Preservation and compensation: The functional neuroanatomy of insight and working memory in schizophrenia

BackgroundPoor insight in schizophrenia has been theorised to reflect a cognitive deficit that is secondary to brain abnormalities, localized in the brain regions that are implicated in higher order cognitive functions, including working memory (WM). This study investigated WM-related neural substrates of preserved and poor insight in schizophrenia.MethodForty stable schizophrenia outpatients, 20 with preserved and 20 with poor insight (usable data obtained from 18 preserved and 14 poor insight patients), and 20 healthy participants underwent functional magnetic resonance imaging (fMRI) during a parametric ‘n-back’ task. The three groups were preselected to match on age, education and predicted IQ, and the two patient groups to have distinct insight levels. Performance and fMRI data were analysed to determine how groups of patients with preserved and poor insight differed from each other, and from healthy participants.ResultsPoor insight patients showed lower performance accuracy, relative to healthy participants (p = 0.01) and preserved insight patients (p = 0.08); the two patient groups were comparable on symptoms and medication. Preserved insight patients, relative to poor insight patients, showed greater activity most consistently in the precuneus and cerebellum (both bilateral) during WM; they also showed greater activity than healthy participants in the inferior–superior frontal gyrus and cerebellum (bilateral). Group differences in brain activity did not co-vary significantly with performance accuracy.ConclusionsThe precuneus and cerebellum function contribute to preserved insight in schizophrenia. Preserved insight as well as normal-range WM capacity in schizophrenia sub-groups may be achieved via compensatory neural activity in the frontal cortex and cerebellum.     

Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders

BackgroundDual-task is a challenge for Parkinson's disease patients with postural instability and gait disorders (PD-PIGD).ObjectiveThis study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI).MethodsTwenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Single and dual-task Timed-Up-and-Go tests were monitored using an optoelectronic system to study turning velocity. Patients underwent executive-attentive function evaluation and two fMRI tasks: motor-task (foot anti-phase movements), and dual-task (foot anti-phase movements while counting backwards by threes starting from 100). Twenty-three healthy subjects underwent neuropsychological and fMRI assessments.ResultsDual-task in PD-PIGD patients resulted in worse gait performance, particularly during turning. Performing the dual-task relative to the motor-fMRI task, healthy subjects showed widespread increased recruitment of sensorimotor, cognitive and cerebellar areas and reduced activity of inferior frontal and supramarginal gyri, while PD-PIGD patients showed increased recruitment of inferior frontal gyrus and supplementary motor area and reduced activity of primary motor, supramarginal and caudate areas. Dual-task gait alterations in patients correlated with balance and executive deficits and with altered dual-task fMRI brain activity of frontal areas.ConclusionsThis study suggested the correlation between dual-task gait difficulties, postural instability and executive dysfunction in PD-PIGD patients. FMRI results suggest that an optimized recruitment of motor and cognitive networks is associated with a better dual-task performance in PD-PIGD. Future studies should evaluate the effect of specific gait/balance and dual-task trainings to improve gait parameters and optimize brain functional activity during dual-tasks.     

Neural changes following cognitive remediation therapy for schizophrenia

Patients with schizophrenia experience cognitive impairments that relate to poorer social functioning even after amelioration of positive symptoms. Pharmacological treatment and cognitive remediation are the two important therapeutic approaches for cognitive impairment in schizophrenia. Cognitive remediation therapy (CRT) for schizophrenia improves cognitive functioning and induces neuroplasticity, but different approaches and durations of CRT and different neuroimaging devices have led to varying results in meta‐analyses. The objective of this review was to explore the impact of CRT on neurobiology. Several studies have provided evidence of increased activation in the frontal brain regions, such as the prefrontal cortex, anterior cingulate cortex, and parietal and occipital regions during working memory or executive function tasks after CRT. Two studies have shown alterations in resting‐state connectivity between the prefrontal cortex and temporal regions. Two studies have reported that CRT induces changes in gray matter volume in the hippocampus. Further, one study observed that patients who had received CRT had elevated fractional anisotropy in the basal ganglia. We conclude that neuroimaging studies assessing CRT in patients with schizophrenia showed functional, structural, and connectivity changes that were positively correlated with cognitive improvements despite heterogeneous CRT approaches. Future studies that combine multiple modalities are required to address the differences, effects of intrinsic motivation, and pharmacological augmentation of CRT. Further understanding of the biological basis might lead to predictions of the CRT response in patients with schizophrenia and contribute to identification of schizophrenia patients for future interventions.     

Context-dependent amygdala-prefrontal connectivity in youths with autism spectrum disorder

BackgroundThe amygdala-prefrontal cortex circuit is involved in processing socio-emotional cues and may partially mediate social impairment in autism spectrum disorder (ASD). Past task-based fMRI studies in ASD indicate a mix of hypo- and hyper-connectivity in response to socio-emotional stimuli whereas resting state studies report hypoconnectivity between these regions. However, it is still unknown whether ASD-related alterations in amygdala-prefrontal circuitry are present across socio-emotional tasks and resting state contexts within the same sample or instead, depend on context.MethodASD (n = 47) and typically developing individuals (TD; n = 72) underwent fMRI during an implicit emotional face processing task and during rest, and whole-brain amygdala connectivity was calculated to determine patterns that differed by context and diagnosis.ResultsRelative to TD, the ASD group demonstrated weaker left amygdala connectivity with the medial frontal gyrus and the left superior frontal gyrus during rest, but stronger connectivity during task. Furthermore, across both contexts, ASD vs. TD had stronger right amygdala connectivity with the left insula/superior temporal gyrus.ConclusionFindings suggest some alterations in amygdala connectivity of ASD may depend on context while others are pervasive across task and rest conditions. Understanding context-dependent brain alterations in ASD may help disambiguate the mechanisms subserving social impairment and provide targets for treatment.     

White matter abnormalities and brain activation in schizophrenia: a combined DTI and fMRI study

Diffusion tensor imaging (DTI) studies of schizophrenia have revealed white matter abnormalities in several areas of the brain. The functional impact on either psychopathology or cognition remains, however, poorly understood. Here we analysed both functional MRI (during a working memory task) and DTI data sets in 18 patients with schizophrenia and 18 controls. Firstly, DTI analyses revealed reductions of fractional anisotropy (FA) in the right medial temporal lobe adjacent to the right parahippocampal gyrus, likely to contain fibres of the inferior cingulum bundle, and in the right frontal lobe. Secondly, functional MRI revealed prefrontal, superior parietal and occipital relative hypoactivation in patients with the main effect of task. This was accounted for by reduced prefrontal activation during the encoding phase of the task, but not during maintenance or retrieval phases. Thirdly, we found a direct correlation in patients between the frontal FA reduction (but not medial temporal reductions) and fMRI activation in regions in the prefrontal and occipital cortex. Our study combining fMRI and DTI thus demonstrates altered structure-function relationships in schizophrenia. It highlights a potential relationship between anatomical changes in a frontal-temporal anatomical circuit and functional alterations in the prefrontal cortex.     

EEG-Informed fMRI Reveals a Disturbed Gamma-Band–Specific Network in Subjects at High Risk for Psychosis

Objectives. Abnormalities of oscillatory gamma activity are supposed to reflect a core pathophysiological mechanism underlying cognitive disturbances in schizophrenia. The auditory evoked gamma-band response (aeGBR) is known to be reduced across all stages of the disease. The present study aimed to elucidate alterations of an aeGBR-specific network mediated by gamma oscillations in the high-risk state of psychosis (HRP) by means of functional magnetic resonance imaging (fMRI) informed by electroencephalography (EEG). Methods. EEG and fMRI were simultaneously recorded from 27 HRP individuals and 26 healthy controls (HC) during performance of a cognitively demanding auditory reaction task. We used single trial coupling of the aeGBR with the corresponding blood oxygen level depending response (EEG-informed fMRI). Results. A gamma-band–specific network was significantly lower active in HRP subjects compared with HC (random effects analysis, P < .01, Bonferroni-corrected for multiple comparisons) accompanied by a worse task performance. This network involved the bilateral auditory cortices, the thalamus and frontal brain regions including the anterior cingulate cortex, as well as the bilateral dorsolateral prefrontal cortex. Conclusions. For the first time we report a reduced activation of an aeGBR-specific network in HRP subjects brought forward by EEG-informed fMRI. Because the HRP reflects the clinical risk for conversion to psychotic disorders including schizophrenia and the aeGBR has repeatedly been shown to be altered in patients with schizophrenia the results of our study point towards a potential applicability of aeGBR disturbances as a marker for the prediction of transition of HRP subjects to schizophrenia.Key words: prodromal state of schizophrenia, auditory evoked gamma-band response, simultaneous EEG-fMRI, anterior cingulate cortex, auditory cortex     

The Effects of Methylphenidate on Neural Substrates Associated with Interference Suppression in Children with ADHD: A Preliminary Study Using Event Related fMRI

Objective

The core deficit of attention deficit hyperactivity disorder (ADHD) is associated with frontal cortex and related circuitry. Children with ADHD and a medication history have shown atypical brain activation in prefrontal and striatal brain regions during cognitive challenge. We investigated two cognitive control operations such as interference suppression (IS) and response inhibition (RI) in children with ADHD. We also assessed the brain functions affected by the methylphenidate (MPH) effect by comparing the blood-oxygen level dependent (BOLD) signals in ADHD children on and off medication.

Methods

Eight children (9-11 years of age) with combined-type ADHD underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Two fMRI (3.0 T) scans were conducted with a one week interval-one with MPH treatment and the other without. Functional maps were generated through group averaging and performance-based correlational analyses.

Results

Performances of the two cognitive control operations did not differ significantly between on-MPH and off-MPH status other than the reaction time to incongruent stimuli in ADHD children. In those affected by MPH treatment, an increased activation in the right prefrontal cortex during incongruent task was observed relative to a neutral trial in children with ADHD.

Conclusion

On the treatment of MPH, the ADHD children exhibited increased activation of the right frontal cortex during interference suppression. This finding suggested that MPH affected the right frontal cortex in ADHD compensating for a reduced level of interference suppression. Future studies will be required to ascertain the MPH effect of cognitive brain regions among large number of children with ADHD.     

Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease

BackgroundVerbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinson’s disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas.ObjectiveThe aim of this study was to assess the differences in the effects induced by tDCS applied to frontal and temporo-parietal areas on phonemic and semantic fluency functional networks in patients with PD.MethodSixteen patients were randomized to receive tDCS to left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex (TPC) in a counterbalanced order. Immediately following stimulation, patients underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by tDCS in activation and deactivation task-related pattern networks were studied using free-model independent component analyses (ICA).ResultsFunctional connectivity in verbal fluency and deactivation task-related networks was significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS increased performance on the phonemic fluency task, after adjusting for baseline phonemic performance.ConclusionsThese findings provide evidence that tDCS to specific brain regions induces changes in large scale functional networks that underlay behavioural effects, and suggest that tDCS might be useful to enhance phonemic fluency in PD.     

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

BackgroundPrefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia.Objective/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity.MethodsWe enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition.ResultsOf the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004).ConclusionsSubjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.     

An fMRI investigation of procedural learning in unaffected siblings of individuals with schizophrenia

Vulnerability for schizophrenia is related, in part, to genetic predisposition. The identification of pathophysiological abnormalities associated with the disorder that are also present in unaffected family members of individuals with schizophrenia may assist in delineating the genetic contributions to vulnerability for schizophrenia. Previous functional Magnetic Resonance Imaging (fMRI) investigations of procedural learning in patients with schizophrenia identified reduced activity in the frontal cortex, basal ganglia, and parietal cortex during performance of the serial reaction time (SRT) task suggesting that abnormal function of these regions may relate to genetic vulnerability for schizophrenia. In order to examine this hypothesis, 12 unaffected siblings of patients and 15 controls underwent fMRI during performance of the SRT task. Unaffected siblings demonstrated normal performance on the SRT task. However, compared to controls unaffected siblings demonstrated less activity in regions of the frontal and parietal lobes and, to a lesser extent, basal ganglia, during procedural learning. Interestingly, unaffected siblings demonstrated greater activity in regions of the frontal cortex during the control condition compared to the procedural learning condition of the SRT task, an idiosyncratic pattern that was also observed in patient groups but not control subjects of two prior imaging studies. The findings support previous investigations suggesting that altered cerebral neurophysiology during performance of cognitive tasks may be related to genetic vulnerability for schizophrenia. Identification of genes related to the function of cerebral regions such as the prefrontal cortex, parietal lobe, and basal ganglia may assist in delineating the genetic contributions to schizophrenia.     

Working memory dysfunction in schizophrenia patients with obsessive-compulsive symptoms: An fMRI study

BackgroundA substantial proportion of schizophrenia patients also meets DSM-IV criteria for obsessive-compulsive disorder (OCD). Schizophrenia with OCD (“schizo-obsessive”) patients are characterized by distinct clinical characteristics, treatment response and prognosis. Whether schizo-obsessive patients exhibit a distinct pattern of brain activation is yet unknown. To address this question, the present functional magnetic resonance imaging (fMRI) study explicitly compared alterations in brain activation and functional connectivity (FC) underlying a working memory deficit in schizophrenia patients with and without OCD.MethodsfMRI was applied during the N-back working memory (WM) task in three groups: schizo-obsessive (n = 16), schizophrenia (n = 17) and matched healthy volunteers (n = 20). WM-related activation in the right dorsolateral prefrontal cortex (DLPFC) and the right caudate nucleus, brain areas relevant to schizophrenia and OCD, and FC analysis were used for the evaluation.ResultsThe two schizophrenia groups with and without OCD exhibited a similar reduction in activation in the right DLPFC and right caudate, as well as decreased FC compared to the healthy controls. Notably, reduced regional brain activation was not related to severity of schizophrenic or OCD symptoms.ConclusionsSchizo-obsessive patients do not differ from their non-OCD schizophrenia counterparts in brain activation patterns during the N-back WM task. Cognitive paradigms taping alternative neural networks (e.g., orbitofrontal cortex) particularly relevant to OCD, are warranted in the search for potential distinctive brain activation patterns of the schizo-obsessive subgroup.     

Resting state brain network function in major depression – Depression symptomatology,antidepressant treatment effects,future research

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.     

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. © 2015 Wiley Periodicals, Inc .     

fMRI reveals alteration of spatial working memory networks across adolescence.

Recent studies have described neuromaturation and cognitive development across the lifespan, yet few neuroimaging studies have investigated task-related alterations in brain activity during adolescence. We used functional magnetic resonance imaging (fMRI) to examine brain response to a spatial working memory (SWM) task in 49 typically developing adolescents (25 females and 24 males; ages 12-17). No gender or age differences were found for task performance during SWM. However, age was positively associated with SWM brain response in left prefrontal and bilateral inferior posterior parietal regions. Age was negatively associated with SWM activation in bilateral superior parietal cortex. Gender was significantly associated with SWM response; females demonstrated diminished anterior cingulate activation and males demonstrated greater response in frontopolar cortex than females. Our findings indicate that the frontal and parietal neural networks involved in spatial working memory change over the adolescent age range and are further influenced by gender. These changes may represent evolving mnemonic strategies subserved by ongoing adolescent brain development.     

Altered executive function in the lead-exposed brain: A functional magnetic resonance imaging study

IntroductionIt is well known that lead exposure induces neurotoxic effects, which can result in dysfunction in a variety of cognitive capacities including executive function. However, few studies have used fMRI to examine the direct neural correlates of executive function in participants with past lead exposure. Therefore, this study aimed to investigate possible alterations in the neural correlates of executive function in the previously lead-exposed brain.MethodsForty-three lead-exposed and 41 healthy participants were enrolled. During the fMRI scans, participants performed two modified versions of the Wisconsin Card Sorting Task (WCST) differing in cognitive demand, and a task that established a high-level baseline condition (HLB).ResultsThe neural activation of left dorsolateral prefrontal cortex was greater in healthy controls than in participants with lead exposure when contrasting the difficult version of the WCST with the HLB. Moreover, cortical activation was found to be inversely associated with blood lead concentration after controlling for covariates.DiscussionThese data suggest that lead exposure can induce functional abnormalities in distributed cortical networks related to executive function, and that lead-induced neurotoxicity may be persistent rather than transient.     

Altered Amygdala Connectivity Within the Social Brain in Schizophrenia

Background: Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. Methods: We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. Results: While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. Discussion: We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.Key words: fMRI, social cognition, approachability, psychosis, neural, psychophysiological interaction     

Cortical hemodynamic mechanisms of reversal learning using high-resolution functional near-infrared spectroscopy: A pilot study

ObjectivesReversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in reversal learning, few studies have focused on whether reward and punishment may have different effects on lateral frontal structures in these tasks.MethodsDuring this pilot study on eight healthy subjects, we used functional near infra-red spectroscopy (fNIRS) to characterize brain activity dynamics and differentiate the involvement of frontal structures in learning driven by reward and punishment.ResultsWe observed functional hemispheric asymmetries between punishment and reward processing by fNIRS following reversal of a learned rule. Moreover, the left dorsolateral prefrontal cortex (l-DLPFC) and inferior frontal gyrus (IFG) were activated under the reward condition only, whereas the orbito-frontal cortex (OFC) was significantly activated under the punishment condition, with a tendency towards activation for the right cortical hemisphere (r-DLPFC and r-IFG). Our results are compatible with the suggestion that the DLPFC is involved in the detection of contingency change. We propose a new representation for reward and punishment, with left lateralization for the reward process.ConclusionsThe results of this pilot study provide insights into the indirect neural mechanisms of reversal learning and behavioral flexibility and confirm the use of fNIRS imaging in reversal-learning tasks as a translational strategy, particularly in subjects who cannot undergo fMRI recordings.     

Abnormal brain activity patterns during spatial working memory task in patients with end-stage renal disease on maintenance hemodialysis: a fMRI study

Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.

     

Reduced language lateralization in first-episode schizophrenia: An fMRI index of functional asymmetry

Patients with schizophrenia exhibit a decrease or loss of normal anatomical brain asymmetry that also extends to functional levels. We applied functional magnetic resonance imaging (fMRI) to investigate language lateralization in patients with schizophrenia during their first episode of illness, thus excluding effects of chronic illness and treatment. Brain regions activated during language tasks of verb generation and passive music listening were explored in 12 first-episode patients with schizophrenia and 17 healthy controls. Regions of interest corresponded to Broca's area in the inferior frontal gyrus (IFG) and Wernicke's area in the superior temporal sulcus (STS). Patients with schizophrenia had significantly smaller lateralization indices in language-related regions than controls. A similar effect was observed in their IFG and STS regions. There was no difference between the groups in the auditory cortex for the music task. Patients with schizophrenia demonstrated greater activation than the controls in temporal regions: the difference was larger in patients with more severe positive symptom subscores. In conclusion, patients with schizophrenia demonstrated loss of normal functional brain asymmetry, as reflected in diminished lateralization of language-related activation in frontal and temporal regions. This phenomenon was already present during their first episode of psychosis, possibly reflecting developmental brain abnormalities of the illness.     

Neuroimagerie de l’insight dans la schizophrénie : revue de la littérature

ObjectivesInsight in psychiatry has been defined and conceptualized in a number of ways but none of them was found to be self-explanatory. There has been an exponential rise in studies of insight, in part accelerated by the availability of several psychometric scales for measuring insight. Lack of insight has been associated in schizophrenia with low treatment adherence, a high number of relapses, increased number of hospital admissions, and subsequently poorer psychological and cognitive functioning. For this reason, there is considerable interest in understanding the underlying neural mechanisms of insight, which may have important implications for the development of future insight-oriented neuro-psychiatric treatment. Neuroimaging may be considered an important technique to help understand the anatomical, functional and metabolic neurocircuitry underlying poor insight in schizophrenia. Growing neuroimaging research provides evidence for underlying brain impairment in insight deficits in schizophrenia. In order to expose a panoramic view to the readers, this article reviews the neuroimaging studies conducted to date, which have investigated the neural bases of insight in schizophrenia.MethodsElectronic searches were performed in PubMed, PsycINFO, Sciencedirect and Web of Science databases, using the following keywords: Imaging; neuroimaging; Positron Emission Tomography (PET); spectroscopy; functional Magnetic Resonance Imaging (fMRI); structural Magnetic Resonance Imaging (MRI); Single Photon Emission Computed Tomography (SPECT); Voxel Based Morphometry (VBM); Diffusion Tensor Imaging (DTI); Computed Tomography (CT); Insight; schizophrenia; awareness of illness. Searches were also performed from the references of the systematic review articles on neurobiological correlates of insight in schizophrenia. Animal studies and single case reports were excluded. Twenty-five articles were selected for the present review. From these; 12 used structural MRI; 6 used VBM; 3 used fMRI; 2 used CT; 1 used DTI and 1 used VBM combined to DTI.ResultsThe search showed that studies in this area were published recently and that the neuroanatomic substrate of insight in schizophrenia has not yet been consolidated. This inconsistency could arise from the complex nature of insight and the use of a variety of insight assessments. Most of the studies analyzed in this review used structural neuroimaging techniques to assess brain abnormalities associated with poor insight. The functional neuroanatomy of insight has only recently been investigated and to our knowledge, there are only 3 studies that have examined brain activity with fMRI in relation to insight in schizophrenia.ConclusionThis review investigated the neural deficiencies underlying poor insight in schizophrenic patients. In spite of methodological differences among studies, results provide evidence of structural and functional brain abnormalities in frontal, parietal and temporal region related to insight deficits. Some studies have found a hemispheric asymmetry in relationship to poor in insight (the majority of brain abnormalities concern the right hemisphere). In addition, growing research indicated that the prefrontal cortex, particularly the dorsolateral prefrontal cortex, the anterior cingulated cortex, the insula, the precuneus and the cerebellum can also underlying insight in schizophrenia. It is interesting to mention that some authors have suggested that each dimension of insight can be specifically linked to certain brain structures. Taking together, data on the neuropsychological and neuroanatomical correlates of clinical insight suggested that lack of insight in schizophrenia could be conceived as a neurocognitive deficit, analogously to anosognosia in brain injury and dementia. On the contrary, to date, the neuroanatomical correlates of cognitive insight have been scarcely studied. Only two studies reported that Self-reflectiveness was positively related to gray matter volume of the right ventro-lateral prefrontal cortex, the BCIS composite index was positively correlated with total left hippocampal volume, and Self-certainty was inversely correlated with bilateral hippocampal volumes. However, it is important to note that neuroimaging research on cognitive insight in schizophrenia is in a preliminary, and the results on this are inconclusive. Further research is needed to better understand the causal relationships between brain abnormalities and degradation of insight in schizophrenia.