Treatment with a γ-ketoaldehyde scavenger prevents working memory deficits in hApoE4 mice

Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected.     

Regional striatal volume abnormalities in schizophrenia: effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type

Striatal structures form critical nodes of multiple circuits that are implicated in the pathophysiology of schizophrenia and alcoholism. Here, we examined the separate and combined effects of schizophrenia and alcoholism and effects of medication type and drinking recency on striatal volumes. Accordingly, we measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25 alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse), and 51 age-matched control men. Schizophrenics were classified by antipsychotic medication (typical or atypical), and alcoholics were classified by recency of sobriety. All measured structures were smaller in the patient groups than the control group. The caudate deficit was comparable across groups, whereas putamen and nucleus accumbens deficits were greater in schizophrenia than alcoholism; comorbids fell between these groups. Schizophrenic patients treated with atypical medication showed greater volume deficits in the putamen than those treated with typical medication. Recently sober (<3 weeks) alcoholics had greater deficits in nucleus accumbens than longer sober drinkers. In conclusion, caudate, putamen, and nucleus accumbens exhibited different patterns of volume deficit in patients with alcoholism and schizophrenia alone, with no evidence for compounded deficits in comorbid patients. Further, these cross-sectional data provide indirect support for at least partial recovery of nucleus accumbens volume with sobriety in alcoholics, regardless of schizophrenia comorbidity.     

Reduced striatal activation in females with major depression during the processing of affective stimuli

The extent to which affective reactivity and associated neural underpinnings are altered by depression remains equivocal. This study assessed striatal activation in fifty-one unmedicated female participants meeting DSM-IV criteria for Major Depressive Disorder (MDD) and 61 age-matched healthy females (HC) aged 17–63 years. Participants completed an affective reactivity functional magnetic resonance imaging task. Data were preprocessed using SPM8, and region-of-interest analyses were completed using MarsBaR to extract caudate, putamen, and nucleus accumbens (NAcc) activation. General linear repeated measure ANOVAs were used to assess group differences and correlational analyses were used to measure the association between activation, depression severity, and anhedonia. Main effects of hemisphere, valence, and group status were observed, with MDD participants demonstrating decreased striatal activation compared with HC. Across groups and valence types, the left hemisphere demonstrated greater activation than the right hemisphere in the putamen and nucleus accumbens, whereas the right hemisphere demonstrated greater activation than the left in the caudate. Additionally, unpleasant stimuli elicited greater activation than pleasant and neutral stimuli in the caudate and putamen, and unpleasant stimuli elicited greater activation than neutral stimuli in the NAcc. There were no significant associations between activation, depression severity, and anhedonia. Overall, depression was characterized by reduced affective reactivity in the striatum, regardless of stimuli valence, supporting the emotion context insensitivity model of depression.     

Altered white matter/gray matter proportions in the striatum of patients with schizophrenia: a volumetric MRI study

OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.     

Shape analysis of subcortical nuclei in Huntington's disease, global versus local atrophy--results from the TRACK-HD study

Huntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than global volume variation. We examined 90 TRACK-HD participants of which 30 were premanifest HD, 30 were manifest HD and 30 were controls. Using FMRIB's Integrated Registration and Segmentation Tool, segmentations were obtained for the pallidum, caudate nucleus, putamen, thalamus, accumbens nucleus, amygdala, and hippocampus and overall volumes were calculated. A point distribution model of each structure was obtained using Growing and Adaptive Meshes. Permutation testing between groups was performed to detect local displacement in shape between groups. In premanifest HD overall volume loss occurred in the putamen, accumbens and caudate nucleus. Overall volume reductions in manifest HD were found in all subcortical structures, except the amygdala, as compared to controls. In premanifest HD shape analysis showed small areas of displacement in the putamen, pallidum, accumbens and caudate nucleus. When the premanifest group was split into two groups according to predicted disease onset, the premanifest HD group close to expected disease onset showed more pronounced displacements in caudate nucleus and putamen compared to premanifest HD far from disease onset or the total premanifest group. Analysis of shape in manifest HD showed widespread shape differences, most prominently in the caudal part of the accumbens nucleus, body of the caudate nucleus, putamen and dorsal part of the pallidum. We conclude that shape analysis provides new insights in localized intrastructural atrophy patterns in HD, but can also potentially serve as specific target areas for disease tracking.     

Normal sexual dimorphism in the human basal ganglia

Male and female brains differ in both structure and function. Investigating this sexual dimorphism in healthy subjects is an important first step to ultimately gain insight into sex-specific differences in behavior and risk for neuropsychiatric disorders. The basal ganglia are among the main regions containing sex steroid receptors in the brain and play a central role in cognitive (dys)functioning. However, little is known about sexual dimorphism of different basal ganglia nuclei. The aim of the present study was to investigate sex-specific differences in basal ganglia morphology using MRI. We applied automatic volumetry on anatomical MRI data of two large cohorts of healthy young adults (n = 463 and n = 541) and assessed the volume of four major nuclei of the basal ganglia: caudate nucleus, globus pallidus, nucleus accumbens, and putamen, while controlling for total gray matter volume, total white matter volume, and age of the participant. No significant sex differences were found for caudate nucleus and nucleus accumbens, but males showed significantly larger volumes for globus pallidus and putamen, as confirmed in both cohorts. These results show that sexual dimorphism is neither a general effect in the basal ganglia nor confined to just one specific nucleus, and will aid the interpretation of differences in basal ganglia (dys)function between males and females.     

Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects.

BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido-thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia but also show that basal ganglia structure is highly plastic and may be influenced by antipsychotic treatments. Controversy remains about whether basal ganglia pathology can be detected in vivo among treatment-na?ve patients. We conducted a magnetic resonance imaging (MRI) study to examine basal ganglia structures and the limbic forebrain in first episode schizophrenia and healthy comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia and 28 healthy comparison subjects participated in the study. A high-resolution, special contrast (white matter nulling) MRI sequence was used to measure the caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain. RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total brain volume and age) did not differ significantly between the groups. Age correlated significantly with caudate and putamen volumes bilaterally in the healthy comparison group, but not among patients. CONCLUSIONS: The findings suggest that there are no volumetric abnormalities in basal ganglia before treatment in first-episode schizophrenia. The lack of a negative correlation between age and striatal volume among patients may implicate illness-associated factors that alter normal age-related changes in basal ganglia size.     

Structural analysis of the basal ganglia in schizophrenia

Increases in the total volume of basal ganglia structures have been reported in schizophrenia. However, patterns of basal ganglia shape change, which can reveal localized changes in substructure volumes, have not been investigated. In this study, the total volume and shape of several basal ganglia structures were compared in subjects with and without schizophrenia. T(1)-weighted magnetic resonance scans were collected in 54 schizophrenia and 70 comparison subjects. High-dimensional (large-deformation) brain mapping was used to assess the shape and volume of several basal ganglia structures. The relationships of shape and volume measures with psychopathology, cognition and motor function were also assessed. Left and right volumes of the caudate and putamen, as well as the right globus pallidus volume, were significantly increased in subjects with schizophrenia as compared to comparison subjects after total brain volume was included as a covariate. Significant differences in shape accompanied these volume changes in the caudate, putamen and globus pallidus, after their total volumes were included as covariates. There were few significant correlations between volume or shape measures and either cognitive function or clinical symptoms, other than a positive correlation between an attention/vigilance cognitive dimension and the volume of the caudate and putamen, and a negative correlation between nucleus accumbens volume and delusions. In conclusion, basal ganglia volumes relative to total brain volume were larger in schizophrenia subjects than healthy comparison subjects. Specific patterns of shape change accompanied these volume differences.     

Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia.

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.     

Early atrophy of pallidum and accumbens nucleus in Huntington��s disease

In Huntington's disease (HD) atrophy of the caudate nucleus and putamen has been described many years before clinical manifestation. Volume changes of the pallidum, thalamus, brainstem, accumbens nucleus, hippocampus, and amygdala are less well investigated, or reported with contradicting results. The aim of our study is to provide a more precise view of the specific atrophy of the subcortical grey matter structures in different stages of Huntington's disease, and secondly to investigate how this influences the clinical manifestations. All TRACK-HD subjects underwent standardised T1-weighted 3T MRI scans encompassing 123 manifest HD (stage 1, n = 77; stage 2, n = 46), 120 premanifest HD (close to onset n = 58, far from onset n = 62) and 123 controls. Using FMRIB's FIRST and SIENAX tools the accumbens nucleus, amygdala, brainstem, caudate nucleus, hippocampus, pallidum, putamen, thalamus and whole brain volume were extracted. Results showed that volumes of the caudate nucleus and putamen were reduced in premanifest HD far from predicted onset (>10.8 years). Atrophy of accumbens nucleus and pallidum was apparent in premanifest HD in the close to onset group (0-10.8 years). All other structures were affected to some degree in the manifest group, although brainstem, thalamus and amygdala were relatively spared. The accumbens nucleus, putamen, pallidum and hippocampus had a strong significant correlation with functional and motor scores. We conclude that volume changes may be a sensitive and reliable measure for early disease detection and in this way serve as a biomarker for Huntington's disease. Besides the caudate nucleus and putamen, the pallidum and the accumbens nucleus show great potential in this respect.     

Dendritic morphology in the striatum and hypothalamus differentially exhibits experience-dependent changes in response to maternal care and early social isolation

Changes in neuron morphology, stemming from experiences in early life or adulthood, may be the basis for changes in behavior and their underlying functional mechanisms. For example, reproductive experience has been shown to significantly alter neuron morphology in the hippocampus and prefrontal cortex. In contrast to the effects of reproductive experience, a form of enrichment, on neuron morphology, our understanding of the effects of early social isolation on adult neuron morphology is limited. Therefore, the present study examined changes in neuron morphology in the dorsal (caudate nucleus) and ventral (nucleus accumbens, shell region) striatum and the medial preoptic area of adult virgin and postpartum females exposed to either artificial or maternal rearing during development. Primary results show that regardless of early social isolation, neurons in the caudate nucleus of postpartum females have decreased dendritic complexity compared to virgin females. Maternal experience also increased dendritic complexity in neurons of the nucleus accumbens shell. However, both early social isolation and maternal experience in adulthood influenced dendritic complexity in the medial preoptic area. Together these findings suggest that hypothalamic and striatal neurons show experience-dependent dendritic plasticity and the type and timing of these experiences differentially affect the location and degree of these morphological changes.     

Schizophrenia, tardive dyskinesia, and brain GABA

We measured the contents of gamma-aminobutyric acid (GABA) and of other amino compounds in five regions of autopsied brain from 18 patients with schizophrenia and from a large group of adult control subjects dying without any neurological or psychiatric disorder. In addition, concentrations of GABA were measured in the cerebrospinal fluid (CSF) of living schizophrenic patients and control subjects. No deficiency of GABA was found in the frontal cortex, caudate nucleus, putamen, nucleus accumbens, or medial dorsal thalamus of patients dying with schizophrenia, nor were GABA concentrations low in the CSF of living schizophrenic patients. These results do not confirm our earlier report of low levels of GABA in the nucleus accumbens and thalamus of some schizophrenic patients. We do not find neurochemical evidence favoring an involvement of GABAergic neuronal hypofunction in the etiology either of schizophrenia or of neuroleptic-induced tardive dyskinesia.     

Development of gray matter atrophy in relapsing–remitting multiple sclerosis is not gender dependent: Results of a 5-year follow-up study

ObjectivesThe aim of this study was to explore the evolution of MRI related gender differences in patients with relapsing–remitting (RR) multiple sclerosis (MS) who participated in a clinical trial over the 5 years.Methods181 patients (39 males and 142 females) were assessed for clinical and neuroradiological disease activity over a period of 5 years. Clinical and MRI examination were performed at the baseline, 6, 12, 24, 36, 48 and 60 months. Longitudinal percentage volume changes in whole brain (PBVC), gray matter (PGMVC) white matter (PWMVC) cortex (PCVC), and lateral ventricles (PLVVC) were calculated by using direct methods (SIENA and SIENAX-multitimepoint). Absolute tissue volume changes of subcortical deep GM structures including caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala and nucleus accumbens were estimated using FIRST, a model based segmentation/registration tool. T2 lesion volume (T2-LV) and lesion activity analyses were performed, using a contouring-threshold and subtraction techniques. All clinical and MRI variables were analyzed between males and females.ResultsGlobal (PBVC) and tissue specific (PGMVC, PWMVC, PCVC, PLVVC) brain volume changes showed no significant gender differences over the 5-year follow-up period. Although total subcortical deep GM, caudate, putamen, globus palidus, thalamus and nucleus accumbens normalized volumes were significantly larger in male subjects at baseline, the follow-up analysis showed no differences over the 5 years. There were no gender differences in lesion activity or T2-LV changes over the 5 years.ConclusionNo MRI lesion, global, tissue specific or regional brain volume gender change differences were found over the 5-year follow-up.     

Oestradiol Modulation of Serotonin Reuptake Transporter and Serotonin Metabolism in the Brain of Monkeys

Serotonin (5-hydroxytryptamine; 5-HT) is an important brain neurotransmitter that is implicated in mental and neurodegenerative diseases and is modulated by ovarian hormones. Nevertheless, the effect of oestrogens on 5-HT neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, which are major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus, is not well documented. The present study evaluated 5-HT reuptake transporter (SERT) and 5-HT metabolism in these brain regions in response to 1-month treatment with 17β-oestradiol in short-term (1 month) ovariectomised (OVX) monkeys (Macaca fascicularis). SERT-specific binding was measured by autoradiography using the radioligand [³H]citalopram. Biogenic amine concentrations were quantified by high-performance liquid chromatography. 17β-Oestradiol increased SERT in the superior frontal cortex and in the anterior cingulate cortex, in the nucleus accumbens, and in subregions of the caudate nucleus of OVX monkeys. 17β-Oestradiol left [³H]citalopram-specific binding unchanged in the putamen, as well as the dorsal and medial raphe nucleus. 17β-Oestradiol treatment decreased striatal concentrations of the precursor of 5-HT, 5-hydroxytryptophan, and increased 5-HT, dopamine and 3-methoxytyramine concentrations in the nucleus accumbens, caudate nucleus and putamen, whereas the concentrations of the metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid remained unchanged. No effect of 17β-oestradiol treatment was observed for biogenic amine concentrations in the cortical regions. A significant positive correlation was observed between [³H]citalopram-specific binding and 5-HT concentrations in the caudate nucleus, putamen and nucleus accumbens, suggesting their link. These results have translational value for women with low oestrogen, such as those in surgical menopause or perimenopause.     

Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks

The organization of projections from the prefrontal cortex (PFC) to the striatum in relation to previously defined "orbital" and "medial" networks within the PFC were studied in monkeys using anterograde and retrograde tracing techniques. The results indicate that the orbital and medial networks connect to different striatal regions. The ventromedial striatum (the medial caudate nucleus, accumbens nucleus, and ventral putamen) receives input predominantly from the medial PFC (mPFC) and orbital areas 12o, Iai, and 13a, which constitute the "medial" network. More specifically, caudal medial areas 32, 25, and 14r project to the medial edge of the caudate nucleus, accumbens nucleus, and ventromedial putamen, whereas rostral areas 10o, 10m, and 11m are restricted to the medial edge of the caudate. Projections from orbital areas 12o, 13a, and Iai extend more laterally into the lateral accumbens and the ventral putamen. Area 24 gives rise to a divided pattern of projections, including fibers to the ventromedial striatum, apparently from area 24b, and fibers to the dorsolateral striatum, apparently from area 24c. Other areas of orbital cortex (11l, 12m, 12l, 13m, 13l, Ial, and Iam) that constitute the "orbital" network project primarily to the central part of the rostral striatum. This region includes the central and lateral parts of the caudate nucleus, and the ventromedial putamen, on either side of the internal capsule. The results support the subdivision of the orbital and medial PFC into "medial" and "orbital" networks and suggest that the prefrontostriatal projections reflect the functional organization of the PFC rather than topographic location.     

Anterior to posterior variations in the concentration of somatostatin-like immunoreactivity in human basal ganglia

Serial coronal sections were cut from frozen right cerebral hemispheres from five normal human brains. From each section samples of caudate nucleus, putamen, internal and external globus pallidus and substantia nigra were removed. Sampling was such that the entire structure was removed from each slice. The concentration of somatostatin-like immunoreactivity, expressed as units per mg protein, was found to vary between nuclei, and to vary along the anterior to posterior axis of some nuclei. Highest concentrations were found in the caudate nucleus, with the head and tail containing greater amounts than the body. The high concentrations in the head of the caudate may be due to contamination of samples of this region with adjacent nucleus accumbens. In a separate series of cases, the nucleus accumbens was shown to be considerably higher concentrations of somatostatin-like immunoreactivity than the head of the caudate. Concentrations in the putamen tended to decrease along the anterior to posterior axis. In the external globus pallidus, levels of somatostatin-like immunoreactivity showed the most striking changes along the anterior to posterior axis, rising 2.5 fold in the first three samples, and then falling 4 fold in the more posterior sections. The internal globus pallidus had generally lower concentrations, and these varied in a pattern opposite to that in the external globus pallidus. Levels in the substantia nigra were low compared to those in caudate and putamen.     

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum

Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.     

Sex differences in neurotensin and substance P following nicotine self‐administration in rats

Investigator‐administered nicotine alters neurotensin and substance P levels in Sprague‐Dawley rats. This finding suggested a role of the dopamine‐related endogenous neuropeptides in nicotine addiction. We sought to extend this observation by determining the responses of neurotensin and substance P systems (assessed using radioimmunoassay) in male and female rats following nicotine self‐administration (SA). Male and female Sprague‐Dawley were trained to self‐administer nicotine, or receive saline infusions yoked to a nicotine‐administering rat during daily sessions (1‐h; 21 days). Brains were extracted 3 h after the last SA session. Nicotine SA increased tissue levels of neurotensin in the males in the anterior and posterior caudate, globus pallidus, frontal cortex, nucleus accumbens core and shell, and ventral tegmental area. Nicotine SA also increased tissue levels of neurotensin in the females in the anterior caudate, globus pallidus, nucleus accumbens core and shell, but not in the posterior caudate, frontal cortex, or ventral tegmental area. There were fewer sex differences observed in the substance P systems. Nicotine SA increased tissue levels of substance P in both the males and females in the posterior caudate, globus pallidus, frontal cortex, nucleus accumbens shell, and ventral tegmental area. A sex difference was observed in the nucleus accumbens core, where nicotine SA increased tissue levels of substance P in the males, yet decreased levels in the females. The regulation of neuropeptides following nicotine SA may play a role in the susceptibility to nicotine dependence in females and males. Synapse 70:336–346, 2016 . © 2016 Wiley Periodicals, Inc.     

Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism.

BACKGROUND: Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholism's effect on volumes of these structures has seldom been considered with in vivo measurement. METHODS: We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober. RESULTS: Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics. CONCLUSIONS: Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.     

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.