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.     

Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage

The volume of several parts of the basal ganglia and of the limbic system was measured by planimetry of myelin-stained serial sections in postmortem brains of 13 schizophrenic patients and nine control cases. The medial limbic structures of the temporal lobe (amygdala, hippocampal formation, and parahippocampal gyrus) and the pallidum internum were significantly smaller in the schizophrenic group, whereas the pallidum externum showed only a modest trend toward volume reduction. The volumes of the putamen, nucleus caudatus, nucleus accumbens, and the bed nucleus of the stria terminalis did not differ between patients and controls. The volume reductions of the limbic temporal structures and of the pallidum internum of schizophrenics are interpreted as degenerative shrinkages of unknown etiology.     

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV‐seronegative controls. T1‐weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp 38:1025–1037, 2017. © 2016 Wiley Periodicals, Inc.     

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.     

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.     

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.     

Cortex, white matter, and basal ganglia in schizophrenia: a volumetric postmortem study

Postmortem volumetry of cortex, white matter, and basal ganglia was performed in 23 brains of schizophrenic patients and 23 brains of controls closely matched for gender, age, and hemisphere. Stereological methods were applied to serial coronal sections of complete hemispheres. We found no significant volume changes of cortex and white matter in schizophrenics. Striatal volume of schizophrenics was increased bilaterally reaching a significant level on the left side. Volumes of the globus pallidus were increased in both hemispheres reaching a significant level on the right side. After psychopathological differentiation, basal ganglia volume increase was also found in the subgroup of paranoid-hallucinatory schizophrenics.     

Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Volume deficits of subcortical nuclei in mood disorders

Structural changes in subcortical nuclei may underlie clinical symptoms of mood disorders. The goal was to determine whether macrostructural changes exist in brain areas assumed to be involved in regulation of mood and whether such changes differ between major depressive disorder and bipolar disorder. A case-control design was used to compare volumes of all major subcortical nuclei. Brains of patients with major depressive disorder (n = 9) or bipolar disorder (n = 11) or of individuals without a neuropsychiatric disorder (n = 22) were included. Exclusion criteria were a history of substance abuse or histological signs of neurodegenerative disorders.Volumes of the striato-pallidal nuclei, of the hypothalamus, thalamus, amygdala, hippocampus and basal limbic forebrain were determined in the right and left hemisphere by planimetry of 20 mum whole brain serial paraffin sections. Comparisons between patients with bipolar disorder, major depressive disorder and controls showed a significant (Lambda = 0.35, F(20,56) = 1.93, P = 0.028) overall difference in volumes of all investigated regions with strong effect sizes ( f > 0.40) contributed by the hypothalamus, external pallidum, putamen and thalamus. As compared to controls, a strong effect size (f > 0.40) was found in the bipolar group for smaller volumes of the hypothalamus, external pallidum, putamen and thalamus,whereas in patients with major depressive disorder a strong effect size was only found for a smaller volume of the external pallidum. In conclusion our data suggest that pathways presumably involved in mood regulation have structural pathology in affective disorders with more pronounced abnormalities in bipolar disorder.     

Hippocampal volume in schizophrenia and its relationship with risperidone treatment: a stereological study

The purpose of this study was to assess the significance of the hippocampal volume differences and its relation with risperidone treatment in schizophrenia. In schizophrenic patients who were on risperidone treatment (n = 11) and in healthy volunteers (n = 11), volumes of the hippocampi were estimated using magnetic resonance images (MRIs). A detailed systematic series of coronal MRIs of the entire brain (3 mm thickness, T(1)-weighted, TR/TE 400/10 ms) was obtained for each subject. All estimations were done according to Cavalieri's method by a modified point-counting grid placed on surface areas of hippocampal slices. The mean right and left hippocampal volumes in schizophrenics and control subjects were 1059.4 and 1003.2 mm(3), and 1780.1 and 1589.1 mm(3), respectively. The corresponding coefficients of errors were 0.05 and 0.068, and 0.059 and 0.081, respectively. The volumes of left and right hemispheres were not significantly different in both schizophrenic patients and controls (p > 0.05). However, a statistically significant difference (p < 0.05) was found between hippocampal volumes of the schizophrenic patients and controls. In conclusion, the hippocampal volume of the schizophrenic patients is significantly smaller than of the healthy controls. The patients who responded well to risperidone treatment had significantly greater hippocampal volumes than the patients who did not respond properly. Thus, hippocampal volume may be a predictor of the treatment response of schizophrenics to risperidone.     

Substance P immunoreactivity in the post-mortem parkinsonian brain

The amount of substance P immunoreactivity (SPI) was measured by radioimmunoassay from the cerebral cortex, caudate nucleus, putamen, pallidum, substantia nigra, hypothalamus, nucleus accumbens, amygdala and hippocampus from autopsy brains. The whole material consisted of 42 parkinsonian patients and 31 controls. The amount of SPI was significantly decreased in the substantia nigra of the parkinsonian brain. There was also a significant decrease of SPI in the putamen of those parkinsonian patients, who had not received levoDOPA treatment. The levels of SPI in the other brain regions studied did not show any difference between parkinsonian patients and controls. The results obtained suggest that substance P (SP) may have a role in the pathophysiology of Parkinson's disease.     

Anatomical MRI study of borderline personality disorder patients

Hippocampal volume reduction has been reported in patients with borderline personality disorder (BPD), and is hypothesized to be associated with traumatic childhood experiences. We extended this investigation to explore additional brain regions and other potential clinical correlates of structural brain changes in BPD. Ten unmedicated BPD subjects and 20 healthy controls were assessed for current and past Axis I and II comorbidities and histories of childhood abuse. All had magnetic resonance imaging (MRI) studies with a 1.5 T GE Signa Imaging System, performing three-dimensional-gradient echo imaging (SPGR) with the following parameters: TR=25 ms, TE=5 ms, and slice-thickness=1.5 mm. Compared with healthy controls, BPD subjects had significantly smaller right and left hippocampal volumes, most marked in subjects with childhood abuse, and significantly increased right and left putamen volumes, especially in subjects with substance use disorders. No significant differences between groups were found for caudate, amygdala, temporal lobes, dorsolateral prefrontal cortex and total brain volumes. This study replicated prior findings of diminished hippocampal volumes in subjects with BPD. Also, increased putamen volumes were found in BPD, a finding that has not been previously reported. Early traumatic experiences may play a role in hippocampal atrophy, whereas substance use disorders may contribute to putamen enlargement.     

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.     

Dopamine transporter change in drug-naive schizophrenia: an imaging study with 99mTc-TRODAT-1

The aim of this study was to use a specific dopamine transporter (DAT) ligand, 99mTc-TRODAT-1 with single photon emission computed tomography (SPECT) to investigate the densities of DAT in the striatal dopaminergic system in patients with schizophrenia.Striatal DAT uptakes were measured in 12 drug-nai;ve schizophrenic patients and 12 age- and sex-matched healthy volunteers. The psychometric tools included the Standardized Clinical Assessment for Neuropsychiatry (SCAN) and the Positive and Negative Syndrome Scale (PANSS). Semiquantitative analyses using the ratio of uptake in caudate, putamen, and striatum to occipital lobe, and left-right asymmetry were performed.Decreased TRODAT uptake in the right striatum and increased uptake in the left striatum were found in the schizophrenics. However, there is no overall difference in the average striatum uptake. The right-left asymmetry of the caudate and putamen DAT binding seen in the healthy control group disappeared in the schizophrenia group. The decreased right uptake and increased left uptake in the striatum might lead to the lack of right-left asymmetry in neuroleptic-nai;ve schizophrenia patients, confirming that the disorder could be due to a disruption in brain lateralization.This is the first report on the use TRODAT to evaluate the DAT density in schizophrenia patients and shows lack of asymmetry in striatal uptake of TRODAT in schizophrenics. The findings also suggest that TRODAT SPECT may be a useful technique to measure dopamine transmission in the human brain and for understanding the pathophysiology of neuropsychiatric disorders.     

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.     

Positive parenting predicts the development of adolescent brain structure: A longitudinal study

Little work has been conducted that examines the effects of positive environmental experiences on brain development to date. The aim of this study was to prospectively investigate the effects of positive (warm and supportive) maternal behavior on structural brain development during adolescence, using longitudinal structural MRI. Participants were 188 (92 female) adolescents, who were part of a longitudinal adolescent development study that involved mother–adolescent interactions and MRI scans at approximately 12 years old, and follow-up MRI scans approximately 4 years later. FreeSurfer software was used to estimate the volume of limbic-striatal regions (amygdala, hippocampus, caudate, putamen, pallidum, and nucleus accumbens) and the thickness of prefrontal regions (anterior cingulate and orbitofrontal cortices) across both time points. Higher frequency of positive maternal behavior during the interactions predicted attenuated volumetric growth in the right amygdala, and accelerated cortical thinning in the right anterior cingulate (males only) and left and right orbitofrontal cortices, between baseline and follow up. These results have implications for understanding the biological mediators of risk and protective factors for mental disorders that have onset during adolescence.     

Changes in angiotensin II receptors in dopamine-rich regions of the mouse brain with age and ethanol consumption

The density of angiotensin II (Ang II) receptors was determined in three dopaminergic nerve terminal-rich brain regions (caudate putamen, nucleus accumbens, and ventral pallidum) of mice that were given either water (control) or 20% w/v ethanol (EtOH) to drink for either 2–8 weeks (young) or 46 weeks (old). The receptors were labeled with ¹²⁵I-sarcosine¹, isoleucine⁸ angiotensin II (¹²⁵I-SI Ang II) and measured by quantitative densitometric image analysis (receptor autoradiography) or by saturation binding assays on homogenates of these brain regions. The selective AT₂ receptor subtype antagonist PD 123319 (10 μM) was used to inhibit ¹²⁵I-SI Ang II binding to AT₂ receptors to determine AT₁ receptor density in brain sections. In young control mice the density of Ang II receptor binding sites in the caudate putamen was 407±26 fmol/g, in the nucleus accumbens the density was 346±27 fmol/g, and in the ventral pallidum the density was 317±27 fmol/g. Less than 5% of specific ¹²⁵I-SI Ang II binding was displaced by PD 123319, suggesting that nearly all of the Ang II receptors in these brain regions were the AT₁ subtype. The B_max in homogenates of these three regions in young control mice was 11.0±2.1 fmol/mg protein. The K_D was 0.49±0.13. Ang II receptors in old mouse brains were decreased, respectively, by 32%, 35% and 30% in the caudate putamen, nucleus accumbens and ventral pallidum (p<0.001). Ang II receptors were slightly, but not significantly increased in both young and old EtOH-consuming mice.     

Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients

Glucose metabolic rate in the basal ganglia, thalamus, and somatosensory cortex was examined in eight patients with schizophrenia before and after receiving neuroleptic medication. Basal ganglia metabolic rates were increased with medication: more on the right than on the left and more in putamen than caudate. The cortical anteroposterior ratio, an index of relative hypofrontality, was not affected by neuroleptics. The brain areas that were found to be altered by neuroleptics were selected for comparison between off-medication schizophrenics and controls. Metabolic rates in the basal ganglia tended to be low in patients with schizophrenia in comparison to 24 age- and sex-matched controls.     

轻度认知损害患者空间导航能力相关皮质下核团体积研究

目的探讨轻度认知损害患者皮质下核团体积与空间导航能力之间的关系。方法采用计算机空间导航障碍测试系统测试30例轻度认知损害患者和性别、年龄、受教育程度相匹配的28例正常对照者空间导航能力,FreeSurfer 5.3.0软件对三维T1WI图像进行结构分割,计算皮质下核团(双侧丘脑、尾状核、壳核、苍白球、海马、杏仁体和伏隔核)体积以及全脑体积。Pearson相关分析分析空间导航能力与皮质下核团体积的相关性。结果轻度认知损害患者混合(环境参照和自我参照)导航(P=0.034)、自我参照导航(P=0.004)、环境参照导航(P=0.011)误差距离均大于正常对照者,而双侧丘脑(P=0.953,0.250)、尾状核(P=0.938,0.672)、壳核(P=0.421,0.912)、苍白球(P=0.446,0.360)、海马(P=0.545,0.647)、杏仁体(P=0.565,0.993)、伏隔核(P=0.271,0.796)和全脑(P=0.567)体积组间差异无统计学意义。Pearson相关分析显示,轻度认知损害患者混合(环境参照和自我参照)导航误差距离与左侧苍白球(r=-0.284,P=0.034)和左侧海马(r=-0.265,P=0.048)体积呈负相关,环境参照导航误差距离与左侧壳核体积呈负相关(r=-0.305,P=0.022)。结论轻度认知损害患者空间导航能力与皮质下核团体积相关,对进一步研究空间导航障碍的发生机制具有重要意义。     

Leucotomized schizophrenics lose neurons in the mediodorsal thalamic nucleus

It has previously been shown that chronic schizophrenic patients have a 40–50% reduction in the total number of nerve and glia cells in the mediodorsal thalamic nucleus and the nucleus accumbens compared with controls, while the total neuron and glia number is the same in the two groups in the ventral pallidum. Using new stereological cell counting methods, neuron and glia cell numbers were estimated in the mediodorsal thalamic nucleus, the ventro-medial part of nucleus accumbens and the ventral pallidum in nine brains from leucotomized schizophrenics. This number was compared with counts from control cases and chronic schizophrenics without leucotomy. The results showed that the total number of nerve cells in the mediodorsal thalamic nucleus was statistically significantly reduced from 1.08 × 10⁶ in chronic schizophrenics to 0.88 × 10⁶ in leucotomized schizophrenics. Total neuron number was statistically significantly reduced in the ventro-medial part of the nucleus accumbens in schizophrenics without further reduction in leucotomized schizophrenics. The total neuron number in ventral pallidum was normal. With frontal leucotomy it is possible to investigate the consequences of disconnection of the prefrontal cortex to central regions in the human brain. The mediodorsal nucleus of thalamus represents a major efferent projection to the prefrontal cortex. The dorsal prefrontal cortex projects to nucleus caudatus and the orbital prefrontal cortex to the nucleus accumbens, a prominent region in the limbic system. It was expected that a lesion to the prefrontal region by anterograde, retrograde degeneration may affect the mediodorsal nucleus of thalamus.