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Author: Lena Palaniyappan (56)


Feb
2018

Schizophrenia spectrum disorders (SSD) and psychotic bipolar disorder share a number of genetic and neurobiological features, despite a divergence in clinical course and outcome trajectories. We studied the diagnostic classification potential that can be achieved on the basis of the structure and connectivity within a triple network system (the default mode, salience and central executive network) in patients with SSD and psychotic bipolar disorder.
Directed static connectivity and its dynamic variance was estimated among 8 nodes of the three large-scale networks.

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Nov
2017

Whether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia.
To understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how first-episode patients (FEP) may differ from multiple episode patients (MEP).
These issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks.

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Nov
2017

The distributed connectivity among brain regions is in a constant state of flux, even when a subject is at rest. This instability (temporal variability), when optimal, may contribute to efficient cross-network communications. We investigate the role of this variability in the genetic diathesis and symptom expression of schizophrenia.

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Nov
2017

Developing a mechanistic insight into the specific brain processes that underpin improvement in negative symptoms can help us design novel chemical and physical treatments against these unrelenting symptoms. The aim of the present study is to explore the longitudinal changes in the brain's regional functional efficiency that accompany improvement in negative symptoms seen in first-episode patients with schizophrenia when treated with antipsychotic for 1 year. Forty-seven first-episode patients with schizophrenia were scanned at a drug-naive baseline state and followed up for 1 year to identify negative symptom responders (Rn) and non-responders (NRn).

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Sep
2017

The prepsychotic phase of schizophrenia is not only important for indicated prevention strategies, but also crucial for developing mechanistic models of the emergence of frank psychosis (transition). This commentary highlights the work of Dukart and colleagues, published in this issue of the, who sought to identify MRI-based anatomic endophenotypes of psychosis in a well-characterized sample of patients with at-risk mental state (ARMS) and first-episode psychosis (FEP). Conceptual and translational challenges in clarifying the neurobiology of transitional prepsychotic states are discussed.

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Aug
2017

One of the few well-replicated features of schizophrenia is the demonstration of neuroanatomical abnormalities affecting cortical and subcortical grey matter (GM). Evidence to date suggests that the greatest reduction in GM occurs in the immediate post-onset phase. The predominant view to date is that the accelerated grey matter (GM) loss represents an adverse process (degenerative or developmental deficit) contributing to the unfavourable course of schizophrenia.

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Oct
2016

Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored.

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Feb
2017

Repetitive transcranial magnetic stimulation (rTMS) has been used worldwide to treat depression. However, the exact physiological effects are not well understood. Pathophysiology of depression involves crucial limbic structures (e.

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Dec
1969

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients).

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Dec
1969

Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes.

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Dec
2015

This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion) techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsychiatric disorders. An overview of clinical hybrid brain imaging technologies for human use is followed by a selective review of the literature that conceptualizes the use of these technologies in understanding basic mechanisms of major neuropsychiatric disorders and their therapeutics.

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Apr
2016

Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity.

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Mar
2016

Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia.

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Mar
2016

Subtle but widespread deficit in the cortical and subcortical grey matter is a consistent neuroimaging observation in schizophrenia. Several studies have used voxel based morphometry (VBM) to investigate the nature of this structural deficit. We conducted a diagnostic test review to explore the diagnostic potential of VBM in differentiating schizophrenia from other types of first-episode psychoses.

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Dec
1969

Subtle disturbances of visual and motor function are known features of schizophrenia and can greatly impact quality of life; however, few studies investigate these abnormalities using simple visuomotor stimuli. In healthy people, electrophysiological data show that beta band oscillations in sensorimotor cortex decrease during movement execution (event-related beta desynchronisation (ERBD)), then increase above baseline for a short time after the movement (post-movement beta rebound (PMBR)); whilst in visual cortex, gamma oscillations are increased throughout stimulus presentation. In this study, we used a self-paced visuomotor paradigm and magnetoencephalography (MEG) to contrast these responses in patients with schizophrenia and control volunteers.

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Nov
2015

Spatial variation in connectivity is an integral aspect of the brain's architecture. In the absence of this variability, the brain may act as a single homogenous entity without regional specialization. In this study, we investigate the variability in functional links categorized on the basis of the presence of direct structural paths (primary) or indirect paths mediated by one (secondary) or more (tertiary) brain regions ascertained by diffusion tensor imaging.

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Aug
2015

Schizophrenia is a psychiatric disorder which involves distortions in thought and perception, blunted affect, and behavioural disturbances. The longer psychosis goes unnoticed and untreated, the more severe the repercussions for relapse and recovery. There is some evidence that early intervention services can help, and diagnostic techniques that could contribute to early intervention may offer clinical utility in these situations.

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Oct
2015

Persistent formal thought disorder (FTD) is one of the most characteristic features of schizophrenia. Several neuroimaging studies report spatially distinct neuroanatomical changes in association with FTD. Given that most studies so far have employed a univariate localisation approach that obscures the study of covarying interregional relationships, the present study focussed on the multivariate systemic pattern of anatomical changes that contribute to FTD.

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Nov
2015

In 41 patients with schizophrenia, we used neuroanatomical information derived from structural imaging to identify patients with more severe illness, characterised by high symptom burden, low processing speed, high degree of illness persistence and lower social and occupational functional capacity. Cortical folding, but not thickness or volume, showed a high discriminatory ability in correctly identifying patients with more severe illness.

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Aug
2015

Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n = 25, 1 female) and typically developing controls (n = 24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area.

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Jun
2015

As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are of significant benefit to depressed working age adults. Repetitive transcranial magnetic stimulation (rTMS) is a novel physical treatment approach used mostly in working age adults with depression.

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Jun
2015

An imbalance in neural activity within large-scale networks appears to be an important pathophysiological aspect of depression. Yet, there is little consensus regarding the abnormality within the default mode network (DMN) in major depressive disorder (MDD). In the present study, 16 first-episode, medication-naïve patients with MDD and 16 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest.

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Dec
1969

This paper details a methodology which, when applied to magnetoencephalography (MEG) data, is capable of measuring the spatio-temporal dynamics of 'disorder' in the human brain. Our method, which is based upon signal entropy, shows that spatially separate brain regions (or networks) generate temporally independent entropy time-courses. These time-courses are modulated by cognitive tasks, with an increase in local neural processing characterised by localised and transient increases in entropy in the neural signal.

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May
2015


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Apr
2015

Resting-state fMRI studies investigating the pathophysiology of depression have identified prominent abnormalities in large-scale brain networks. However, it is unclear if localized dysfunction of specialized brain regions contribute to network-level abnormalities. We employed a meta-analytical procedure and reviewed studies conducted in China investigating changes in regional homogeneity (ReHo), a measure of localized intraregional connectivity, from resting-state fMRI in depression.

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Dec
1969

Wernicke's concept of 'sejunction' or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits.
We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs.

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Oct
2014

Although oxytocin is one of the most widely studied neuropeptides in recent times, the mechanistic process by which it modulates social-affective behavior in the brain is not yet clearly understood. Thus, to understand the neurophysiological basis of oxytocin effects, we used resting-state functional MRI to examine the effects of intranasal oxytocin on brain connectivity in healthy males.
Using a randomized, double-blinded, placebo-controlled, crossover design, 15 healthy male volunteers received 24 IU intranasal oxytocin or placebo prior to resting-state functional MRI acquisition at 3T.

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Mar
2015

wMania and depression in bipolar disorder (BP) manifest two extremes of aberrant emotional, physiologic and behavioral arousal states despite similarities in treatment response and neurocognitive deficits. We used resting-state functional magnetic resonance imaging (rsfMRI) to explore the common and unique abnormal functional connectivity underlying acute manic or depressed state in BP.
18 Patients with bipolar mania (BM), 10 patients with bipolar depression (BD) and 28 healthy controls underwent resting-state functional magnetic resonance imaging scanning.

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Mar
2015

Structural connectivity of the salience-executive loop in schizophrenia.

Eur Arch Psychiatry Clin Neurosci 2015 Mar 26;265(2):163-6. Epub 2014 Sep 26.
Sarina J Iwabuchi, Peter F Liddle, Lena Palaniyappan
Previously, differences have been shown in effective connectivity of the salience network between healthy controls and patients with schizophrenia. Specifically, the right anterior insula (rAI) fails to modulate the dorsolateral prefrontal cortex (DLPFC). In 35 controls and 31 patients with schizophrenia, we extended these findings by investigating the white matter connectivity of this pathway using tractography, and its relationship with the disrupted effective connectivity.

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Nov
2014

Recent work has identified disruption of several brain networks involving limbic and cortical regions that contribute to the generation of diverse symptoms of major depressive disorder (MDD). Of particular interest are the networks anchored on the right anterior insula, which binds the cortical and limbic regions to enable key functions that integrate bottom-up and top-down information in emotional and cognitive processing. Emotional appraisal has been linked to a presumed hierarchy of processing, from sensory percepts to affective states.

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Jul
2015

The highly convoluted shape of the adult human brain results from several well-coordinated maturational events that start from embryonic development and extend through the adult life span. Disturbances in these maturational events can result in various neurological and psychiatric disorders, resulting in abnormal patterns of morphological relationship among cortical structures (structural covariance). Structural covariance can be studied using graph theory-based approaches that evaluate topological properties of brain networks.

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Jun
2014

Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes.

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Mar
2014

The efficiency of human brain depends on the integrity of both long- and short-range connections, but the long-range connections need to be "penalized" to reduce overall wiring costs. This principle, termed as the anatomical distance function (ADF), refers to the presence of an inverse relationship between anatomical distance and connectivity. A crucial developmental feature that occurs in normal adolescence is the weakening of ADF, which is characterized by a selective strengthening of long-distance connections.

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Dec
1969

Machine-learning approaches are becoming commonplace in the neuroimaging literature as potential diagnostic and prognostic tools for the study of clinical populations. However, very few studies provide clinically informative measures to aid in decision-making and resource allocation. Head-to-head comparison of neuroimaging-based multivariate classifiers is an essential first step to promote translation of these tools to clinical practice.

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Aug
2013

For effective information processing, two large-scale distributed neural networks appear to be critical: a multimodal executive system anchored on the dorsolateral prefrontal cortex (DLPFC) and a salience system anchored on the anterior insula. Aberrant interaction among distributed networks is a feature of psychiatric disorders such as schizophrenia. We used whole-brain Granger causal modeling using resting fMRI and observed a significant failure of both the feedforward and reciprocal influence between the insula and the DLPFC in schizophrenia.

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Oct
2013

At present, no reliable predictors exist to distinguish future responders from nonresponders to treatment during the first episode of psychosis. Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterize, already at illness onset, a subgroup of patients with particularly poor outcome.
To determine whether patients with first-episode psychosis who do not respond to 12 weeks of antipsychotic treatment already have significant gyrification defects at illness onset.

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May
2014

The point of rarity in brain structure and function that separates the 2 major psychotic disorders--schizophrenia and bipolar disorder--is presently unknown. The aim of this study is to combine surface anatomical and functional imaging modalities to quantify the integrity of cortical connectivity in pursuit of the neural basis of the Kraepelinian "line of divide." We tested the hypothesis that multimodal brain regions show overlapping abnormalities in both disorders, while schizophrenia-specific defects are likely to be localized to sensory processing regions.

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Aug
2013

Diverse pathological changes occur in the white matter (WM) of patients with schizophrenia. Various microstructural alterations including a reduction in axonal number or diameter, reduced myelination, or poor coherence of fibers could account for these changes. Abnormal integrity of macromolecules such as myelin ('dysmyelination') can be studied by applying multiple modalities of WM imaging such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) in parallel.

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Jan
2013

Neuroimaging studies of brain anatomy in autism spectrum disorder (ASD) have mostly been based on measures of cortical volume (CV). However, CV is a product of 2 distinct parameters, cortical thickness (CT) and surface area (SA), that in turn have distinct genetic and developmental origins.
To investigate regional differences in CV, SA, and CT as well as their relationship in a large and well-characterized sample of men with ASD and matched controls.

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Oct
2012

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries.

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Oct
2012

Several studies have found widespread structural changes affecting the grey matter at various stages of schizophrenia (the prodrome, first-episode, and the chronic stage). It is unclear which of these neuroanatomical changes are associated with a predisposition or vulnerability to develop schizophrenia rather than the appearance of the clinical features of the illness.
16 voxel-based morphometry (VBM) analyses involving 733 genetically high-risk relatives (HRR) of patients with schizophrenia, 563 healthy controls and 474 patients were meta-analysed using the Signed Differential Mapping (SDM) technique.

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Nov
2012

Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in connectivity at an early period of cortical maturation can result in widespread defects in gyrification. Investigating the anatomic distribution of gyrification defects can provide important information about neurodevelopment in patients with schizophrenia.

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Jun
2012

To date, magnetic resonance imaging (MRI)-based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS).

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Oct
2012

Dissociable morphometric differences of the inferior parietal lobule in schizophrenia.

Eur Arch Psychiatry Clin Neurosci 2012 Oct 28;262(7):579-87. Epub 2012 Mar 28.
Lena Palaniyappan, Peter F Liddle
Inferior parietal lobule (IPL) forms an integral part of a critical frontoparietal network, which has been implicated in various clinical symptoms and cognitive deficits seen in schizophrenia. Despite its functional relevance, the relatively few studies that have investigated the structural changes in the IPL report inconsistent findings concerning the nature and localization of these changes. We employed a blinded, automated labelling procedure to measure cortical thickness, surface area and the degree of cortical folding of the two distinct subregions of the IPL (Angular Gyrus and Supramarginal Gyrus) in 57 patients with schizophrenia and 41 controls using high-resolution magnetic resonance imaging.

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May
2012

Despite being one of the most common symptoms of schizophrenia, determining the neural correlates of auditory hallucinations still remains elusive with various studies providing inconsistent results.
We conducted a voxel-based meta-analysis of studies investigating the structural correlates of auditory hallucinations in schizophrenia.
7 datasets including 350 patients were identified.

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Mar
2012

Voxel Based Morphometry (VBM) and Surface Based Morphometry (SBM) are the two most commonly used methods to study the structure of gray matter in various disease states such as schizophrenia. Though overlapping changes have been observed in same datasets using the two procedures, the proportional contribution of the anatomical properties of the cortical mantle such as thickness, surface area and gyrification to the group differences in gray matter volume (GMV) observed using VBM is unknown. In the present study, we investigate the relationship between the GMV and the anatomical properties of the cortical mantle in regions showing significant VBM changes in schizophrenia using a sample of 57 patients and 41 healthy controls.

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Jan
2012

The insular cortex is one of the brain regions that show consistent abnormalities in both structural and functional neuroimaging studies of schizophrenia. In healthy individuals, the insula has been implicated in a myriad of physiologic functions. The anterior cingulate cortex (ACC) and insula together constitute the salience network, an intrinsic large-scale network showing strong functional connectivity.

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Jul
2011

In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls.

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May
2011

Anatomy of prefrontal cortex in schizophrenia has been studied previously by quantifying the degree of gyrification. Conflicting results exist, with some studies showing hypergyria and others showing hypogyria. It is likely that regional variations in cortical folding exist within the prefrontal cortex that could be explored by studying the anatomical subdivisions formed by the sulci and gyri.

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