Short Term Exposure to a Violent Video Game Induces Changes in Frontolimbic Circuitry in Adolescents

Despite evidence of effects of violent video game play on behavior, the underlying neuronal mechanisms involved in these effects remain poorly understood. We report a functional MRI (fMRI) study during two modified Stroop tasks performed immediately after playing a violent or nonviolent video game. Compared with the violent video game group, the nonviolent video game group demonstrated more activation in some regions of the prefrontal cortex during the Counting Stroop task. In contrast to the violent video game group, significantly stronger functional connectivity between left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) was identified in the nonviolent video game group. During an Emotional Stroop task, the violent video game group showed more activity in the right amygdala and less activation in regions of the medial prefrontal cortex (MPFC). Furthermore, functional connectivity analysis revealed the negative coupling between right amygdala and MPFC in the nonviolent video game group. By contrast, no significant functional connectivity between right amygdala and MPFC was found in the violent video game group. These results suggest differential engagement of neural circuitry in response to short term exposure to a violent video game as compared to a nonviolent video game.     

Prefrontal Brain Network Connectivity Indicates Degree of Both Schizophrenia Risk and Cognitive Dysfunction

Objective:

Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study, we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia risk.

Methods:

A total of 235 adults representing 3 levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls [HCs]) completed resting-state functional magnetic resonance imaging and a battery of attention and working memory tasks (Brief Test of Attention, Hopkins Verbal Learning Test, and Brief Visuospatial Memory Test) on the same day. Functional networks were defined based on coupling with seeds in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and primary visual cortex. Networks were then dissected into regional clusters of connectivity that were used to generate individual interaction matrices representing functional connectivity within each network.

Results:

Both patients with schizophrenia and their first-degree relatives showed cognitive dysfunction compared with HCs. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC and MPFC networks. Multivariate analysis of variance revealed multivariate main effects of higher schizophrenia risk status on increased connectivity within the DLPFC and MPFC networks.

Conclusions:

These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working memory tasks to brain changes associated with schizophrenia.Key words: resting state, fMRI, default-mode network, attention, working memory     

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.     

Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia

Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.     

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.     

Detection of PCC functional connectivity characteristics in resting-state fMRI in mild Alzheimer's disease

Resting-state networks dissociate in the early stage of Alzheimer's disease (AD). The posterior cingulate cortex (PCC) in AD brain is vulnerable to isolation from the rest of brain. However, it remains unclear how this functional connectivity is related to PCC changes. We employed resting-state functional MRI (fMRI) to examine brain regions with a functional connection to PCC in a mild AD group compared with matched control subjects. PCC connectivity was gathered by investigating synchronic low frequency fMRI signal fluctuations with a temporal correlation method. We found asymmetric PCC-left hippocampus, right dorsal-lateral prefrontal cortex and right thalamus connectivity disruption. In addition, some other regions such as the bilateral visual cortex, the infero-temporal cortex, the posterior orbital frontal cortex, the ventral medial prefrontal cortex and the precuneus showed decreased functional connectivity to the PCC. There were also some regions, primarily in the left frontal-parietal cortices, that showed increased connectivity. These regions included the medial prefrontal cortex, bilateral dorsal-lateral prefrontal cortex, the left basal ganglia and the left primary motor cortex. Impairments to memory, high vision-related functions and olfaction in AD can be explained by a disruption to the functional connection of resting-state networks. The results of increased connectivity may support the compensatory-recruitment hypothesis. Our findings suggest that the characteristics of resting-state functional connectivity could plausibly provide an early imaging biomarker for AD.     

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.     

Temporally anticorrelated brain networks during working memory performance reveal aberrant prefrontal and hippocampal connectivity in patients with schizophrenia

Functional neuroimaging studies on cognitive dysfunction in schizophrenia have suggested regional brain activation changes in the dorsolateral prefrontal cortex and the medial temporal lobe. However, less is known about the functional coupling of these areas during cognitive performance. In this study, we used functional magnetic resonance imaging, a verbal working memory (WM) task and multivariate statistical techniques to investigate the functional coupling of temporally anticorrelated neural networks during cognitive processing in patients with schizophrenia (n = 16) compared to healthy controls (n = 16). Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included temporally anticorrelated networks which were most highly associated with the delay period of the task in both healthy controls and patients with schizophrenia. Functional network abnormalities in patients with schizophrenia were detected within a “task-positive” lateral frontoparietal network, where increased functional connectivity was found in bilateral dorsolateral prefrontal regions. In addition, aberrant functional coupling of the hippocampal cortex in patients with schizophrenia was detected within a “task-negative” medial frontotemporal network. In patients with schizophrenia, functional connectivity indices in the left dorsolateral prefrontal cortex and the right hippocampal cortex were positively correlated with accuracy during the WM task, while the connectivity strength in the right dorsolateral prefrontal cortex was negatively correlated with measures of symptom severity. These data suggest that within two temporally anticorrelated network states, patients with schizophrenia exhibit increased and persistent dorsolateral prefrontal and hippocampal connectivity during WM performance.     

The neural basis of relational memory deficits in schizophrenia

CONTEXT: Memory deficits are common in schizophrenia. Recent studies have demonstrated that relational memory is particularly impaired. OBJECTIVE: To study the neural correlates of relational memory in schizophrenia using functional magnetic resonance imaging. DESIGN: Cross-sectional case-control study. SETTING: Academic medical center.Subjects Twenty patients with schizophrenia and 17 control subjects. MAIN OUTCOME MEASURES: Behavioral performance and brain activity were assessed during the discrimination of previously seen and novel pairs of visual stimuli, which varied in the degree of relational memory load. We performed whole-brain and region-of-interest (hippocampus) analyses. RESULTS: Schizophrenic subjects displayed normal activation of the presupplementary motor area and ventral prefrontal cortex, but significantly decreased recruitment of the right parietal cortex and anterior cingulate cortex when discriminating novel pairs derived from a sequence of stimuli. Discrimination accuracy was decreased in schizophrenia only when the flexible representation of a sequence was required. This selective deficit was associated with decreased activation of the right parietal cortex and left hippocampus. CONCLUSIONS: Schizophrenia is characterized by a specific deficit of relational memory, which is associated with impaired function of the parietal cortex and hippocampus. Abnormal relational memory may be at the core of 2 prominent features of schizophrenia, ie, cognitive deficits and psychosis.     

Domain-related differentiation of working memory in the Japanese macaque (Macaca fuscata) frontal cortex: a positron emission tomography study

The lateral prefrontal cortex (LPFC) is important for working memory (WM) task performance. Neuropsychological and neurophysiological studies in monkeys suggest that the lateral prefrontal cortex is functionally segregated based on the working memory domain (spatial vs. non-spatial). However, this is not supported by most human neuroimaging studies, and the discrepancy might be due to differences in methods and/or species (monkey neuropsychology/physiology vs. human neuroimaging). We used positron emission topography to examine the functional segregation of the lateral prefrontal cortex of Japanese macaques (Macaca fuscata) that showed near 100% accuracy on spatial and non-spatial working memory tasks. Compared with activity during the non-working memory control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during the non-spatial, but not during the spatial, working memory task, although a muscimol microinjection into the dorsolateral prefrontal cortex significantly impaired the performance of both working memory tasks. A direct comparison of the brain activity between the two working memory tasks revealed no differences within the lateral prefrontal cortex, whereas the premotor area was more active during the spatial working memory task. Comparing the delay-specific activity, which did not include task-associated stimulus/response-related activity, revealed more spatial working memory-related activity in the posterior parietal and premotor areas, and more non-spatial working memory-related activity in the dorsolateral prefrontal cortex and hippocampus. These results suggest that working memory in the monkey brain is segregated based on domain, not within the lateral prefrontal cortex but rather between the posterior parietal-premotor areas and the dorsolateral prefrontal-hippocampus areas.     

Prefrontal activity and impaired memory encoding strategies in schizophrenia

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.     

Caudate dopamine D1 receptor density is associated with individual differences in frontoparietal connectivity during working memory

We assess the relationship of age-related losses in striatal D1 receptor densities to age-related reductions in functional connectivity between spatially distinct cortical regions in healthy human participants. Previous neuroimaging studies have reported age-related differences in functional connectivity of the frontoparietal working memory network and the default mode network during task performance. We used functional magnetic resonance imaging and seed-based connectivity (right dorsolateral and medial prefrontal cortex) to extend these findings: Anterior-posterior connectivity of both these functional networks was reduced in older (65-75 years, n = 18) compared with younger (20-30 years, n = 19) adults, whereas bilateral connectivity in prefrontal cortex was increased in older adults. Positron emission tomography with the D1 receptor ligand [(11)C]SCH23390 was used to assess caudate D1 receptor density in the same sample. Older adults showed significantly reduced caudate D1 receptor density compared to the younger adults. Of key interest, partial correlations showed that individual differences in caudate D1 receptor density were positively associated with individual differences in dorsolateral prefrontal connectivity to right parietal cortex (BA40) and negatively with medial prefrontal connectivity to right parietal cortex (BA40 and postcentral gyrus), after controlling for age. We found no correlation of caudate D1 receptor density with anterior-posterior coupling within the default mode network or with bilateral frontal connectivity. These results are consistent with animal work that has identified a role for caudate D1 receptors in mediating information transfer between prefrontal areas and parietal cortex.     

Altered frontostriatal coupling in pre‐manifest Huntington’s disease: effects of increasing cognitive load

Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre‐symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre‐HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre‐HD individuals. Methods: Sixteen healthy controls and sixteen pre‐HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load‐dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre‐HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre‐HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre‐HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre‐HD individuals are modulated by cognitive demand.     

Default mode network abnormalities in idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.     

Neural basis of the association between depressive symptoms and memory deficits in nondemented subjects: resting-state fMRI study

Depressive symptoms often coexist with memory deficits in older adults and also are associated with incident cognitive decline in the elderly. However, little is known about the neural correlates of the association between depressive symptoms and memory deficits in nondemented elderly. Fifteen amnestic mild cognitive impairment (aMCI) and 20 cognitively normal (CN) subjects completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Multiple linear regression analysis was performed to test the main effects of the Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test delayed recall (RAVLT-DR) scores, and their interaction on the intrinsic amygdala functional connectivity (AFC) network activity. Severer depressive symptoms and memory deficits were found in the aMCI group than in the CN group. Partial correlation analysis identified that the RAVLT-DR scores were significantly correlated with the AFC network in the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial and anterior prefrontal cortex, posterior cingulate cortex (PCC), middle occipital gyrus, right inferior parietal cortex, and left middle temporal gyrus (MTG). The GDS scores were positively correlated with the AFC network in the bilateral PCC and MTG, and left DLPFC. The interactive effects of the GDS and RAVLT-DR scores on the AFC network were seen in the bilateral PCC, MTG, and left DLPFC. These findings not only supported that there were interactive neural links between depressive symptoms and memory functions in nondemented elderly at the system level, but also demonstrated that R-fMRI has advantages in investigating the interactive nature of different neural networks involved in complex functions, such as emotion and cognition.     

Working memory maintenance contributes to long-term memory formation: neural and behavioral evidence

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.     

Aberrant Coupling Within and Across the Default Mode,Task-Positive,and Salience Network in Subjects at Risk for Psychosis

The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. We characterized spatial differences in connectivity patterns, as well as internetwork connectivity. Right anterior insula (rAI) was selected as seed region for identifying the SN; medioprefrontal cortex (MPFC) for the DMN and TPN. The 3 groups differed in connectivity patterns between the MPFC and right dorsolateral prefrontal cortex (rDLPFC), and between the rAI and posterior cingulate cortex (PCC). In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.Key words: resting-state fMRI, schizophrenia, anticorrelated networks, functional connectivity, central executive network, anterior insula, prodrome, intrinsic connectivity, brain     

Dynamic causal modeling of load‐dependent modulation of effective connectivity within the verbal working memory network

Neuroimaging studies have consistently shown that working memory (WM) tasks engage a distributed neural network that primarily includes the dorsolateral prefrontal cortex, the parietal cortex, and the anterior cingulate cortex. The current challenge is to provide a mechanistic account of the changes observed in regional activity. To achieve this, we characterized neuroplastic responses in effective connectivity between these regions at increasing WM loads using dynamic causal modeling of functional magnetic resonance imaging data obtained from healthy individuals during a verbal n‐back task. Our data demonstrate that increasing memory load was associated with (a) right‐hemisphere dominance, (b) increasing forward (i.e., posterior to anterior) effective connectivity within the WM network, and (c) reduction in individual variability in WM network architecture resulting in the right‐hemisphere forward model reaching an exceedance probability of 99% in the most demanding condition. Our results provide direct empirical support that task difficulty, in our case WM load, is a significant moderator of short‐term plasticity, complementing existing theories of task‐related reduction in variability in neural networks. Hum Brain Mapp 35:3025–3035, 2014. © 2013 Wiley Periodicals, Inc.     

Medial prefrontal cortex plays a critical and selective role in 'feeling of knowing' meta-memory judgments

The frontal lobes are thought to play a role in the monitoring of memory performance, or 'meta-memory', but the specific circuits involved have yet to be definitively established. Medial prefrontal cortex in general and the anterior cingulate cortex in particular, have been implicated in other forms of monitoring, such as error and conflict monitoring. Here, we tested the hypothesis that medial prefrontal cortex plays a critical role in memory monitoring, aiming to determine whether this region contributed to all, or only some classes of meta-memory judgments. We also investigated the relationship between these judgments and memory performance itself. Three types of meta-memory judgment were measured in 5 subjects with focal damage to medial prefrontal cortex, with maximal overlap in dorsal anterior cingulate cortex, compared to 19 healthy, demographically matched control subjects performing a face-name episodic memory task. Judgment-of-learning accuracy was not affected by such damage. In contrast, both recall confidence and feeling-of-knowing judgments were impaired. Memory performance was itself impaired in the patient group, so we performed a second experiment to examine the relationship between memory and meta-memory deficits. In an easier memory task, where patients performed as well as controls, recall confidence accuracy improved to within the control range despite medial prefrontal damage. In contrast, feeling-of-knowing judgments remained less accurate in the patient group. These results argue that medial prefrontal cortex plays a critical role in generating accurate recall confidence and feeling-of-knowing judgments, but is not necessary for judgment-of-learning. The role of this region in feeling-of-knowing seems to be, at least in part, independent of its role in memory itself.     

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention‐deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.