An event-related functional magnetic resonance imaging study of prefrontal cortex was conducted during which subjects performed a visual "oddball" target detection task. Exemplars of three stimulus ...categories were presented at a rate of one per 1.5 sec for 10 runs, each consisting of 132 trials. Standards were color squares of varying sizes that were presented on approximately 92% of trials. Targets were color circles of varying sizes presented irregularly on approximately 4% of trials. Novels were pictures of everyday objects that were also presented irregularly on approximately 4% of trials. Ten subjects participated in two separate sessions in which they were required to count mentally or to push a button whenever a target appeared. Targets evoked activation within prefrontal cortex, primarily within the middle frontal gyri (MFG). This MFG activation did not differ as a function of the required response. Novels did not evoke significant activity within this region despite evidence from a separate behavioral and event-related potential study demonstrating their strong influence on processing. In additional imaging sessions with two subjects, the rules were reversed to require a button press whenever an object, but not a circle, appeared. These former novels now evoked activation in the MFG, but the former target circles did not. These experiments indicate that MFG activation is reliably evoked by exemplars from arbitrary stimulus categories that are mapped by experimental rules onto an arbitrary covert or overt response.
The present study examined the integrity of the P300 component of the event-related potential (ERP) in patients at high imminent risk for schizophrenia in relation to healthy comparison subjects and ...patients in the recent-onset and chronic stages of schizophrenia.
The P300 was recorded by using an auditory oddball task in 10 patients clinically considered at risk of being prodromally symptomatic for schizophrenia, 10 patients with recent-onset schizophrenia, 14 patients with chronic schizophrenia, 14 young healthy comparison subjects, who were age-matched to the high-risk and recent-onset schizophrenia groups, and 14 older healthy comparison subjects, who were age-matched to the chronic schizophrenia group.
High-risk subjects displayed smaller than normal P300 amplitudes at the parietal, centroparietal and central scalp locations. The observed P300 amplitude abnormalities in high-risk subjects were severe, being comparable in magnitude to the abnormalities seen in recent-onset and chronic schizophrenia subjects. However, whereas high-risk subjects showed P300 amplitude abnormalities that were bilaterally symmetrical, subjects with recent-onset schizophrenia and, particularly, subjects with chronic schizophrenia exhibited abnormalities that were markedly larger over the left temporal scalp sites.
Patients at high imminent risk for developing a first florid psychotic episode seem to manifest auditory P300 amplitude abnormalities that are similar, but not identical, to those observed in patients in the recent-onset and chronic stages of schizophrenia. These results support the idea that auditory P300 abnormalities in schizophrenia reflect a primary cognitive and pathophysiological feature of the illness.
Abstract Schizophrenia patients show significant subcortical brain abnormalities. We examined these abnormalities using automated image analysis software and provide effect size estimates for ...prospective multi-scanner schizophrenia studies. Subcortical and intracranial volumes were obtained using FreeSurfer 5.0.0 from high-resolution structural imaging scans from 186 schizophrenia patients (mean age±S.D.=38.9±11.6, 78% males) and 176 demographically similar controls (mean age±S.D.=37.5±11.2, 72% males). Scans were acquired from seven 3-Tesla scanners. Univariate mixed model regression analyses compared between-group volume differences. Weighted mean effect sizes (and number of subjects needed for 80% power at α =0.05) were computed based on the individual single site studies as well as on the overall multi-site study. Schizophrenia patients have significantly smaller intracranial, amygdala, and hippocampus volumes and larger lateral ventricle, putamen and pallidum volumes compared with healthy volunteers. Weighted mean effect sizes based on single site studies were generally larger than effect sizes computed based on analysis of the overall multi-site sample. Prospectively collected structural imaging data can be combined across sites to increase statistical power for meaningful group comparisons. Even when using similar scan protocols at each scanner, some between-site variance remains. The multi-scanner effect sizes provided by this study should help in the design of future multi-scanner schizophrenia imaging studies.
Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia ...patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.
Previous studies suggested that auditory change-specific neural responses are attention-independent and reflect central auditory processing. The automaticity of the brain's response to infrequent ...changes in pitch within a series of auditory tone pips was examined in parallel functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies. Subjects performed a continuous perceptual-motor visual tracking task at two levels of difficulty while simultaneously hearing a series of task-irrelevant standard tone pips and infrequent pitch-deviant tones. fMRI results revealed that the unattended pitch-deviant tones strongly activated superior temporal and frontal cortical regions. These activations were significantly modulated by the tracking difficulty of the primary task. ERP results revealed that the amplitude of the scalp-negative component evoked by deviant tones (MMN) was attenuated during the more difficult tracking task. Our results demonstrate that the brain's response to task-irrelevant sensory changes is strongly influenced by intermodal attentional demands.
Utilizing national longitudinal data, this study examines how polygenic depression risk and childhood abuse interactively influence the life-course development of depressive conditions from middle to ...late adulthood.
Data from 7512 participants (4323 females and 3189 males) of European ancestry aged 51–90, retrieved from the U.S. Health and Retirement Study (1992–2020), were analyzed. Childhood physical abuse and polygenic depression score were the primary predictors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CESD) scale, and clinical depression risk was a binary indicator. Growth-curve linear mixed and logit mixed-effects models were conducted for analysis.
Increasing polygenic depression scores were associated with elevated CES-D levels and potential risks of clinical depression. Males experienced more detrimental effects of childhood abuse on depression development from ages 51 to 90 years. In contract, non-maltreated females generally exhibited higher depressive symptoms and clinical depression risk than males. A significant interactive effect was found between polygenic depression risk and childhood abuse among males. Higher depression levels and clinical risk were observed with increasing polygenic depression score among maltreated males, surpassing those of females with standardized polygenic score ≥0 from age 51 to 90 years.
The interaction between childhood abuse and genetic factors significantly shaped lifelong depression trajectories in males, while the negative impact of abusive parenting remained constant regardless of polygenic depression risk among females. Individualized prevention and intervention strategies could be crucial in mitigating lifelong depression development, especially for high-genetic-risk males with a history of childhood physical abuse.
•First study on childhood-abuse-genetic-risk interaction with lifelong depression.•Higher polygenic scores elevated depressive symptoms and clinical depression risk.•Childhood abuse worsened depression symptoms & clinical risk, especially in males.•Males with high genetic risk were more mentally harmed by childhood abuse.•Targeted interventions for high-risk males crucial to reduce lifelong depression.
Background: Prior studies suggest that auditory hallucinations of “voices” arise from activation of speech perception areas of the cerebral cortex. Low frequency transcranial magnetic stimulation ...(TMS) can reduce cortical activation.
Methods: We have studied three schizophrenic patients reporting persistent auditory hallucinations to determine if low frequency TMS could curtail these experiences. One hertz stimulation of left temporoparietal cortex was compared with sham stimulation using a double-blind, cross-over design.
Results: All three patients demonstrated greater improvement in hallucination severity following active stimulation compared to sham stimulation. Two of the three patients reported near total cessation of hallucinations for ⩾ 2 weeks.
Conclusions: TMS may advance our understanding of the mechanism and treatment of auditory hallucinations.
Electrophysiological correlates of the processing of visual information were studied in epileptic patients with electrodes chronically implanted on the surface of striate and extrastriate cortex. In ...separate experiments patients viewed faces, letter strings (words and non-words), numbers, and control stimuli. A negative potential, N200, was evoked by faces, letter strings, and numbers, but not by the control stimuli. N200 was recorded bilaterally from discrete regions of the fusiform and inferior temporal gyri. These category-specific face, letter-string, and number "modules" vary in location. In most cases there was no overlap in the location of face and letter-string modules, suggesting a mosaic of functionally discrete regions. In some cases letter-string and number N200s were recorded from the same location, suggesting that these modules may be less spatially and functionally discrete. Face N200-like potentials can be recorded from temporal scalp, allowing the possibility of studying early face processing in normal subjects. Longer-latency face-specific potentials were recorded from the inferior surface of the anterior temporal lobe. Potentials evoked by colored checkerboards were recorded from a region of the fusiform gyrus posterior to the fusiform region from which category-specific N200s were recorded. These results suggest that there are several processing streams in inferior extrastriate cortex. In addition to object recognition systems previously proposed for faces and words, our preliminary results suggest a separate system dealing with numbers. Postulated systems dealing with larger manipulable objects and animals have not been detected.
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