Abnormal interhemispheric functional cooperation in schizophrenia follows the neurotransmitter profiles.

BACKGROUND: Interhemispheric cooperation is one of the most prominent functional architectures of the human brain. In patients with schizophrenia, interhemispheric cooperation deficits have been reported using increasingly powerful neurobehavioural and neuroimaging measures. However, these methods rely in part on the assumption of anatomic symmetry between hemispheres. In the present study, we explored interhemispheric cooperation deficits in schizophrenia using a newly developed index, connectivity between functionally homotopic voxels (CFH), which is unbiased by hemispheric asymmetry. METHODS: Patients with schizophrenia and age- and sexmatched healthy controls underwent multimodal MRI, and whole-brain CFH maps were constructed for comparison between groups. We examined the correlations of differing CFH values between the schizophrenia and control groups using various neurotransmitter receptor and transporter densities. RESULTS: We included 86 patients with schizophrenia and 86 matched controls in our analysis. Patients with schizophrenia showed significantly lower CFH values in the frontal lobes, left postcentral gyrus and right inferior temporal gyrus, and significantly greater CFH values in the right caudate nucleus than healthy controls. Moreover, the differing CFH values in patients with schizophrenia were significantly correlated with positive symptom score and illness duration. Functional connectivity within frontal lobes was significantly reduced at the voxel cluster level compared with healthy controls. Finally, the abnormal CFH map of patients with schizophrenia was spatially associated with the densities of the dopamine D1 and D2 receptors, fluorodopa, dopamine transporter, serotonin transporter and acetylcholine transporter. CONCLUSION: Regional abnormalities in interhemispheric cooperation may contribute to the clinical symptoms of schizophrenia. These CFH abnormalities may be associated with dysfunction in neurotransmitter systems strongly implicated in schizophrenia.

Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson's disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double-blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta-burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long-lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA-GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA-GP pathway.

Dynamic brain connectome and high risk of mental problem in clinical nurses.

With the growing population and rapid change in the social environment, nurses in China are suffering from high rates of stress; however, the neural mechanism underlying this occupation related stress is largely unknown. In this study, mental status was determined for 81 nurses and 61 controls using the Symptom Checklist 90 (SCL-90) scale. A subgroup (n = 57) was further scanned by resting-state functional MRI with two sessions. Based on the SCL-90 scale, "somatic complaints" and "diet/sleeping" exhibited the most prominent difference between nurses and controls. This mental health change in nurses was further supported by the spatial independent component analysis on functional MRI data. First, dynamic functional connectome analysis identified two discrete connectivity configurations (States I and II). Controls had more time in the State I than II, while the nurses had more time in the State II than I. Second, nurses showed a similar static network topology as controls, but altered dynamic properties. Third, the symptom-imaging correlation analysis suggested the functional alterations in nurses as potential imaging biomarkers indicating a high risk for "diet/sleeping" problems. In summary, this study emphasized the high risk of mental deficits in nurses and explored the underlying neural mechanism using dynamic brain connectome, which provided valuable information for future psychological intervention.

Regional and network properties of white matter function in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract-based spatial statistical analyses of regional activity, patients showed decreased structural-functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post-central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small-worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un-evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.

Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke.

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

Decreased inter-hemispheric cooperation in major depressive disorder and its association with neurotransmitter profiles.

BACKGROUND: Inter-hemispheric cooperation is a prominent feature of the human brain, and previous neuroimaging studies have revealed aberrant inter-hemispheric cooperation patterns in patients with major depressive disorder (MDD). Typically, inter-hemispheric cooperation is examined by calculating the functional connectivity (FC) between each voxel in one hemisphere and its anatomical (structurally homotopic) counterpart in the opposite hemisphere. However, bilateral hemispheres are actually asymmetric in anatomy. METHODS: In the present study, we utilized connectivity between functionally homotopic voxels (CFH) to investigate abnormal inter-hemispheric cooperation in 96 MDD patients compared to 173 age- and sex-matched healthy controls (HCs). In addition, we analyzed the spatial correlations between abnormal CFH and the density maps of 13 neurotransmitter receptors and transporters. RESULTS: The CFH values in bilateral orbital frontal gyri and bilateral postcentral gyri were abnormally decreased in patients with MDD. Furthermore, these CFH abnormalities were correlated with clinical symptoms. In addition, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR. LIMITATIONS: drug effect; the cross-sectional research design precludes causal inferences; the neurotransmitter atlases selected were constructed from healthy individuals rather than MDD patients. CONCLUSION: These findings characterized the abnormal inter-hemispheric cooperation in MDD using a novel method and the underlying neurotransmitter mechanism, which promotes our understanding of the pathophysiology of depression.

Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

BACKGROUND AND HYPOTHESIS: There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. STUDY DESIGN: We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. STUDY RESULTS: We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. CONCLUSIONS: Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

SARS-CoV-2 prevalence in wildlife 2020-2022: a worldwide systematic review and meta-analysis.

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.

A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice.

Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5-2.5 mg/kg, i.p.) reduces body and brain temperature by 2-5°C in 15-30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ∼30-40% when PIH therapy is initiated either immediately after stroke induction or after 30-60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries.

Eagle Syndrome with Internal Carotid Artery Compression Causing Recurred Syncope.

We herein report a 54-year-old man with eagle syndrome who presented with repeated episodes of syncope, especially after moving his head to a downward position. Computed tomography with contrast revealed a bilateral elongated styloid process. The left internal carotid artery was obviously compressed by the left elongated styloid processes. A transcranial Doppler examination detected a significantly decreased blood flow velocity in the left middle cerebral artery when the patient slightly lowered his head position. After surgery, the positional cerebral blood flow alteration disappeared. No further similar syncope episodes have been reported to date.

Brain functional specialization in obsessive-compulsive disorder associated with neurotransmitter profiles.

BACKGROUND: Cerebral specialization is an important functional architecture of the human brain. Abnormal cerebral specialization may be the underlying pathogenesis of obsessive-compulsive disorder (OCD). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to show that the specialization pattern of OCD was of great significance for early warning and precise intervention of the disease. METHOD: The autonomy index (AI) based on the rs-fMRI was calculated to compare brain specializations between 80 OCD patients and 81 matched healthy controls (HCs). In addition, we also correlated the AI alteration patterns with neurotransmitter receptor/transporter densities. RESULTS: OCD patients showed increased AI in the right insula and right superior temporal gyrus when compared with HCs. In addition, AI differences were associated with serotonin receptors (5-HT1AR and 5HT4R), dopamine D2 receptors, norepinephrine transporters, and metabotropic glutamate receptor densities. LIMITATIONS: Drug effect; cross-sectional study design; the selection of positron emission tomography template. CONCLUSIONS: This study showed abnormal specialization patterns in OCD patients, which may lead to the elucidation of the underlying pathological mechanism of the disease.

Mesenchymal stromal cell biotherapy for Parkinson's disease premotor symptoms.

Parkinson's disease (PD) is a neurodegenerative disorder with motor deficits due to nigrostriatal dopamine depletion and with the non-motor/premotor symptoms (NMS) such as anxiety, cognitive dysfunction, depression, hyposmia, and sleep disorders. NMS is presented in at least one-fifth of the patients with PD. With the histological information being investigated, stem cells are shown to provide neurotrophic supports and cellular replacement in the damaging brain areas under PD conditions. Pathological change of progressive PD includes degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain. The current stem cell beneficial effect addresses dopamine boost for the striatal neurons and gliovascular mechanisms as competing for validated PD drug targets. In addition, there are clinical interventions for improving the patient's NMS and targeting their autonomic dysfunction, dementia, mood disorders, or sleep problems. In our and many others' research using brain injury models, multipotent mesenchymal stromal cells demonstrate an additional and unique ability to alleviate depressive-like behaviors, independent of an accelerated motor recovery. Intranasal delivery of the stem cells is discussed for it is extensively tested in rodent animal models of neurological and psychiatric disorders. In this review, we attempt to discuss the repairing potentials of transplanted cells into parkinsonism pathological regions of motor deficits and focus on preventive and treatment effects. From new approaches in the PD biological therapy, it is believed that it can as well benefit patients against PD-NMS.

Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response.

BACKGROUND AND HYPOTHESIS: Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS). STUDY DESIGN: The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient's personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient's atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map. RESULTS: The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients. CONCLUSIONS: Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.

Brain functional specialization and cooperation in Parkinson's disease.

Cerebral specialization and inter-hemispheric cooperation are two of the most prominent functional architectures of the human brain. Their dysfunctions may be related to pathophysiological changes in patients with Parkinson's disease (PD), who are characterized by unbalanced onset and progression of motor symptoms. This study aimed to characterize the two intrinsic architectures of hemispheric functions in PD using resting-state functional magnetic resonance imaging. Seventy idiopathic PD patients and 70 age-, sex-, and education-matched healthy subjects were recruited. All participants underwent magnetic resonance image scanning and clinical evaluations. The cerebral specialization (Autonomy index, AI) and inter-hemispheric cooperation (Connectivity between Functionally Homotopic voxels, CFH) were calculated and compared between groups. Compared with healthy controls, PD patients showed stronger AI in the left angular gyrus. Specifically, this difference in specialization resulted from increased functional connectivity (FC) of the ipsilateral areas (e.g., the left prefrontal area), and decreased FC in the contralateral area (e.g., the right supramarginal gyrus). Imaging-cognitive correlation analysis indicated that these connectivity were positively related to the score of Montreal Cognitive Assessment in PD patients. CFH between the bilateral sensorimotor regions was significantly decreased in PD patients compared with controls. No significant correlation between CFH and cognitive scores was found in PD patients. This study illustrated a strong leftward specialization but weak inter-hemispheric coordination in PD patients. It provided new insights to further clarify the pathological mechanism of PD.

Minimal scanning duration for producing individualized repetitive transcranial magnetic stimulation targets.

This study aimed to determine the minimal scanning duration of functional magnetic resonance imaging (fMRI) for producing individualized repetitive transcranial magnetic stimulation (rTMS) targets that are superior to the group-level targets. This study included 30 healthy subjects and 20 depressive patients with high-sampled fMRI data (> 69 min). We computed suboptimal targets by gradually increasing the scanning duration beginning at 6 min. The suboptimal target connectivity and spatial distance to the optimal target (based on the full-duration scanning data) were compared to an anatomically fixed target from a group analysis (termed as the group target). These analyses were repeated for healthy subjects and depressive patients, as well as for target masks in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). As the scanning duration increased, the suboptimal targets gradually approached the optimal targets in the healthy subjects. Compared with the group targets, the suboptimal targets in the DLPFC showed higher connectivity strength after 10 min of data collection and shorter spatial distance after 40 min. Similar results were found in major depressive patients. In the IPL, the minimal scanning duration decreased to 6 and 8 min for connectivity strength and distance, respectively. These findings provide an important reference for individualized target definition in terms of scanning duration, which may standardize connectivity-based personalized studies. Future research is needed to further validate the therapeutic effects of the approach.

A landmark-based approach to locate symptom-specific transcranial magnetic stimulation targets of depression.

Objective: Two subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation (rTMS) targets for the "anxiosomatic" and "dysphoric" symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp. Materials and methods: In a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This "landmark-based approach" was replicated and validated in an independent cohort (N = 25). Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution (i.e., 5 mm). We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation. Results: The parameters of the "landmark-based approach" in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm. Conclusion: The "landmark-based approach" can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed.

Efficacy of twice-daily high-frequency repetitive transcranial magnetic stimulation on associative memory.

Objectives: Several studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM. Methods: In this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS). Results: There was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction. Conclusion: Our prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.

Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice.

OBJECTIVE: To investigate the effects of DL-3-N-butylphthalide (NBP) via intranasal delivery after ischaemic stroke in mice. METHODS: C57BL/6 mice were divided into three groups: sham, stroke with vehicle and stroke with NBP treatment. Ischaemic stroke was induced by permanent ligation of right middle cerebral artery with 7 min common carotid artery occlusion. NBP (100 mg/kg) or vehicle was intranasally administered at 1 hour after stroke and repeated once a day until sacrifice. Bromodeoxyuridine (BrdU) (50 mg/kg/day) was given from the third day until sacrifice. Sensorimotor function was tested during 1-21 days after stroke. Local cerebral blood flow in the ischaemic and peri-infarct regions was measured using laser Doppler flowmetry before, during and 3 days after ischaemia. Expressions of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase as well as regenerative marker BrdU in the peri-infarct region were analysed by western blotting and immunohistochemical methods. RESULTS: Compared with the vehicle group, NBP treatment significantly increased the VEGF expression in the poststroke brain. Stroke mice that received NBP showed significantly less vascular damage after stroke and more new neurons and blood vessels in the peri-infarct region at 21 days after stroke. In the adhesive removal test, the sensorimotor function of stroke mice treated with NBP performed significantly better at 1, 3 and 7 days after stroke compared with vehicle controls. CONCLUSION: Daily intranasal NBP treatment provides protective and neurogenic/angiogenic effects in the poststroke brain, accompanied with functional improvements after a focal ischaemic stroke in mice.

Associative memory improvement after 5 days of magnetic stimulation: A replication experiment with active controls.

Associative memory (AM) is an essential function of everyday life, but is often disrupted in many neurological diseases. Recent studies have found that repetitive transcranial magnetic stimulation (rTMS) can effectively enhance AM and have shown its potential in clinical applications. In this study, we aimed to reproduce the 5-day rTMS effect on AM in a Chinese version of a face-cued word recall task. In an open-label experiment, AM scores were significantly improved after active 20-Hz rTMS on individualized inferior parietal lobule (IPL) targets. To exclude the placebo effect, we performed a second experiment and added rTMS of the pre-supplementary motor area (preSMA) as an active control. In this within-subject crossover experiment, participants received active rTMS on IPL and preSMA targets, separated by at least 2 weeks. A Stroop task was included as a control test, which was more likely to be modulated by preSMA stimulations. We found that stimulations on IPL targets significantly improved AM, but this change did not significantly higher than that induced by preSMA stimulations. No significant change in Stroop measures were found in either IPL or preSMA condition. In summary, this study did not support that the 5 days of rTMS on individualized IPL targets could improve AM more than placebo rTMS. Further work is required to improve the rTMS paradigms to enhance the aftereffects in memory.

Pharmacological hypothermia induced neurovascular protection after severe stroke of transient middle cerebral artery occlusion in mice.

Therapeutic hypothermia is a potential protective strategy after stroke. The present study evaluated the neurovascular protective potential of pharmacological hypothermia induced by the neurotensin receptor 1 agonist HPI-201 after severe ischemic stroke. Adult C57BL/6 mice were subjected to filament insertion-induced occlusion of the middle cerebral artery (60 min MCAO). HPI-201 was i.p. injected 120 min after the onset of MCAO to initiate and maintain the body temperature at 32-33°C for 6 hrs. The infarct volume, cell death, integrity of the blood brain barrier (BBB) and neurovascular unit (NVU), inflammation, and functional outcomes were evaluated. The hypothermic treatment significantly suppressed the infarct volume and neuronal cell death, accompanied with reduced caspase-3 activation and BAX expression while Bcl-2 increased in the peri-infarct region. The cellular integrity of the BBB and NVU was significantly improved and brain edema was attenuated in HPI-201-treated mice compared to stroke controls. The hypothermic treatment decreased the expression of inflammatory factors including tumor necrosis factor-α (TNF-α), MMP-9, interleukin-1ß (IL-1ß), the M1 microglia markers IL-12 and inducible nitric oxide synthase (iNOS), while increased the M2 marker arginase-1 (Arg-1). Stroke mice received the hypothermic treatment showed lower neurological severity score (NSS), performed significantly better in functional tests, the mortality rate in the hypothermic group was noticeably lower compared with stroke controls. Taken together, HPI-201 induced pharmacological hypothermia is protective for different neurovascular cells after a severely injured brain, mediated by multiple mechanisms.