Korey Wylie

Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia ☆

OBJECTIVE Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia. METHODS Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired-stimulus conditioning-test paradigm were obtained from the same subjects. RESULTS Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure. CONCLUSIONS Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia.

Gray matter volume differences and the effects of smoking on gray matter in schizophrenia

OBJECTIVE Many studies have evaluated differences in gray matter volume in schizophrenia, but have not considered the possible effects of smoking, which is extraordinarily common in people with the illness. The present study used voxel-based morphometry (VBM) to examine differences in gray matter in subjects with schizophrenia and evaluate the effects of smoking on this measure. METHODS Thirty-two subjects with schizophrenia (14 smokers, 18 non-smokers) and 32 healthy comparison subjects participated in the study. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS Reduced gray matter was observed in the schizophrenia group in the orbitofrontal cortex, bilateral insula and superior temporal gyri (STG), bilateral dorsolateral prefrontal cortices (DLPFC), medial frontal gyrus, and cingulate gyrus. Within this group, smoking subjects had greater lateral prefrontal and STG gray matter volumes relative to non-smoking subjects. CONCLUSIONS The finding of reduced gray matter volume in prefrontal and temporal regions in schizophrenia is consistent with prior anatomical tracing and whole-brain voxel-based studies. Greater gray matter volumes in smoking relative to non-smoking subjects with schizophrenia highlight a potential experimental confound in volumetric studies and suggests that smoking may be associated with a relative preservation of lateral prefrontal and temporal gray matter in schizophrenia.

Reducing Susceptibility Artifacts in fMRI Using Volume- Selective z-Shim Compensation

Susceptibility‐induced magnetic field gradients (SFGs) can result in severe signal loss in the orbitofrontal cortex (OFC) in gradient‐echo‐based functional MRI (fMRI) studies. Although conventional z‐shim techniques can effectively recover the MRI signal in this region, the substantial penalty in imaging time hampers their use in routine fMRI studies. A modified z‐shim technique with high imaging efficiency is presented in this study. In this technique, z‐shim compensations are applied only to a selective volume where the susceptibility artifact is severe. The results of an fMRI study (N = 6) demonstrate the feasibility of detecting the OFC activation with z‐shim in whole‐brain fMRI studies at a temporal resolution of 2 s. Magn Reson Med 57:396–404, 2007.

Altered Default Network Activity in Obesity

The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. To better understand the neurobiology of this process and how it may be dysfunctional in obesity, this study examined activity of the brains “default network” in reduced‐obese (RO) as compared to lean individuals. The default network is a group of functionally connected brain regions thought to play an important role in internally directed cognitive activity and the interplay between external and internal sensory processing. Functional magnetic resonance imaging was performed in 24 lean and 18 RO individuals in the fasted state after 2 days of eucaloric energy intake and after 2 days of 30% overfeeding in a counterbalanced design. Scanning was performed while subjects passively viewed images of food and nonfood objects. Independent component analysis was used to identify the default network component. In the eucaloric state, greater default network activity was observed in RO compared to lean individuals in the lateral inferior parietal and posterior cingulate cortices. Activity was positively correlated with appetite. Overfeeding resulted in increased default network activity in lean but not RO individuals. These findings suggest that the function of the default network, a major contributor to intrinsic neuronal activity, is altered in obesity and/or obese‐prone individuals. Future studies of the networks function and its relationship to other brain networks may improve our understanding of the mechanisms and treatment of obesity.

Reduced brain resting-state network specificity in infants compared with adults.

Purpose Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. Patients and methods Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. Results Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. Conclusion We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience.

Nicotine Increases Cerebellar Activity during Finger Tapping

Nicotine improves performance on several cognitive and sensorimotor tasks. The neuronal mechanisms associated with these changes in performance are, however, largely unknown. Functional magnetic resonance imaging (fMRI) was used to examine the effect of nicotine on neuronal response in nineteen healthy subjects while they performed an auditory-paced finger tapping task. Subjects performed the task, after receiving either a nicotine patch or placebo treatment, in a single blind, crossover design. Compared to placebo, nicotine treatment increased response in the cerebellar vermis. Increased vermal activity, in the absence of changes in other task-related regions suggests specificity in nicotine’s effects.

Top-Down Network Effective Connectivity in Abstinent Substance Dependent Individuals

Objective We hypothesized that compared to healthy controls, long-term abstinent substance dependent individuals (SDI) will differ in their effective connectivity between large-scale brain networks and demonstrate increased directional information from executive control to interoception-, reward-, and habit-related networks. In addition, using graph theory to compare network efficiencies we predicted decreased small-worldness in SDI compared to controls. Methods 50 SDI and 50 controls of similar sex and age completed psychological surveys and resting state fMRI. fMRI results were analyzed using group independent component analysis; 14 networks-of-interest (NOI) were selected using template matching to a canonical set of resting state networks. The number, direction, and strength of connections between NOI were analyzed with Granger Causality. Within-group thresholds were p<0.005 using a bootstrap permutation. Between group thresholds were p<0.05, FDR-corrected for multiple comparisons. NOI were correlated with behavioral measures, and group-level graph theory measures were compared. Results Compared to controls, SDI showed significantly greater Granger causal connectivity from right executive control network (RECN) to dorsal default mode network (dDMN) and from dDMN to basal ganglia network (BGN). RECN was negatively correlated with impulsivity, behavioral approach, and negative affect; dDMN was positively correlated with impulsivity. Among the 14 NOI, SDI showed greater bidirectional connectivity; controls showed more unidirectional connectivity. SDI demonstrated greater global efficiency and lower local efficiency. Conclusions Increased effective connectivity in long-term abstinent drug users may reflect improved cognitive control over habit and reward processes. Higher global and lower local efficiency across all networks in SDI compared to controls may reflect connectivity changes associated with drug dependence or remission and requires future, longitudinal studies to confirm.

Targeting Functional Biomarkers in Schizophrenia with Neuroimaging

Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutical companies downsizing or eliminating research programs needed to develop these drugs. One way of increasing the probability of success for investigational compounds is to incorporate alternative methods of identifying biological targets in order to more effectively screen new drugs. A promising method of accomplishing this goal for psychiatric drugs is to use functional magnetic resonance imaging (fMRI). fMRI investigates neural circuits, shedding light on the biology that generates symptoms such as hallucinations. Once identified, relevant neural circuits can be targeted with pharmacologic interventions and the response to these drugs measured with fMRI. This review describes the early use of fMRI in this context, and discusses the alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A), as an example of the potential value of fMRI for psychiatric drug development.

Large-Scale Network Involvement in Language Processing

The human brains proficiency for language and speech combines a vast reservoir of stored knowledge with flexibility in perceiving and producing subtle nuances of sound. A century ago, Wernicke and Broca discovered regions responsible for fluent and nonfluent aphasia, respectively ([Kandel et al.,

Stimulus-dependent effects on right ear advantage in schizophrenia

Background When presented with different sounds in each ear (dichotic listening), healthy subjects typically show a preference for stimuli heard in the right ear, an effect termed “right ear advantage”. Previous studies examining right ear advantage in schizophrenia have been inconsistent, showing either decreased or increased advantage relative to comparison subjects. Given evidence for enhanced semantic processing in schizophrenia, some of this inconsistency may be due to the type of stimuli presented (words or syllables). The present study examined right ear advantage in patients and controls using both words and syllables as stimuli. Methods Right ear advantage was compared between 20 patients with schizophrenia and 17 healthy controls. Two versions of the task were used, ie, a consonant-vowel pairing task and a fused rhymed words task. Results A significant group × task interaction was observed. Relative to healthy controls, patients showed a greater difference on the syllable-based task compared with the word-based task. The number of distractors marked during the syllable-based task was inversely correlated with score on the Global Assessment of Function Scale. Conclusion The findings are consistent with a left hemisphere dysfunction in schizophrenia, but also suggest that differences may be stimulus-specific, with a relative sparing of the deficit in the context of word stimuli. Performance may be related to measures of social, occupational, and psychological function.