Courtney Lang

Anatomical brain difference of subthreshold depression in young and middle-aged individuals

Background Subthreshold depression (StD) is associated with substantial functional impairments due to depressive symptoms that do not fully meet the diagnosis of major depressive disorder (MDD). Its high incidence in the general population and debilitating symptoms has recently put it at the forefront of mood disorder research. Aim In this study we investigated common volumetric brain changes in both young and middle-aged StD patients. Methods Two cohorts of StD patients, young and middle-aged, (n = 57) and matched controls (n = 76) underwent voxel-based morphometry (VBM). Results VBM analysis found that: 1) compared with healthy controls, StD patients showed decreased gray matter volume (GMV) in the bilateral globus pallidus and precentral gyrus, as well as increased GMV in the left thalamus and right rostral anterior cingulate cortex/medial prefrontal cortex; 2) there is a significant association between Center for Epidemiological Studies Depression Scale scores and the bilateral globus pallidus (negative) and left thalamus (positive); 3) there is no interaction between age (young vs. middle-age) and group (StD vs. controls). Conclusions Our findings indicate significant VBM brain changes in both young and middle-aged individuals with StD. Individuals with StD, regardless of age, may share common neural characteristics.

Tai Chi Chuan and Baduanjin Increase Grey Matter Volume in Older Adults: A Brain Imaging Study

The aim of this study is to investigate and compare how 12-weeks of Tai Chi Chuan and Baduanjin exercise can modulate brain structure and memory function in older adults. Magnetic resonance imaging and memory function measurements (Wechsler Memory Scale-Chinese revised, WMS-CR) were applied at both the beginning and end of the study. Results showed that both Tai Chi Chuan and Baduanjin could significantly increase grey matter volume (GMV) in the insula, medial temporal lobe, and putamen after 12-weeks of exercise. No significant differences were observed in GMV between the Tai Chi Chuan and Baduanjin groups. We also found that compared to healthy controls, Tai Chi Chuan and Baduanjin significantly improved visual reproduction subscores on the WMS-CR. Baduanjin also improved mental control, recognition, touch, and comprehension memory subscores of the WMS-CR compared to the control group. Memory quotient and visual reproduction subscores were both associated with GMV increases in the putamen and hippocampus. Our results demonstrate the potential of Tai Chi Chuan and Baduanjin exercise for the prevention of memory deficits in older adults.

Disrupted functional connectivity of striatal sub-regions in Bell's palsy patients

The striatum plays an important role in controlling motor function in humans, and its degeneration has the ability to cause severe motor disorders. More specifically, previous studies have demonstrated a disruption in the connectivity of the cortico-striatal loop in patients suffering from motor disorders caused by dopamine dysregulation, such as Parkinsons disease. However, little is known about striatal functional connectivity in patients with motor dysfunction not caused by dopamine dysregulation. In this study, we used early-state Bells palsy (BP) patients (within 14 days of onset) to investigate how functional connectivity between the striatum and motor cortex is affected by peripheral nerve injury in which the dopamine system remains fully functional. We found a significant increase in the connectivity between the contralateral putamen, and the ipsilateral primary sensory (S1) and motor cortex (M1) in BP patients compared to healthy controls. We also found increased connectivity between the ventral striatum and supplementary motor area (SMA), and the dorsal caudate and medial prefrontal lobe in BP patients compared to healthy controls. Our results demonstrate that the entirety of the striatum is affected following acute peripheral nerve injury, and suggests that this disrupted striatal functional connectivity may reflect a compensatory mechanism for the sensory-motor mismatch caused by BP.

Decreased structural connectivity and resting-state brain activity in the lateral occipital cortex is associated with social communication deficits in boys with autism spectrum disorder

ABSTRACT Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical social communication and repetitive behaviors. In this study, we applied a multimodal approach to investigate brain structural connectivity, resting state activity, and surface area, as well as their associations with the core symptoms of ASD. Data from forty boys with ASD (mean age, 11.5 years; age range, 5.5–19.5) and forty boys with typical development (TD) (mean age, 12.3; age range, 5.8–19.7) were extracted from the Autism Brain Imaging Data Exchange II (ABIDE II) for data analysis. We found significantly decreased structural connectivity, resting state brain activity, and surface area at the occipital cortex in boys with ASD compared to boys with TD. In addition, we found that resting state brain activity and surface area in the lateral occipital cortex was negatively correlated with communication scores in boys with ASD. Our results suggest that decreased structural connectivity and resting‐state brain activity in the occipital cortex may impair the integration of verbal and non‐verbal communication cues in boys with ASD, thereby impacting their social development. HighlightsWe applied a multimodal approach to investigate the neuropathology of ASD.ASD showed decreased fALFF and surface area at the occipital cortex.ASD is associated with decreased FA and track length in left CCG and right UNC.Functional and structural changes were associated with ASD communication scores.

The functional and structural alterations of the striatum in chronic spontaneous urticaria

The brain has long been known to be the regulation center of itch, but the neuropathology of chronic itch, such as chronic spontaneous urticaria (CSU), remains unclear. Thus, we aimed to explore the brain areas involved in the pathophysiology of CSU in hopes that our results may provide valuable insights into the treatment of chronic itch conditions. 40 CSU patients and 40 healthy controls (HCs) were recruited. Urticaria activity scores 7 (UAS7) were collected to evaluate patient’s clinical symptoms. Amplitude of low frequency fluctuations (ALFF), voxel-based morphometry (VBM), and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess brain activity and related plasticity. Compared with HCs, CSU patients exhibited 1) higher ALFF values in the right ventral striatum / putamen, which were positively associated with clinical symptoms as measured by UAS7; 2) gray matter volume (GMV) increase in the right ventral striatum and putamen; and 3) decreased rs-FC between the right ventral striatum and the right occipital cortex and between the right putamen and the left precentral gyrus. Using multiple-modality brain imaging tools, we demonstrated the dysfunction of the striatum in CSU. Our results may provide valuable insights into the neuropathology and development of chronic itch.

A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder

BACKGROUND Major depression is the fourth leading cause of disability worldwide and poses a socioeconomic burden worldwide. Transcutaneous vagus nerve stimulation (tVNS) is a promising noninvasive clinical device that may reduce the severity of major depression. However, the neural mechanism underlying continuous tVNS has not yet been elucidated. OBJECTIVE We aimed to explore the effect of hypothalamic subregion functional connectivity (FC) changes during continuous tVNS treatment on major depressive disorder (MDD) patients and to identify the potential biomarkers for treatment outcomes. METHODS Forty-one mild to moderate MDD patients were recruited and received either real or sham tVNS treatment for 4 weeks. We used a seed-to-whole brain approach to estimate the FC changes of hypothalamic subregions and their surrounding control areas during continuous tVNS treatment and explored their association with clinical outcome changes after 4 weeks of treatment. RESULTS Of the thirty-six patients that completed the study, those in the tVNS group had significantly lower scores on the 24-item Hamilton Depression (HAM-D) Rating Scale compared to the sham tVNS group after 4 weeks of treatment. The FC between the bilateral medial hypothalamus (MH) and rostral anterior cingulate cortex (rACC) was significantly decreased during tVNS but not during sham tVNS. The strength of this FC was significantly correlated with HAM-D improvements after 4 weeks of tVNS. CONCLUSION The FC between the bilateral MH and rACC may serve as a potential biomarker for the tVNS state and predict treatment responses. Our results provide insights into the neural modulation mechanisms of continuous tVNS and reveal a potential therapeutic target for MDD patients.

Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell’s Palsy

Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brains ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bells palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations.

Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder

Transcutaneous vagus nerve stimulation (tVNS) may be a promising treatment for major depressive disorder (MDD). In this exploratory study, fMRI scans were acquired during continuous real or sham tVNS from 41 MDD patients. Then, all patients received real or sham tVNS treatment for four weeks. We investigated the functional connectivity (FC) of the nucleus accumbens (NAc) at different frequency bands during real and sham tVNS and explored their associations with depressive symptom changes after one month of treatment. The results revealed: 1) significant positive FCs between the NAc and surrounding areas including the putamen, caudate, and distinct areas of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) during continuous real and sham tVNS; 2) compared with sham tVNS, real tVNS increased the FC between the left NAc and bilateral MPFC/rACC in the slow-5 band (0.008-0.027) and between the right NAc and left insula, occipital gyrus, and right lingual/fusiform gyrum in the typical low band (0.008-0.09); and 3) the FC of the NAc-MPFC/rACC during real tVNS showed a negative association with Hamilton Depression Rating Scale (HAMD) score changes in the real tVNS group after one month of treatment, but not in the sham group. Our findings demonstrate that tVNS can modulate low frequency intrinsic FC among key brain regions involved in reward and motivation processing and provide insights into the brain mechanism underlying tVNS treatment of MDD.

Altered Functional Connectivity of Striatal Subregions in Patients with Multiple Sclerosis

Abnormal corticostriatal resting-state functional connectivity (rsFC) has been implicated in the neuropathology of multiple sclerosis. The striatum, a component of the basal ganglia, is involved in diverse functions including movement, cognition, emotion, and limbic information processing. However, the brain circuits of the striatal subregions contributing to the changes in rsFC in relapsing–remitting multiple sclerosis (RRMS) patients remain unknown. We used six subdivisions of the striatum in each hemisphere as seeds to investigate the rsFC of striatal subregions between RRMS patients and matched healthy controls (HCs). In addition, we also scanned a subcohort of RRMS patients after an average of 7 months to test the reliability of our findings. Compared to HCs, we found significantly increased dorsal caudal putamen (DCP) connectivity with the premotor area, dorsal lateral prefrontal cortex (DLPFC), insula, precuneus, and superior parietal lobule, and significantly increased connectivity between the superior ventral striatum and posterior cingulate cortex (PCC) in RRMS patients following both scans. Furthermore, we found significant associations between the Expanded Disability Status Scale and the rsFC of the left DCP with the DLPFC and parietal areas in RRMS patients. Our results suggest that the DCP may be a critical striatal subregion in the pathophysiology of RRMS.

A neural mechanism of direct and observational conditioning for placebo and nocebo responses

&NA; Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on expectation and conditioned experience. Whereas the neural mechanism of how expectation modulates placebo and nocebo effects during pain anticipation have been extensively studied, little is known about how experience may change brain networks to produce placebo and nocebo responses. We investigated the neural pathways of direct and observational conditioning for conscious and nonconscious conditioned placebo/nocebo effects using magnetoencephalography and a face visual cue conditioning model. We found that both direct and observational conditioning produced conscious conditioned placebo and nocebo effects and a nonconscious conditioned nocebo effect. Alpha band brain connectivity changes before and after conditioning could predict the magnitude of conditioned placebo and nocebo effects. Particularly, the connectivity between the rostral anterior cingulate cortex and middle temporal gyrus was an important indicator for the manipulation of placebo and nocebo effects. Our study suggests that conditioning can mediate our pain experience by encoding experience and modulating brain networks. HighlightsDirect and observational conditioning could produce placebo/nocebo effectsDirect and observational conditioning could modulate alpha band brain connectivityAlpha band brain connectivity was predictive for placebo/nocebo responsesrACC‐MTG connectivity was an indicator of placebo/nocebo response magnitude