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.

Schizophrenia patients and their healthy siblings share decreased prefronto-thalamic connectivity but not increased sensorimotor-thalamic connectivity.

The pattern of decreased prefronto-thalamic connectivity and increased sensorimotor-thalamic connectivity has been consistently documented in schizophrenia. However, whether this thalamo-cortical abnormality pattern is of genetic predisposition remains unknown. The present study for the first time aimed to investigate the common and distinct characteristics of this circuit in schizophrenia patients and their unaffected siblings who share half of the patient's genotype. Totally 293 participants were recruited into this study including 94 patients with schizophrenia, 96 their healthy siblings, and 103 healthy controls scanned using gradient-echo echo-planar imaging at rest. By using a fine-grained atlas of thalamus with 16 sub-regions, we mapped the thalamocortical network in three groups. Decreased thalamo-prefronto-cerebellar connectivity was shared between schizophrenia and their healthy siblings, but increased sensorimotor-thalamic connectivity was only found in schizophrenia. The shared thalamo-prefronto-cerebellar dysconnectivity showed an impressively gradient reduction pattern in patients and siblings comparing to controls: higher in the controls, lower in the patients and intermediate in the siblings. Anatomically, the decreased thalamic connectivity mostly centered on the pre-frontal thalamic subregions locating at the mediodorsal nucleus, while the increased functional connectivity with sensorimotor cortices was only observed in the caudal temporal thalamic subregion anchoring at the dorsal and ventral lateral nuclei. Moreover, both decreased thalamo-prefronto-cerebellar connectivity and increased sensorimotor-thalamic connectivity were related to clinical symptoms in patients. Our findings extend the evidence that the decreased thalamo-prefronto-cerebellar connectivity may be related to the high genetic risk in schizophrenia, while increased sensorimotor-thalamic connectivity potentially represents a neural biomarker for this severe mental disorder.

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.

Betel quid chewing alters functional connectivity in frontal and default networks: A resting-state fMRI study.

PURPOSE: To explore the acute effect of betel quid (BQ) use on functional network connectivity by comparing the global functional brain networks and their subsets before and immediately after BQ chewing. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) was performed in 27 healthy male participants before and just after chewing BQ on a 3.0T scanner with a gradient-echo echo planar imaging sequence. Independent component analysis (ICA) was used to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. A paired t-test was used for exploring the connectivity differences in each network before and after BQ chewing. RESULTS: Sixteen networks were identified by ICA. Nine of them showed connectivity differences before and after BQ chewing (P < 0.05 false discovery rate corrected): (A) orbitofrontal, (B) left frontoparietal, (C) visual, (D) right frontoparietal, (E) anterior default mode, (F) medial frontal/anterior cingulate (G) frontotemporal, (H) occipital/parietal, (I) occipital/temporal/cerebellum. Moreover, networks A, B, C, D, G, H, and I showed increased connectivity, while networks E and F showed decreased connectivity in participants after BQ chewing compared to before chewing. CONCLUSION: The acute effects of BQ use appear to actively alter functional connectivity of frontal and default networks that are known to play a key role in addictive behavior. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:157-166.