L-labeled terminals from MD made synaptic junctions with GABA-immunoreactive dendritic shafts and spines. Nonlabeled dendritic spines were found to receive both axonal inputs from MD with PHA-L labelings and from GABAergic cells. In addition, synapses were found between dendritic shafts and axon terminals that were both immunoreactive for GABA. Third, synaptic connections between corticothalamic neurons that project to MD and GABAergic terminals were investigated by using wheat germ agglutinin conjugated to horseradish peroxidase and postembedding GABA immunocytochemistry. GABAergic terminals in the prelimbic cortex made symmetrical synaptic contacts with retrogradely labeled corticothalamic neurons to MD. All of the synapses were found on cell somata and thick dendritic trunks. These results provide the first demonstration of synaptic contacts in the prelimbic cortex not only between thalamocortical terminals from MD and GABAergic interneurons but also between GABAergic terminals and corticothalamic neurons that project to MD. The anatomical findings indicate that GABAergic interneurons have a modulatory influence on excitatory reverberation between MD and the prefrontal cortex.

Animals↗
PubMed2004

Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes.

BACKGROUND: A previous study reported reductions in glial density and glia/neuron ratio in the amygdala of individuals with major depressive disorder (MDD), without a change in neuronal density. It is not known, however, whether this glial loss is due to astrocytes, oligodendrocytes, or microglia. METHODS: Tissue samples, equally from the right and left hemispheres, were obtained from subjects diagnosed with MDD (n = 8), bipolar disorder (BD) (n = 9), or no psychiatric disorders (n = 10). Sections were stained immunohistochemically for S-100beta (for astrocytes) and human leukocyte antigen (for microglia), and with the Nissl method. In Nissl-stained sections, oligodendrocytes have more compact, darker-stained nuclei, whereas astrocytes and microglia have larger, lighter-stained nuclei, with more granular chromatin. Neurons are larger, with a nucleolus and stained cytoplasm. The density of glia was determined with stereologic methods. RESULTS: The density of total glia and oligodendrocytes in the amygdala was significantly lower in MDD than in control subjects, but not significantly lower in BD compared with control subjects. The decreases were largely accounted for by differences in the left hemisphere. There was no significant decrease in astrocyte or microglia density in MDD or BD subjects. CONCLUSIONS: The glial cell reduction previously found in the amygdala in MDD is primarily due to oligodendrocytes.

Adolescent↗
PubMed2004

Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type.

Universally accepted neuropathologic criteria for differentiating Alzheimer disease (AD) from healthy brain aging do not exist. We tested the hypothesis that Bielschowsky silver stained total, cored, and neuritic senile plaques (TSPs, CSPs, and NSPs, respectively), rather than neurofibrillary tangles (NFTs), best discriminate between the 2 conditions using rigorously defined nondemented (n = 7) and AD (n = 35) subjects with no known co-morbidities. We compared lesions in 3 neocortical regions, in hippocampal CA1, and in entorhinal cortex in 19 men and 13 women between 74 and 86 years at death. The Clinical Dementia Rating (CDR) was used to assess degree of cognitive impairment within a year of demise. Neocortical TSP measures provided the highest correlation with expiration CDR: area under the curve (AUC) = 0.986 with 97.8% sensitivity at 90% specificity with an estimated cut-point of 6.0 TSP/ mm2. All SP measures yielded higher estimated AUC and sensitivity for 90% specificity compared to NFTs. Derived TSP cut-points applied to 149 persons with clinical AD regardless of their neuropathologic diagnosis yielded a sensitivity of 97% and specificity of 84% for TSPs in the 3 neocortical areas. Thus cut-points based on both diffuse and neuritic SP in neocortical regions distinguished nondemented and AD subjects with high sensitivity and specificity.

Adult↗
PubMed2003

Differential connections of the temporal pole with the orbital and medial prefrontal networks in macaque monkeys.

Previous studies indicate that the orbital and medial prefrontal cortex (OMPFC) is organized into "orbital" and "medial" networks, which have distinct connections with cortical, limbic, and subcortical structures. In this study, retrograde and anterograde tracer experiments in monkeys demonstrated differential connections between the medial and orbital networks and the dorsal and ventral parts of the temporal pole. The dorsal part, including dysgranular and granular areas (TGdd and TGdg), is reciprocally connected with the medial network areas on the medial wall and gyrus rectus (areas 10m, 10o, 11m, 13a, 14c, 14r, 25, and 32) and on the lateral orbital surface (areas Iai and 12o). The strongest connections are with areas 10m (caudal part), 14c, 14r, 25, 32, and Iai. The agranular temporal pole (TGa) is connected with several areas, but most strongly with medial network area 25. The granular area around the superior temporal sulcus (TGsts) and the ventral dysgranular and granular areas (TGvd and TGvg) are reciprocally connected with the orbital network (especially areas 11l, 13b, 13l, 13m, Ial, Iam, and Iapm). TGsts is strongly connected with the entire orbital network, whereas areas TGvd and TGvg have lighter and more limited connections. Intrinsic connections within the temporal pole are also restricted to dorsal or ventral parts. Together with evidence that the dorsal and ventral temporal pole are differentially connected to auditory and visual areas of the superior and inferior temporal cortex, the results indicate separate connections between these systems and the medial and orbital prefrontal networks.

Animals↗
PubMed2003

Architectonic subdivision of the human orbital and medial prefrontal cortex.

The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 11l, 13a, 13b, 13m, 13l, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 12l, and 12o. The agranular insula (areas Iam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex.

Acetylcholinesterase↗
PubMed2003

Persistence and brain circuitry.

The orbitofrontal and adjacent medial prefrontal cortex may play an important role in normal social functioning and affect modulation. Recent anatomical studies of this area of the prefrontal cortex have demonstrated a striking correspondence of fine-grained architectonic partitioning schemes in humans and nonhuman primates. This finding allows neurophysiological recording and anatomical connectivity data in animals to be considered together with functional imaging data and lesion studies in humans. In a functional MRI study, we show that individual differences in Persistence, a dimensional trait assessed with a seven-factor personality model, may be linked to specific areas in the lateral orbital and medial prefrontal cortex and the ventral striatum. These areas are part of an anatomical circuit that has been defined in nonhuman primates and has been implicated in functions related to behavioral persistence. These findings represent a fresh approach to linking normal individual differences in personality and behavior to specific neuronal structures and subsystems.

Adult↗
PubMed2003

Comparative aspects of amygdala connectivity.

The connections of the amygdala in rats, cats, and monkeys can be divided into three systems: (1) A largely forebrain system provides sensory information to the amygdala from the olfactory cortex, ascending taste/visceral pathways, posterior thalamus and sensory association cortex. Most of these connections are reciprocal and also support amygdaloid modulation of sensory processing. (2) A set of projections extends from the amygdala to the hypothalamus and brain stem, which appears to modulate visceral function in relation to emotional stimuli. (3) A forebrain circuit involves the amygdala with the ventromedial frontal, rostral insular, and rostral temporal cortical areas, the medial thalamus and ventromedial basal ganglia, and seems to be directly involved in emotional behavior and mood. All of these systems are present in all mammals studied; the major differences lie in the greater elaboration of the cerebral cortex in primates.

Amygdala↗
PubMed2003

High-dimensional mapping of the hippocampus in depression.

OBJECTIVE: Abnormalities of the hippocampus may play a role in the pathophysiology of depression, but efforts to identify a structural abnormality in this brain structure among depressed patients have produced mixed results. Previous research may have been limited by exclusive reliance on measures of hippocampal volume. High-dimensional brain mapping is a new analytic method that quantitatively characterizes the shape as well as volume of a brain structure. In this study, high-dimensional brain mapping was used to evaluate hippocampal shape and volume in patients with major depressive disorder and healthy comparison subjects. METHOD: By using magnetic resonance imaging, brain scans were obtained from 27 patients with major depressive disorder and 42 healthy comparison subjects. High-dimensional brain mapping generated a series of 10 variables (components) that represented hippocampal shape, and hippocampal volumes were also computed. Analysis of variance techniques were used to compare depressed patients and comparison subjects on hippocampal shape and volume. RESULTS: While the depressed patients and comparison subjects did not differ in hippocampal volume, there were highly significant group differences in hippocampal shape. The two groups did not overlap on a discriminant function computed from a model comprising the 10 components. The pattern of hippocampal surface deformation in the depressed patients suggested specific involvement of the subiculum. CONCLUSIONS: Patients with major depression may have structural abnormalities of the hippocampus that can be detected by analysis of hippocampal shape but not volume. A specific defect in the subiculum could have widespread effects throughout neurocircuits that appear to be abnormal in depression.

Adult↗
PubMed2002

A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

Dopamine can induce fascinating, complex human behavioral states, including disinhibition, euphoria, or elaborate stereotypies, whereas dopamine deficiency can cause anxiety or sadness. Limited data suggest that these phenomena may involve dysfunction of orbital frontal cortex, cingulate cortex, or ventral striatum. The dopamine D3 receptor (D3R) has an anatomic distribution that suggests it could mediate these effects, but almost no data directly demonstrate the regional functional effects of D3R activation. We used quantitative positron emission tomography (PET), [15O]water, and the D3-preferring dopamine agonist pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. We studied seven normal baboons ventilated with 70% nitrous oxide, and analyzed results voxelwise in a common atlas space. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. The dose-response curve and duration of pramipexole's effects suggest that these rCBF responses indicate functional effects of a D3-preferring agonist. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. We conclude that a dopamine D3 receptor agonist preferentially affects brain activity in prefrontal and limbic cortex, and speculate that dopamine's effects on these regions via D3Rs may mediate some of the known psychiatric complications of dopamine deficiency or excess.

Animals↗
PubMed2002

Low glial numbers in the amygdala in major depressive disorder.

BACKGROUND: Functional imaging studies implicate the prefrontal cortex and amygdala in major depressive disorder and bipolar disorder, and glial decreases have been reported in the prefrontal cortex. Here, glia and neurons were counted in the amygdala and entorhinal cortex in major depressive disorder, bipolar disorder, and control cases. METHODS: Tissue blocks from major depressive disorder (7), bipolar disorder (10), and control (12) cases, equally divided between right and left, were cut into 50 microm sections and stained with the Nissl method. One major depressive disorder and all but two bipolar disorder cases had been treated with lithium or valproate. Neurons and glia were counted using stereological methods. RESULTS: Glial density and the glia/neuron ratio were substantially reduced in the amygdala in major depressive disorder cases. The reduction was mainly accounted for by counts in the left hemisphere. No change was found in neurons. Average glia measures were not reduced in bipolar disorder cases; however, bipolar disorder cases not treated with lithium or valproate had significant glial reduction. Similar but smaller changes were found in the entorhinal cortex. CONCLUSIONS: Glia are reduced in the amygdala in major depressive disorder, especially on the left side. The results suggest that lithium and valproate may moderate the glial reduction.

Amygdala↗
PubMed2002

Axo-axonic synapses formed by somatostatin-expressing GABAergic neurons in rat and monkey visual cortex.

In cerebral cortex of rat and monkey, the neuropeptide somatostatin (SOM) marks a population of nonpyramidal cells (McDonald et al. [1982] J. Neurocytol. 11:809-824; Hendry et al. [1984] J. Neurosci. 4:2497:2517; Laemle and Feldman [1985] J. Comp. Neurol. 233:452-462; Meineke and Peters [1986] J. Neurocytol. 15:121-136; DeLima and Morrison [1989] J. Comp. Neurol. 283:212-227) that represent a distinct type of gamma-aminobutyric acid (GABA) -ergic neuron (Gonchar and Burkhalter [1997] Cereb. Cortex 7:347-358; Kawaguchi and Kubota [1997] Cereb. Cortex 7:476-486) whose synaptic connections are incompletely understood. The organization of inhibitory inputs to the axon initial segment are of particular interest because of their role in the suppression of action potentials (Miles et al. [1996] Neuron 16:815:823). Synapses on axon initial segments are morphologically heterogeneous (Peters and Harriman [1990] J. Neurocytol. 19:154-174), and some terminals lack parvalbumin (PV) and contain calbindin (Del Rio and DeFelipe [1997] J. Comp. Neurol. 342:389-408), that is also expressed by many SOM-immunoreactive neurons (Kubota et al. [1994] Brain Res. 649:159-173; Gonchar and Burkhalter [1997] Cereb. Cortex 7:347-358). We studied the innervation of pyramidal neurons by SOM neurons in rat and monkey visual cortex and examined putative contacts by confocal microscopy and determined synaptic connections in the electron microscope. Through the confocal microscope, SOM-positive boutons were observed to form close appositions with somata, dendrites, and spines of intracortically projecting pyramidal neurons of rat area 17 and pyramidal cells in monkey striate cortex. In addition, in rat and monkey, SOM boutons were found to be associated with axon initial segments of pyramidal neurons. SOM axon terminals that were apposed to axon initial segments of pyramidal neurons lacked PV, which was shown previously to label axo-axonic terminals provided by chandelier cells (DeFelipe et al. [1989] Proc. Natl. Acad. Sci. USA 86:2093-2097; Gonchar and Burkhalter [1999a] J. Comp. Neurol. 406:346:360). Electron microscopic examination directly demonstrated that SOM axon terminals form symmetric synapses with the initial segments of pyramidal cells in supragranular layers of rat and monkey primary visual cortex. These SOM synapses differed ultrastructurally from the more numerous unlabeled symmetric synapses found on initial segments. Postembedding immunostaining revealed that all SOM axon terminals contained GABA. Unlike PV-expressing chandelier cell axons that innervate exclusively initial segments of pyramidal cell axons, SOM-immunoreactive neurons innervate somata, dendrites, spines, and initial segments, that are just one of their targets. Thus, SOM neurons may influence synaptic excitation of pyramidal neurons at the level of synaptic inputs to dendrites as well as at the initiation site of action potential output.

Animals↗
PubMed2002

Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels.

In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1<P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.

Adolescent↗