Thalamic Abnormalities Research Articles

Cerebrovascular disorders in diabetic patients with resistant hypertension and factors associated with their severity

Abstract Introduction Diabetes mellitus (DM) and hypertension (HTN) are associated with accelerated brain damage that often precedes the development of stroke and dementia. However, little is known about the features of silent brain damages and possible mechanisms of their development in patients with resistant hypertension (RHTN) and type 2 DM. Objective To study the features of MRI- sings of silent brain damage in patients RHTN with type 2 DM and to establish the factors associated with their development. Methods We studied 46 with RHTN and type 2 DM (mean age 60.3±7.9 years; 27 females (59%), mean 24-hour (systolic/diastolic) BP 169.0±16.4/89.0±14.7 mmHg, HbA1c 7.4±1.3%). On average, patients were taking 4.3±1.0 antihypertensive drugs. Patients were subjected to brain MRI (1.5 T), 24-hour BP monitoring, lab tests (HbA1c, TNF-α, hsCRP, leptin, resistin, aldosterone, basal end postprandial serum glucose, insulin, C-peptide). According to MRI linear dimensions of liquor spaces (subarachnoidal spaces (SAS), lateral ventricles, III and IV ventricles), white matter lesions (WMLs), basal ganglia and thalamus abnormalities were assessed. In addition, severity of periventricular WMLs (PWMLs) was evaluated semi-quantitatively on a scale of 0 to 4. Results The frequency of ventricular dilatation was 45%, expansion of SAS – 65%, lacunar infarctions – 25%, focal WMLs (diameter <3 mm) – 52%, PWMLs – 89%. According to the correlation analysis, an increase in density of the MR signal of PWMLs was associated with an increase in levels of TNF-α (r=0.55 p=0.01) and hsCRP (r=0.64 p=0.045). The increase in density of the MR signal from basal ganglia and thalamus correlated with postprandial levels of glucose (r=0,48 p=0,025; r=0.46 p=0.04, respectively), insulin (r=0.54 p=0.011; r=0.52 p=0.017, respectively) and C-peptide (r=0.54 p=0.011; r=0.46 p=0.037, respectively), as well as with basal level of insulin (r=0.52 p=0.007; r=0.48 p=0.012, respectively) and the leptin (r=0.40 p=0.027; r=0.36 p=0.048, respectively). The severity of PWMLs depended on the level of basal glycaemia (r=0.35, p=0.020) and HbA1c (r=0.37, p=0.04). The transverse size of the chiasmal cistern had a relationship with of the resistin level (r=0.43, p=0.03), and the transverse size of the III ventricle correlated with the serum aldosterone level (r=0.51, p=0.13). There were no direct correlations between MRI- sings of silent brain damage and blood pressure levels. Conclusion Thus, diabetic patients with resistant hypertension have a high frequency of white matter lesions and of liquorodynamics dysturbanses. The severity of these changes depends on a complex of metabolic, pro-inflammatory and neurohormonal factors in the absence of a direct relationship with the blood pressure level. Funding Acknowledgement Type of funding sources: None.

Individualized diagnosis of major depressive disorder via multivariate pattern analysis of thalamic sMRI features

BackgroundMagnetic resonance imaging (MRI) studies have found thalamic abnormalities in major depressive disorder (MDD). Although there are significant differences in the structure and function of the thalamus between MDD patients and healthy controls (HCs) at the group level, it is not clear whether the structural and functional features of the thalamus are suitable for use as diagnostic prediction aids at the individual level. Here, we were to test the predictive value of gray matter density (GMD), gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) in the thalamus using multivariate pattern analysis (MVPA).MethodsSeventy-four MDD patients and 44 HC subjects were recruited. The Gaussian process classifier (GPC) was trained to separate MDD patients from HCs, Gaussian process regression (GPR) was trained to predict depression scores, and Multiple Kernel Learning (MKL) was applied to explore the contribution of each subregion of the thalamus.ResultsThe primary findings were as follows: [1] The balanced accuracy of the GPC trained with thalamic GMD was 96.59% (P < 0.001). The accuracy of the GPC trained with thalamic GMV was 93.18% (P < 0.001). The correlation between Hamilton Depression Scale (HAMD) score targets and predictions in the GPR trained with GMD was 0.90 (P < 0.001, r2 = 0.82), and in the GPR trained with GMV, the correlation between HAMD score targets and predictions was 0.89 (P < 0.001, r2 = 0.79). [2] The models trained with ALFF and fALFF in the thalamus failed to discriminate MDD patients from HC participants. [3] The MKL model showed that the left lateral prefrontal thalamus, the right caudal temporal thalamus, and the right sensory thalamus contribute more to the diagnostic classification.ConclusionsThe results suggested that GMD and GMV, but not functional indicators of the thalamus, have good potential for the individualized diagnosis of MDD. Furthermore, the thalamus shows the heterogeneity in the structural features of thalamic subregions for predicting MDD. To our knowledge, this is the first study to focus on the thalamus for the prediction of MDD using machine learning methods at the individual level.

Thalamus Radiomics-Based Disease Identification and Prediction of Early Treatment Response for Schizophrenia.

BackgroundEmerging evidence suggests structural and functional disruptions of the thalamus in schizophrenia, but whether thalamus abnormalities are able to be used for disease identification and prediction of early treatment response in schizophrenia remains to be determined. This study aims at developing and validating a method of disease identification and prediction of treatment response by multi-dimensional thalamic features derived from magnetic resonance imaging in schizophrenia patients using radiomics approaches.MethodsA total of 390 subjects, including patients with schizophrenia and healthy controls, participated in this study, among which 109 out of 191 patients had clinical characteristics of early outcome (61 responders and 48 non-responders). Thalamus-based radiomics features were extracted and selected. The diagnostic and predictive capacity of multi-dimensional thalamic features was evaluated using radiomics approach.ResultsUsing radiomics features, the classifier accurately discriminated patients from healthy controls, with an accuracy of 68%. The features were further confirmed in prediction and random forest of treatment response, with an accuracy of 75%.ConclusionOur study demonstrates a radiomics approach by multiple thalamic features to identify schizophrenia and predict early treatment response. Thalamus-based classification could be promising to apply in schizophrenia definition and treatment selection.

Thalamic reticular nucleus impairments and abnormal prefrontal control of dopamine system in a developmental model of schizophrenia: prevention by N-acetylcysteine.

Recent evidence showed thalamic abnormalities in schizophrenia involving disruptions to the parvalbumin neurons in the thalamic reticular nucleus (TRN). However, their functional consequences, as well as a potential linkage to oxidative stress, are unclear. The TRN is posited to gate prefrontal control of dopamine neuron activity in the ventral tegmental area (VTA). Thus, we hypothesized that schizophrenia-related TRN abnormalities might contribute to dopamine dysregulation, a well-known feature of the disorder. To test this, in adult rats exposed prenatally to methylazoxymethanol acetate (MAM rats), oxidative impairments to the parvalbumin neurons in the anterior TRN were assessed by immunohistochemistry. Using in vivo electrophysiology, we investigated whether inactivation of the prefrontal cortex would produce differential effects on VTA dopamine neurons in MAM rats. We show that MAM rats displayed reduced markers of parvalbumin and wisteria floribunda agglutinin-labeled perineuronal nets, correlating with increased markers of oxidative stress (8-oxo-7, 8-dihydro-20-deoxyguanosine and 3-Nitrotyrosine). Moreover, MAM rats displayed heightened baseline and abnormal prefrontal control of VTA dopamine neuron activity, as tetrodotoxin-induced inactivation of the infralimbic prefrontal cortex decreased the dopamine population activity, contrary to the normal increase in controls. Such dopamine neuron dysregulation was recapitulated by enzymatic perineuronal net digestion in the TRN of normal rats. Furthermore, juvenile (postnatal day 11-25) antioxidant treatment (N-acetyl-cysteine; 900mg/L; drinking water) prevented all these impairments in MAM rats. Our findings suggest that early accumulation of oxidative stress in the TRN may shape the later onset of schizophrenia pathophysiology, highlighting redox regulation as a potential target for early intervention.

Distinct Thalamic Abnormalities Differentially Relate to Cognition in Early-Onset Relative to Adult-Onset Schizophrenia

Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS). However, EOS may represent a subgroup with greater susceptibility for disease progression and presentation. The neurobiology of schizophrenia is known to involve deep-brain structures, particularly the thalamus. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS group and determine whether unique behavioral profiles related to these differences.

Thalamic Nuclei Volumes in Psychotic Disorders and Youth With Psychosis Spectrum Symptoms

Several influential models posit that the pathophysiology of psychosis includes thalamic association nuclei and that thalamic abnormalities are due, at least in part, to atypical brain development, and related to mechanisms of cognitive impairment. While multiple lines of evidence are consistent with thalamic involvement in psychosis, evidence that association nuclei are differentially affected is sparse.

Individualized Thalamic Parcellation Reveals Alterations in Shape and Microstructure of Thalamic Nuclei in Patients with Disorder of Consciousness.

The thalamus plays crucial roles in consciousness generation and information processing. Previous evidence suggests that disorder of consciousness (DOC) caused by severe brain injury, is potentially related to thalamic abnormalities. However, how the morphology and microstructure change in thalamic subfields and thalamocortical fiber pathways in patients with DOC, and the relationships between these changes and the consciousness status remain unclear. Here, we generated the individual-specific thalamic parcellation in 10 DOC patients and 10 healthy controls (HC) via a novel thalamic segmentation framework based on the fiber orientation distribution (FOD) derived from 7-Tesla diffusion MRI, and investigated the shape deformation of thalamic nuclei as well as the microstructural changes associated with thalamic nuclei and thalamocortical pathways in patients with DOC. Enlargement of dorsal posterior nucleus and atrophy of anterior nucleus in the right thalamus were observed in DOC cohort relative to the HCs, and the former was closely linked to the consciousness level of the patients. We also found significant reductions of fiber density, but not fiber bundle cross-section, within several thalamic nuclei and most of the thalamocortical fiber pathways, suggesting that loss of axons might take primary responsibility for the impaired thalamocortical connections in patients with DOC rather than the change in fiber-bundle morphology. Furthermore, the individual-specific thalamic parcellation achieved 80% accuracy in classifying patients at the minimally conscious state from the vegetative state, compared with ~60% accuracy based on group-level parcellations. Our findings provide the first evidence for the shape deformation of thalamic nuclei in DOC patients and the microstructural basis of the disrupted thalamocortical connections.

Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue.

Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.

Thalamic Structural Connectivity Abnormalities in Minimal Hepatic Encephalopathy.

Background and Aims: Numerous studies have demonstrated thalamus-related structural, functional, and metabolic abnormalities in minimal hepatic encephalopathy (MHE). We conducted the first study to investigate thalamic structural connectivity alterations in MHE.MethodsDiffusion tensor imaging (DTI)-based probabilistic tractography was employed to determine the structural linkage between the thalamus and cortical/subcortical regions in 52 cirrhotic patients [22 with MHE; 30 without MHE (NHE)] and 30 controls. We measured these thalamic connections, which included connectivity strength (CS), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and then compared these among the three groups. Neurocognitive assessment was also performed. Correlation analysis was conducted to investigate the relationship between neurocognitive performance and the above measurements. Classification analysis was performed to determine whether thalamic connection measurements can distinguish MHE from NHE.ResultsThe probabilistic tractography revealed thalamic structural connections, which were disrupted in cirrhotic patients (as reflected by a decrease in CS/FA and an increase in MD/AD/RD). Abnormal thalamic connections primarily involved the prefrontal cortex, sensorimotor cortex, parietal cortex, medial temporal cortex and hippocampus, and striatum. Thalamic connectivity abnormalities deteriorated from NHE to MHE, and they were correlated with patients’ neurocognitive performance. The moderate classification accuracy was obtained using CS and MD as discriminating indexes.ConclusionOur results demonstrated the altered thalamic structural connectivity involving both cortical and subcortical regions in MHE, which could be regarded as representative of MHE-related widespread impairments in white matter pathways. The disturbed thalamic connectivity may underlie the mechanism of cognitive deficits in MHE and may potentially be utilized as a biomarker for diagnosing MHE and in monitoring disease progression. In addition to thalamic–cortical/subcortical connections, further studies are recommended to explore the structural alterations in other white matter pathways in MHE.

Reduced GABA/glutamate in the thalamus of individuals at clinical high risk for psychosis.

Youth at clinical high risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, especially schizophrenia (SCZ). Recent neuroimaging findings point to abnormalities in the thalamus of patients with SCZ, including chronic and early course patients, as well as in CHR individuals relative to healthy comparison groups, thus suggesting that thalamic dysfunctions are present even before illness onset. Furthermore, modeling data indicate that alteration between excitatory and inhibitory control, as reflected by alteration in GABAergic and glutamatergic balance (i.e., GABA/Glu), may underlie thalamic deficits linked to the risk and development of psychosis. There is, however, a lack of in vivo evidence of GABA/Glu thalamic abnormalities in the CHR state. Magnetic resonance spectroscopic imaging (MRSI) 7 Tesla (7 T) provides enhanced resolution to quantify GABA and Glu levels in the thalamus of CHR individuals. In this study, we performed 7 T MRSI in 15 CHR and 20 healthy control (HC) participants. We found that GABA/Glu was significantly reduced in the right medial anterior and right medial posterior thalamus of CHR relative to HC groups. The GABA/Glu reduction was negatively correlated with general symptoms in the right medial anterior thalamus, as well as with disorganization symptoms in the right medial posterior thalamus. Altogether, these findings indicate that GABA/Glu abnormalities are present in the thalamus before the onset of full-blown psychosis and are associated with symptom severity, thus providing putative molecular and neuronal targets for early interventions in youth at CHR.

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology.

The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics-including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio-in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183-0.369; P range = 0.010-0.046), while we found significant mean diffusivity (f2 range = 0.101-0.369; P range = 0.018-0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = -0.27-0.34; P range = 0.004-0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24-0.27; P range = 0.006-0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

Thalamic Nuclei Volumes in Psychotic Disorders and in Youths With Psychosis Spectrum Symptoms.

Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental cohort, and to determine whether nuclear volumes were associated with cognitive function. Thalamic nuclei volumes were tested in a cross-sectional sample of 472 adults (293 with psychosis) and the Philadelphia Neurodevelopmental Cohort (PNC), consisting of 1,393 youths (398 with psychosis spectrum symptoms and 609 with other psychopathologies), using a recently developed, validated method for segmenting thalamic nuclei and complementary voxel-based morphometry. Cognitive function was measured with the Screen for Cognitive Impairment in Psychiatry in the psychosis cohort and the Penn Computerized Neurocognitive Battery in the PNC. The psychosis group had smaller pulvinar, mediodorsal, and, to a lesser extent, ventrolateral nuclei volumes compared with the healthy control group. Youths with psychosis spectrum symptoms also had smaller pulvinar volumes, compared with both typically developing youths and youths with other psychopathologies. Pulvinar volumes were positively correlated with general cognitive function. The study findings demonstrate that smaller thalamic association nuclei represent a neurodevelopmental abnormality associated with psychosis, risk for psychosis in youths, and cognitive impairment. Identifying specific thalamic nuclei abnormalities in psychosis has implications for early detection of psychosis risk and treatment of cognitive impairment in psychosis.

Thalamic Nuclei Volumes in Psychotic Disorders and Youth With Psychosis Spectrum Symptoms

Several influential models posit that the pathophysiology of psychosis includes thalamic association nuclei and that thalamic abnormalities are due, at least in part, to atypical brain development, and related to mechanisms of cognitive impairment. While multiple lines of evidence are consistent with thalamic involvement in psychosis, evidence that association nuclei are differentially affected is sparse.

Clinical predictivity of thalamic sub-regional connectivity in clinically isolated syndrome: a 7-year study.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability.

Migraine with aura in women is not associated with structural thalamic abnormalities

Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent.Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified from the Danish Twin Registry. We used two advanced, validated analysis methods to assess the volume of the thalamus and its nuclei; the MAGeT Brain Algorithm and a recently developed FreeSurfer-based method based on a probabilistic atlas of the thalamic nuclei combining ex vivo MRI and histology. These approaches were very similar to the methods used in each of the two previous studies.Between-group comparisons were corrected for potential effects of age, educational level, BMI, smoking, alcohol, and hypertension using a linear mixed model. Further, we used linear mixed models and visual inspection of data to assess relations between migraine aura frequency and thalamic nuclei volumes in patients. In addition, we performed paired t-tests to compare volumes of twin pairs (N = 29) discordant for migraine with aura. None of our analyses showed any between-group differences in volume of the thalamus or of individual thalamic nuclei. Our results indicate that the pathophysiology of migraine with aura does not involve alteration of thalamic volume.

Modification of both functional neurological symptoms and neuroimaging patterns with a good anatomoclinical concordance: a case report

BackgroundIn the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a “psychodynamic” lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder.Case presentationHerein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology.ConclusionsThis case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of “dynamic lesion”.

Thalamic and thalamic projection abnormalities on DTI and NODDI analysis following acute concussion

ObjectiveTo compare preseason and post-concussive MRI in a cohort of collegiate football players utilizing Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) post processing.BackgroundAcute post-concussive symptoms can vary in clinical characteristics and severity. However, vestibular and ocular dysfunction in particular, has been associated with poor clinical outcomes. The vestibular system comprises a complex network of projections from peripheral vestibular organs to thalamic relay systems and numerous cortical regions. The visual/oculomotor system is also complex, involving brainstem, subcortical-cortical and thalamo-cortical connections. Oculomotor deficits are thought to involve the midbrain and the visual and parietal association cortices, both of which have thalamic projections.Design/MethodsWe gathered pre-season MR diffusion weighted imaging on a cohort of 30 collegiate football players. We performed repeat imaging within 36 hours of any diagnosed concussion in the same subject cohort. DTI metrics: mean diffusivity (MD), axial diffusivity (AD), fractional anisotropy (FA), and radial diffusivity (RD) along with NODDI metric: orientation dispersion index (ODI), were analyzed for statistical comparisons between groups.Results4 subjects with pre-season MRI underwent repeat MRI within 36 hours of concussive injury. A paired t-test between these two groups using DTI and NODDI metrics showed significant (p &lt; 0.05) decreases in: AD and MD in the left posterior thalamic radiations, FA in the column and body of the fornix, and MD in the right anterior corona radiata and superior fronto-occipital fasciculus, and a significant decrease in ODI in the anterior thalamus.ConclusionsDisruptions in the thalamus and its white matter projections may play a role in the vestibular/ocular dysfunction associated with acute concussive injury. While our numbers are small, the findings suggest that DTI and NODDI processing techniques have the capability to locate and measure grey and white matter injury patterns after concussive injury.

Multivariate patterns of gray matter volume in thalamic nuclei are associated with positive schizotypy in healthy individuals.

Previous models suggest biological and behavioral continua among healthy individuals (HC), at-risk condition, and full-blown schizophrenia (SCZ). Part of these continua may be captured by schizotypy, which shares subclinical traits and biological phenotypes with SCZ, including thalamic structural abnormalities. In this regard, previous findings have suggested that multivariate volumetric patterns of individual thalamic nuclei discriminate HC from SCZ. These results were obtained using machine learning, which allows case-control classification at the single-subject level. However, machine learning accuracy is usually unsatisfactory possibly due to phenotype heterogeneity. Indeed, a source of misclassification may be related to thalamic structural characteristics of those HC with high schizotypy, which may resemble structural abnormalities of SCZ. We hypothesized that thalamic structural heterogeneity is related to schizotypy, such that high schizotypal burden would implicate misclassification of those HC whose thalamic patterns resemble SCZ abnormalities. Following a previous report, we used Random Forests to predict diagnosis in a case-control sample (SCZ = 131, HC = 255) based on thalamic nuclei gray matter volumes estimates. Then, we investigated whether the likelihood to be classified as SCZ (π-SCZ) was associated with schizotypy in 174 HC, evaluated with the Schizotypal Personality Questionnaire. Prediction accuracy was 72.5%. Misclassified HC had higher positive schizotypy scores, which were correlated with π-SCZ. Results were specific to thalamic rather than whole-brain structural features. These findings strengthen the relevance of thalamic structural abnormalities to SCZ and suggest that multivariate thalamic patterns are correlates of the continuum between schizotypy in HC and the full-blown disease.

Thalamus-related anomalies as candidate mechanism-based biomarkers for psychosis

Identification of reliable biomarkers of prognosis in subjects with high risk to psychosis is an essential step to improve care and treatment of this population of help-seekers. Longitudinal studies highlight some clinical criteria, cognitive deficits, patterns of gray matter alterations and profiles of blood metabolites that provide some levels of prediction regarding the conversion to psychosis. Further effort is warranted to validate these results and implement these types of approaches in clinical settings. Such biomarkers may however fall short in entangling the biological mechanisms underlying the disease progression, an essential step in the development of novel therapies. Circuit-based approaches, which map on well-identified cerebral functions, could meet these needs. Converging evidence indicates that thalamus abnormalities are central to schizophrenia pathophysiology, contributing to clinical symptoms, cognitive and sensory deficits. This review highlights the various thalamus-related anomalies reported in individuals with genetic risks and in the different phases of the disorder, from prodromal to chronic stages. Several anomalies are potent endophenotypes, while others exist in clinical high-risk subjects and worsen in those who convert to full psychosis. Aberrant functional coupling between thalamus and cortex, low glutamate content and readouts from resting EEG carry predictive values for transition to psychosis or functional outcome. In this context, thalamus-related anomalies represent a valuable entry point to tackle circuit-based alterations associated with the emergence of psychosis. This review also proposes that longitudinal surveys of neuroimaging, EEG readouts associated with circuits encompassing the mediodorsal, pulvinar in high-risk individuals could unveil biological mechanisms contributing to this psychiatric disorder.

Regional Shape Abnormalities in Thalamus and Verbal Memory Impairment After Subcortical Infarction

Background. Subcortical infarcts can result in verbal memory impairment, but the potential underlying mechanisms remain unknown. Objective. We investigated the spatiotemporal deterioration patterns of brain structures in patients with subcortical infarction and identified the regions that contributed to verbal memory impairment. Methods. Cognitive assessment and structural magnetic resonance imaging were performed 1, 4, and 12 weeks after stroke onset in 28 left-hemisphere and 22 right-hemisphere stroke patients with subcortical infarction. Whole-brain volumetric analysis combined with a further-refined shape analysis was conducted to analyze longitudinal morphometric changes in brain structures and their relationship to verbal memory performance. Results. Between weeks 1 and 12, significant volume decreases in the ipsilesional basal ganglia, inferior white matter, and thalamus were found in the left-hemisphere stroke group. Among those 3 structures, only the change rate of the thalamus volume was significantly correlated with that in immediate recall. For the right-hemisphere stroke group, only the ipsilesional basal ganglia survived the week 1 to week 12 group comparison, but its change rate was not significantly correlated with the verbal memory change rate. Shape analysis of the thalamus revealed atrophies of the ipsilesional thalamic subregions connected to the prefrontal, temporal, and premotor cortices in the left-hemisphere stroke group and positive correlations between the rates of those atrophies and the change rate in immediate recall. Conclusions. Secondary damage to the thalamus, especially to the left subregions connected to specific cortices, may be associated with early verbal memory impairment following an acute subcortical infarct.