Zhiqi Mao

Convergent and divergent functional connectivity patterns in patients with long-term left-sided and right-sided deafness

Cortical reorganization may be induced in long-term single-sided deafness (SD); however, the influence of the deafness side on the functional changes remains poorly understood. Here, we investigated whole-brain functional connectivity patterns in long-term SD patients. The normalized voxel-based functional connectivity strength (FCS) was determined using resting-state fMRI (rs-fMRI) in 17 left-sided deafness (LD) patients, 21 right-sided deafness (RD) patients and 21 healthy controls (HCs). Relative to the HCs, both the LD and RD patients exhibited a reduction in the FCS in the ipsilateral visual cortex. However, compared to that in the HCs, a significantly higher FCS was observed in some regions in the salience and default-mode networks in the RD patients, but this FCS alternation pattern was not observed in the LD patients. A direct comparison of the two patient groups revealed a significantly increased FCS in the supplemental motor area in the LD group. Altogether, the long-term SD groups with LD and RD exhibited convergent and divergent functional connectivity patterns in whole-brain networks, providing promising evidence that the functional changes in long-term SD are highly deafness-side-dependent.

In vivo visualization of connections among revised Papez circuit hubs using full q-space diffusion spectrum imaging tractography

Structural connections among the hubs of the revised Papez circuit remain to be elucidated in the human brain. As the original Papez circuit failed to explain functional imaging findings, a more detailed investigation is needed to delineate connections among the circuits key hubs. Here we acquired diffusion spectrum imaging (DSI) from eight normal subjects and used data from the Human Connectome Project (HCP) to elucidate connections among hubs in the retrosplenial gyrus, hippocampus, mammillary bodies, and anterior thalamic nuclei. Our results show that the ventral hippocampal commissure (VHC) was visualized in all eight individual DSI datasets, as well as in the DSI and HCP group datasets, but a strictly defined VHC was only visualized in one individual dataset. Thalamic fibers were observed to connect with both the posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). The RSC was mainly responsible for direct hippocampal connections, while the PCC was not. This indicates that the RSC and PCC represent separate functional hubs in humans, as also shown by previous primate axonal tracing studies and functional magnetic resonance imaging observations.

Connection between bilateral temporal regions: Tractography using human connectome data and diffusion spectrum imaging

Temporal lobe epilepsy often propagates inter-hemispherically. Although the pathway of the propagation was verified by electrophysiology, the trajectory remains poorly defined. DTI can depict fiber trajectory but it has limited angular resolution and cannot adequately assess cortical regions. We visualized potential pathways of bitemporal epilepsy propagation using diffusion spectrum imaging (DSI) with data consisting of 8 groups of 514 directions and diffusion templates of 842 subjects from the human connectome project (HCP). We verified the results with reference to the axonal-tracing literature. Both the large population overall and individual connection properties were investigated. In both the HCP 842 atlas and DSI individual data, the bilateral temporal pole was found to connect via the anterior commissure. The splenium of the corpus callosum was divided into 3 subregions (CS1, CS2, CS3) according to the form of connections. CS1 was predominately located at the rostral third and the dorsal part of middle third of the splenium; it communicated with the bilateral parietal lobe. SC2 was predominately located at the ventral middle third of the splenium. Fibers passed through the lateral wall of the lateral ventricle and connected to regions lateral of the occipitotemporal sulci. CS3 was located at the caudal third of the splenium. Together with the hippocampal commissure, its fibers constituted the medial wall of the lateral ventricle and distributed medially to the occipitotemporal sulci. The trajectory of bilateral temporal connections was visualized in this study; the results might help in the understanding and treatment of inter-hemispherical propagation of temporal-lobe epilepsy.

Dysregulation of Pain- and Emotion-Related Networks in Trigeminal Neuralgia

Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder associated with increased risks of anxiety and depression. Converging evidence suggests that chronic pain pathophysiology involves dysfunctional pain-related and emotion-related networks. However, whether these systems are also among the culprit networks for TN remains unclear. Here, we aimed to assess TN-related anatomical and functional brain anomalies in pain-related and emotion-related networks. We investigated differences in gray matter (GM) volume and the related resting-state functional connectivity (rsFC) between 29 classical TN patients and 34 matched healthy controls. Relationships between brain measurement alterations, clinical pain and emotional states were identified. A longitudinal observation was further conducted to determine whether alterations in the brain could renormalize following pain relief. Reduced GM volumes in the bilateral amygdala, periaqueductal gray (PAG) and right insula were found in TN patients compared with healthy control subjects. Whole-brain rsFC analyses with the four above-mentioned anatomical regions as seeds identified three significantly altered functional circuits, including amygdala-DLPFC, amygdala-mPFC and amygdala-thalamus/putamen circuitry. The amygdala-DLPFC and amygdala-mPFC circuits were associated with clinical pain duration and emotional state ratings, respectively. Further longitudinal analysis found that rsFC strength abnormalities in two fronto-limbic circuits (left amygdala/left DLPFC and right amygdala/right PFC) were resolved after pain relief. Together, structural and functional deficits in pain-related and emotion-related networks were associated with TN patients, as demonstrated by our multimodal results. Pain relief had protective effects on brain functional connectivity within fronto-limbic circuits. Our study provides novel insights into the pathophysiology of TN, which may ultimately facilitate advances in TN intervention.

Deep brain stimulation for treatment of severe Alzheimer's disease: Study protocol for a prospective, self-controlled, phase I trial (case observation)

Background: With the aging of the global population, an increasing number of people are at risk of developing Alzheimers disease. There is currently no effective treatment to hinder or postpone the progression of Alzheimers disease. Cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist Memantine are the commonly prescribed drugs for this disease, but their therapeutic effects are still unsatisfactory. Therefore, there is an urgent need to investigate novel treatment methods. Many animal experiments have suggested that deep brain stimulation benefits Alzheimers disease, but clinical trials investigating this are still in their infancy. This study aims to investigate the safety and effectiveness of deep brain stimulation in the treatment of severe Alzheimers disease. Methods/Design: This study is a prospective, self-controlled, phase I trial (case observation), which will be performed in the Department of Neurosurgery, Chinese PLA General Hospital (Beijing, China). Six patients with severe Alzheimers disease will be enrolled to receive continuous bilateral deep brain stimulation of the fornix. Evaluations will be performed at baseline (prior to surgery) and at 1, 6, and 12 months after surgery. The primary outcome measures are disability and mortality rates during the 12-month deep brain stimulation trial period. Secondary outcome measures include the incidence of complications and Clinical Dementia Rating scale, Zarit Caregiver Burden Interview, Mini-Mental State Examination, and Barthel Index of Activities of Daily Living Scale scores. Patient recruitment will begin in August 2017, the analysis of primary outcome measures will be completed in October 2018, and the study will finish in June 2019. Discussion: The results of this study will help to determine the safety of deep brain stimulation for the treatment of severe Alzheimers disease. We will also assess whether deep brain stimulation can improve the cognition, symptoms, and activities of daily living of patients with Alzheimers disease. If the study succeeds, a novel option for patients with Alzheimers disease who respond poorly to current treatments may be provided. Trial registration: The study protocol is registered with ClinicalTrials.gov (identifier: NCT03115814). Ethics: The study protocol was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2015-013-02) and will be performed in accordance with the Declaration of Helsinki formulated by the World Medical Association in 2013. Informed consent: Written informed consent will be obtained from each patients legal representative.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation

Deep brain stimulation is a therapy for Alzheimers disease (AD) that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov (NCT03115814) on April 14, 2017.

Intracerebral Hemorrhage and Venous Infarction after Deep Brain Stimulation Lead Placement

To the Editor: Cerebral vascular events (intracerebral hemorrhage [ICH] or venous infarction) are the most feared complications of deep brain stimulation (DBS) surgery. The estimated risk of ICH in DBS surgery reportedly varies from 0.2% to 5.6%.[1‐3] ICH may develop at one of two sites depending on the puncture tract: (1) in the basal ganglia or target area or (2) in the puncture channel or cortex area. However, venous infarction in association with DBS surgery has rarely been described.[4‐6]

Altered functional networks in long-term unilateral hearing loss: A connectome analysis

In neuroimaging studies, long‐term unilateral hearing loss (UHL) is associated with functional changes in specific brain regions and connections; however, little is known regarding alterations in the topological organization of whole‐brain functional networks and whether these alterations are related to hearing behavior in UHL patients.

Altered emotional prosody processing in patients with Parkinson’s disease after subthalamic nucleus stimulation

Background Patients with Parkinson’s disease (PD) exhibit deficits in recognizing and expressing vocal emotional prosody. The aim of this study was to explore emotional prosody processing in patients with PD shortly after subthalamic nucleus (STN) deep brain stimulation (DBS). Methods Two groups of patients with PD (pre-DBS and post-DBS) and one healthy control (HC) group were recruited as participants. All participants (PD and HC) were assessed using the Montreal Affective Voices database 50 Voices Recognition test. All participants were asked to nonverbally express five basic emotions (happiness, anger, fear, sadness, and neutral) to test emotional prosody expression. Fifteen native Chinese speakers were recruited as raters. We recorded the accuracy rate, reaction time, confidence level, and two acoustic parameters (mean pitch and mean intensity). Results The PD groups scored lower than the HC group in recognizing and expressing emotional prosody. STN DBS had no significant effect on the recognition of emotional prosody but had a significant effect on fear prosody expression. Pearson’s correlation analysis revealed significant correlations between performance on emotional prosody recognition tests and performance on emotional prosody expression tests in both the pre-DBS PD and post-DBS PD groups. Conclusion Shortly after STN DBS, the ability to recognize emotional prosody was not altered, but fear expression was impaired. We identified associations between abnormalities in emotional prosody recognition and expression deficits both before and after STN DBS, indicating that the processes involved in recognizing and expressing emotional prosody may share a common system.

Altered emotional recognition and expression in patients with Parkinson’s disease

Background Parkinson’s disease (PD) patients exhibit deficits in emotional recognition and expression abilities, including emotional faces and voices. The aim of this study was to explore emotional processing in pre-deep brain stimulation (pre-DBS) PD patients using two sensory modalities (visual and auditory). Methods Fifteen PD patients who needed DBS surgery and 15 healthy, age- and gender-matched controls were recruited as participants. All participants were assessed by the Karolinska Directed Emotional Faces database 50 Faces Recognition test. Vocal recognition was evaluated by the Montreal Affective Voices database 50 Voices Recognition test. For emotional facial expression, the participants were asked to imitate five basic emotions (neutral, happiness, anger, fear, and sadness). The subjects were required to express nonverbal vocalizations of the five basic emotions. Fifteen Chinese native speakers were recruited as decoders. We recorded the accuracy of the responses, reaction time, and confidence level. Results For emotional recognition and expression, the PD group scored lower on both facial and vocal emotional processing than did the healthy control group. There were significant differences between the two groups in both reaction time and confidence level. A significant relationship was also found between emotional recognition and emotional expression when considering all participants between the two groups together. Conclusion The PD group exhibited poorer performance on both the recognition and expression tasks. Facial emotion deficits and vocal emotion abnormalities were associated with each other. In addition, our data allow us to speculate that emotional recognition and expression may share a common system.