Involvement of the insular cortex is a common finding in neuroanatomical studies of schizophrenia, yet its contribution to disease pathology remains unknown. This review describes the normal function of the insula and examines pathology of this region in schizophrenia. The insula is a cortical structure with extensive connections to many areas of the cortex and limbic system. It integrates external sensory input with the limbic system and is integral to the awareness of the body's state (interoception). Many deficits observed in schizophrenia involve these functions and may relate to insula pathology. Furthermore, reports describing deficits caused by lesions of the insula parallel deficits observed in schizophrenia. Examples of insula-related functions that are altered in schizophrenia include the processing of both visual and auditory emotional information, pain, and neuronal representations of the self. The last of these functions, processing representations of the self, plays a key role in discriminating between self-generated and external information, suggesting that insula dysfunction may contribute to hallucinations, a cardinal feature of 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, have 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.

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 brain’s “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 network’s function and its relationship to other brain networks may improve our understanding of the mechanisms and treatment of obesity.

Background PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. Objectives We used resting state functional MRI (rsfMRI) and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. Methods Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and one hour after 200mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost thresholded, binarized adjacency matrices. Cost-integrated whole brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. Results Data from two patients and four controls were excluded due to excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in Executive (p=0.006), and Salience (p=0.018) networks. Levodopa significantly decreased local (p=0.039) efficiency in patients except within the Subcortical network where it significantly increased local efficiency (p=0.007). Conclusions Levodopa modulates global and local efficiency measures of small-world topology in PD suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization, and that levodopa tends to normalize the disrupted network topology in PD.

In fMRI experiments signal loss can occur in regions of brain adjacent to air cavities where susceptibility-induced magnetic field gradients (SFGs) perpendicular to the slice plane are the primary source of intravoxel dephasing. This signal loss often precludes the acquisition of fMRI data in regions that are of considerable interest for functional studies, including the orbitofrontal cortex (OFC) and inferior temporal regions (1,2). In addition, this susceptibility artifact becomes more severe at high magnetic field strengths (3T or higher). Tailored RF pulses (3), spin-echobased fMRI (4), spiral-in/out (5-7), and passive shim (8 -10) methods have been used to reduce the signal loss in regions compromised by SFGs.A technique known as "z-shim" was developed to effectively compensate for this susceptibility artifact in fMRI (1,(11)(12)(13). In the z-shim technique, additional image volumes are acquired with a compensation gradient applied to the slice direction. These additional image volumes are then combined with the original image volume acquired without z-shim to form a composite 3D fMRI data set (14). Previous studies demonstrated the effectiveness of the zshim technique in recovering fMRI signal in the OFC and inferior temporal regions (15-18). However, the need to acquire multiple volumes prolongs the acquisition time for each time frame, or effective repetition time (eTR). Several variations of the z-shim technique with improved imaging efficiency have been developed recently. These include a 3D z-shim method with extended k z coverage (19), a single-shot double-echo echo-planar imaging (EPI) scan with z-shim applied to one of the echoes (20), and a single-shot z-shim method with hybrid gradient-spin-echo acquisition (21).In whole-brain fMRI experiments the spatial extension of the regions with severe susceptibility artifact is typically in the range of 20 mm along the superior/inferior (S/I) direction (19,22,23), which is a small fraction of the size of the brain. The benefit of applying z-shim to other regions with mild field inhomogeneity is usually outweighed by the penalty in imaging time. In this study we developed a fast scheme for the z-shim technique in which the z-shim compensation is applied only to the selective volume where severe susceptibility-induced signal loss occurs ( Fig. 1) (24). A scheme for reordering of data acquisition in compensated and noncompensated slice locations is presented to ensure a steady state in the compensated slices. We conducted fMRI experiments with a reward-punishment task to demonstrate the feasibility of this technique for detecting fMRI signal in the OFC. THEORYThe presence of SFGs in the slice selection, G s , introduces a signal weighting function:where t is the time starting from the isocenter of the excitation RF pulse, ⌬z is the slice thickness, and ␥ is the gyromagnetic ratio. The first null point of this sinc function in an image acquired with an echo time (TE) is at: ␥G s ⌬zTE ϭ 2. The corresponding gradient area, A null , is thenNote that A null is so...

By examining alpha7 nicotinic receptor biology and recent efforts to target the receptor in clinical trials, it is hoped that investigators will be motivated to explore novel, promising directions focusing on the receptor as a strategy to treat cognitive symptoms in schizophrenia.

Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function.

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