Branisalava Curcic-Blake

Insight and Psychosis

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self‐reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty‐five schizophrenia patients and 19 healthy subjects performed a self‐reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small‐scale significant changes in white matter integrity associated with clinical insight. Self‐reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small‐scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self‐processing regions. Similarly, the observed hyper‐connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. Hum Brain Mapp 36:4859–4868, 2015.

Source location encoding in the fish lateral line canal

SUMMARY The position of a hydrodynamic dipole source, as encoded in a linear array of mechano-detecting neuromasts in the fish lateral line canal, was electrophysiologically investigated. Measured excitation patterns along the lateral line were compared to theoretical predictions and were found to be in good agreement. The results demonstrate that information on the position of a vibrating source from a fish is linearly coded in the spatial characteristics of the excitation pattern of pressure gradients distributed along the lateral line canal. Several algorithms are discussed that could potentially be used by a fish to decode lateral line excitation patterns, in order to localise a source and its axis of vibration. Specifically, a wavelet transform of a 1-D excitation pattern is shown to reconstruct a 2-D image of dipole sources located within a distance comparable to the body length of a fish and with a close range spatial accuracy twice the inter-neuromast distance.

cTBS delivered to the left somatosensory cortex changes its functional connectivity during rest

The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI.

Insight and Psychosis: Functional and Anatomical Brain Connectivity and Self-Reflection in Schizophrenia

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self‐reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty‐five schizophrenia patients and 19 healthy subjects performed a self‐reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small‐scale significant changes in white matter integrity associated with clinical insight. Self‐reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small‐scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self‐processing regions. Similarly, the observed hyper‐connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. Hum Brain Mapp 36:4859–4868, 2015.

Cortical connective field estimates from resting state fMRI activity

One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that—despite some variability in CF estimates between RS scans—neural properties such as CF maps and CF size can be derived from resting state data.

Neurodegeneration beyond the primary visual pathways in a population with a high incidence of normal-pressure glaucoma

Glaucoma is the most common age‐related neurodegenerative eye disease in western society. It is an insidious disease that, when untreated or detected too late, leads inevitably to blindness. An outstanding issue is whether glaucoma should be considered exclusively an eye disease or also a brain disease. To further examine it, we used Diffusion Tensor Imaging (DTI) to study white matter integrity in a Japanese glaucoma population. This population has a very high incidence of normal‐pressure glaucoma, in which optic nerve damage occurs in the absence of the elevated eye pressure that characterises the more common form of glaucoma.

Glutamate in dorsolateral prefrontal cortex and auditory verbal hallucinations in patients with schizophrenia: A (1)H MRS study

Purpose: Glutamatergic models of psychosis propose that dysfunction of N‐methyl‐d‐aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate + glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy (1H MRS) to calculate their association with AVH. Methods: Sixty‐seven patients with schizophrenia and thirty healthy control participants (HC) underwent magnetic resonance spectroscopy (MRS) to estimate levels of Glx in the white matter of the left prefrontal lobe. The spectrum was estimated from an 8 mm3 voxel placed in the left lateral prefrontal region, belonging to both the cingulum and forceps minor. Patients with lifetime AVH (AVH group; n = 45) and patients without lifetime AVH were compared (NoAVH group; n = 22) to control participants. Results: Levels of Glx were significantly different between the groups (F(2,94) = 5.27, p = 0.007). Planned comparisons showed that higher Glx levels were found in control participants than in the total patient group (p = 0.010). However, patients with lifetime AVH had higher levels of Glx compared to patients without lifetime AVH (p = 0.019). Creatin levels were similar in all three groups. We found no association between Glx and the severity of symptoms (item P3 of the PANSS or PANSS positive subscale). Conclusion: The higher Glx levels in patients with lifetime AVH as compared to patients without lifetime AVH suggest a mediating role for Glx in AVH. Our results are consistent with a previous study that found similar decreased levels of Glx in patients with schizophrenia, and increased levels in an AVH group as compared to a NoAVH group. The role of the glutamatergic system deserves further investigation, for example in different brain regions and in relation to clinical variables. HIGHLIGHTWe examined glutamate + glutamine (Glx) levels in the left prefrontal tracts of patients with schizophrenia.Schizophrenia patients have lower levels of Glx than healthy controls in this specific region.Patients with AVH experience have Glx levels closer to healthy controls compared to patients who have never experienced AVH.Results point toward a mediating role of Glx in auditory verbal hallucinations.Future studies should investigate Glx levels in association to AVH in different brain areas.Further investigations should be directed towards illuminating cellular mechanisms of Glx dysfunction.

Association between prefrontal N-acetylaspartate and insight in psychotic disorders

Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in psychosis. The association between prefrontal WM abnormalities and insight has not been studied yet by means of proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS can be used to measure N-acetylaspartate (NAA), which is considered to be a marker of neuronal integrity. We measured insight with the Birchwood Insight Scale (BIS) as well as item G12 of the Positive and Negative Syndrome Scale (PANSS) in 88 patients with psychosis. Prefrontal WM concentrations of NAA and ratios of NAA to creatine (Cr) were assessed with 1H-MRS. Nonparametric partial correlational analyses were conducted between NAA concentrations and insight controlling for illness duration, standardized antipsychotic dose, symptom scores, voxel grey matter content and voxel cerebrospinal fluid content. We found a significant correlation between reduced NAA/Cr ratios and poorer insight as measured with the BIS, which remained significant after additional correction for full width at half maximum, signal/noise and age. This is the first study reporting a relationship between lower prefrontal concentrations of a marker of neuronal integrity and impaired insight, providing further evidence that prefrontal pathology may play an important role in impaired insight in psychosis. This may be explained by the involvement of the prefrontal cortex in several executive and metacognitive functions, such as cognitive flexibility and perspective taking.

Lateral and Medial Ventral Occipitotemporal Regions Interact During the Recognition of Images Revealed from Noise

Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, 13 subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM)—a method to characterize network interactions—to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1), the lingual gyrus (LG) in medial ventral cortex and the lateral occipital cortex (LO). We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape—rather than by a single categorically specialized region—within the ventral visual cortex.