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.     

Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study

The underlying mechanisms and neuroanatomical correlates of theory of mind (ToM), the ability to make inferences on others' mental states, remain largely unknown. While numerous studies have implicated the ventromedial (VM) frontal lobes in ToM, recent findings have questioned the role of the prefrontal cortex. We designed two novel tasks that examined the hypothesis that affective ToM processing is distinct from that related to cognitive ToM and depends in part on separate anatomical substrates. The performance of patients with localized lesions in the VM was compared to responses of patients with dorsolateral lesions, mixed prefrontal lesions, and posterior lesions and with healthy control subjects. While controls made fewer errors on affective as compared to cognitive ToM conditions in both tasks, patients with VM damage showed a different trend. Furthermore, while affective ToM was mostly impaired by VM damage, cognitive ToM was mostly impaired by extensive prefrontal damage, suggesting that cognitive and affective mentalizing abilities are partly dissociable. By introducing the concept of 'affective ToM' to the study of social cognition, these results offer new insights into the mediating role of the VM in the affective facets of social behavior that may underlie the behavioral disturbances observed in these patients.     

Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.     

An fMRI paradigm based on Williams inhibition test to study the neural substrates of attention and inhibitory control

The purpose of this study is to present an fMRI paradigm, based on the Williams inhibition test (WIT), to study attentional and inhibitory control and their neuroanatomical substrates. We present an index of the validity of the proposed paradigm and test whether the experimental task discriminates the behavioral performances of healthy participants from those of individuals with acquired brain injury. Stroop and Simon tests present similarities with WIT, but this latter is more demanding. We analyze the BOLD signal in 10 healthy participants performing the WIT. The dorsolateral prefrontal cortex, the inferior prefrontal cortex, the anterior cingulate cortex, and the posterior cingulate cortex were defined for specified region of interest analysis. We additionally compare behavioral data (hits, errors, reaction times) of the healthy participants with those of eight acquired brain injury patients. Data were analyzed with GLM-based random effects and Mann-Whitney tests. Results show the involvement of the defined regions and indicate that the WIT is sensitive to brain lesions. This WIT-based block design paradigm can be used as a research methodology for behavioral and neuroimaging studies of the attentional and inhibitory components of executive functions.     

Schizophrenia and frontal cortex: where does it fail?

Schizophrenia is characterized by cognitive, social, and emotional impairments and by psychotic symptoms. Neuroimaging studies have reported abnormalities within the prefrontal cortex and it has been hypothesized that schizophrenia results from poor or miswired anatomical/functional connections. We have compared the functional connectivity within the frontal cortex in control and schizophrenic subjects during the realization of a Continuous Performance Task. The connectivity pattern within the frontal cortex was uncovered by the analysis of the correlation matrix computed from the fMRI time series in frontal areas for 14 schizophrenic patients and 14 control subjects. In control subjects, the right dorsolateral prefrontal cortex (DLFCr) activity correlated i) positively with the left dorsolateral prefrontal cortex and the posterior part of the supplementary motor area, ii) negatively with the medial and anterior/inferior part of the frontal cortex. In the schizophrenic group, these relations were abolished or strongly lowered. The negative relation between the DLFCr and the medial frontal cortex has been proposed to play a key role in setting a harmonious balance between the direction of attention to the external world and the expression of the individual believes and self-referential activities, and therefore, the impaired relation of right DLFCr with other frontal areas could explain a distorted perception of external world in relation with internal motivations.     

Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis

Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-na?ve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.     

Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex

OBJECTIVES: Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. METHODS: Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. RESULTS: There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. CONCLUSIONS: Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder.     

A functional MRI study of multimodal selective attention following mild traumatic brain injury

Previous work suggests that the ability to selectively attend to and resolve conflicting information may be the most enduring cognitive deficit following mild traumatic brain injury (mTBI). The current study used fMRI to evaluate potential differences in hemodynamic activation in 22 mTBI patients and 22 carefully matched healthy controls (HC) during a multimodal selective attention task (numeric Stroop). Behavioral data indicated faster reaction times for congruent versus incongruent trials and for stimuli presented at 0.66 compared to 0.33 Hz across both groups, with minimal differences in behavioral performance across the groups. Similarly, there were no group-wise differences in functional activation within lateral and medial prefrontal cortex during the execution of cognitive control (incongruent versus congruent trials). In contrast, within-group comparisons indicated robust patterns of attention-related modulations (ARM) within the bilateral dorsolateral prefrontal cortex and bilateral visual streams for HC but not mTBI patients. In addition, mTBI patients failed to exhibit task-induced deactivation within the default-mode network (DMN) under conditions of higher attentional load. In summary, in spite of near normal behavioral performance, current results suggest within-group abnormalities during both the top-down allocation of visual attention and in regulating the DMN during the semi-acute stage of mTBI.     

皮质下血管性痴呆患者脑注意和执行功能区激活特征及与认知功能损害的相关性

目的 分析皮质下血管性痴呆( subcortical ischemic vascular dementia,SIVD)患者脑注意和执行功能区激活特征及其与认知功能损害的相关性.方法 SIVD患者20例,健康对照组20名,按年龄、性别、文化层次进行配对.采用Stroop任务和SEMENTS 3.0T MRI仪行功能MRI,将脑功能区激活表现与认知功能损害特征进行相关分析.结果 SIVD患者双侧背外侧前额叶、腹外侧前额叶和后顶叶激活体积均与MoCA总分、视空间与执行、注意、语言、延迟回忆、定向分项得分明显相关(r =0.447～0.837,P＜0.05).结论 Stroop任务引起的功能MRI脑激活图可以反映SIVD患者认知功能的损害.     

Relationship between performance on the Stroop test and N-acetylaspartate in the medial prefrontal cortex in deficit and nondeficit schizophrenia: preliminary results

The aim of this research was to investigate the relationship between performance on the Stroop test and N-acetylaspartate/creatine assessed using proton magnetic resonance spectroscopy in the medial prefrontal cortex (MPFC) of schizophrenia patients. The Schedule for the Deficit Syndrome was used to subdivide the schizophrenia patients into deficit (n=5) and nondeficit (n=17) subtypes. Twenty-one control subjects served as a comparison group. A strong correlation between right-sided N-acetylaspartate/creatine levels and Stroop scores was found in the deficit patients but not in the nondeficit patients and the controls. This result suggests a relationship between a dysfunction of the right medial prefrontal cortex and a deficit in selective attention in schizophrenia patients with the deficit syndrome.     

Brain activation patterns during a selective attention test--a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.     

Brain activation patterns during a selective attention test — a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.     

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

OBJECTIVE: To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). BACKGROUND: Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. METHOD: The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. RESULTS AND CONCLUSIONS: The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.     

皮质下缺血性血管性认知损害扩散张量成像研究

目的通过扩散张量成像(DTI)探讨皮质下缺血性血管性认知损害患者白质微结构变化及其与认知功能之间的相关性。方法采集49例皮质下缺血性脑血管病患者[轻度血管性痴呆(VaD)10例、非痴呆型血管性认知损害(VCIND)20例、认知功能正常19例]DTI数据并观察皮质下白质微结构改变,分析VaD组患者DTI参数与认知功能间的相关性。结果与对照组相比,VaD组内侧前额叶、前扣带回、胼胝体干、双侧顶叶、右侧颞叶、双侧眶额叶,以及VCIND组右侧额下回、右侧海马、双侧楔前叶FA值减低(均P=0.000);与VCIND组比较,VaD组内侧前额叶、前扣带回、胼胝体、双侧顶叶、右侧颞叶FA值减低(P=0.000)。与对照组相比,VaD组内侧前额叶、胼胝体、双侧顶叶、双侧颞叶、前扣带回,以及VCIND组双侧楔前叶、右侧海马MD值升高(均P=0.000);与VCIND组相比,VaD组右侧内侧前额叶、前扣带回、胼胝体干、双侧顶叶、双侧颞叶MD值升高(均P=0.000)。VaD组内侧前额叶FA值与数字连线测验A时呈显著负相关(r=-0.782,P=0.007),双侧额下回MD值与数字连线试验A时程呈显著正相关(r=0.877,P=0.001)。结论 DTI对皮质下缺血性认知损害患者白质微结构改变更敏感,能够反映患者认知功能早期异常改变;内侧前额叶白质微结构的改变是影响患者执行能力的重要因素。     

Cognitive patterns in subtypes of schizophrenia.

AIM: Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS: The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION: This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.     

An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers

OBJECTIVE: Function of the ventromedial prefrontal cortex has been implicated in impulse control. The authors used the Stroop paradigm to test attention and response inhibition during the presentation of congruent and incongruent stimuli in male pathological gamblers and a group of comparison subjects. METHOD: Event-related functional magnetic resonance imaging was used to examine ventromedial prefrontal cortex function during Stroop performance. RESULTS: In response to infrequent incongruent stimuli, pathological gamblers demonstrated decreased activity in the left ventromedial prefrontal cortex relative to the comparison subjects. Both groups demonstrated similar activity changes in multiple brain regions, including activation of the dorsal anterior cingulate and dorsolateral frontal cortex. CONCLUSIONS: Pathological gamblers share many neural correlates of Stroop task performance with healthy subjects but differ in a brain region previously implicated in disorders characterized by poor impulse control.     

Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location

There were three primary objectives: to examine the usefulness of the Stroop interference effect as a measure of frontal lobe function; to investigate the possibility of distinct lesion effects for word reading or color naming; and to specifically determine the brain regions necessary for the performance of the incongruent condition. Fifty-one patients with single focal brain lesions in frontal and non-frontal regions and 26 normal control subjects (CTL) were administered the word reading, color naming and incongruent conditions of the Stroop task. Only frontal lesions produced significant impairment. Patients with posterior lesions were not significantly deficient in any condition. Damage to the left dorsolateral frontal lobe resulted in increased errors and slowness in response speed for color naming. Contrary to Perret (Neuropsychology, 1974; 12: 323-330), lesions of the left frontal lobe did not result in a selective interference deficit on the Stroop incongruent condition. Rather, bilateral superior medial frontal damage was associated with increased errors and slowness in response time for the incongruent condition. This result is interpreted as failure of maintenance of consistent activation of the intended response in the incongruent Stroop condition. The results and conclusion are compatible with the prevalent theories of both the Stroop effect and the role of the superior medial frontal regions. The role of the anterior cingulate cortex on performance of the Stroop task is likely related to task and patient context.     

The ventromedial prefrontal cortex is involved in understanding affective but not cognitive theory of mind stories

Lesion and neuroimaging studies have implicated the medial frontal lobes as playing an important role in our ability to predict other people's behavior by attributing to them mental states, such as beliefs, intention and emotion (termed "Theory of Mind"; ToM). However, recent studies have challenged these findings by highlighting the role of the temporal-parietal junction (TPJ) in ToM. In the present study, we tested the hypothesis that the ventromedial (VM) prefrontal cortex plays a unique role in affective ToM reasoning rather than a general role in ToM. We compared the performance of patients with lesions localized either in the VM, dorsolateral, TPJ, or superior parietal to healthy controls, with a battery of naturalistic affective and cognitive ToM stories (about false beliefs, false attribution, irony and lies). Patients with VM damage were impaired at providing appropriate mental state explanations for the affective ToM stories, compared to healthy controls and patients with posterior damage. In the VM group, performance in the affective ToM was significantly impaired as compared to cognitive ToM stories. Furthermore, in the VM group, ratings of levels of emotionality of each story suggested that levels of affective load correlated with number of errors in the stories, indicating that the more the emotional load involved in the story the greater the difficulty posed for the subjects in this group.     

Altered neural mechanisms of cognitive control in patients with primary progressive multiple sclerosis: An effective connectivity study

Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search‐based effective connectivity method. Fourteen patients with PPMS and 22 age‐ and gender‐matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition. Results showed that compared to HC, PPMS patients exhibited poor behavioral performance and alterations in information flow, manifested in the form of the loss of top‐down connections, reversal of connections, and hyperconnectivity. Significant correlations were observed between connection strengths and behavioral measures. The connection between the posterior parietal cortex (PCC) and left posterior parietal lobule, which was present in both groups, showed a negative correlation with performance accuracy on incongruent trials. The connection between the left dorsolateral prefrontal cortex and PCC showed a positive correlation with performance accuracy on incongruent trials. However, the adaptive nature of this connection was not significant on a behavioral level as the PPMS group performed significantly worse compared to the HC group during the Stroop task. Thus, the current study provides important evidence about effective connectivity patterns that can be characterized as maladaptive cerebral re‐organization in the PPMS brain. Hum Brain Mapp 38:2580–2588, 2017. © 2017 Wiley Periodicals, Inc.     

Increased attentional blink after focal cerebral lesions

BACKGROUND: Once a person identifies a visual object, the ability to detect a second object is impaired for the next few hundred milliseconds. This attentional blink is reported to increase in subjects with neglect due to acute right hemisphere lesions. METHOD: To examine neural substrates of the attentional blink, the authors examined the performance of 13 subjects with chronic focal brain lesions visualized by MRI and nine control subjects without neurologic impairments on a rapid serial visual presentation task that used letters as targets. RESULTS: Attentional blink length in the lesion group was more than twice that of controls (p < 0.05). The magnitude of the attentional blink deficit was greatest when the second target appeared 200 ms after the first target, recovering close to baseline by 1,200 ms. Abnormal attentional blink occurred (even in the absence of neglect) with lesions in the occipitotemporal areas (associated with "object" vision) and the prefrontal cortices (thought to mediate visual working memory). CONCLUSIONS: Attentional blink length and attentional blink magnitude measure different components of the attentional blink process. Abnormal attentional blink can occur with different chronic focal brain lesions in a network of structures for vision and attention, and it has no special status in hemispatial neglect. Abnormal attentional blink may help explain difficulties on rapid, visually demanding cognitive tasks such as reading and automobile driving and may explain performance deficits in brain damaged patients with nonspatial disorders of visual processing.