Basal Ganglia Injury Research Articles

Neonatal brain imaging and the identification of metabolic acidemia and hypoxic–ischemic encephalopathy

Objective. To determine the precision with which intrapartum metabolic acidemia and hypoxic–ischemic encephalopathy (HIE) in term and near-term infants can be identified by neonatal brain imaging.Study design. This is a case–control study whose inclusion criteria were neonates born at ≥34 weeks gestation with a cord gas at delivery, suspected neurological abnormalities, and computed tomography (CT) or magnetic resonance (MR) imaging of the brain. Neonates with chromosomal and major congenital malformations were excluded. Brain imaging for neonates with and without metabolic acidemia (pH < 7.0 and base deficit > 12 mM) at birth and HIE were retrospectively reviewed by a neuroradiologist blinded to their clinical course and compared.Results. There were 54 neonates admitted to the NICU at a single university hospital between 1992 and 2006 that met these inclusion criteria of which 27 had metabolic acidemia at birth. There were 16 diagnosed clinically as having HIE at the time of neonatal discharge, 13 from the acidemic group and 3 from the nonacidemic group. Radiological signs of basal ganglia injury were significantly more common in neonates with metabolic acidemia (29.6%, 3.7%, p = 0.02) and HIE (37.5%, 7.9%, p = 0.01). Logistic regression corrected for gestational age showed that radiological signs of basal ganglia injury could identify the presence of HIE with area under the ROC curve of 0.71, sensitivity 37.5%, specificity 92.1%, positive predictive value 66.7%, and negative predictive value of 77.8%.Conclusion. Radiological signs of basal ganglia injury on early neonatal imaging are associated with metabolic acidemia and HIE, but is not precise enough to serve as a gold standard in the identification of these conditions.

Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson's disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear extinction compared to controls. High Performance Liquid Chromatography analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light–dark preference, or hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain.

Diffuse Cerebral Cortex, Cerebellar Cortex and Basal Ganglia Injury: A Rare MR Imaging Manifestation of Heat Stroke

We present a case of heat stroke with rare magnetic resonance (MR) imaging manifestations. In addition to abnormal high signals in bilateral cerebellum and basal ganglia seen on T2-weighted MR images (T2WI), the case showed diffuse cerebral cortical high signals on T2WI and diffusion-weighted images (DWI). Heat stroke with diffuse hypoperfusion to the brain due to diversion of blood circulation was hypothesized as the cause of brain injury, including the cerebral cortex.

Induced cerebral hypothermia reduces post-hypoxic loss of phenotypic striatal neurons in preterm fetal sheep

Perinatal hypoxic–ischemic injury of the basal ganglia is a significant cause of disability in premature infants. Prolonged, moderate cerebral hypothermia has been shown to be neuroprotective after experimental hypoxia–ischemia; however, it has not been tested in the preterm brain. We therefore examined the effects of severe hypoxia and the potential neuroprotective effects of delayed hypothermia on phenotypic striatal neurons. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4 ± 0.3°C to 29.5 ± 2.6°C) from 90 min to 70 h after the end of occlusion. Hypothermia was associated with a significant overall reduction in striatal neuronal loss compared with normothermia-occlusion fetuses (mean ± SEM, 5.5 ± 1.2% vs. 38.1 ± 6.5%, P < 0.01). Immunohistochemical studies showed that occlusion resulted in a significant loss of calbindin-28 kd, glutamic acid decarboxylase isoform 67 and neuronal nitric oxide synthase-immunopositive neurons ( n = 7, P < 0.05), but not choline acetyltransferase-positive neurons, compared with sham controls ( n = 7). Hypothermia ( n = 7) significantly reduced the loss of calbindin-28 kd and neuronal nitric oxide synthase, but not glutamic acid decarboxylase-immunopositive neurons. In conclusion, delayed, prolonged moderate head cooling was associated with selective protection of particular phenotypic striatal projection neurons after severe hypoxia in the preterm fetus. These findings suggest that head cooling may help reduce basal ganglia injury in some premature babies.

Control de la epilepsia en niños y adolescentes con parálisis cerebral con respecto a la etiología y la lesión cerebral de base

Epilepsy in children with cerebral palsy is a very important problem of public health, with a prevalence 750/1,000. AIM. To describe the relationship between cerebral palsy-etiologies and the cerebral injuries in the epilepsy control. Retrospective study included 398 subjects, both genders, subjects under 18 years old with evidence of epilepsy related to infantile cerebral palsy (ICP). For comparison analysis purposes the entire population was studied on two principally aspects: ICP based on its etiology, and ICP based on cerebral injury background by means of computer tomography (CT). The etiology was subdivided into: hypoxic-ischemic encephalopathy (HIE), cerebral malformation (CM), and others causes (O). Cerebral lesions were classified into: diffuse cerebral injury (DCI), focal location injury (FLI), basal ganglia injury (BGI), cerebral dysgenesia (CD), hydrocephaly (H) and non-CT evidence (N). The impact of the epileptic seizures was determined according to the cerebral injury background and its etiology. The findings after clinical surveillance and statistical analysis were able to affirm that seizures control with respect to etiology was: HIE: 77.9%, CM: 72%, O: 86% without statistical significance (p < 0.28). We found in the cerebral lesion: DCI: 70.7 %, FLI: 82.4%, BGI: 87.5%, CD: 79.3%, H: 77.8%, N: 83.3%, statistical significance was found in these subgroups (p < 0.04). Cerebral injury in children suffering from cerebral has a prognostic reliance value in the control of epilepsy, regardless its etiology.

Risk, Recognition, and Prevention of Kernicterus

Kernicterus (neonatal bilirubin encephalopathy) is a serious and disabling disease that may be increasingly common in industrialized nations. In this retrospective chart review from one Canadian hospital, the authors identified 12 infants admitted between 1990 and 2000 with elevated unconjugated bilirubin levels (>23.4 mg/dL) and with the pattern of brainstem and basal-ganglia injury suggestive of kernicterus. Three fourths were boys, and 11 were full term. All but one had been discharged home 1 day after birth and returned at 3 to …

Persisting Dementia After Isoniazid Overdose

Back to table of contents Previous article Next article LetterFull AccessPersisting Dementia After Isoniazid OverdoseRobert N. McLay, M.D. Ph.D., Angela Drake, Ph.D., and Timothy Rayner, M.D., Robert N. McLaySearch for more papers by this author, M.D. Ph.D., Angela DrakeSearch for more papers by this author, Ph.D., and Timothy RaynerSearch for more papers by this author, M.D., Department of Mental Health Services, Naval Medical Center, San Diego, San Diego, CAPublished Online:1 May 2005AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Isoniazid (INH) overdose can result in neuropsychological sequelae, including cognitive deficits.1 These deficits are generally regarded as transient and rapidly reversible with pyridoxine.2 We report a case in which, despite appropriate treatment with pyridoxine, INH overdose resulted in Substance-Induced Persisting Dementia.Case ReportMr. A is a 20-year-old, single, white male, with above-average cognitive abilities, as assessed by his scores on the Armed Services Vocational Aptitude Battery (ASVAB) upon entering the Navy. Two years into his service, Mr. A. attempted suicide by overdosing on and estimated 9000 to 12,000 mg of INH.Mr. A was intubated and treated for persistent seizures. Lavage was initiated, and IV pyridoxine was administered. As sequelae to his overdose, Mr. Anderson developed an acute toxic encephalopathy. At worst, the patient was noted to have fixed and dilated pupils and decerebrate posturing. After treatment in an intensive care unit, Mr. A. recovered medically but was discovered to have significant persisting deficits, specifically retrograde amnesia for 1 and ½ years, previously; anterograde learning difficulties; apraxia; and personality change in the form of a newly acquired passivity.Repeated psychiatric interviews and neuropsychological testing did not support the diagnosis of a major depressive disorder, conversion disorder, or malingering. Similarly, a thorough work up by infectious disease showed no indications of central nervous system (CNS) tuberculosis or other infectious etiologies.Formal neuropsychological testing showed impairment in speech initiation and verbal fluency. Tests of attention ranged from severely impaired to low average. Mr. A experienced significant difficulties encoding new verbal information and, to a lesser degree, stored data. Visual memory was below expectations. Fine motor skills were poor. Overall intelligence quotient (IQ) was average but below expectations for his previous baseline.A neurological examination was negative for evidence of INH-induced peripheral neuropathy but did show changes consistent with a basal ganglia injury. Electroencephalogram (EEG) showed prominent slow delta and scattered theta activity, particularly in the temporal areas. Magnetic resonance imaging (MRI) showed increased signal involving bilateral mesotemporal lobes, which could be consistent with the sort of learning difficulties exhibited.To target memory problems, Mr. A was treated with continuing PO pyridoxine and donepezil. After 20 days on the inpatient psychiatric service and 2 months of outpatient cognitive rehab, the patient regained function to the point at which he could return to live with his family. Several months later, he was able to obtain a job in a fast food restaurant. One year after the initial overdose, however, he continued to have cognitive difficulties and had not returned to his baseline.CommentNeuropsychiatric changes are a well-known complication of INH overdose, but it has been assumed that lasting deficits do not result.1,3 The case of Mr. A illustrates that such complications can occur. Persistent seizures, encephalopathy, and other medical consequences that Mr. A suffered as a result of his overdose could have contributed to significant neurotoxicity.3 Long-term, neuropsychiatric screening may, therefore, be warranted in patients who have experienced significant INH overdose.References1 Wallace RJ: Antimycobacterial agents, in Principles and Practice of Infectious Diseases, 5th ed. Edited by Madell GL, Bennett JE, Dolin R. Philadelphia, Churchill Livingston, 2000, pp 436–437Google Scholar2 Watkins RC, Hambrick EL, Benjamin G, et al: Isoniazid toxicity presenting as seizures and metabolic acidosis. J Natl Med Assoc 1990; 82:57, 62, 64Medline, Google Scholar3 Temmerman W, Dhondt A, Vandewoude K: Acute isoniazid intoxication: seizures, acidosis and coma. Acta Clin Belg 1999; 54:211–216Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 17Issue 2 May 2005Pages 256-257 Metrics PDF download History Published online 1 May 2005 Published in print 1 May 2005

Glutaric aciduria type 1: a clinician's view of progress

Glutaric aciduria type 1 (GA1) arises from an enzymatic block in the common degradation pathway for lysine and tryptophan. It is a cause of crippling striatal necrosis during infancy (Strauss et al ., 2003). Clinical experience teaches us two things about GA1. First, predicting precisely when and if basal ganglia injury will occur in an individual is presently difficult, if not impossible. Second, when such injuries ensue, we have no therapeutic instruments to stop them. Thus, to prevent injuries we need prediction, and there is ample clinical evidence that plasma and urine organic acid measurements are inadequate for this purpose (Strauss et al ., 2003). Real progress in the treatment of GA1 requires a deeper understanding of the premorbid state—the set of physiological adaptations entrained by abnormal organic acid metabolism in the brain. For this knowledge to be applied physiological changes that precede the catastrophic event must be defined, anatomical or biochemical abnormalities causatively can be linked to brain injury so that monitored in the clinical setting. Such a picture does not readily emerge from in vitro experiments, which generally use isolated single cell types from a variety of non-human species assayed under non-physiological conditions (see Kolker et al ., 2004, for review), Nevertheless, these results cannot be reproduced consistently (Freudenberg et al ., 2004), and are difficult to reconcile with the complex conditions that prevail in a living patient. Careful post-mortem studies are an invaluable tool for understanding physiological derangements that occur in life. In this issue of Brain , Dr Funk and colleagues report on six post-mortem brains from aboriginal Ojibway–Cree GA1 patients of Northern Canada to, in their words, ‘offer additional insight into the pathogenesis of the disorder … [to] help us develop an intervention strategy that could prevent the episode associated with acute striatal …

Neuroradiological findings in glutaric aciduria type I (glutaryl‐CoA dehydrogenase deficiency)

This article summarizes the magnetic resonance imaging features of glutaric aciduria type I (GA I) based on the cases presented at the 3rd International Workshop on Glutaryl-CoA Dehydrogenase Deficiency together with a review of previously reported neuroimaging characteristics of GA I. Previous reports have focused on characteristic findings, such as basal ganglia injury and frontotemporal atrophy or hypoplasia, subdural effusions and white-matter disease. Most of these findings have been demonstrated in symptomatic children, i.e. after manifestation of acute encephalopathic crises. In contrast, prospective investigations in presymptomatically diagnosed children are rare. Since more recent investigations have highlighted CNS changes in patients without encephalopathic crises, systematic prospective investigations of neuroradiological findings in this disease are indispensable for a better understanding of this disease. Based on these findings a suggestion for a MRI protocol is presented, supporting a standardized evaluation of patients with GA I.

Neonatal Movement Disorders

After completing this article, readers should be able to: 1. Delineate the characteristics that differentiate hyperkinetic neonatal movement disorders from neonatal seizures. 2. Describe the primary characteristics of and treatment for hyperekplexia. 3. Explain the relationship between gastroesophageal reflux and movement disorders in neonates. 4. Describe the primary ocular movement disorders in neonates. Neonates often exhibit paroxysmal behaviors that are nonepileptic in nature, such as oral-buccal-lingual movements, pedaling, stepping, and rotatory arm movements. The electroencephalogram (EEG) is of particular value for distinguishing these nonepileptic behaviors from subtle seizures. EEG and video-EEG studies in such movement disorders do not exhibit seizure discharges during the events. This distinction is important because nonepileptic events do not require treatment with anticonvulsants. Although the absence of surface ictal activity does not exclude entirely the possibility of seizures arising from deeper structures, it generally is accepted that these disorders are not epileptic. For the purposes of this review, we include common nonepileptic paroxysmal (episodic) movements that occur from birth to early infancy (onset between birth and 3 months of age). Many of these movement disorders may persist during infancy or early childhood. We do not discuss more persistent motor problems, such as spasticity, hypotonia, or myotonia. Also, disorders that occur after 3 months of age are not included. We have classified the movement disorders into two major categories: 1) hyperkinetic movements and 2) dystonic or extrapyramidal type of movements. Because the pathophysiologic mechanisms underlying neonatal movement disorders often are unknown, they are categorized on the basis of phenomenology, rather than presumed cause. Some of these disorders may have overlapping symptomatology. A third category encompasses “ocular movement disorders.” ### Jitteriness of the Newborn Jitteriness may be due to many factors, including metabolic disturbance, hypoxic-ischemic encephalopathy, drug withdrawal, hypoglycemia, and hypocalcemia. Although jitteriness may be mistaken for neonatal seizures, a distinguishing feature of jitteriness is that the …

Type I glutaric aciduria, part 1: natural history of 77 patients.

Type I glutaric aciduria (GA1) results from mitochondrial matrix flavoprotein glutaryl-CoA dehydrogenase deficiency and is a cause of acute striatal necrosis in infancy. We present detailed clinical, neuroradiologic, molecular, biochemical, and functional data on 77 patients with GA1 representative of a 14-year clinical experience. Microencephalic macrocephaly at birth is the earliest sign of GA1 and is associated with stretched bridging veins that can be a cause of subdural hematoma and acute retinal hemorrhage. Acute striatal necrosis during infancy is the principal cause of morbidity and mortality and leads to chronic oromotor, gastroesophageal, skeletal, and respiratory complications of dystonia. Injury to the putamen is heralded by abrupt-onset behavioral arrest. Tissue degeneration is stroke-like in pace, radiologic appearance, and irreversibility. It is uniformly symmetric, regionally selective, confined to children under 18 months of age, and occurs almost always during an infectious illness. Our knowledge of disease mechanisms, though incomplete, is sufficient to allow a rational approach to management of encephalopathic crises. Screening of asymptomatic newborns with GA1 followed by thoughtful prospective care reduces the incidence of radiologically and clinically evident basal ganglia injury from approximately 90% to 35%. Uninjured children have good developmental outcomes and thrive within Amish and non-Amish communities.

Una rara alteración del habla de origen neurológico: El Síndrome del Acento Extranjero

Foreign accent syndrome (FAS) is an unusual neurological speech disorder documented in not more than twenty specific studies. As a consequence of a cerebral mainly subcortical injury, the patient s speech is foreign sounding to native listeners. As subject cannot avoid this foreign accent, and given its abrupt emergence, this disorder usually involves emotional consequences by loss of identity and of belonging to a speech community. In this paper, a case from Castellón de la Plana (Spain) is presented with a injury in right basal ganglia and the literature about this topic is revised. From the available data, we describe the main characteristics of the syndrome and discuss the possible role of basal ganglia

Parkinsonism as unusual neurological complication in childhood systemic lupus erythematosus

Parkinsonism complicating systemic lupus erythematosus (SLE) is extremely rare. We report two girls with SLE who developed extrapyramidal parkinsonian features after an initial stormy course. One patient presented with generalized tonic clonic seizure and was then noted to have akinetic mutism and masked face. MRI brain revealed abnormal signals in bilateral basal ganglia and single photon emission computed tomography (SPECT) showed hypoperfusion in the same area. EEG background was slow and disorganized. Symptoms persisted despite high dose intravenous methylprednisolone and cyclophosphamide. Intravenous immunoglobulin (IVIG) was prescribed empirically and was followed by complete recovery. Both EEG and MRI brain were normal on follow-up. The second patient was found unconscious and then developed bradykinesia, mutism and shuffling gait. MRI and SPECT both detected abnormalities in basal ganglia. EEG was slow. Intravenous immunoglobulin was given after methylprednisolone and cyclophosphamide. This was followed by clinical improvement. The pathogenesis of basal ganglia injury in SLE, along with the management of cerebral lupus and the mechanisms of action of IVIG, are discussed.

A Lesion Analysis of Visual Orienting Performance in Children With Cerebral Vascular Injury

Anterior brain insults during development have been shown to result in visual orienting deficits; however, the type of orienting deficit has varied across studies. Performance on an orienting task was examined in relation to the location and volume of injury on magnetic resonance exams in 15 children with cerebral infarction and 32 control children. Contralateral lesions including the parietal lobe were associated with larger validity effects, suggesting difficulties disengaging attention. A similar trend was found for the middle-frontal gyrus. Basal ganglia injury contralateral to a given hemifield was associated with less facilitation of attention. Lesion volume in each hemisphere did not show a significant relation with contralateral validity effects. The data suggest that variability in the type of visual orienting deficits shown in prior studies of children with anterior brain insults may be related in part to the specific location of lesions within the frontal lobe.

Neuroimaging variables related to development of Secondary Attention Deficit Hyperactivity Disorder after closed head injury in children and adolescents

Objective: To characterize children who develop Secondary Attention Deficit Hyperactivity Disorder (S-ADHD) after severe and moderate closed head injury (CHI) according to neuroimaging variables. Method : Ninety-nine children from 4-19 years who suffered severe and moderate CHI were prospectively followed for a year after injury. Premorbid psychiatric status was determined by administration to the parent of a structured psychiatric interview. This interview was readministered 1 year after injury to determine the presence of post-closed head injury S-ADHD. An MRI was performed 3 months after injury to define lesion locations and volumes. Results : A set of multiple logistic regression models determined that the odds of developing S-ADHD were 3.64 times higher among children with thalamus injury, and 3.15 times higher among children with basal ganglia injury. There was no significant difference in lesion volumes in any of the locations of interest between the group who developed S-ADHD and the group who did not develop SADHD. Conclusion : The data support an association between S-ADHD and injury in either or both the thalamus and basal ganglia, but they do not definitively demonstrate whether injury in either structure has an effect on S-ADHD in the absence of injury in the other.

The Syndrome of Acute Near-Total Intrauterine Asphyxia in the Term Infant

Eleven term infants sustained an acute, near-total intrauterine asphyxia at the end of labor. Imaging studies documented a consistent pattern of injury in subcortical brain nuclei, including thalamus, basal ganglia, and brainstem; in contrast the cerebral cortex and white matter were completely or relatively spared. This pattern of injury correlated with the acute and long-term neurologic syndromes in these patients. Four patients had a severe neonatal encephalopathy that included prominent signs of brainstem dysfunction. The other seven patients had a moderate neonatal encephalopathy. Three of these patients had dystonia consistent with basal ganglia injury; all seven remained normocephalic and had good cognitive outcomes consistent with sparing of cerebral cortex and white matter. Finally, in all 11 patients, injury to organs other than the brain was usually subtle. The distribution of injury in these patients reflects the hierarchy of metabolic needs that are unmet after a severe, sudden disruption of substrate supply as occurs in an acute, severe asphyxia. Thus, the higher metabolic rate of the brain compared with other organs explains the significant neonatal encephalopathy with relative sparing of nonbrain organs. Similarly, the higher metabolic rate of subcortical nuclei compared with cerebral hemispheres explains the preponderance of subcortical damage. This clinical and imaging syndrome is in contrast with that seen in more prolonged but less severe intrauterine asphyxia, in which shunting of blood flow from nonbrain organs to the brain and from cerebral hemispheres to the thalamus and brainstem renders nonbrain organs and cerebral hemispheres most vulnerable.

Oral pharmacotherapy for the movement disorders of cerebral palsy.

Movement disorders are a well-recognized feature of some patients with cerebral palsy and often require treatment. However, treatments have been symptomatic and empiric, and there have been few pharmacologic studies. The major movement disorders in cerebral palsy are dystonia and the hyperkinesias choreoathetosis and myoclonus. They may occur in combination, often accompanied by spasticity and sometimes by epilepsy. Some drugs are useful treatments for all of these problems, but others may improve one while worsening another. Pitfalls in management include not diagnosing metabolic/degenerative disorders, which may mimic cerebral palsy, or not recognizing reversible complications of cerebral palsy, which may exacerbate symptoms. This review attempts to summarize empiric drug use and recommendations for therapy, drug studies in extrapyramidal cerebral palsy, and prospects for new drugs or models for the problem. Many new pharmacologic agents are available for study in cerebral palsy. Better methods of detecting basal ganglia injury after perinatal injury in asymptomatic infants may allow early intervention in the biologic process of recovery and adaptation.

Functional Imaging Studies in Secondary Depression

ABSTRACT Depression is common in certain neurological diseases and is clinically indistinguishable from mood symptoms characteristic of primary affective illness. The association of depression with diseases involving the basal ganglia is particularly well recognized. While the specific mechanisms of mood disorders in these neurological patients are unknown, selective neural pathways affected directly and indirectly by basal ganglia injury provide a strategy for examining these patients with functional imaging techniques. Glucose metabolism has been measured with p 18 F-fluoro-deoxy-glucose (FDG) and positron emission tomography (PET) in depressed and nondepressed patients with Parkinson's disease, Huntington's disease, and caudate strokes. These studies have demonstrated bilateral hypometabolism of orbital-inferior prefrontal cortex and anterior temporal cortex in depressed subjects, independent of disease etiology. This pattern is similar to that seen in patients with primary unipolar depression studied using comparable acquisition and analysis strategies. These findings suggest that disruption of paralimbic pathways linking frontal cortex, temporal cortex, and striatum may contribute to depression in patients with both primary depression and depression associated with basal ganglia disease, and support the concept of a neuroanatomical locus for mood regulation.

Frontal lobe dysfunction in secondary depression.

Depression is common in patients with neurological disease, particularly with diseases involving the basal ganglia. Although the mechanisms of mood disorders in these patients are poorly understood, selective neural pathways affected directly and indirectly by basal ganglia injury provide a strategy for examining these patients with functional imaging techniques. Studies of regional cerebral glucose metabolism by use of positron-emission tomography are reviewed. These studies demonstrate bilateral hypometabolism of orbital-inferior prefrontal cortex and anterior temporal cortex in depressed subjects, independent of disease etiology. This pattern is similar to that seen in patients with primary unipolar depression. These findings suggest that disruption of paralimbic pathways linking frontal cortex, temporal cortex, and striatum may contribute to both primary depression and depression associated with basal ganglia disease. The findings support the evolving concept of a neuroanatomical locus for mood regulation.