Resting state alpha-band functional connectivity and recovery after stroke

After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify the plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential.     

Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

GABAA and GABAB receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus

The subthalamic nucleus (STN) is a critical excitatory signaling center within the basal ganglia circuitry. The activity of subthalamic neurons is tightly controlled by upstream inhibitory signaling centers in the basal ganglia. In this study, we used immunohistochemical techniques to firstly, visualize and quantify the STN neurochemical organization based on neuronal markers including parvalbumin (PV), calretinin (CR), SMI‐32, and GAD_65/67. Secondly, we characterized the detailed regional, cellular and subcellular expression of GABA_A (α₁, α₂, α₃, β_2/3, and γ₂) and GABA_B (R1 and R2) receptor subunits within the normal human STN. Overall, we found seven neurochemically distinct populations of principal neurons in the human STN. The three main populations detected were: (a) triple‐labeled PV⁺/CR⁺/SMI32⁺; (b) double‐labeled PV⁺/CR⁺; and (c) single‐labeled CR⁺ neurons. Subthalamic principal neurons were found to express GABA_A receptor subunits α₁, α₃, β_2/3, γ₂, and GABA_B receptor subunits R1 and R2. However, no expression of GABA_A receptor α₂ subunit was detected. We also found a trend of increasing regional staining intensity for all positive GABA_A receptor subunits from the dorsolateral pole to ventromedial extremities. The GAD⁺ interneurons showed relatively low expression of GABA_A receptor subunits. These results provide the morphological basis of GABAergic transmission within the normal human subthalamic nucleus and evidence of GABA innervation through both GABA_A and GABA_B receptors on subthalamic principal neurons.     

Creating a neurogenic environment: the role of BDNF and FGF2

Regional environmental cues present in the adult brain determine the fate of adult neural progenitor cells. To determine whether the growth factors BDNF or FGF2 can create a neurogenic environment outside the SVZ, we used AAV(1/2)-mediated gene transfer to produce ectopic BDNF or FGF2 expression in the normal adult rat striatum and transplanted SVZ-derived progenitor cells into this region. We observed that ectopic expression of BDNF in the striatum promoted neuronal differentiation of transplanted adult neural progenitor cells, while FGF2 expression supported the survival and proliferation of transplanted progenitor cells in the adult striatum. However, region-specific neuronal differentiation of transplanted progenitor cells was not observed in the adult striatum, suggesting ectopic BDNF or FGF2 expression was insufficient for the generation of mature neuronal phenotypes. This study provides direct in vivo evidence that ectopic striatal expression of either BDNF or FGF2 can induce neurogenesis in non-neurogenic regions of the adult brain.     

Traumatic brain injury and prospective memory: influence of task complexity

A quantitative review indicated that prospective memory impairment is a consistent feature of traumatic brain injury (TBI). However, evidence also suggests that manipulations that increase demands on controlled attentional processes moderate the magnitude of observed deficits. A total of 16 TBI participants were compared with 15 matched controls on a task in which the number of prospective target events was manipulated. This manipulation was of interest because two competing models make different predictions as to its effect on controlled attentional processes. In the context of Smith and Bayen's (2004) preparatory attentional processes and memory processes (PAM) model increasing the number of target events should increase requirements for controlled attentional processing. In contrast, McDaniel and Einstein's (2000) multiprocess framework assumes that distinct target events presented in focal awareness of the processing activities required for the ongoing task are likely to depend on automatic processes. This latter model therefore leads to the prediction that increasing the number of target events should not increase demands upon controlled attentional processes. Consistent with McDaniel and Einstein's (2000) multiprocess framework, TBI patients were significantly and comparably impaired on the one- and the four-target-event conditions relative to controls. Further, TBI deficits could not be attributed to increased difficulty with the retrospective component of the prospective memory task. The practical and theoretical implications of these results are discussed.     

Prevalence and correlates of comorbidity 8 years after a first psychotic episode

OBJECTIVE: While rates and correlates of comorbidity have been investigated in the early course of psychosis, little is known about comorbidity in the medium-to-longer term or its relationship with outcome. METHOD: A total of 182 first-episode psychosis (FEP) patients who met DSM-IV criteria for a current psychotic disorder 8 years after index presentation were grouped according to concurrent comorbidity [no concurrent axis I disorder; concurrent substance use disorder (SUD); other concurrent axis I disorder; concurrent SUD and other axis I disorder]. Outcomes were compared between groups controlling for relevant covariates. RESULTS: As much as 39% met criteria for one or more concurrent axis 1 diagnoses. Comorbidity was associated with greater severity of general psychopathology, but not with measures of functioning, treatment or negative symptoms. CONCLUSION: Specific combinations of comorbid disorders may influence patterns of psychotic symptomatology. Routine examination of axis I disorders is warranted in the ongoing management of psychosis.     

Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3

To date, nearly 30 distinct genetic forms of dominantly inherited ataxia are known to exist. Of these, Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is perhaps the most common in many regions of the world including the United States. This article discusses MJD/SCA3 as a paradigm example of the dominant ataxias, which are collectively known as the spinocerebellar ataxias. Using MJD/SCA3 as a starting point, the article reviews common clinical and genetic features of the SCAs and highlights new insights into molecular mechanisms, especially of the SCAs caused by polyglutamine expansion. Also discussed are current and future therapeutic opportunities for MJD/SCA3 in particular, many of which have relevance to other SCAs.     

Effect of varied gestational stress on acquisition of spatial memory, hippocampal LTP and synaptic proteins in juvenile male rats

Some but not other forms of prenatal stress have been shown to impair spatial memory in adult male offspring. It is not clear if this is because of the intensity of the stress, age of rats, or the way in which learning is assessed. We examined the effect of daily varied prenatal stress consisting of 30 min restraint, saline injections and 15 min forced swim on day 17-21 of gestation on spatial learning, synaptic plasticity and the expression of key proteins of the post synaptic density (PSD) in the hippocampus of males aged 4-5 weeks. Prenatal stress impaired spatial learning in the Morris water maze and induced a significant decrease in long-term potentiation (LTP) in hippocampal slices. There was no change in the paired pulse facilitation ratio but there was a significant reduction in the expression of the NR2B subunit of the glutamate type NMDA receptor and the GluR1 subunit of the AMPA receptor, both of which are important modulators of LTP. These changes were accompanied by a remarkable increase in the scaffolding protein PSD95, which interacts with the intracellular carboxy terminal domains of the NR2 subunits. The high levels of PSD95 may have contributed to the impairment of LTP by disrupting the clustering of NMDA receptors in CA1 synapses. The alteration by prenatal stress in the relative amounts of scaffolding proteins and those which compose glutamate receptors could explain the depression of LTP and impairment in the acquisition of spatial learning.     

Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n = 20) and the total BPD cohort (n = 20). However, within the BPD cohort, those exposed to childhood trauma (n = 9) tended to have smaller pituitaries (− 18%) than those with no history of childhood trauma (n = 10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic–pituitary–adrenal axis dysfunction.