Parietal connectivity mediates multisensory facilitation.

Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.

Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases.

The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood-brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases.

Stereotactic Radiosurgery Treatment of Trigeminal Neuralgia: Clinical Outcomes and Prognostic Factors.

BACKGROUND: Stereotactic radiosurgery (SRS) is a minimally invasive surgical option for the treatment of trigeminal neuralgia (TN). Here we review our institutional experience to identify prognostic factors associated with pain relief after SRS. METHODS: 263 patients with TN treated at the University of California, San Diego/San Diego Gamma Knife (2001-2013) were followed for more than 6 months. Univariate and multivariate Cox proportional hazard models analysis of factors associated with outcome was performed. RESULTS: Of the 263 patients, 229 (87%) presented with classical idiopathic TN, 31 (12%) presented with atypical TN, and 4 (1%) presented with secondary TN. 143 (54%) had undergone prior treatment. Most patients were treated with 85 (52%) or 90 Gy (42%). 79% of the SRS treated patients experienced a favorable response (defined as Barrow Neurological Institute Pain Scale <3 pain relief), with a median time to relief of 2.5 months. In a multivariate analysis, diagnosis of classical TN, previous percutaneous procedures, and age older than 70 years were associated with favorable responses; classical TN was associated with sustained pain relief. Dose prescription >85 Gy and prior SRS were associated with bothersome facial numbness posttreatment. For patients presenting with classical TN, diagnosis of multiple sclerosis (MS) did not decrease the likelihood of pain relief after SRS. CONCLUSIONS: Excellent TN pain relief was achieved with the delivery of 85 Gy in a single-shot, 4-mm isocenter SRS targeting the dorsal root entry zone. Patients with classical TN, with age older than 70 years, or who underwent previous percutaneous procedures were more likely to benefit from SRS. SRS is efficacious in patients with classical TN despite concurrent diagnosis of MS.

Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas.

The intrinsic signaling cascades and cell states associated with the Glioma CpG Island Methylator Phenotype (G-CIMP) remain poorly understood. Using published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling using three independent datasets, including the Chinese Glioma Genome Atlas(CGGA; n=155), the REMBRANDT dataset (n=288), and The Cancer Genome Atlas (TCGA; n=406). Additionally, an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (p<0.001), indicating suppressed EGFR signaling. Analysis of TCGA glioblastomas revealed that G-CIMP+ glioblastomas harbored lowered mRNA levels for EGFR and H-Ras. Induction of G-CIMP+ state by exogenous expression of a mutated isocitrate dehydrogenase 1, IDH1-R132H, suppressed EGFR and H-Ras protein expression as well as pERK accumulation in independent glioblastoma models. These suppressions were associated with increased deposition of the repressive histone markers, H3K9me3 and H3K27me3, in the EGFR and H-Ras promoter regions. The IDH1-R132H expression-induced pERK suppression can be reversed by exogenous expression of H-RasG12V. Finally, the G-CIMP+ Ink4a-Arf-/- EGFRvIII glioblastoma line was more resistant to the EGFR inhibitor, Gefitinib, relative to its isogenic G-CIMP- counterpart. These results suggest that G-CIMP epigenetically regulates EGFR signaling and serves as a predictive biomarker for EGFR inhibitors in glioblastoma patients.