Moreover, as molecular changes typically precede gross pathology,

Moreover, as molecular changes typically precede gross pathology, molecular imaging may enable early diagnosis and treatment of diseases. Molecular imaging has provided a number of key insights into the pathophysiology and treatment of central nervous system (CNS) disorders such as schizophrenia, Parkinson’s disease, depression, and dementia. This review considers the application of molecular imaging to CNS disorders, focusing on its potential to inform

the Selleckchem Volasertib development and evaluation of treatments. We focus on schizophrenia, Parkinson’s Inhibitors,research,lifescience,medical disease, depression, and dementia as major CNS disorders where molecular imaging has provided a number of key insights. We also review the potential of molecular imaging to guide new drug development for CNS disorders. Table I summarizes the ways molecular imaging has advanced our understanding of CNS disorders, while Table II outlines its advantages and limitations. Inhibitors,research,lifescience,medical Table I. How molecular imaging has advanced understanding of central nervous system disorders. Table

II. Advantages and limitations of molecular imaging. Schizophrenia Schizophrenia is a chronic, Inhibitors,research,lifescience,medical severe mental illness characterized by psychotic symptoms such as hallucinations and delusions often coupled with cognitive and social impairments. The discovery of the first antipsychotic drug, chlorpromazine, was the outcome of serendipity rather than rational drug design based on understanding of pathophysiology.3 It was

subsequently discovered that chlorpromazine blocks dopamine receptors, and, despite varying widely in their affinity at other receptors, all antipsychotic drugs currently in the market block dopamine D2 receptors4 and their affinity for D2 receptors closely parallels their clinical Inhibitors,research,lifescience,medical effectiveness.5,6 Thus the discovery of antipsychotic drugs informed understanding of the pathophysiology of schizophrenia, by providing indirect evidence that dopamine dysfunction contributed to the disorder. The focus then was on D2/3 receptors, Inhibitors,research,lifescience,medical and postmortem studies suggested there was a large elevation in schizophrenia (see paper by Cross et al7 and review by Howes and Kapur8). However, it was not until the application of molecular imaging to schizophrenia research that it became possible to test the dopamine hypothesis in the living brain and to investigate the locus of dopamine abnormalities in detail. Since Carnitine dehydrogenase then there have been more than fifty molecular imaging studies of the dopaminergic system in schizophrenia, beginning with seminal findings in the mid-1980s and 1990s.9-15 These provide consistent and robust evidence for subcortical presynaptic dopamine abnormalities, specifically elevated dopamine synthesis and release capacity. A recent meta-analysis found the effect size for this was large — Cohen’s d=0.8 — whilst there was little if any alteration in D2/3 receptors.

Selected abbreviations and acronyms ADHD attention deficit-hyper

Selected abbreviations and acronyms ADHD attention deficit-hyperactivity disorder OCD obsessive-compulsive disorder PANDAS pediatric autoimmune neuropsychiatrie disorder associated with streptococcal infection TS Tourette’s syndrome
Visual hallucinations came of age In 1936 with the publication of two clinical reviews. The first, a modest 2-page essay, appeared in the relative backwater of a parochial Swiss medical journal, authored by George de Morsier, then a

recently appointed lecturer in neurology.1 The second appeared in the Annales Médico-Psychologiques, the high-profile voice of French-speaking psychiatry, Inhibitors,research,lifescience,medical coauthored by the neurologist Jean L’Hermitte, an established expert in the field following his earlier description of peduncular hallucinations, and the psychiatrist Julian de Ajuriaguerra, then aged 25 and at the beginning of his career.2 Both reviews shared three important breaks with tradition. First, visual hallucinations were deemed worthy of study in their own right, distinct from Inhibitors,research,lifescience,medical hallucinations in other modalities and from other forms of psychopathology Second, they were to be considered a unitary symptom. An earlier generation

of psychiatrists had hoped that different types of visual hallucination might carry Inhibitors,research,lifescience,medical different diagnostic implications; however, from here on, the important clinical detail became whether a given patient experienced visual hallucinations of any kind, not whether they had hallucinated a simple lattice pattern Inhibitors,research,lifescience,medical as opposed to a procession of animals or an elaborately costumed figure, for example. The third break with tradition was to distance visual hallucinations from visual

illusions, giving them a higher clinical status. Yet, although sharing much in common, the two papers differed in their conception of the brain and its disorders. L’Hermitte and de Ajuriaguerra looked forward to emerging holistic models of psychopathology, viewing visual hallucinations as part of a general hallucinatory state. Although Inhibitors,research,lifescience,medical classifying the clinical conditions associated with visual hallucinations by the location of the underlying visual system lesion, their scheme was not intended to imply a range of distinct syndromes. In contrast, de Morsier’s approach looked back to the classical era of associationism (see ref 3), viewing visual hallucinations as a localizing neurological Metalloexopeptidase symptom that, when considered in its wider clinical context, formed distinct syndromic entities. This syndromic approach captured the clinical imagination and remains an important find more influence today, in part the result of later disagreement between de Morsier and de Ajuriaguerra over the role of the eye in visual hallucinations. In order to understand the origin of de Morsier’s syndromes, we must first turn to the Parisian Central Police station.

8 Adolescence is a crucial developmental stage, marked by a confl

8 Adolescence is a crucial developmental stage, marked by a confluence of biological, psychological, and social challenges.143-146 There arc significant physical maturational changes (eg, the onset of puberty), social-cognitive Etoposide order advances (eg, ability for more abstract thinking and generalizations across situations and time), interpersonal transitions (eg, changes in social roles in family and peer relationships), and social-contextual changes (eg, school Inhibitors,research,lifescience,medical transitions). Although these maturational transitions offer tremendous opportunities for youth, because the developing brain and behavioral

and cognitive systems mature at different rates, and because these systems are under the control of both common and independent biological processes, this developmental period also is marked by heightened vulnerability. The normative developmental transitions associated with adolescence might serve as sensitive periods for the activation of specific processes involved in the onset, persistence, and recurrence of depressive episodes.147-148 Family-genetic factors There is clear Inhibitors,research,lifescience,medical evidence of familial transmission of depression.149-151 These data, however, cannot

distinguish environmental from genetic causes of transmission. Family, twin, and adoption studies indicated effects of both genetic and environmental factors for unipolar depression.152,153 Based on epidemiological data, the Inhibitors,research,lifescience,medical proportion of variance attributed to genetic factors is between 24% and 58% for depressive illness.154 Genetic influences have Inhibitors,research,lifescience,medical been found to vary with age and sex. Shared environmental influences may be more important in younger children, and these influences may be replaced by new genetic and unique environmental influences as children

grow older.150,155 In one study, the increased hcritability effect in adolescents was found only for girls, and not boys.156 Research on behavioral genetics initially partitioned population variance into two components, one due to genetic factors and the second due to environmental influences. The implication was that the two were separate, and it was assumed Inhibitors,research,lifescience,medical that gene-environment interactions were usually of so little importance that they could be ignored. Theoretical considerations suggested that this was not likely to be true, and empirical findings are now accumulating Endonuclease on the interactions between identified common single genetic variants and environmentally-mediated risks.157 Indeed, the important role of environmental factors in modulating vulnerability and their interactions with genetic variants has been specifically demonstrated for depression. 152,158,159 Recent research on genetic liability for depression has begun to address the mode of inheritance, such as temperament characteristics associated with emotionality and emotional regulation, a tendency toward stress exposure and reactivity, and alterations in neurobiological regulation.

However, in infantile onset patients, the clinical manifestations

However, in infantile onset patients, the clinical manifestations are somehow similar among all types of lipid dysmetabolism, including hypotonia, hypoketotic hypoglycemic encephalopathy, hepatomegaly and cardiomyopathy. In this review, we would like to go NVP-BKM120 through CPTII and VLCAD deficiencies briefly but mainly focus on four LSMs with known causative genes, PCD, MADD, NLSDI and NLSDM. Inhibitors,research,lifescience,medical Carnitine palmitoyltransferase

II deficiency (CPTII deficiency) CPTII, located at the inner mitochondrial membrane, is responsible for the transfer of long-chain acyl-CoA (Fig. 1), thus the defects in CPTII would apparently affect the access of long-chain acyl-CoA to β-oxidation. CPTII deficiency caused

by the mutations Inhibitors,research,lifescience,medical in the CPT2 gene is the first inherited defect of fatty acid oxidation to be identified (2). Three clinical subtypes, neonatal, infantile and mild late-onset forms, have been described but muscular symptoms including recurrent rhabdomyolysis and muscle pain after long-term exercise were mainly associated with the late-onset form (3). Infantile cases usually present recurrent attacks of acute liver failure with hypoketotic hypoglycemia, cardiomyopathy and sudden Inhibitors,research,lifescience,medical death while neonatal-onset patients demonstrate a more severe phenotype with dysmorphic features. There is a good correlation between genotype, metabolic dysfunction and phenotype as null or truncated mutations often cause absent enzyme activity and earlier-onset phenotype (2). A common mutation, p.S113L, has been found in more than 50% of Inhibitors,research,lifescience,medical mutant alleles in mild late-onset patients. Figure 1. Scheme of selected metabolic pathways of lipid. (OCTN2: plasma membrane sodium-dependent Inhibitors,research,lifescience,medical carnitine transporter; TG: triglycerides; DG: diglycerides; ATGL: adipose triglyceride lipase; CGI-58: comparative

gene identification-58; CPTI: carnitine palmitoyltransferase I; … Metabolic profiles in CPTII deficiency patients usually show increased long-chain acylcarnitines. Creatine kinase (CK) level is markedly elevated after prolonged fasting or exercise. Muscle pathology is typically characterized by nonspecific next changes without increased lipid droplets. Therefore, enzymatic assay in leukocyte, cultured fibroblasts or biopsied muscles may be the most reliable diagnostic test, as well as the mutation analysis for CPT2. The treatment for CPTII deficiency is mainly dependent on restricting the diet and avoiding fasting. Long-chain fat –restricted diet with medium-chain triglycerides (MCT) supplementation is recommended (4). Recently, bezafibrate, a commonly used hypolipidemic drug, has shown to restore the capacity for normal fatty acid oxidation in muscle cells from patients with a mild form of CPTII deficiency (5).

2007), a reasonable interpretation of this habituation is that it

2007), a reasonable interpretation of this habituation is that it reflects decreased engagement in worry over time (although see the Limitations section below). A decrease in worry over time is consistent with evidence that worry is cognitively taxing and engages resources that can be depleted with continued use (Hayes et al. 2008). As activation in Broca’s area decreased over time, response to negative words increased Inhibitors,research,lifescience,medical in right SFG (and a lateralized effect appeared in right MFG). As discussed above, these areas are in or adjacent to FEF, which has been associated

with top-down biasing of attention. Therefore, a potential interpretation is that the findings in right SFG/MFG indicate that anxious apprehension is associated with increased attention to negative stimuli over time. Although these findings are consistent with the hypothesis that habituation in Broca’s area is associated with a concurrent increase in activation in attention-related areas, they do not represent a direct Inhibitors,research,lifescience,medical test of this

hypothesis. Therefore, direct tests were conducted Inhibitors,research,lifescience,medical using PPI analyses, which indicated that Broca’s area time series was negatively correlated with the time series of a right SFG cluster (adjacent to the SFG cluster identified in earlier analyses) during the negative word condition, and the magnitude of this relationship was larger in individuals high in anxious apprehension. This finding is important, because it provides more direct support for the hypothesis that the IWR-1 research buy opposing pattern of activation change over time in these areas is due to the influence (direct or indirect) of Broca’s area on right SFG. Given that Inhibitors,research,lifescience,medical the present analyses do not assess causality or direction of effect, this inference is very preliminary. Rather, the present finding serves to support the existence of a relationship between Inhibitors,research,lifescience,medical these regions, and future research should assess its direction and causality. No direct relationship was found between anxious apprehension and behavior. However, present findings partially supported the

hypothesis that the effect of anxious apprehension on habituation of behavior is mediated, in opposing directions, by Broca’s area and right SFG. Specifically, there was a significant indirect effect through Broca’s area, with anxious apprehension positively associated with habituation, either whereas the indirect effect through SFG was not significant, although in the hypothesized direction for RT (i.e., anxious apprehension negatively associated with habituation). Therefore, present findings suggest that anxious apprehension is associated with habituation in behavior, although additional mediators likely remain to be discovered. The findings that anxious apprehension was associated with decreased response in dACC over time to neutral words and no change over time in response to negative words was unexpected.

Another Phase II study published by Gogas et al [66] included 35

Another Phase II study published by Gogas et al. [66] included 35 Epigenetic Reader Domain inhibitor patients receiving treatment with PLD 35mg/m2 in combination with paclitaxel 175mg/m2 every 3 weeks for 6 cycles. Response rate was 71%. Grade 3 toxicity was cutaneous (11%), hand-foot syndrome

(9%), and leukopenia (11%). No cardiac toxicity was observed. 7. HER-2-Positive Early Breast Cancer There has been a greater interest in the use of liposomal anthracyclines in early breast cancer overexpressing HER2 oncogene, as this subgroup Inhibitors,research,lifescience,medical of patients could obtain the greatest benefit from treatment with anthracyclines [67] and combining them with trastuzumab may be difficult due to the high cardiotoxicity that could be induced. Our group designed a Phase I-II study (GEICAM 2003-03) in patients with early breast cancer to be given as neoadjuvant therapy to deal with Inhibitors,research,lifescience,medical the dose variability of LD (Myocet) in combination with other drugs and the lack of evidence for a maximum tolerated dose when combined with docetaxel and trastuzumab [68, 69]. The results for Phase I after the inclusion of 19 patients with stages II and IIIA HER2-positive breast cancer determined the recommended dose for Phase II to be LD 50mg/m2 plus docetaxel 60mg/m2 every three weeks with standard dose Inhibitors,research,lifescience,medical trastuzumab when prophylactic pegylated-filgrastim was administered. Only one of the 19 patients presented with cardiac

toxicity and it was an asymptomatic grade 2 reduction in LVEF. Pathologic complete response rate in the primary tumour and axillary lymph nodes was 33%. With such stimulating data on activity and safety, Phase II of the study was completed. Fifty-nine patients with Inhibitors,research,lifescience,medical HER2-positive breast cancer were included: stages II, 40p and IIIA, 19p. The recommended dose from prior Phase I was administered every 21 days: liposomal doxorubicin 50mg/m2, docetaxel 60mg/m2 and trastuzumab 2mg/kg/weekly along with prophylactic pegylated-filgrastim. The clinical response rate was 86% and radiological response rate was 81%. No patient progressed

Inhibitors,research,lifescience,medical during treatment. All patients underwent surgery which was conservative in 42 cases. Seventeen patients (29%, 95% CI 17.2–40.4) obtained a pathologic complete response in the breast tumour (G5 Miller and Resminostat Payne) and 16 of them (27%, 95% CI 15.8–38.4) also obtained a pathologic complete response in the axillary lymph nodes. An additional 15% obtained a grade 4 Miller and Payne response in the primary tumour. Neutropenia was the most significant grade 3-4 haematological toxicity (17 patients, 29%), but only 3 developed neutropenic fever. Grade 3 nonhaematological toxicity was infrequent: asthenia in 5 patients, nausea in 3, diarrhoea in 3, and stomatitis in one patient. Grade 2 (>20% reduction of the baseline value or reduction below the normal value of 50%) asymptomatic reduction of LEVF was observed in 5 patients (9%) and treatment was withheld in only one of them. By the end of treatment, 3 of the patients had recovered a LVEF greater than 50%.

Other concepts

had to be integrated in order to utilize c

Other concepts

had to be integrated in order to utilize complex biological systems for predictive, preventive, personalized, and participatory (P4) medicine.1–3,7 These concepts included: treating biology as an information science, creating a cross-disciplinary, systems biology infrastructure and culture, designing an experimental holistic integrative approach to biology along with developing new technologies (and improving the old technologies) that will allow the exploration of new dimensions of patient data space, and, lastly, inventing Inhibitors,research,lifescience,medical analytic tools that will analyze and interpret all the information generated by the newly developed technologies (Figure 2). Figure 2. The elements that will allow systems medicine to tackle deciphering biological complexity. Inhibitors,research,lifescience,medical The nature of the infrastructure needed for creating systems biology and systems medicine is one that encompasses widely disparate cross-disciplinary backgrounds.3,8 The human infrastructure includes biologists, chemists, computer scientists, engineers, physicists, and mathematicians. Cross-disciplinary environments cannot be divided into separate departments as is done in most universities. They must be in close proximity to each other, where random collisions create new opportunities and Inhibitors,research,lifescience,medical new ideas. This is how the Institute for Systems Biology is structured, where productive cross-disciplinary cross-talk is the norm and not

the exception. Leading-edge biology dictates and mandates the creation of new technologies. These technologies in turn specify the nature of the new analytic tools that must be created to handle the information (Figure 3). As noted earlier, the situation in which biology drives technology which in turn drives computation can only work in the context of a cross-disciplinary Inhibitors,research,lifescience,medical environment where scientists learn to speak each other’s languages and learn to work effectively together in teams. Figure 3. Holy trinity Inhibitors,research,lifescience,medical of the biological cross-disciplinary culture—“biology drives technology drives analytical tools revolutionizes biology.” Biology as an Information Science Biology can be defined as an informational science. This definition

is important since it gives us a conceptual framework to deal with biological complexities. There are two types of information in biological systems: the digital information of the Edoxaban genome and the environmental information which consists of signals brought from outside the genome. These data are integrated in the organism to create either the normal or the diseased phenotype. Two information-handling systems connect the two types of biological information with the phenotype. The first system is made up of biological networks that capture, transmit, modulate, and finally pass the information off to the http://www.selleckchem.com/products/Rapamycin.html second system. The second system consists of both simple and complex molecular machines which execute the commands given by the signals they receive.

In general, all SSRIs exert their therapeutic actions and their

In general, all SSRIs exert their therapeutic actions and their undesirable effects

by increasing synaptic serotonin concentration, where re-uptake is blocked and serotonin release is disinhibited. Ultimately, increasing serotonin in desirable pathways and at targeted receptor subtypes leads to well-known therapeutic actions of all SSRIs and vice versa [Stahl, 2000; Goodnick and Goldstein, 1998; Hyttel, 1984; Tatsumi et al. 1997; Dubovsky, 1994]. While several SSRIs interact differentially with other neurotransmitter systems including dopamine (sertraline) and Inhibitors,research,lifescience,medical norepinephrine (paroxetine), stimulation of prolactin probably involves inhibition of dopaminergic neurotransmission not only by their effects on dopamine secretion or recapture on dopaminergic receptors, but also indirectly check details through serotonergic mediation, as all SSRIs have been implicated in hyperprolactinemia, Inhibitors,research,lifescience,medical regardless of their effects on these other transmitter systems [Peterson, 2001; Bronzo and Stahl, 1993; Morrison et al. 2001; Spigset and Mjorndal, 1997; Cowen and Sargent, 1997; Attenburrow et al. 2001; Goodnick and Goldstein, 1998; Hyttel, 1984; Tatsumi et al. 1997]. Inhibitors,research,lifescience,medical The incidence and prevalence of hyperprolactinemia in patients taking SSRIs will be important to pursue in future controlled

studies. Based on cumulative case reports, all SSRIs have the potential to cause elevation of basal prolactine. This observation was recently confirmed by the French Pharmacovigilance

Database Study, an epidemiological Inhibitors,research,lifescience,medical study that investigated the rates of hyperprolactinemia induced by multiple prescription medications from 1985–2000 [Petit et al. 2003]. Of the total of 159 cases of drug induced hyperprolactinemia studied, 17% had been induced by SSRIs, which included sertraline [odds ratio (OR) 15.74], fluoxetine (OR 49), paroxetine (OR 8.10), fluvoxamine Inhibitors,research,lifescience,medical (OR 5.96), and citalopram (OR 3.62). Citalopram was the only SSRI not to reach any statistical significance. The available data indicate that SSRI-induced hyperprolactinemia is a class related effect [Petit et al. 2003]. If we change our notion here towards the management strategy of each individual patient as depicted in cases one and four, hyperprolactinemia nearly and associated amenorrhea resolved within 2 months of withdrawal of fluoxetine and both the patients responded well to sertraline. In case three escitalopram was tried initially without any positive impact on the patient’s condition, rather it resulted in further elevation of prolactin. The resolution of hyperprolactinemia-associated symptoms was achieved after 3 weeks of escitalopram withdrawal and almost 5 months of fluoxetine discontinuation and the patient remained psychiatrically stable while being maintained on venlafaxine.

Currently, there is no specific medical therapy #

Currently, there is no specific medical therapy for PAM. And it is also deserving of note that the majority of PAM patients suffer from respiratory insufficiency and the only option left for them is lung transplantation, which can relatively improve respiratory insufficiency.11

Novelty of the case described in the present study is that it presents a rare, chronic lung disease, the likes of which have been few and far between in the existing literature. Occupational lung diseases such as allergies, bronchitis, bronchial asthma, and asbestosis have been previously reported among carpenters, but there has been no report on Inhibitors,research,lifescience,medical pulmonary alveolar microlithiasis in carpenters. It can, therefore, be concluded that PAM was unrelated to the profession of carpentry in our patient. Conclusion PAM is a rare lung disease and should be considered in the differential diagnosis of diffuse parenchymal disease of chest. HRCT should always be performed as it reveals the characteristic patterns of PAM; however, Inhibitors,research,lifescience,medical confirmatory diagnosis is established by transbronchial or Inhibitors,research,lifescience,medical open lung biopsy. There is no specific treatment for PAM; nonetheless, lung transplantation

can provide improvement in respiratory insufficiency. Conflict of interest: None declared.
Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium’s neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this Inhibitors,research,lifescience,medical study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal

and Inhibitors,research,lifescience,medical mixed neuron-astrocyte cultures. Methods: Rat primary astrocyte, neuronal, and mixed neuron-astrocyte learn more cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and second ELISA, respectively. Results: Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. Conclusion: Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium’s action.

75 The ventral pallidum provides limited input to the magnocellul

75 The ventral pallidum provides limited input to the magnocellular mediodorsal thalamus.74 The anterior cingulate circuit is closed with projections from the dorsal portion of the magnocellular mediodorsal thalamus to the anterior cingulate.40,76 “Akinetic mutism” is closely related to lesions to the anterior cingulate.77,78 It represents #Quisinostat manufacturer keyword# a wakeful state of profound apathy, with indifference to pain, thirst, or hunger; absence of motor or psychic initiative, manifested by lack of spontaneous movement; absent verbalization; and failure to respond

to questions or commands. The most dramatic examples of akinetic mutism follow bilateral lesions of the anterior cingulate cortex43,79,80 and may be predicted by lesions that extend from the cognitive effector region posteriorly into the skeletomotor effector division of the cingulate.81 Unilateral lesions of the anterior cingulate cortex tend to produce transient akinetic mutism.82,83 Inhibitors,research,lifescience,medical The term “abulia,” derived from the

Greek boul, or “will,”77 refers to a similar but less severe psychomotor syndrome, encompassing lack of spontaneity, Inhibitors,research,lifescience,medical apathy, and paucity of speech and movement. Akinetic mutism has been described with cerebrovascular disease, craniopharyngiomas, obstructive hydrocephalus, tumors in the region of the third ventricle, and other conditions involving the ventral striatum (nucleus accumbens and ventromedial caudate), ventral GP, and medial thalamus. In an analogous syndrome, patients with circumscribed supplementary motor Inhibitors,research,lifescience,medical area lesions demonstrated by computed tomography (CT) may demonstrate a disorder affecting the “drive” for both willed movement and speech.77 Such patients evidence initial global akinesia and neglect, which subsequently tends to lateralize in unilateral cases.

Part of the Inhibitors,research,lifescience,medical motor circuit, the supplementary motor area, also receives reciprocal projections from the anterior cingulate. Several studies have examined the association between abulia or apathy and location of brain lesions.73 Bilateral lesions of ventrolateral and dorsomedial thalamic nuclei frequently produce apathy.84 Other studies have revealed a high frequency of apathy after lesions involving the GP and the adjacent internal capsule.85,86 One of the main internal pallidal outputs, which traverses the posterior limb of the internal capsule en route to the pedunculopontine nucleus, is the ansa lenticularis77 and this pathway may have a prominent and role in goal-oriented behavior.3,87 In a review of patients with focal lesions of the basal ganglia,88 abulia occurred with 6 of 22 (27%) restricted GP lesions, all bilateral, and with 18 of 64 (28%) small and large caudate lesions sparing the lentiform nucleus, 15 of which were unilateral. In this study, abulia was not observed with isolated putamenal lesions, consistent with the integration of this structure with motor rather than limbic system circuitry.