Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia

BACKGROUND: Schizophrenia patients show reduced neural activity, relative to controls, in the amygdala and its projection to the medial prefrontal cortex (MPFC) in response to fear perception. In this study we tested the hypothesis that schizophrenia is characterized by abnormal functional connectivity in the amygdala network underlying fear perception. METHODS: Functional MRI images were acquired from 14 schizophrenia patients and 14 matched healthy control subjects during an emotion perception task, in which fearful and neutral facial expression stimuli were presented pseudorandomly under nonconscious (using masking) and conscious conditions. Both subtraction and functional connectivity analyses were undertaken using a region of interest approach. RESULTS: In response to fearful facial expressions, schizophrenia patients displayed reduced amygdala activity, compared to controls, in both the conscious and nonconscious conditions. The amygdala displayed a reversal of the normal pattern of connectivity with the brainstem, visual cortex, and also with the dorsal and ventral divisions of the MPFC in the schizophrenia patients. CONCLUSIONS: The presence of functional disconnections in amygdala pathways suggests that schizophrenia patients have a failure in coordinating their automatic orienting to salient signals and the associated prefrontal monitoring of these signals.     

Medial prefrontal functional connectivity--relation to memory self-appraisal accuracy in older adults with and without memory disorders

It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals. The current project builds on this work - examining changes in MPFC functional connectivity that correspond to impaired self-appraisal accuracy early in the AD time course. Our behavioral focus was self-appraisal accuracy for everyday memory function, and this was measured using the Memory Function Scale of the Memory Awareness Rating Scale - an instrument psychometrically validated for this purpose. Using regression analysis of data from people with healthy memory (n=12) and people with impaired memory due to amnestic mild cognitive impairment or early AD (n=12), we tested the hypothesis that altered MPFC functional connectivity - particularly with other cortical midline structures and dorsolateral prefrontal cortex - explains variation in memory self-appraisal accuracy. We spatially constrained (i.e., explicitly masked) our regression analyses to those regions that work in conjunction with the MPFC to evoke self-appraisals in a normative group. This empirically derived explicit mask was generated from the result of a psychophysiological interaction analysis of fMRI self-appraisal task data in a separate, large group of cognitively healthy individuals. Results of our primary analysis (i.e., the regression of memory self-appraisal accuracy on MPFC functional connectivity) were generally consistent with our hypothesis: people who were less accurate in making memory self-appraisals showed attenuated functional connectivity between the MPFC seed region and proximal areas within the MPFC (including subgenual anterior cingulate cortex), bilateral dorsolateral prefrontal cortex, bilateral caudate, and left posterior hippocampus. Contrary to our expectations, MPFC functional connectivity with the posterior cingulate was not significantly related to accuracy of memory self-appraisals. Results reported here corroborate findings of variable memory self-appraisal accuracy during the earliest emergence of AD symptoms and reveal alterations in MPFC functional connectivity that correspond to impaired memory self-appraisal.     

静息状态功能磁共振成像观察轻度阿尔茨海默病后扣带回功能连通性的变化

目的 利用静息状态功能磁共振成像(fMRI)研究阿尔茨海默病(AD)早期后扣带回相关的静息脑网络连通性是如何变化的.方法 运用fMRI研究了16例轻度AD患者和16名健康对照者在静息状态后扣带回的功能连通性.与后扣带回有功能连通性的脑区是通过检测低频波动信号的时程相关性获得的.应用通用的SPM2图像统计软件计算组间和组内连通性差异,激活区阈值设置:P<0.01(校正),像素范围>5.利用SPM2软件随机效应分析t检验(经校正P<0.01,t=2.47,像素范围>5),比较患者组和对照组连通性激活的脑区.结果 与后扣带回有功能连通性减弱的脑区包括前额叶中线区、楔前叶、双侧视皮质、双侧颞下回、左侧海马、右侧丘脑、右侧额叶背外侧区;偏左侧化的连通性增高的脑区包括前额叶中线区、左侧颞下回、左侧基底节区、双侧额叶背外侧区及左侧中央前区.结论 与后扣带回相关的静息状态脑网络连通性减低与AD早期情节记忆损害和高级视觉功能损害有关系,轻度AD保留着功能连接的重塑性以便维持脑功能.静息fMRI是一种探索AD脑功能机制的适宜方法.     

Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study

Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.     

Differences in resting corticolimbic functional connectivity in bipolar I euthymia

Objective: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. Methods: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low‐frequency fluctuations in blood oxygen level‐dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed‐to‐voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. Results: The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). Conclusions: Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait‐related and clinically important imaging biomarker.     

Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing

The human immunodeficiency virus (HIV) damages fronto-striatal regions, and is associated with deficits in executive functioning. We recently developed a semantic event sequencing task based on the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III for use with functional magnetic resonance imaging (fMRI) and found recruitment of dorsolateral prefrontal cortex and basal ganglia in healthy participants. To assess the impact of HIV on the functioning of the basal ganglia and prefrontal cortex, we administered this task to 11 HIV+ and 11 Control participants matched for age and education. Neuropsychological evaluation demonstrated that the HIV+ group had mild impairment in memory retrieval and motor functioning, but was not demented. Morphometric measurements suggested no atrophy in basal ganglia regions. The results of the fMRI analysis revealed hypoactivation of the left caudate, left dorsolateral prefrontal cortex, and bilateral ventral prefrontal cortex in the HIV+ group. Functional connectivity analysis demonstrated less functional connectivity between the caudate and prefrontal cortex and basal ganglia regions in the HIV+ group. In contrast, the HIV+ group demonstrated increased activation of right postcentral/supramarginal gyrus, and greater connectivity between the caudate and this same anterior parietal region. The results of this study extend previous investigations by demonstrating compromised function of the caudate and connected prefrontal regions in HIV during cognition. This disruption of fronto-striatal circuitry likely precedes the development of cognitive impairment in HIV.     

Neural circuitry of emotional face processing in autism spectrum disorders

Background

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.

Methods

Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.

Results

In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.

Limitations

The small sample size may have affected our ability to detect additional group differences.

Conclusion

When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.     

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     

Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control

Several lines of evidence suggest that the lateral prefrontal cortex (PFC), the dorsal anterior cingulate cortex (dACC), the parietal cortex, and the thalamus are central cortical nodes in a network underlying cognitive control. However, the role of catecholamine producing midbrain and brainstem structures has rarely been addressed by functional magnetic resonance imaging (fMRI). We hypothesized differential activation patterns in the ventral tegmental area (VTA)/substantia nigra (SN) and locus coeruleus (LC) with respect to the degree of cognitive control during a Stroop task in healthy subjects. Forty‐five healthy subjects were investigated by the manual version of the Stroop task in an event‐related fMRI design. We observed significant BOLD activation of both the SN/VTA and LC during the Stroop interference condition (incongruent vs. congruent condition). LC, but not SN/VTA activation significantly correlated with the Stroop interference. Interestingly, a significant linear decrease in BOLD activation during the incongruent condition during the experiment was mainly observed in the fronto‐cingulo‐striatal network, but not in SN/VTA and LC. Using psychophysiological (PPI) analyses, a significant functional connectivity during cognitive control was observed between SN/VTA and the nigrostriatal/mesolimbic dopaminergic system. For the LC, distinct functional connectivity pattern was observed mainly to the dorsolateral and ventrolateral PFC. Both regions revealed significant functional connectivity to the dACC, parietal and occipital regions. Thus, we demonstrate for the first time that functional activation patterns in the SN/VTA and the LC are modulated by different demands of cognitive control. In addition, these nuclei exhibit distinguishable functional connectivity patterns to cortical brain networks. Hum Brain Mapp 37:2305–2318, 2016. © 2016 Wiley Periodicals, Inc.     

Altered default mode network connectivity in Alzheimer's disease--a resting functional MRI and Bayesian network study

A number of functional magnetic resonance imaging (fMRI) studies reported the existence of default mode network (DMN) and its disruption due to the presence of a disease such as Alzheimer's disease (AD). In this investigation, first, we used the independent component analysis (ICA) technique to confirm the DMN difference between patients with AD and normal control (NC) reported in previous studies. Consistent with the previous studies, the decreased resting-state functional connectivity of DMN in AD was identified in posterior cingulated cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal cortex (IPC), inferior temporal cortex (ITC), and hippocampus (HC). Moreover, we introduced Bayesian network (BN) to study the effective connectivity of DMN and the difference between AD and NC. When compared the DMN effective connectivity in AD with the one in NC using a nonparametric random permutation test, we found that connections from left HC to left IPC, left ITC to right HC, right HC to left IPC, to MPFC and to PCC were all lost. In addition, in AD group, the connection directions between right HC and left HC, between left HC and left ITC, and between right IPC and right ITC were opposite to those in NC group. The connections of right HC to other regions, except left HC, within the BN were all statistically in-distinguishable from 0, suggesting an increased right hippocampal pathological and functional burden in AD. The altered effective connectivity in patients with AD may reveal more characteristics of the disease and may serve as a potential biomarker.     

Changes of brain activity in the neural substrates for theory of mind during childhood and adolescence

Theory of mind (ToM) refers to the ability to attribute independent mental states, such as beliefs, preferences and desires, to the self and others. Neuroimaging studies of normal adults have consistently demonstrated the importance of particular brain regions for ToM, the superior temporal sulcus (STS), temporal pole (TP) and the medial prefrontal cortex (MPFC). However, there are little data showing how ToM develops during childhood and adolescence. Such data are important for understanding the development of social functioning and its disorders. The authors used functional magnetic resonance imaging to study age-related changes in brain activity associated with ToM during childhood and early adolescence (9-16 years). Normally developed children and adolescents demonstrated significant activation in the bilateral STS, the TP adjacent to the amygdala (TP/Amy) and the MPFC. Furthermore, the authors found a positive correlation between age and the degree of activation in the dorsal part of the MPFC; in contrast, a negative correlation was found for the ventral part of the MPFC. The authors also found a positive correlation between the Z coordinate of the peak activation in the MPFC and age. The data indicated that activity in the MPFC associated with ToM shifted from the ventral to the dorsal part of the MPFC during late childhood and adolescence. No age-related changes were found in the STS and the TP/Amy regions. The authors consider that the age-related brain activity observed in the present study may be associated with the maturation of the prefrontal cortex and the associated development of cognitive functions.     

Disrupted neural processing of emotional faces in psychopathy

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths’ affective–interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.     

Telomere length as a predictor of emotional processing in the brain

Shorter telomere length (TL) has been associated with the development of mood disorders as well as abnormalities in brain morphology. However, so far, no studies have considered the role TL may have on brain function during tasks relevant to mood disorders. In this study, we examine the relationship between TL and functional brain activation and connectivity, while participants (n = 112) perform a functional magnetic resonance imaging (fMRI) facial affect recognition task. Additionally, because variation in TL has a substantial genetic component we calculated polygenic risk scores for TL to test if they predict face‐related functional brain activation. First, our results showed that TL was positively associated with increased activation in the amygdala and cuneus, as well as increased connectivity from posterior regions of the face network to the ventral prefrontal cortex. Second, polygenic risk scores for TL show a positive association with medial prefrontal cortex activation. The data support the view that TL and genetic loading for shorter telomeres, influence the function of brain regions known to be involved in emotional processing.     

Age‐related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

The S and L_G alleles of the serotonin transporter‐linked polymorphic region (5‐HTTLPR) lower serotonin transporter expression. These low‐expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala–prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces depression that emerges in adolescence, whereas decreased serotonin transporter that occurs later in development ameliorates depression. However, no brain imaging research has yet investigated the moderating influence of human development on the link between 5‐HTTLPR and effect‐related brain function. We investigated the age‐related effect of 5‐HTTLPR on amygdala activation and amygdala–prefrontal cortex connectivity using a well‐replicated probe, an emotional face task, in children and adolescents aged 9–19 years. A significant genotype‐by‐age interaction predicted amygdala activation, such that the low‐expressing genotype (S/S and S/L_G) group showed a greater increase in amygdala activation with age compared to the higher expressing (L_A/L_A and S/L_A) group. Additionally, compared to the higher expressing group, the low‐expressing genotype group exhibited decreased connectivity between the right amygdala and ventromedial prefrontal cortex with age. Findings indicate that low‐expressing genotypes may not result in the corticolimbic profile associated with depression risk until later adolescence. Hum Brain Mapp 35:646–658, 2014. © 2012 Wiley‐Periodicals, Inc.     

Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe (MTL), right hippocampus, parahippocampal cortex (PHC) and amygdala. Further, there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.     

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.     

Activity and functional connectivity of inferior frontal cortex associated with response conflict

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.     

Color Stroop and negative priming in schizophrenia: An fMRI study

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention—the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions–medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls–but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.     

Brain activation patterns during a selective attention test-a functional MRI study in healthy volunteers and patients with schizophrenia

Functional magnetic resonance imaging was used to compare cortical activation patterns in healthy volunteers with those in patients with schizophrenia during a modified verbal Stroop task. Healthy subjects (n=13) and patients with schizophrenia (n=13) on stable antipsychotic treatment, matched on demographic variables, were included. Patients were preselected on the basis of good performance on a selective attention test. Patients with schizophrenia showed a significantly increased pattern of activation in the left and right inferior frontal cortex and the anterior cingulate cortex. A significant negative correlation between activation of the left prefrontal cortex and accuracy in the modified Stroop test was observed for healthy controls but not schizophrenia patients. Although both groups recruited the prefrontal cortex during the modified Stroop task, for the schizophrenia patients this activation was bilateral, whereas for the controls this activation was primarily in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls. Our findings of increased activity across multiple areas of the brain, including dorsolateral frontal cortex and anterior cingulate, in patients with schizophrenia who perform relatively well on a task of selective attention give further evidence that task performance may be a confounding factor in the interpretation of neuroimaging results.     

Remote effects of hippocampal damage on default network connectivity in the human brain

In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.