Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia

BACKGROUND: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI. METHODS: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with high-resolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status. RESULTS: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was reduced in all 3 nuclei; differences in relative reduction did not differ among the nuclei. The remainder of the thalamic volume (whole thalamus minus the volume of the 3 delineated nuclei) was not different between schizophrenic patients and controls, indicating that the volume reduction was specific to these nuclei. Volume relative to brain size was reduced in all 3 nuclei and remained significant when only patients who had never been exposed to neuroleptic medication (n = 15) were considered. For the MDN, women had larger relative volumes than men among controls, but men had larger volumes than women among schizophrenic patients. CONCLUSIONS: Three association regions of the thalamus that have reciprocal connectivity to schizophrenia-associated regions of the cortex have significantly smaller volumes on MRI in patients with schizophrenia.     

Low medial and lateral right pulvinar volumes in schizophrenia: a postmortem study

OBJECTIVE: In this study, the volume and neuronal number of the pulvinar thalamic nucleus in schizophrenia patients were measured. METHOD: The authors examined medial and lateral pulvinar nuclei bilaterally in 27 patients with schizophrenia and 28 normal comparison subjects. RESULTS: In the comparison subjects, the medial pulvinar was larger on the right. The right but not left pulvinar nuclei were smaller in the schizophrenia patients than in the comparison subjects. The number of neurons showed similar trends. CONCLUSIONS: These findings confirm low pulvinar volume in schizophrenia and show that it affects both medial and lateral nuclei. The lateralized findings may reflect pulvinar connections with asymmetrical neocortical regions and their asymmetrical involvement in schizophrenia.     

Structural abnormalities of the adhesio interthalamica and mediodorsal nuclei of the thalamus in schizophrenia

Objective: Several studies have suggested the existence of thalamic volume reduction in patients with schizophrenia. However, the precise locus of volume reduction within the thalamus has scarcely been investigated. On the other hand, underdevelopment of the adhesio interthalamica [AI; Danos, P., Baumann, B., Kramer, A., Bernstein, H.G., Stauch, R., Krell, D., Falkai, P., Bogerts, B., 2003. Volumes of association thalamic nuclei in schizophrenia: a post-mortem study. Schizophr. Res. 60 141–155], which bridges bilateral medial edges of the thalamus, has been reported in patients with schizophrenia. We assessed the volumes of mediodorsal nuclei (MDN) of thalami, level of AI development, and their interrelationship, in patients with schizophrenia. Method: A sample of 58 patients with schizophrenia and 44 matched healthy volunteers underwent assessment with high-resolution 1-mm-thick anatomical MRI. Volume measurements of the MDN of the thalamus and whole thalamus were performed by manual tracing. The level of AI development was quantitatively defined as the maximal anterior-to-posterior length of the AI. Results: Schizophrenia patients had significantly smaller volumes of bilateral MDN. AI ratings were twice as high in women than in men among the control subjects; however, no gender difference emerged in the schizophrenia group due to reduced ratings in female patients. No significant correlation was found between MDN volumes and AI ratings among both groups. Conclusions: These results provide evidence of volume reduction of the MDN, and female-specific underdevelopment of the AI in schizophrenia. As we did not demonstrate a relationship between MDN volume and AI ratings, it is suggested that these two measures of medial thalamic abnormality are manifestations of different neuropathological processes in schizophrenia patients.     

Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia.

OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.     

Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia

The thalamus plays a central and dynamic role in information transmission and processing in the brain. Multiple studies reveal increasing association between schizophrenia and dysfunction of the thalamus, in particular the medial dorsal nucleus (MDN), and its projection targets. The medial dorsal thalamic connections to the prefrontal cortex are of particular interest, and explicit in vivo evidence of this connection in healthy humans is sparse. Additionally, recent neuroimaging evidence has demonstrated disconnection among a variety of cortical regions in schizophrenia, though the MDN thalamic prefrontal cortex network has not been extensively probed in schizophrenia. To this end, we have examined thalamo-anterior cingulate cortex connectivity using detection of low-frequency blood oxygen level dependence fluctuations (LFBF) during a resting-state paradigm. Eleven schizophrenic patients and 12 healthy control participants were enrolled in a study of brain thalamocortical connectivity. Resting-state data were collected, and seed-based connectivity analysis was performed to identify the thalamocortical network. First, we have shown there is MDN thalamocortical connectivity in healthy controls, thus demonstrating that LFBF analysis is a manner to probe the thalamocortical network. Additionally, we have found there is statistically significantly reduced thalamocortical connectivity in schizophrenics compared with matched healthy controls. We did not observe any significant difference in motor networks between groups. We have shown that the thalamocortical network is observable using resting-state connectivity in healthy controls and that this network is altered in schizophrenia. These data support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia.     

Volumes of association thalamic nuclei in schizophrenia: a postmortem study

The major association thalamic nuclei, the mediodorsal nucleus (MD) and the medial pulvinar nucleus (PUM) are regarded as important parts of the circuits among association cortical regions. Association cortical regions of the frontal, parietal and temporal lobes have been repeatedly implicated in the neuropathology of schizophrenia. Thus, the aim of the present postmortem study was to investigate the volumes of association thalamic nuclei in this disease. The volumes of the whole thalamus (THAL), MD and PUM were measured in each hemisphere of brains of 12 patients with schizophrenia and 13 age-matched and gender-matched normal control subjects without neuropsychiatric disorders. Patients with schizophrenia exhibited significant volume reductions in both the MD and the PUM, the reductions being more pronounced in the PUM. The volume of the PUM in the left (−19.7%, P=0.02) and right (−22.1%, P=0.01) hemispheres was significantly reduced in the schizophrenia group. The volume of the MD was reduced in both hemispheres in the schizophrenia group. However, the volume reduction was only significant in the left hemisphere (−9.3%, P=0.03). Patients with schizophrenia also exhibited a decreased volume of the THAL in the left (−16.4%, P=0.003) and right (−15.2%, P=0.006) hemispheres. There were no significant correlations between thalamic volumes and duration of illness or age of the patients.

In conclusion, the present data indicate volume reductions of association thalamic nuclei in schizophrenia. These anatomical findings are consistent with the view that schizophrenia may be associated with disturbances of association cortical networks. However, the findings of a substantial volume reduction of the THAL suggest that the volumes of additional thalamic nuclei may be also reduced in schizophrenia.     

Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia.

BACKGROUND: The thalamus is a brain region of interest in the study of schizophrenia because it provides critical input to brain regions such as the prefrontal, cingulate, and temporal cortices, where abnormalities have been repeatedly observed in patients with schizophrenia. Postmortem anatomic studies have rarely investigated the thalamus in this population. METHODS: Postmortem tissue was obtained from the left hemisphere of eight male schizophrenic patients and eight male age-matched control subjects. The optical dissector stereologic procedure was used to count neurons in the mediodorsal (MD) and anteroventral/anteromedial (AV/AM) nuclei of the thalamus. RESULTS: The number of neurons and volume of the MD were significantly reduced by 35% and 24%, respectively. The MD cell number reduction was a consistent finding; every control subject had more and every schizophrenic subject had fewer than 3.5 million neurons. Neuron number was also significantly reduced (16%) in the AV/AM nuclei. CONCLUSIONS: The present data indicate that schizophrenia is associated with robust reductions in nerve cell numbers in nuclei that communicate with the prefrontal cortex and limbic system. These thalamic anatomic deficits may be responsible, in part, for previous reports of such prefrontal cortical abnormalities as reduced synaptic density, reduced volume, and metabolic hypofunction.     

Pathology of the thalamus and schizophrenia--an overview

Since the beginning of the 20 (th) century, the thalamus was regarded as a brain region which may be involved in the pathogenesis of schizophrenia. Distinct thalamic nuclei were morphologically analyzed with qualitative methods with an emphasis on the mediodorsal nucleus. However, the reported results were inconsistent. After the introduction of quantitative neuroanatomical methods, it became obvious that the volume and cell reductions are not only present in the association nuclei, but also in the limbic (N. anteroventralis) and motor thalamic nuclei (N. ventrolateralis posterior). The involvement of distinct thalamic nuclei is supported by structural MRI studies which have shown a moderate but significant volume reduction of the whole thalamus in this disease. The majority of fMRI and PET studies reported a reduction of the metabolic activity or blood flow in the thalamus in patients with schizophrenia. The similarity between the structural changes in animal models of thalamic plasticity and the structural thalamic alterations in schizophrenia suggest an involvement of neuroplasticity mechanisms in the pathogenesis of these alterations. Post-mortem studies and In-vivo receptor studies suggest altered glutamatergic, dopaminergic and membrane-associated mechanisms within thalamic pathology in schizophrenia. On the psychopathological level, there is a similarity between some of the psychic manifestations of thalamic lesions and symptoms of the schizophrenic disease. There are also reports on volume reduction of the whole thalamus in first-episode neuroleptic-free patients. It appears unlikely that the neuroleptic medication plays an etiological important role, since no significant correlations were found between the volume and cell reductions and the neuroleptic treatment period. The reviewed data suggest that distinct thalamic nuclei and therefore distinct neuronal circuits are involved in the pathogenesis of schizophrenia.     

Meta-analysis of thalamic size in schizophrenia.

BACKGROUND: This article presents a meta-analysis of thalamic size reduction in schizophrenia. METHODS: Reviewed studies were based on magnetic resonance imaging or postmortem material and included measures of thalamic volume or thalamic area in schizophrenic patients and comparison subjects. Meta-analysis I was based on absolute thalamic values (not controlled for overall brain size), and Meta-analysis II evaluated thalamic size adjusted for brain size. RESULTS: Meta-analysis I included data from 15 studies (485 schizophrenic subjects and 500 control subjects). Twelve (80%) of the studies had negative effect sizes, which is consistent with the hypothesis that thalamic size is smaller in schizophrenic subjects compared to control subjects. The composite effect size was -0.29 (p <.0001; without outliers: -0.41, p <.0001). Meta-analysis II included data from 11 studies (313 schizophrenic patients and 434 control subjects). Ten (91%) of the studies had negative effect sizes. The composite effect size was -0.35 (p <.0001; without outlier: -0.30, p <.0001). CONCLUSIONS: Both meta-analyses indicate a statistically significant, small-to-moderate effect size for thalamic size reduction in schizophrenia; however, the effect size for thalamic size reduction is modest in comparison to that of other structural abnormalities noted in schizophrenia.     

Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.

OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.     

Selective reduction of neuron number and volume of the mediodorsal nucleus of the thalamus in macaques following irradiation at early gestational ages

Neurons in the macaque brain arise from progenitors located near the cerebral ventricles in a temporally segregated manner such that lethal doses of ionizing irradiation, if administered over a discrete time interval, can deplete individual nuclei selectively. A previous study showed that neuron number in the dorsal lateral geniculate nucleus is reduced following early gestational exposure to x‐irradiation (Algan and Rakic [ 1997 ] J. Comp. Neurol. 12:335–352). Here we examine whether similarly timed irradiation decreases neuron number in three associational thalamic nuclei: mediodorsal (MD), anterior, and pulvinar. Ten macaques were exposed to multiple doses of x‐rays (total exposure (175–350 cGy) in early gestation (E33–E42) or midgestation (E70–E90); eight nonirradiated macaques were controls. Only the early‐irradiated monkeys, not the midgestationally irradiated animals, exhibited deficits in whole‐thalamic neuron (–15%) and glia numbers (–21%) compared with controls. Reduction of neuron number (–26%) and volume (–29%) was particularly pronounced in MD. In contrast, cell number and volume were not significantly decreased in the anterior or pulvinar nuclei following early gestational irradiation. Thus, reduced thalamic neuron number was associated specifically with irradiation in early gestation. Persistence of the thalamic neuronal deficit in adult animals indicates that prenatally deleted neurons had not been replenished during maturation or in adulthood. The selective reduction of MD neuron number also supports the protomap hypothesis that neurons of each thalamic nucleus originate sequentially from separate lines of neuronal stem cells (Rakic [ 1977a ] J. Comp. Neurol. 176:23–52). The early gestationally irradiated macaque is discussed as a potentially useful model for studying the neurodevelopmental pathogenesis of schizophrenia. J. Comp. Neurol. 515:454–464, 2009. © 2009 Wiley‐Liss, Inc.     

The thalamus and schizophrenia: current status of research

The thalamus provides a nodal link for multiple functional circuits that are impaired in schizophrenia (SZ). Despite inconsistencies in the literature, a meta analysis suggests that the volume of the thalamus relative to that of the brain is decreased in SZ. Morphometric neuroimaging studies employing deformation, voxel-based and region of interest methodologies suggest that the volume deficit preferentially affects the thalamic regions containing the anterior and mediodorsal nuclei, and the pulvinar. Postmortem design-based stereological studies have produced mixed results regarding volume and neuronal deficits in these nuclei. This review examines those aspects of thalamic circuitry and function that suggest salience to SZ. Evidence for anomalies of thalamic structure and function obtained from postmortem and neuroimaging studies is then examined and directions for further research proposed.     

Abnormalities of thalamic volume and shape detected in fetally irradiated rhesus monkeys with high dimensional brain mapping.

BACKGROUND: Prior research has indicated neuroanatomical abnormalities of the thalamus in schizophrenia. To study the possible pathogenesis, an animal model of neurodevelopmental thalamic damage has been developed by applying low-dose radiation to rhesus monkeys in early gestation. Irradiated monkeys sacrificed as infants demonstrate neuronal losses in specific thalamic nuclei and decreases in cortical neuropil. METHODS: Magnetic resonance scans were collected in adult Rhesus monkeys exposed to irradiation during thalamic neurogenesis (E33-42), after thalamic neurogenesis (E70-81), and in nonirradiated control animals. High dimensional brain mapping was used to compare thalamic volumes and shape characteristics in the three groups of animals. RESULTS: Animals exposed to irradiation at E33-42 showed a significant bilateral loss of thalamic volumes (> 20%) compared with controls and with animals irradiated at E70-81 when total brain volume was used as a covariate in the analysis. Thalamic volume loss was associated with a nonuniform deformation of thalamic shape. CONCLUSIONS: A first-trimester, neurodevelopmental insult in the nonhuman primate during thalamic neurogenesis produces a complex pattern of thalamic volume loss and shape deformation in adulthood. Low-dose irradiation of the fetal primate may be useful for modeling key features of the pathology described in schizophrenic patients.     

Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia.

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.     

Abnormalities of thalamic volume and shape in schizophrenia

OBJECTIVE: Postmortem and neuroimaging studies of schizophrenia have reported deficits in the volume of the thalamus and its component nuclei. However, the pattern of shape change associated with such volume loss has not been investigated. In this study, alterations in thalamic volume, shape, and symmetry were compared in subjects with and without schizophrenia. METHOD: T(1)-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects matched for age, gender, race, and parental socioeconomic status. High-dimensional (large-deformation) brain mapping was used to assess thalamic morphology. RESULTS: Significant differences in thalamic volume, deformities of thalamic shape at the anterior and posterior extremes of the structure, and a significant exaggeration of thalamic asymmetry (i.e., left smaller than right) were found in the schizophrenia subjects. After covarying for total cerebral volume, the difference in thalamic volume became insignificant. When information about thalamic shape was combined with previously collected information about hippocampal shape, the discrimination between schizophrenia patients and comparison subjects was improved. CONCLUSIONS: Thalamic volume was smaller than normal in schizophrenia patients, but only proportionate to reductions in reduced total cerebral volume. The presence of changes in thalamic shape and asymmetry suggest greater pathologic involvement of individual nuclei at its anterior and posterior extremes of the thalamic complex.     

D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia

BACKGROUND: Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities. METHODS: Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug na?ve schizophrenics (10 men, 5 women, mean age 28.5 years) and 15 matched controls (9 men, 6 women, mean age 27.4 years). Dopamine D2/D3 receptor levels were measured as binding potential (BP). The fallypride BP images of each subject were spatially normalized and subsequently smoothed for group comparison. Measures of significance between the schizophrenic and control groups were determined using statistical parametric mapping (SPM). The medial dorsal nucleus and pulvinar were also traced on coregistered MRI for detailed assessment of BP in these regions. RESULTS: The thalamus of patients with schizophrenia had lower [F-18]fallypride BP than normal controls and this was the brain area with the greatest difference (range -8.5% to -27.2%). Left medial dorsal nucleus and left pulvinar showed the greatest decreases (-21.6% and -27.2% respectively). The patients with schizophrenia also demonstrated D2/D3 BP reduction in the amygdala region, cingulate gyrus, and the temporal cortices. CONCLUSIONS: These findings suggest that drug na?ve patients with schizophrenia have significant reductions in extrastratial D2/D3 receptor availability. The reductions were most prominent in regions of the thalamus, replicating other studies both with high affinity D2/D3 ligands and consistent with FDG-PET studies, further supporting the hypothesis of thalamic abnormalities in this patient population.     

Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [123I]iodobenzamide.

BACKGROUND: Previous imaging studies demonstrated that schizophrenia is associated with increased amphetamine-induced dopamine (DA) release in the striatum, most pronounced during episodes of illness exacerbation. Schizotypal personality disorder (SPD) is a schizophrenia spectrum disorder, genetically related to schizophrenia. The goal of this study was to investigate striatal DA function in patients with SPD. METHODS: In our study, 13 SPD patients and 13 matched healthy control subjects underwent single photon emission computed tomography (SPECT) scan during bolus plus constant infusion of the D2/3 radiotracer [123I]iodobenzamide (IBZM). Striatal specific to nonspecific equilibrium partition coefficient (V(3)") was measured at baseline and following amphetamine administration (.3 mg/kg). RESULTS: No significant differences were observed in baseline V(3)" between groups. Amphetamine induced a larger decrease in [123I]IBZM V(3)" in SPD patients (-12 +/- 5%) compared with control subjects (-7 +/- 5%, p =.03). CONCLUSIONS: The reduction in [123I]IBZM V(3)" induced by amphetamine in SPD was similar to that observed in remitted schizophrenia patients (-10 +/- 9%, n = 17), but significantly lower than that observed during illness exacerbation (-24 +/- 13%, n = 17). This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD.     

A magnetization transfer analysis of the thalamus in schizophrenia

The authors investigated the thalamus in schizophrenia by using magnetization transfer ratio (MTR), a novel structural magnetic resonance technique sensitive to subtle neuropathological abnormalities. The dorsomedial nucleus (DMN) and pulvinar were selected because of their connections to limbic, prefrontal, and temporal regions, putatively relevant in schizophrenia. Volume (intracranial; thalamic) and MTR (whole thalamus; DMN; pulvinar) were determined in 25 patients with chronic schizophrenia by DSM-IV criteria and 25 control subjects. There were no significant differences between patients and control subjects in thalamic volume (corrected for intracranial volume) or MTR in whole thalamus, DMN, or pulvinar. No volumetric or MTR abnormalities could be detected in the thalamus of patients with schizophrenia. The findings suggest that abnormalities, if present, are very subtle and beyond the power of resolution of these techniques.     

Abnormalities of thalamic activation and cognition in schizophrenia

OBJECTIVE: Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. METHOD: Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. RESULTS: Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. CONCLUSIONS: These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.     

Quantitative neuroanatomy in schizophrenia. A controlled magnetic resonance imaging study

Twenty-four patients with schizophrenia and 14 normal control subjects underwent magnetic resonance imaging scans using a 0.5-tesla scanner and 600-ms inversion recovery technique. A midsagittal section and twelve 1-cm coronal sections beginning at the frontal pole were obtained, and linear, area, and signal intensity measurements were made on nine brain regions. Volume estimates were made by summing consecutive sections for four of the following regions: the precallosal frontal lobes, temporal lobes, lateral ventricles, amygdala-hippocampal complexes, and cerebral hemispheres. The area of the third ventricle in its most anterior coronal slice was increased by 73% in schizophrenic subjects (0.83 +/- 0.08 cm2) in comparison with controls (0.48 +/- 0.04 cm2). Lateral ventricular volume was increased by 62% in schizophrenic subjects (24.7 +/- 2.6 mL) in comparison with controls (15.2 +/- 1.4 mL). The lateral ventricular enlargement in schizophrenic subjects was more pronounced posteriorly than anteriorly, especially at the level of the anterior thalamus and the colliculi. There were no other significant differences between schizophrenic and control groups in any other spatial or signal intensity measures. There was no brain region the size of which correlated with ventricular size. These data corroborate third and lateral ventriculomegaly in schizophrenia using magnetic resonance imaging but fail to further localize the structural abnormality.