Aberrant connectivity of lateral prefrontal networks in presymptomatic Huntington's disease

In clinically presymptomatic individuals with the Huntington's disease (HD) gene mutation, functional neuroimaging data have suggested a dysfunction of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional coupling of neural networks associated with cognitive performance has not been investigated so far. In this study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls (n = 16) and pre-HD individuals (n = 16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest an early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing.     

Reduced neural connectivity but increased task‐related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task‐related brain networks. We investigated this hypothesis by studying task‐related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n‐back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions‐of‐interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task‐related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend‐significantly decreased task accuracy, significantly increased task‐related activity in the left DLPFC and a trend‐significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task‐related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory‐related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554–1566, 2015. © 2015 Wiley Periodicals, Inc.     

Association of rs1006737 in CACNA1C with alterations in prefrontal activation and fronto‐hippocampal connectivity

Background: Genome‐wide association studies have identified the rs1006737 single nucleotide polymorphism (SNP) in the CACNA1C gene as a susceptibility locus for schizophrenia and bipolar disorder. On the neural systems level this association is explained by altered functioning of the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF), brain regions also affected by mental illness. In the present study we investigated the association of rs1006737 genotype with prefrontal activation and fronto‐hippocampal connectivity. Methods: We used functional magnetic resonance imaging to measure neural activation during an n‐back working memory task in 94 healthy subjects. All subjects were genotyped for the SNP rs1006737. We tested associations of the rs1006737 genotype with changes in working‐memory‐related DLPFC activation and functional integration using a seed region functional connectivity approach. Results: Rs1006737 genotype was associated with altered right‐hemispheric DLPFC activation. The homozygous A (risk) group showed decreased activation compared to G‐allele carriers. Further, the functional connectivity analysis revealed a positive association of fronto‐hippocampal connectivity with rs1006737 A alleles. Conclusions: We did not replicate the previous findings of increased right DLPFC activation in CACNA1C rs1006737 A homozygotes. In fact, we found the opposite effect, thus questioning prefrontal inefficiency as rs1006737 genotype‐related intermediate phenotype. On the other hand, our results indicate that alterations in the functional coupling between the prefrontal cortex and the medial temporal lobe could represent a neural system phenotype that is mediated by CACNA1C rs1006737 and other genetic susceptibility loci for schizophrenia and bipolar disorder. Hum Brain Mapp 35:1190–1200, 2014. © 2013 Wiley Periodicals, Inc.     

Functional magnetic resonance imaging of working memory in Huntington's disease: Cross‐sectional data from the IMAGE‐HD study

We used functional magnetic resonance imaging (fMRI) to investigate spatial working memory (WM) in an N–BACK task (0, 1, and 2‐BACK) in premanifest Huntington's disease (pre‐HD, n = 35), early symptomatic Huntington's disease (symp‐HD, n = 23), and control (n = 32) individuals. Overall, both WM conditions (1‐BACK and 2‐BACK) activated a large network of regions throughout the brain, common to all groups. However, voxel‐wise and time‐course analyses revealed significant functional group differences, despite no significant behavioral performance differences. During 1‐BACK, voxel‐wise blood‐oxygen‐level‐dependent (BOLD) signal activity was significantly reduced in a number of regions from the WM network (inferior frontal gyrus, anterior insula, caudate, putamen, and cerebellum) in pre‐HD and symp‐HD groups, compared with controls; however, time‐course analysis of the BOLD response in the dorsolateral prefrontal cortex (DLPFC) showed increased activation in symp‐HD, compared with pre‐HD and controls. The pattern of reduced voxel‐wise BOLD activity in pre‐HD and symp‐HD, relative to controls, became more pervasive during 2‐BACK affecting the same structures as in 1‐BACK, but also incorporated further WM regions (anterior cingulate gyrus, parietal lobe and thalamus). The DLPFC BOLD time‐course for 2‐BACK showed a reversed pattern to that observed in 1‐BACK, with a significantly diminished signal in symp‐HD, relative to pre‐HD and controls. Our findings provide support for functional brain reorganisation in cortical and subcortical regions in both pre‐HD and symp‐HD, which are modulated by task difficulty. Moreover, the lack of a robust striatal BOLD signal in pre‐HD may represent a very early signature of change observed up to 15 years prior to clinical diagnosis. Hum Brain Mapp 35:1847–1864, 2014. © 2013 Wiley Periodicals, Inc.     

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Transcranial magnetic stimulation of left prefrontal cortex impairs working memory.

OBJECTIVES: Several lines of evidence suggest that the prefrontal cortex is involved in working memory. Our goal was to determine whether transient functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair performance in a sequential-letter working memory task. METHODS: Subjects were shown sequences of letters and asked to state whether the letter just displayed was the same as the one presented 3-back. Single-pulse transcranial magnetic stimulation (TMS) was applied over the DLPFC between letter presentations. RESULTS: TMS applied over the left DLPFC resulted in increased errors relative to no TMS controls. TMS over the right DLPFC did not alter working memory performance. CONCLUSION: Our results indicate that the left prefrontal cortex has a crucial role in at least one type of working memory.     

Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia

BACKGROUND: Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas. METHODS: We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate "functional connectivity" between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model. RESULTS: During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity-while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction. CONCLUSIONS: Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC.     

Dissociating the effects of Sternberg working memory demands in prefrontal cortex

Earlier neuroimaging studies of working memory (WM) have demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. However, few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. The objective of the present functional resonance imaging (fMRI) study was to map within prefrontal cortex locales that are selectively load sensitive, delay sensitive, or both. We studied 18 right-handed normal subjects with fMRI at 3 Tesla during a block design version of the Sternberg task. WM load was manipulated by varying the memory set size (3, 5, or 8 letters). The effect of memory maintenance was examined by employing two time delays (1 s and 6 s) between the letter set and probe stimuli. The DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Broca's areas. Moreover, regions of prefrontal cortex on the right (BA 46) were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decisionmaking may be mediated by these areas.     

Disrupted functional connectivity for controlled visual processing as a basis for impaired spatial working memory in schizophrenia

Although regional brain abnormalities underlying spatial working memory (SWM) deficits in schizophrenia have been identified, little is known about which brain circuits are functionally disrupted in the SWM network in schizophrenia. We investigated SWM-related interregional functional connectivity in schizophrenia using functional magnetic resonance imaging (fMRI) data collected during a memory task that required analysis of spatial information in object structure. Twelve schizophrenia patients and 11 normal control subjects participated. Patients had SWM performance deficits and deficient neural activation in various brain areas, especially in the high SWM load condition. Examination of the covariation of regional brain activations elicited by the SWM task revealed evidence of functional disconnection between prefrontal and posterior visual association areas in schizophrenia. Under low SMW load, we found reduced functional associations between dorsolateral prefrontal cortex (DLPFC) and inferior temporal cortex (ITC) in the right hemisphere in patients. Under high SWM load, we found evidence for further functional disconnection in patients, including additional reduced functional associations between left DLPFC and right visual areas, including the posterior parietal cortex (PPC), fusiform gyrus, and V1, as well as between right inferior frontal cortex and right PPC. Greater prefrontal-posterior cortical functional connectivity was associated with better SWM performance in controls, but not in patients. These results suggest that prefrontal-posterior functional connectivity associated with the maintenance and control of visual information is central to SWM, and that disruption of this functional network underlies SWM deficits in schizophrenia.     

Cortical dysfunction in patients with Huntington's disease during working memory performance

Previous functional neuroimaging studies on executive function suggested multiple functionally aberrant cortical regions in patients with Huntington's disease (HD). However, little is known about the neural mechanisms of working memory (WM) function in this patient population. The objective of this study was to investigate the functional neuroanatomy of WM in HD patients. We used event-related functional magnetic resonance imaging and a parametric verbal WM task to investigate cerebral function during WM performance in 16 healthy control subjects and 12 mild to moderate stage HD patients. We excluded incorrectly performed trials to control for potential accuracy-related activation confounds. Voxel-based morphometry (VBM) was used to control for confounding cortical and subcortical atrophy. We found that HD patients were slower and less accurate than healthy controls across all WM load levels. In addition, HD patients showed lower activation in the left dorso- and ventrolateral prefrontal cortex, the left inferior parietal cortex, the left putamen, and the right cerebellum at high WM load levels only. VBM revealed gray matter differences in the bilateral caudate nucleus and the thalamus, as well as in inferior parietal and right lateral prefrontal regions. However, volumetric abnormalities in the patient group did not affect the activation differences obtained during WM task performance. These findings demonstrate that WM-related functional abnormalities in HD patients involve distinct WM network nodes associated with cognitive control and subvocal rehearsal. Moreover, aberrant cortical function in HD patients may occur in brain regions, which are relatively well preserved in terms of brain atrophy.     

Specialized neural dynamics for verbal and tonal memory: fMRI evidence in congenital amusia

Behavioral and neuropsychological studies have suggested that tonal and verbal short‐term memory are supported by specialized neural networks. To date however, neuroimaging investigations have failed to confirm this hypothesis. In this study, we investigated the hypothesis of distinct neural resources for tonal and verbal memory by comparing typical nonmusician listeners to individuals with congenital amusia, who exhibit pitch memory impairments with preserved verbal memory. During fMRI, amusics and matched controls performed delayed‐match‐to‐sample tasks with tones and words and perceptual control tasks with the same stimuli. For tonal maintenance, amusics showed decreased activity in the right auditory cortex, inferior frontal gyrus (IFG) and dorso‐lateral‐prefrontal cortex (DLPFC). Moreover, they exhibited reduced right‐lateralized functional connectivity between the auditory cortex and the IFG during tonal encoding and between the IFG and the DLPFC during tonal maintenance. In contrasts, amusics showed no difference compared with the controls for verbal memory, with activation in the left IFG and left fronto‐temporal connectivity. Critically, we observed a group‐by‐material interaction in right fronto‐temporal regions: while amusics recruited these regions less strongly for tonal memory than verbal memory, control participants showed the reversed pattern (tonal > verbal). By benefitting from the rare condition of amusia, our findings suggest specialized cortical systems for tonal and verbal short‐term memory in the human brain.     

Longitudinal functional magnetic resonance imaging of cognition in preclinical Huntington's disease

Neuropsychological and functional neuroimaging studies have revealed early changes of cognition and brain function in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disease (preHD). However, little is known about whether changes of neural function progress over time. In this study, we used neuropsychological tests of attention, working memory and executive function, functional magnetic resonance imaging and voxel-based analyses of high-resolution structural data to explore the temporal dynamics of potential cognitive, functional and structural biomarkers in far from onset preHD (n = 13, mean time to the estimated motor symptom onset = 19.5 years) and healthy controls (n = 13) followed over a 2-year period. Behavioral measures were similar in preHD individuals and controls at baseline and remained normal 2 years later. At both time points, the left dorsolateral prefrontal cortex was less active in preHD than in controls during working memory performance. The left dorsolateral prefrontal cortex did not exhibit further loss of activity over time. Regions showing less gray matter volume in preHD at baseline did not show further volume loss over time. These data indicate that the activity in brain regions contributing to working memory processing differs consistently in HD expansion mutation carriers while cognitive performance remains normal. However, the present data do not support the notion of a progressive decline of left prefrontal cortex activity in far from onset preHD followed over a 2-year period.     

Abnormal resting‐state functional connectivity of the nucleus accumbens in multi‐year abstinent heroin addicts

Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross‐sectional study, whole‐brain resting‐state functional magnetic resonance images (8 min) were collected from 30 heroin‐addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting‐state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse‐related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin‐dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long‐term‐abstinent heroin‐dependent individuals. © 2015 Wiley Periodicals, Inc.     

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     

Dysfunctional prefrontal regional specialization and compensation in schizophrenia

OBJECTIVE: It has been suggested that in healthy persons higher-order cognitive processing engaged by incremental working memory load hierarchically employs more dorsal than ventral prefrontal resources in healthy individuals. Given that working memory performance is impaired in schizophrenia, especially at higher executive loads, the authors investigated how this prefrontal functional organization might be altered in disease, independent of performance deficits. METHOD: Using N-back working memory functional magnetic resonance imaging (fMRI) data, the authors studied 15 patients with schizophrenia and 26 healthy comparison subjects. Subgroups based on median performance accuracy at 2-back were analyzed; high performers included eight schizophrenia patients and 14 comparison subjects, and low performers included seven patients and 12 comparison subjects. RESULTS: High-performing but not low-performing comparison subjects responded to incremental working memory executive load with disproportionately greater dorsal but not ventral prefrontal cortex activation, which also predicted performance accuracy. In the high- and low-performing patient groups, incremental working memory load caused a disproportionate increase in ventral but not dorsal prefrontal cortex activation relative to the respective comparison group, which also correlated with accuracy. Functional connectivity between the ventral prefrontal cortex and posterior parietal cortex was relatively greater in patients, whereas comparison subjects had greater functional connectivity between the dorsal prefrontal cortex and posterior parietal cortex. CONCLUSIONS: The hierarchical organization of the prefrontal cortex may be compromised in schizophrenia, resulting in loss of functional specialization and integration at the dorsal prefrontal cortex and in compensatory activation from the ventral prefrontal cortex, which may ultimately affect working memory and executive cognition.     

Effect of rs1063843 in the CAMKK2 gene on the dorsolateral prefrontal cortex

Recently, a single nucleotide polymorphism (SNP) in the CAMKK2 gene (rs1063843) was found to be associated with lower expression of the gene in the dorsolateral prefrontal cortex (DLPFC) and with schizophrenia (SCZ) and deficits in working memory and executive function. However, the brain mechanism underlying this association is poorly understood. A functional magnetic resonance imaging (fMRI) study (N = 84 healthy volunteers) involving multiple cognitive tasks, including a Stroop task (to measure attentional executive control), an N‐back task (to measure working memory), and a delay discounting task (to measure decision making) to identify the brain regions affected by rs1063843 was performed. Across all three tasks, it was found that carriers of the risk allele consistently exhibited increased activation of the left DLPFC. In addition, the risk allele carriers also exhibited increased activation of the right DLPFC and the left cerebellum during the Stroop task and of the left caudate nucleus during the N‐back task. These findings helped to elucidate the role of CAMKK2 in cognitive functions and in the etiology of SCZ. Hum Brain Mapp 37:2398–2406, 2016. © 2016 Wiley Periodicals, Inc .     

Theta burst stimulation‐induced inhibition of dorsolateral prefrontal cortex reveals hemispheric asymmetry in striatal dopamine release during a set‐shifting task – a TMS–[11C]raclopride PET study

The prefrontostriatal network is considered to play a key role in executive functions. Previous neuroimaging studies have shown that executive processes tested with card‐sorting tasks requiring planning and set‐shifting [e.g. Montreal‐card‐sorting‐task (MCST)] may engage the dorsolateral prefrontal cortex (DLPFC) while inducing dopamine release in the striatum. However, functional imaging studies can only provide neuronal correlates of cognitive performance and cannot establish a causal relation between observed brain activity and task performance. In order to investigate the contribution of the DLPFC during set‐shifting and its effect on the striatal dopaminergic system, we applied continuous theta burst stimulation (cTBS) to left and right DLPFC. Our aim was to transiently disrupt its function and to measure MCST performance and striatal dopamine release during [¹¹C]raclopride PET. A significant hemispheric asymmetry was observed. cTBS of the left DLPFC impaired MCST performance and dopamine release in the ipsilateral caudate–anterior putamen and contralateral caudate nucleus, as compared to cTBS of the vertex (control). These effects appeared to be limited only to left DLPFC stimulation while right DLPFC stimulation did not influence task performance or [¹¹C]raclopride binding potential in the striatum. This is the first study showing that cTBS, by disrupting left prefrontal function, may indirectly affect striatal dopamine neurotransmission during performance of executive tasks. This cTBS‐induced regional prefrontal effect and modulation of the frontostriatal network may be important for understanding the contribution of hemisphere laterality and its neural bases with regard to executive functions, as well as for revealing the neurochemical substrate underlying cognitive deficits.     

Specialization in the default mode: Task‐induced brain deactivations dissociate between visual working memory and attention

The idea of an organized mode of brain function that is present as default state and suspended during goal‐directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task‐induced deactivations across a wide range of cognitive tasks. In this event‐related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task‐induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention‐selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM‐selective deactivations were found predominantly in the right hemisphere including the medial‐parietal, the lateral temporo‐parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task‐specific functional connectivity. These findings demonstrate that task‐induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand (“the core DMN”) and a part whose deactivation depends on the specific task. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Functional connectivity changes following interpersonal reactivity

Attachment experiences substantially influence emotional and cognitive development. Narratives comprising attachment‐dependent content were proposed to modulate activation of cognitive‐emotional schemata in listeners. We studied the effects after listening to prototypical attachment narratives on wellbeing and countertransference‐reactions in 149 healthy participants. Neural correlates of these cognitive‐emotional schema activations were investigated in a 7 Tesla rest‐task‐rest fMRI‐study (23 healthy males) using functional connectivity (FC) analysis of the social approach network (seed regions: left and right Caudate Nucleus, CN). Reduced FC between left CN and bilateral dorsolateral prefrontal cortex (DLPFC) represented a general effect of prior auditory stimulation. After presentation of the insecure‐dismissing narrative, FC between left CN and bilateral temporo‐parietal junction, and right dorsal posterior Cingulum was reduced, compared to baseline. Post‐narrative FC‐patterns of insecure‐dismissing and insecure‐preoccupied narratives differed in strength between left CN and right DLPFC. Neural correlates of the moderating effect of individual attachment anxiety were represented in a reduced CN‐DLPFC FC as a function of individual neediness‐levels. These findings suggest specific neural processing of prolonged mood‐changes and schema activation induced by attachment‐specific speech patterns. Individual desire for interpersonal proximity was predicted by attachment anxiety and furthermore modulated FC of the social approach network in those exposed to such narratives.     

前额叶损伤患者的视-空间工作记忆改变

目的 探讨前额叶不同亚区损伤患者的视-空间工作记忆障碍.方法 将20例前额叶不同亚区损伤患者以及20名与其人口学资料相匹配的健康人作为被试,采用视觉面孔和视觉空间的延迟匹配任务对上述2组进行视-空间工作记忆测试.结果 与健康对照组(72.9%±6.1%)相比,前额叶腹侧(ventral prefrontal cortex,VPFC)损伤的患者视觉客体工作记忆的正确率(46.4%±11.4%)明显下降,差异有统计学意义(U=1.00,P<0.01);而前额叶背外侧(dorsolateral prefrontal cortex,DLPFC)损伤的患者在视觉客体(50.4%±15.1%)和视觉空间(72.6%±18.6%)工作记忆均有明显损伤,与对照组(72.9%±6.1%、89.4%±10.1%)比较差异均有统计学意义(U=-20.5、59.5,均P<0.01).对左、右前额叶损伤的2组患者进行分析,结果表明2组患者在视觉客体和空间工作记忆正确率的比较差异均无统计学意义.对前额叶亚区进行左右侧比较,2组VPFC患者在视觉客体和视觉空间工作记忆差异均无统计学意义;左侧DLPFC损伤组和右侧DLPFC损伤组在视觉客体工作记忆正确率和视觉面孔工作记忆正确率方面,差异均无统计学意义.结论 前额叶是工作记忆加工的重要脑区,其不仅参与了视觉客体的工作记忆加工过程,同时参与了视觉空间的工作记忆加工,而且对于前额叶不同亚区在视-空间工作记忆加工过程中还存在分离.