Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia.

BACKGROUND: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia. METHODS: Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis. RESULTS: During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively. CONCLUSIONS: The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function.

Abnormal Thalamocortical Circuit in Adolescents With Early-Onset Schizophrenia.

OBJECTIVE: Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), although it is unclear whether this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset. METHOD: A total of 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were used in functional connectivity analysis. RESULTS: The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the salience network (SN). In addition, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity. CONCLUSION: Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the age of onset, raising the possibility of aberrant but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychosis seen in EOS.

Salience-thalamic circuit uncouples in major depressive disorder, but not in bipolar depression.

BACKGROUND: Bipolar depression (BDD) and major depressive disorder (MDD) are two diseases both characterized by depressed mood and diminished interest or pleasure. Recent neuroimaging studies have implicated the thalamo-cortical circuit in mood disorders, and the present study aimed to map thalamo-cortical connectivity to explore the dissociable and common abnormalities between bipolar and major depression in this circuit. METHOD: Applying resting-state functional magnetic resonance imaging (fMRI), we mapped the thalamo-cortical circuit using a fine-grained thalamic atlas with 8 sub-regions bilaterally in 38 BDD patients, 42 MDD patients and 39 healthy controls (HCs). Correlation analysis was then performed between thalamo-cortical connectivity and clinical variables. RESULT: The findings showed that both patient groups exhibited prefronto-thalamo-cerebellar and sensorimotor-thalamic hypoconnectivity, while the abnormalities in MDD were more extensive. Particularly, MDD group showed decreased thalamic connectivity with the salience network including the insula, anterior cingulate cortex (ACC), and striatum. No correlations were found between the abnormal thalamo-cortical connectivity and clinical symptoms in either patient group. LIMITATION: Most patients in our study were taking drugs at the time of scanning, which may confound our findings. CONCLUSION: Our finding suggest that the thalamo-cortical hypofunction is a common neuro-substrate for BDD and MDD. Specifically, the hypoconnectivity between the thalamus and salience network including the insula, ACC and striatum may be a distinguished biomarker for MDD, which may help to differentiate these two emotional disorders.

Chemical constituents from the stems of Gymnema sylvestre.

AIM: To study the chemical constituents of stems of Gymnema sylvestre (Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis (1D and 2D NMR), as well as chemical methods. RESULTS: Seven compounds were isolated and their structures were elucidated as conduritol A (1), stigmasterol (2), lupeol (3), stigmasterol-3-O-ß-D-glucoside (4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-ß-D-glucopyranosyl-(1→3)-ß-D-glu-curono-pyranosyl-28-O-α-L-rhamnopyranoside (5), oleanolic acid-3-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranoside (6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-ß-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside (7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated. CONCLUSION: Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.

Study on chemical constituents of Cyclocarya paliurus.

A new dammarane triterpenoid glycoside named cyclocarioside J (1) and other three known triterpenoid glycosides were isolated from the leaves of Cyclocarya paliurus. Based on ESI-MS, HR-ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR techniques including (1)H-(1)H COSY, HMBC, HMQC, and NOESY correlations, the structure of cyclocarioside J was elucidated as (20S,24R)-epoxydammarane 3ß,12ß,25-trihydroxy-12-O-ß-d-quinovopyranosyl-3-O-α-l-arabinopyranoside.

A new triterpenoid saponin from Gymnema sylvestre.

Besides four known compounds, a new triterpenoid saponin was isolated from the stems of Gymnema sylvestre. The structure of the new triterpenoid saponin was established as 3ß,16ß,22α-trihydroxy-olean-12-ene 3-O-ß-D-xylopyranosyl-(1 → 6)-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranoside (1) on the basis of 1D and 2D NMR techniques, including COSY, HMBC, HMQC, and NOESY correlations. Four known compounds 2, 3, 4, and 5 were identified on the basis of spectroscopic data.