Metastatic prostate adenocarcinoma to the brain - a clinicopathologic analysis of 21 cases.

BACKGROUND: Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy. DESIGN: A retrospective search spanning 20 years (2003-2022) was conducted on our archives and identified 21 cases diagnosed as "metastatic prostate adenocarcinoma (mPCa)" in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa. RESULT: The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis. CONCLUSION: mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.

Long-latency auditory evoked response amplitudes at first episode of psychosis predict six-month recovery in positive symptom severity.

Predicting treatment response would facilitate individualized medical treatment in first-episode psychosis (FEP). We examined relationships between auditory-evoked M100 and longitudinal change in positive symptoms in FEP. M100 was measured from source-resolved magnetoencephalography and symptoms were assessed at initial contact and six months later. M100 at baseline significantly predicted symptom change. Larger M100 at baseline predicted symptom improvement, as did shorter untreated psychosis. Shorter untreated psychosis also correlated with larger M100, and M100 mediated the effect of untreated psychosis on treatment response. Thus, M100 may provide a proximal and objective index of untreated psychosis and a viable route to individualized medicine.

Predicted Brain Age in First-Episode Psychosis: Association with Inexpressivity.

Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a "younger" PBA was associated with higher vocabulary scores among all individuals, while an "older" PBA was associated with more severe negative symptom "Inexpressivity" component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode.

Intensity-dependent modulation of the early auditory gamma-band response in first-episode schizophrenia and its association with disease symptoms.

BACKGROUND: Gamma-band activity has been the focus of considerable research in schizophrenia. Discrepancies exist regarding the integrity of the early auditory gamma-band response (EAGBR), a stimulus-evoked oscillation, and its relationship to symptoms in early disease. Variability in task design may play a role. This study examined sensitivity of the EAGBR to stimulus intensity and its relation to symptoms and functional impairments in the first-episode schizophrenia spectrum (FESz). METHOD: Magnetoencephalography was recorded from 35 FESz and 40 matched healthy controls (HC) during presentation of 3 tone intensities (75 dB, 80 dB, 85 dB). MRIs were collected to localize auditory cortex activity. Wavelet-transformed single trial epochs and trial averages were used to assess EAGBR intertrial phase coherence (ITPC) and evoked power, respectively. Symptoms were assessed using the Positive and Negative Syndrome Scale. RESULTS: Groups did not differ in overall EAGBR power or ITPC. While HC exhibited EAGBR enhancement to increasing intensity, FESz exhibited reduced power to the 80 dB tone and, relative to HC, increased power to the 75 dB tone. Larger power and ITPC were correlated with more severe negative, thought disorganization, and resistance symptoms. Stronger ITPC was associated with impaired social functioning. DISCUSSION: EAGBR showed no overall deficit at disease onset. Rather, FESz exhibited a differential response across tone intensity relative to HC, emphasizing the importance of stimulus characteristics in EAGBR studies. Associations between larger EAGBR and more severe symptoms suggest aberrant synchronization driving overinclusive perceptual binding that may relate to deficits in executive inhibition of initial sensory activity.

Experimental evaluation of cement integrity on exposure to supercritical CO2 using NMR: Application to geostorage.

Carbon sequestration is one approach to achieve carbon dioxide reduction in the atmosphere. Underground storage of CO2 requires an understanding of geochemical and geomechanical alteration on the integrity of the injection wellbore. In this study, we investigate the reactivity of supercritical CO2 (scCO2) at 65 °C and 20.7 MPa on Portland class G cement plugs used for oil and gas well completion, for exposure of up to 5 weeks. For nanoporous media, such as cement, diffusion is believed to be the major mass transport mechanism (Perkins and Johnston, 1963) [1]. To quantify the extent of the alteration (mineralization/dissolution) on fluid diffusivity through the cement matrix, a novel approach based on Nuclear Magnetic Resonance (NMR) is employed to derive diffusional tortuosity. Comparing pre- and post-scCO2 exposure, deuterium oxide (D2O) intrusion profiles allow us to determine flow path alteration in the cement plugs. Additional characterizations include Fourier Transform Infrared Spectroscopy (FTIR) to observe the change in cement composition, micro X-ray Computed Tomography (µXCT), along with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS) to determine invasion extent and microstructure modifications, Mercury Injection Capillary Pressure (MICP) for pore throat size distribution and BET N2 isothermal adsorption for surface area and pore size distribution. The results show that exposure to scCO2 promotes both calcium carbonate precipitation and dissolution simultaneously. However, the alteration is pore size dependent. After 5 weeks of exposure, there is evidence of carbonate dissolution in smaller pores (<30 nm) and both precipitation and dissolution in larger pores (30-200 nm). The alteration of the cement plugs leads to a decrease in the storage and connectivity of the cement. The porosity decreased from 37 to 33 % in 5 weeks, while the matrix tortuosity increased by 6 and 3 times after 2 and 5 weeks of exposure, respectively. The experimental results imply that the cement carbonate precipitation can limit the migration of scCO2 through the cement matrix. This work also highlights an alternative laboratory approach to quantify the risk associated with scCO2 exposure on Portland cement using NMR-derived tortuosity.

Is source-resolved magnetoencephalographic mismatch negativity a viable biomarker for early psychosis?

Mismatch negativity (MMN) is an auditory event-related response reflecting the pre-attentive detection of novel stimuli and is a biomarker of cortical dysfunction in schizophrenia (SZ). MMN to pitch (pMMN) and to duration (dMMN) deviant stimuli are impaired in chronic SZ, but it is less clear if MMN is reduced in first-episode SZ, with inconsistent findings in scalp-level EEG studies. Here, we investigated the neural generators of pMMN and dMMN with MEG recordings in 26 first-episode schizophrenia spectrum (FEsz) and 26 matched healthy controls (C). We projected MEG inverse solutions into precise functionally meaningful auditory cortex areas. MEG-derived MMN sources were in bilateral primary auditory cortex (A1) and belt areas. In A1, pMMN FEsz reduction showed a trend towards statistical significance (F(1,50) = 3.31; p = .07), and dMMN was reduced in FEsz (F(1,50) = 4.11; p = .04). Hypothesis-driven comparisons at each hemisphere revealed dMMN reduction in FEsz occurred in the left (t(56) = 2.23; p = .03; d = .61) but not right (t(56) = 1.02; p = .31; d = .28) hemisphere, with a moderate effect size. The added precision of MEG source solution with high-resolution MRI and parcellation of A1 may be requisite to detect the emerging pathophysiology and indicates a critical role for left hemisphere pathology at psychosis onset. However, the moderate effect size in left A1, albeit larger than reported in scalp MMN meta-analyses, casts doubt on the clinical utility of MMN for differential diagnosis, as a majority of patients will overlap with the healthy individual's distribution.

Functional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis.

INTRODUCTION: Semantic verbal fluency (SVF) impairments are debilitating and present early in the course of psychotic illness. Deficits within frontal, parietal, and temporal brain regions contribute to this deficit, as long-range communication across this functionally integrated network is critical to SVF. This study sought to isolate disruptions in functional and structural connectivity contributing to SVF deficits during first-episode psychosis in the schizophrenia spectrum (FESz). METHODS: Thirty-three FESz and 34 matched healthy controls (HC) completed the Animal Naming Task to assess SVF. Magnetoencephalography was recorded during an analogous covert SVF task, and phase-locking value (PLV) used to measure functional connectivity between inferior frontal and temporoparietal structures bilaterally. Diffusion imaging was collected to measure fractional anisotropy (FA) of the arcuate fasciculus, the major tract connecting frontal and temporoparietal language areas. RESULTS: SVF scores were lower among FESz compared to HC. While PLV and FA did not differ between groups overall, FESz exhibited an absence of the left-lateralized nature of both measures observed in HC. Among FESz, larger right-hemisphere PLV was associated with worse SVF performance (ρ = -0.51) and longer DUP (ρ = -0.50). DISCUSSION: In addition to worse SVF, FESz exhibited diminished leftward asymmetry of structural and functional connectivity in fronto-temporoparietal SVF network. The relationship between theta-band hyperconnectivity and poorer performance suggests a disorganized executive network and may reflect dysfunction of frontal cognitive control centers. These findings illustrate an aberrant pattern across the distributed SVF network at disease onset and merit further investigation into development of asymmetrical hemispheric connectivity and its failure among high-risk populations.

Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms.

BACKGROUND AND HYPOTHESIS: Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. STUDY DESIGN: Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. STUDY RESULTS: Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). CONCLUSION: Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

Recovery of auditory evoked response attentional gain modulation following the first psychotic episode indexes improvements in symptom severity.

Attentional control of auditory N100/M100 gain is reduced in individuals with first-episode psychosis (FEP). Persistent problems with executive modulation of auditory sensory activity may impact multiple aspects of psychosis. As a follow-up to our prior work reporting deficits in attentional M100 gain modulation in auditory cortex, we examined changes in M100 gain modulation longitudinally, and further examined relationships between auditory M100 and symptoms of psychosis. We compared auditory M100 in auditory sensory cortex between 21 FEP and 29 matched healthy participants and between timepoints separated by 220 ± 100 days. Magnetoencephalography data were recorded while participants alternately attended or ignored tones in an auditory oddball task. M100 was measured as the average of 80-140 ms post-stimulus in source-localized evoked responses within bilateral auditory cortex. Symptoms were assessed using the PANSS and PSYRATS. M100 amplitudes, attentional modulation of M100 amplitudes, and symptom severity all improved in FEP over time. Further, improvement in M100 modulation correlated with improvements in negative symptoms (PANSS) as well as physical, cognitive, and emotional components of hallucinations (PSYRATS). Conversely, improvements in the overall size of the M100, rather than the difference between active and passive M100 amplitudes, were related to worsening of positive symptoms (PANSS) and physical components of hallucinations. Results indicate a link between symptoms (particularly auditory hallucinations) and auditory cortex neurophysiology in FEP, where auditory attention and auditory sensation have opposed relationships to symptom change. These findings may inform current models of psychosis etiology and could provide nonpharmaceutical avenues for early intervention.

Functional connectivity and gray matter deficits within the auditory attention circuit in first-episode psychosis.

Background: Selective attention deficits in first episode of psychosis (FEP) can be indexed by impaired attentional modulation of auditory M100. It is unknown if the pathophysiology underlying this deficit is restricted to auditory cortex or involves a distributed attention network. We examined the auditory attention network in FEP. Methods: MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while alternately ignoring or attending tones. A whole-brain analysis of MEG source activity during auditory M100 identified non-auditory areas with increased activity. Time-frequency activity and phase-amplitude coupling were examined in auditory cortex to identify the attentional executive carrier frequency. Attention networks were defined by phase-locking at the carrier frequency. Spectral and gray matter deficits in the identified circuits were examined in FEP. Results: Attention-related activity was identified in prefrontal and parietal regions, markedly in precuneus. Theta power and phase coupling to gamma amplitude increased with attention in left primary auditory cortex. Two unilateral attention networks were identified with precuneus seeds in HC. Network synchrony was impaired in FEP. Gray matter thickness was reduced within the left hemisphere network in FEP but did not correlate with synchrony. Conclusion: Several extra-auditory attention areas with attention-related activity were identified. Theta was the carrier frequency for attentional modulation in auditory cortex. Left and right hemisphere attention networks were identified, with bilateral functional deficits and left hemisphere structural deficits, though FEP showed intact auditory cortex theta phase-gamma amplitude coupling. These novel findings indicate attention-related circuitopathy early in psychosis potentially amenable to future non-invasive interventions.

Diminished Auditory Cortex Dynamic Range and its Clinical Correlates in First Episode Psychosis.

BACKGROUND AND HYPOTHESIS: There is growing appreciation for the contribution of sensory disruptions to disease morbidity in psychosis. The present study examined auditory cortex (AC) dynamic range: the scaling of neurophysiological responses to stimulus intensity, among individuals with a schizophrenia spectrum illness (FESz) and its relationship to clinical outcomes at disease onset. STUDY DESIGN: Magnetoencephalography (MEG) was recorded from 35 FESz and 40 healthy controls (HC) during binaural presentation of tones at three intensities (75 dB, 80 dB, and 85 dB). MRIs were obtained to enhance cortical localization of MEG sensor-level activity. All participants completed the MATRICS cognitive battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS). Patients were administered the Positive and Negative Syndrome Scale (PANSS). STUDY RESULTS: FESz exhibited reduced AC response relative to HC. Enhancement of AC activity to tones of increasing intensity was blunted in FESz relative to HC. Reduced dynamic range (85-75 dB AC response) was associated with lower GFS (r = .58) and GFR (r = .45) scores, worse MCCB performance (r = .45), and increased PANSS Negative symptom subscale scores (r = -.55) among FESz, relationships not observed with AC responses to individual tones. CONCLUSION: Beyond an impaired AC response to pure tones, FESz exhibit reduced dynamic range relative to HC. This impairment was correlated with markers of disease morbidity including poorer community functioning as well as cognitive and negative symptoms. The relationship with impaired social functioning may reflect the role of AC dynamic range in decoding the emotional content of language and highlights its importance to future therapeutic sensory remediation protocols.

Attentional M100 gain modulation localizes to auditory sensory cortex and is deficient in first-episode psychosis.

Selective attention is impaired in first-episode psychosis (FEP). Selective attention effects can be detected during auditory tasks as increased sensory activity. We previously reported electroencephalography scalp-measured N100 enhancement is reduced in FEP. Here, we localized magnetoencephalography (MEG) M100 source activity within the auditory cortex, making novel use of the Human Connectome Project multimodal parcellation (HCP-MMP) to identify precise auditory cortical areas involved in attention modulation and its impairment in FEP. MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while individuals either ignored frequent standard and rare oddball tones while watching a silent movie or attended tones by pressing a button to oddballs. Because M100 arises mainly in the auditory cortices, MEG activity during the M100 interval was projected to the auditory sensory cortices defined by the HCP-MMP (A1, lateral belt, and parabelt parcels). FEP had less auditory sensory cortex M100 activity in both conditions. In addition, there was a significant interaction between group and attention. HC enhanced source activity with attention, but FEP did not. These results demonstrate deficits in both sensory processing and attentional modulation of the M100 in FEP. Novel use of the HCP-MMP revealed the precise cortical areas underlying attention modulation of auditory sensory activity in healthy individuals and impairments in FEP. The sensory reduction and attention modulation impairment indicate local and systems-level pathophysiology proximal to disease onset that may be critical for etiology. Further, M100 and N100 enhancement may serve as outcome variables for targeted intervention to improve attention in early psychosis.

Pathological resting-state executive and language system perfusion in first-episode psychosis.

BACKGROUND AND HYPOTHESIS: Cortical (e.g., Broca's area and Wernicke's area) and subcortical (e.g., putamen) language-related areas and executive control areas (e.g., inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC)) show functional and structural dysconnectivity in long-term psychosis. We examined whether resting-state basal perfusion levels revealed selective pathophysiology (likely hypo- and hyper-activation) of language-related and executive areas in first-episode psychosis (FEP). STUDY DESIGN: Basal resting-state perfusion was measured using pseudo-continuous Arterial Spin Labeling (pcASL). Relative cerebral blood flow (rCBF) was compared between 32 FEP and 34 matched healthy comparison (HC) individuals. Structural and functional MRI scans were acquired using a 3T Prisma scanner during the same session. STUDY RESULTS: Whole-brain comparison of resting rCBF identified 8 clusters with significant between-group differences. Reduced rCBF was found in executive control areas in left and right IFG, right DLPFC, and right parietal cortex. Increased rCBF was found in left and right temporal cortex (including Wernicke's area), and left and right putamen. A positive correlation was observed between auditory hallucination severity and rCBF in the left putamen. CONCLUSIONS: To the degree that perfusion implies activation, language and auditory processing areas in bilateral temporal lobe and putamen showed pathological hyper-activity, and cognitive control areas (IFG, DLPFC, right parietal) showed pathological hypo-activity in FEP at rest. Pathological basal activity was present across the range of symptom severity, suggesting it may be a common underlying pathology for psychosis that may be targeted with non-invasive brain stimulation to normalize resting activity levels.

SIRT1 inactivation switches reactive astrocytes to an antiinflammatory phenotype in CNS autoimmunity.

Astrocytes are highly heterogeneous in their phenotype and function, which contributes to CNS disease, repair, and aging; however, the molecular mechanism of their functional states remains largely unknown. Here, we show that activation of sirtuin 1 (SIRT1), a protein deacetylase, played an important role in the detrimental actions of reactive astrocytes, whereas its inactivation conferred these cells with antiinflammatory functions that inhibited the production of proinflammatory mediators by myeloid cells and microglia and promoted the differentiation of oligodendrocyte progenitor cells. Mice with astrocyte-specific Sirt1 knockout (Sirt1-/-) had suppressed progression of experimental autoimmune encephalomyelitis (EAE), an animal model of CNS inflammatory demyelinating disease. Ongoing EAE was also suppressed when Sirt1 expression in astrocytes was diminished by a CRISPR/Cas vector, resulting in reduced demyelination, decreased numbers of T cells, and an increased rate of IL-10-producing macrophages and microglia in the CNS, whereas the peripheral immune response remained unaffected. Mechanistically, Sirt1-/- astrocytes expressed a range of nuclear factor erythroid-derived 2-like 2 (Nfe2l2) target genes, and Nfe2l2 deficiency shifted the beneficial action of Sirt1-/- astrocytes to a detrimental one. These findings identify an approach for switching the functional state of reactive astrocytes that will facilitate the development of astrocyte-targeting therapies for inflammatory neurodegenerative diseases such as multiple sclerosis.

Load-dependent functional connectivity deficits during visual working memory in first-episode psychosis.

INTRODUCTION: Aberrant network connectivity is a core deficit in schizophrenia and may underlie many of its associated cognitive deficits. Previous work in first-episode schizophrenia spectrum illness (FESz) suggests preservation of working memory network function during low-load conditions with dysfunction emerging as task complexity increases. This study assessed visual network connectivity and its contribution to load-dependent working memory impairments. METHODS: Magnetoencephalography was recorded from 35 FESz and 28 matched controls (HC) during a lateralized change detection task. Impaired alpha desynchronization was previously identified within bilateral dorsal occipital (Occ) regions. Here, whole-brain alpha-band connectivity was examined using phase-locking (PLV) and bilateral Occ as connectivity seeds. Load effects on connectivity were assessed across participants, and PLV modulation within networks was compared between groups. RESULTS: Occ exhibited significant load modulated connectivity with six regions (FDR-corrected). HC exhibited PLV enhancement with load in all connections. FESz failed to show PLV modulation between right Occ and left inferior frontal gyrus, lateral occipito-temporal sulcus, and anterior intermediate parietal sulcus. Smaller PLVs in all three network connections during both memory load conditions were associated with increased reality distortion in FESz (FDR-corrected.) CONCLUSION: Examination of functional connectivity across the visual working memory network in FESz revealed an inability to enhance communication between perceptual and executive networks in response to increasing cognitive demands. Furthermore, the degree of network communication impairment was associated with positive symptoms. These findings provide insights into the nature of brain dysconnectivity and its contribution to symptoms in early psychosis and identify potential targets for future interventions.

Aberrant attentional modulation of the auditory steady state response (ASSR) is related to auditory hallucination severity in the first-episode schizophrenia-spectrum.

The 40-Hz auditory steady state response (ASSR) is reduced early in schizophrenia, with differences evident even at the first episode of schizophrenia-spectrum psychosis (FESz). Although robust, there is high variability in effect size across studies, possibly due to differences in experimental control of attention and heterogeneity of symptom profiles across studies, both of which may affect the ASSR. We investigated the relationships among ASSR deficits, attention-mediated sensory gain, and auditory hallucinations in 25 FESz (15 male; 23.3 ± 4.5 years) and 32 matched healthy comparison subjects (HC, 22 male; 24.7 ± 5.8 years). ASSR was measured to 40-Hz click trains at three intensities (75, 80, and 85 dB) while participants attended or ignored stimuli. ASSR evoked power and inter-trial phase coherence (ITPC) were measured using the Morlet wavelet transform. FESz did not show overall ASSR power reduction (p > 0.1), but power was significantly increased with attention in HC (p < 0.01), but not in FESz (p > 0.1). Likewise, FESz did not evince overall ASSR ITPC reduction (p > 0.1), and ITPC was significantly increased with attention in HC (p < 0.01), but not in FESz (p > 0.09). Attention-related change in ASSR correlated with auditory hallucination severity for power (r = -0.49, p < 0.05) and ITPC (r = -0.58, p < 0.01). FESz with auditory hallucinations may have pathologically increased basal excitability of auditory cortex and consequent reduced ability to further increase auditory cortex sensory gain with focused attention. These findings indicate hallucination-related pathophysiology early in schizophrenia and may guide novel intervention strategies aimed to modulate basal activity levels.

Shear Bond Strength and Color Stability of Novel Antibacterial Nanofilled Dental Adhesive Resins.

Experimental adhesives containing co-doped metaloxide nanoparticles were demonstrated to display strong and long-term antibacterial properties against Streptococcus mutans biofilms. The present study represents an effort to characterize the shear-bond strength (SBS) and color stability (CS) of these novel biomaterials. Experimental adhesives were obtained by dispersing nitrogen and fluorine co-doped titanium dioxide nanoparticles (NF_TiO2, 10%, 20% or 30%, v/v%) into OptiBond Solo Plus (OPTB). Dentin surfaces were wet-polished (600-Grit). Specimens (n = 5/group) of Tetric EvoCeram were fabricated and bonded using either OPTB or experimental (OPTB + NF_TiO2) adhesives. Specimens were stored in water (37 °C) for twenty-four hours (T1), three months (T2), and six months (T3). At T1, T2, or T3, specimens were removed from water storage and were tested for SBS. Disc-shaped specimens (n = 10/group; d = 6.0 mm, t = 0.5 mm) of adhesives investigated were fabricated and subjected to thermocycling (10,000 cycles, 5−55 °C, 15 s dwell time). Specimens' colors were determined with a VITA Easyshade® V spectrophotometer (after every 1000 cycles). SBS data was analyzed using two-way ANOVA and post-hoc Tukey tests, while CS data was analyzed using one-way ANOVA and post-hoc Tukey tests (α = 0.05). Mean values of SBS ranged from 16.39 ± 4.20 MPa (OPTB + 30%NF_TiO2) to 19.11 ± 1.11 MPa (OPTB), from 12.99 ± 2.53 MPa (OPTB + 30% NF_TiO2) to 14.87 ± 2.02 (OPTB) and from 11.37 ± 1.89 (OPTB + 20% NF_TiO2) to 14.19 ± 2.24 (OPTB) after twenty-four hours, three months, and six months of water storage, respectively. Experimental materials had SBS values that were comparable (p > 0.05) to those from OPTB independently of nanoparticle concentration or time-point considered. Experimental materials with higher NF_TiO2 concentrations had less intense color variations and were more color stable than OPTB even after 10,000 thermocycles. In combination, the results reported have demonstrated that experimental adhesives can establish strong and durable bonds to human dentin while displaying colors that are more stable, thereby suggesting that the antibacterial nanotechnology investigated can withstand the harsh conditions within the oral cavity without compromising the esthetic component of dental restorations.