Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity

Background

Working memory processing and resting-state connectivity in the default mode network are altered in patients with post-traumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity.

Methods

We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls.

Results

During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahip-pocampal gyrus.

Limitations

Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses.

Conclusion

The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).     

Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition

Background

Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated.

Methods

Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues).

Results

We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group.

Limitations

Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups.

Conclusion

Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.     

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

Background

Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance.

Methods

We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-back working memory tasks as well as oddball detection and passive fixation tasks.

Results

We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory–related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls.

Limitations

Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out.

Conclusion

The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.     

Changes in Effective Connectivity According to Working Memory Load: An fMRI Study of Face and Location Working Memory Tasks

Objective

The functional strategic mechanisms in the brain during performing visuospatial working memory tasks, especially tasks with heavy load, are controversial. We conducted the functional magnetic resonance imaging (fMRI) while sixteen subjects were performing face- and location-matching n-back tasks to examine causal relations within the frontoparietal networks.

Methods

We applied a sophisticated method, the structural equation modeling (SEM), to the fMRI data. The imaging data were analyzed by extracting the task-related eigenseries using the principal component analysis (PCA) and then by applying a form of data-driven model called the automated search method.

Results

The SEM analyses revealed a functional shift of network connectivity from the right to the left hemisphere with increasing load in the face-matching n-back tasks while the location-matching tasks required bilateral activation. In the locating matching n-back tasks, a pattern of parallel processing was observed in the left phonological loop and the right inferior parietal regions. Furthermore, object working memory-related activities in the left hemisphere reliably contributed to performance of both the face- and location-matching 2-back tasks.

Conclusion

Our results are consistent with previous reports in terms of demonstrating parallel and distributed information processing during performing working memory tasks with heavy loads. Our results additionally suggest a dynamic shift between the fast imagery circuit (right hemisphere) and the stable verbal circuit (left hemisphere), depending on task load.     

Compensatory hyperactivations as markers of latent working memory dysfunctions in patients with obsessive-compulsive disorder: an fMRI study

Objective

Behavioural studies have implicated working memory (WM) deficits in obsessive–compulsive disorder (OCD). However, findings are inconsistent, which could be explained by compensation strategies used by a subgroup of OCD patients. To test this hypothesis, we examined patients without a behavioural deficit in WM during performance of different WM tasks using functional magnetic resonance imaging (fMRI).

Methods

We scaned 11 patients and 11 matched control subjects while they performed 3 verbal and spatial item-recognition tasks.

Results

Patients and healthy subjects engaged the same set of brain regions. However, in direct comparison, the patients exhibited significantly greater task-related activation in several frontal and parietal brain areas known to underlie WM.

Conclusion

Patients without manifest WM deficits exhibit increased activation in frontal and parietal brain areas relative to healthy subjects during WM task performance. These hyperactivations may permit them to compensate for reduced efficiency of their WM systems and may thus serve as markers of latent WM dysfunctions.Medical subject headings: obsessive–compulsive disorder, memory, magnetic resonance imaging, cognition     

The neural networks of inhibitory control in posttraumatic stress disorder

Objective

Posttraumatic stress disorder (PTSD) involves deficits in information processing that may reflect hypervigilence and deficient inhibitory control. To date, however, no PTSD neuroimaging study has directly examined PTSD-related changes in executive inhibition. Our objective was to investigate the hypothesis that executive inhibitory control networks are compromised in PTSD.

Methods

Functional magnetic resonance imaging (fMRI) was used during a Go/No-Go inhibition task completed by a sample of patients with PTSD (n = 23), a matched sample of healthy (i.e. without trauma exposure) control participants (n = 23) and a sample of control participants with trauma exposure who did not meet criteria for PTSD (n = 17).

Results

Participants with PTSD showed more inhibition-related errors than did individuals without trauma exposure. During inhibition, control participants activated a right-lateralized cortical inhibitory network, whereas patients with PTSD activated only the left lateral frontal cortex. PTSD was associated with a reduction in right cortical activation and increased activation of striatal and somatosensory regions.

Conclusion

The increased inhibitory error and reduced right frontal cortical activation are consistent with compromised inhibitory control in PTSD, while the increased activation of brain regions associated with sensory processing and a greater demand on inhibitory control may reflect enhanced stimulus processing in PTSD, which may undermine cortical control mechanisms.Medical subject headings: inhibition, stress disorders, posttraumatic, motor activity, neurophysiology     

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     

Aberrant connectivity of resting-state networks in borderline personality disorder

Background

Several functional neuroimaging studies have reported regionally abnormal activation of the frontal cortex in individuals with borderline personality disorder (BPD) during cognitive and affective task performance. However, little is known about neural function in individuals with BPD during the resting state. Using functional magnetic resonance imaging (fMRI), this study investigated the functional connectivity of prefrontal and limbic networks in patients with BPD.

Methods

Between January 2009 and March 2010, we investigated patients with BPD according to DSM-IV criteria and healthy controls by means of resting-state fMRI. The data were analyzed using a spatial group independent component analysis, and random effects t tests were used to compare spatial components between groups (p < 0.005, uncorrected).

Results

There were 17 women with BPD and 17 female healthy controls enrolled in this study. Within a network comprising cortical midline regions (“default mode network”), patients with BPD showed an increase in functional connectivity in the left frontopolar cortex (FPC) and the left insula, whereas decreased connectivity was found in the left cuneus. Within a network comprising predominantly right lateral prefrontal and bilateral parietal regions, patients with BPD showed decreased connectivity of the left inferior parietal lobule and the right middle temporal cortex compared with healthy controls. Two networks comprising lateral prefrontal and cingulate regions did not exhibit significant between-group differences. We found correlations between functional connectivity of the FPC and measures of impulsivity as well as between connectivity of the insula/cuneus and dissociation tension.

Limitations

Co-occurrent axis I disorders and medication use in this sample of patients with BPD have to be considered as potential limitations.

Conclusion

These data suggest that abnormal functional connectivity of temporally coherent resting-state networks may underlie certain symptom clusters in patients with BPD.     

Structural alterations in lateral prefrontal, parietal and posterior midline regions of men with chronic posttraumatic stress disorder

Background

So far, the neural network associated with posttraumatic stress disorder (PTSD) has been suggested to mainly involve the amygdala, hippocampus and medial prefrontal cortex. However, increasing evidence indicates that cortical regions extending beyond this network might also be implicated in the pathophysiology of PTSD. We aimed to investigate PTSD-related structural alterations in some of these regions.

Methods

We enrolled highly traumatized refugees with and without (traumatized controls) PTSD and non-traumatized controls in the study. To increase the validity of our results, we combined an automatic cortical parcellation technique and voxel-based morphometry.

Results

In all, 39 refugees (20 with and 19 without PTSD) and 13 controls participated in the study. Participants were middle-aged men who were free of psychoactive substances and consumed little to no alcohol. Patients with PTSD (and to a lesser extent traumatized controls) showed reduced volumes in the right inferior parietal cortex, the left rostral middle frontal cortex, the bilateral lateral orbitofrontal cortex and the bilateral isthmus of the cingulate. An influence of cumulative traumatic stress on the isthmus of the cingulate and the lateral orbitofrontal cortex indicated that, at least in these regions, structural alterations might be associated with repeated stress experiences. Voxel-based morphometry analyses produced largely consistent results, but because of a poorer signal-to-noise ratio, conventional statistics did not reach significance.

Limitations

Although we controlled for several important confounding variables (e.g., sex, alcohol abuse) with our particular sample, this might limit the generalizibility of our data. Moreover, high comorbidity of PTSD and major depression hinders a definite separation of these conditions in our findings. Finally, the results concerning the lateral orbitofrontal cortex should be interpreted with caution, as magnetic resonance imaging acquisition in this region is affected by a general signal loss.

Conclusion

Our results indicate that lateral prefrontal, parietal and posterior midline structures are implicated in the pathophysiology of PTSD. As these regions are particularly involved in episodic memory, emotional processing and executive control, this might have important implications for the understanding of PTSD symptoms.     

Differential patterns of initial and sustained responses in amygdala and cortical regions to emotional stimuli in schizophrenia patients and healthy participants

Background

We sought to investigate the altered brain responses to emotional stimuli in patients with schizophrenia.

Methods

We analyzed data from 14 patients with schizophrenia and 14 healthy controls who performed an emotional face matching task. We evaluated brain activity and connectivity in the amygdala and cortical regions during the initial (first 21 seconds of each stimulation block) and sustained (last 21 seconds) stages of an emotional processing task, and we determined changes in amygdala activity across the emotional processing task.

Results

The patients with schizophrenia showed similar amygdala activation to the controls during the initial stage of processing, but their activation decreased during the sustained stage. The controls showed increasing amygdala activity across the emotional blocks, whereas activity progressively decreased in the schizophrenia group. The patients with schizophrenia showed increased cortical activity and interconnectivity in the medial frontal and inferior parietal cortex in the initial stage of emotional processing. There was increased activity in the superior temporal cortex and greater connectivity with the inferior parietal cortex in the sustained stage. Performance accuracy was lower in the schizophrenia group in the first part of the block, while their reaction time was longer in the latter part of the block.

Limitations

It was not possible to specify the moment at which the switch in amygdala response occurred.

Conclusion

Our findings suggest that patients with schizophrenia have an initial automatic emotional response but that they need to switch to a compensatory cognitive strategy to solve the task.     

Compensatory cortical activation during performance of an attention task by patients with diffuse axonal injury: a functional magnetic resonance imaging study

Objective

To determine how cortical compensation occurs in higher cognitive systems during the recovery phase of diffuse axonal injury (DAI).

Design

12 right‐handed patients with a magnetic resonance imaging (MRI) lesion pattern compatible with pure DAI were identified. Pure DAI was defined as finding of traumatic microbleeds on T2*‐weighted gradient‐echo images in the absence of otherwise traumatic or non‐traumatic MRI abnormalities. 12 matched healthy controls were also enrolled. Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory test (Paced Visual Serial Attention Test (PVSAT)).

Results

No significant group differences were observed in reaction times for the PVSAT. Although patients with pure DAI committed a few errors during the PVSAT, controls respond correctly to each probe. Controls showed activations in the left frontal gyrus, left parietal gyrus and right inferior parietal gyrus. Patients with pure DAI showed activations in the left inferior frontal gyrus, right inferior frontal gyrus and right middle frontal gyrus. Between‐group analysis of the PVSAT task showed significantly greater activation of the right inferior frontal gyrus (BA 45) and right middle frontal gyrus (BA 9) in patient with pure DAI versus controls.

Conclusions

Patients with pure DAI require compensatory activation of the contralateral (right) prefrontal region to carry out activities similar to healthy controls. These findings provide further evidence for the adaptive capacity of neuronal systems and brain plasticity during the recovery stages of DAI.Traumatic brain injury (TBI) is the most common neurological dysfunction in young adults. Gennarelli¹ classified TBI into two categories: focal injuries and diffuse injuries. Diffuse brain injuries, usually caused by sudden head movement, comprise of classical brief cerebral concussion and more prolonged post‐traumatic coma, also called diffuse axonal injury (DAI). DAI is truly a neuropathological diagnosis. Therefore, the method used for its in vivo assessment is of critical importance. In a previous study,² it was shown that T2*‐weighted gradient‐echo magnetic resonance imaging (MRI) is a useful tool for the evaluation of DAI in the chronic stage of TBI. Owing to the frequent haemorrhagic component,^3,4 which has been neuropathologically proved, lesions potentially indicative of DAI appear as small hypointense signal changes (traumatic microbleeds (TMBs)).Patients with DAI often present dysfunction of higher cognitive abilities. Neuropsychological impairment in DAI typically consists of deficits in memory, attention and speed of information processing. Clinical cognitive tests have limited anatomical specificity and are compared with indices of brain function over large pathological lesions; the end result is modest imaging‐behaviour relationship. Functional imaging studies using positron emission tomography⁵ and single‐photon emission tomography⁶ have provided useful information on DAI‐related cognitive decline, showing a relationship between reduced cerebral blood flow and metabolism in specific brain areas, such as the prefrontal cortex, as well as cognitive dysfunction. However, these studies have assessed cerebral blood flow or metabolism at rest, when neural activity does not necessarily correspond to task‐related neural activity.By contrast, functional MRI (fMRI) assays to task‐related activity and has sufficient anatomical resolution to accurately localise cerebral function. Recent research has reported fMRI activation patterns during an attention task in patients with multiple sclerosis. Mainero et al⁷ reported that patients with relapsing–remitting multiple sclerosis showed altered patterns of brain activation during an attention task, and suggested that these change might reflect functional reorganisation.No reports describing fMRI activation patterns were observed in patients with DAI. We aimed to investigate cortical reorganisation in higher cognitive systems during the recovery phase of DAI. To pursue this aim we conducted an fMRI in patients with recovery‐phase DAI using a conventional Paced Visual Serial Addition Test (PVSAT)⁸ as the test paradigm. T2*‐weighted MRI images were used to confirm TMBs in all 12 patients with DAI. Results were compared with those obtained in a group of 12 healthy controls.     

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Background

Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.

Methods

Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.

Results

Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.

Limitations

Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.

Conclusion

These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.     

Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women

Background

Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to anti-depressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI.

Methods

Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period.

Results

We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal).

Limitations

Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted.

Conclusion

These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.     

Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

Background

Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia.

Methods

Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence.

Results

We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex.

Limitations

Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables.

Conclusion

Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life.     

Voxel-wise meta-analysis of fMRI studies in patients at clinical high risk for psychosis

Background

Reliable neurofunctional markers of increased vulnerability to psychosis are needed to improve the predictive value of psychosis risk syndrome and inform preventive interventions.

Methods

I performed a signed differential mapping (SDM) voxel-wise meta-analysis of functional magnetic resonance imaging (fMRI) studies of patients at clinical high risk for psychosis.

Results

Ten studies were included in the analysis. Compared with controls, high-risk patients showed reduced neural activation in the left inferior frontal gyrus (Brodmann area [BA] 9) and in a cluster spanning the bilateral medial frontal gyrus (BA 8,6), bilateral superior frontal gyrus (BA 8,6) and the left anterior cingulate (BA 32). There was no publication bias. Heterogeneity across studies was low. Sensitivity analysis confirmed the robustness of the findings.

Limitations

The cross-sectional nature of the included studies prevented the comparison of high-risk patients who later experienced a psychotic episode with those who did not. Other caveats are reflected in methodologic heterogeneity across tasks employed by different individual imaging studies.

Conclusion

Reduced neurofunctional activation in prefrontal regions may represent a neurophysiologic correlate of increased vulnerability to psychosis.     

Neural Mechanism of Inferring Person's Inner Attitude towards Another Person through Observing the Facial Affect in an Emotional Context

Objective

The goal of the present study was to identify the brain mechanism involved in the attribution of person''s attitude toward another person, using facial affective pictures and pictures displaying an affectively-loaded situation.

Methods

Twenty four right-handed healthy subjects volunteered for our study. We used functional magnetic resonance imaging (MRI) to examine brain activation during attitude attribution task as compared to gender matching tasks.

Results

We identified activation in the left inferior frontal cortex, left superior temporal sulcus, and left inferior parietal lobule during the attitude attribution task, compared to the gender matching task.

Conclusion

This study suggests that mirror neuron system and ventrolateral inferior frontal cortex play a critical role in the attribution of a person''s inner attitude towards another person in an emotional situation.     

Localization of Broca's Area Using Functional MR Imaging: Quantitative Evaluation of Paradigms

Objective

Functional magnetic resonance imaging (fMRI) is frequently used to localize language areas in a non-invasive manner. Various paradigms for presurgical localization of language areas have been developed, but a systematic quantitative evaluation of the efficiency of those paradigms has not been performed. In the present study, the authors analyzed different language paradigms to see which paradigm is most efficient in localizing frontal language areas.

Methods

Five men and five women with no neurological deficits participated (mean age, 24 years) in this study. All volunteers were right-handed. Each subject performed 4 tasks, including fixation (Fix), sentence reading (SR), pseudoword reading (PR), and word generation (WG). Fixation and pseudoword reading were used as contrasts. The functional area was defined as the area(s) with a t-value of more than 3.92 in fMRI with different tasks. To apply an anatomical constraint, we used a brain atlas mapping system, which is available in AFNI, to define the anatomical frontal language area. The numbers of voxels in overlapped area between anatomical and functional area were individually counted in the frontal expressive language area.

Results

Of the various combinations, the word generation task was most effective in delineating the frontal expressive language area when fixation was used as a contrast (p<0.05). The sensitivity of this test for localizing Broca''s area was 81% and specificity was 70%.

Conclusion

Word generation versus fixation could effectively and reliably delineate the frontal language area. A customized effective paradigm should be analyzed in order to evaluate various language functions.     

Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma

Background

The “default network” consists of a number of brain regions that exhibit correlated low-frequency activity at rest and that have been suggested to be involved in the processing of self-relevant stimuli. Activity in many of these areas has also been shown to be altered in individuals with posttraumatic stress disorder (PTSD). We hypothesized that the posterior cingulate cortex (PCC)/precuneus, part of the default network, would exhibit altered connectivity at rest with other areas of the default network and regions associated with PTSD.

Methods

Seventeen medicated and unmedicated female patients with chronic posttraumatic stress disorder (PTSD) related to early-life trauma and 15 healthy female controls underwent a 5.5-minute functional magnetic resonance imaging scan with their eyes closed. We assessed areas of the brain whose activity positively and negatively correlated with that of the PCC/precuneus in both groups.

Results

At rest, spontaneous low-frequency activity in the PCC/precuneus was more strongly correlated with activity in other areas of the default network in healthy controls than in patients with PTSD. Direct comparison of the 2 groups showed that PCC/ precuneus connectivity was also greater in healthy controls than in patients with PTSD in a number of areas previously associated with PTSD, including the right amygdala and the hippocampus/parahippocampal gyrus.

Limitations

Because our PTSD sample comprised only women with chronic early-life trauma exposure, our results may not be generalizeable to male patients, to a population with single trauma exposure or to those who were adults when the trauma occurred. In addition, our sample included patients taking medication and it is not yet clear how altered connectivity is affected by medication.

Conclusion

Spontaneous activity in the default network during rest, as measured using PCC correlations, is altered in patients with PTSD. The potential effects of psychotropic medications on default network connectivity in the present sample remain unknown. In this patient population, the observed alterations may be associated with the disturbances in self-referential processing often observed in patients with chronic PTSD related to early-life trauma.     

Activation of working memory in patients at the earliest stage of multiple sclerosis—An fMRI study

Objective

Previous fMRI studies on activation of working memory in multiple sclerosis (MS) patients presented heterogeneous results. Patients were reported to have altered brain activation patterns either in typical working memory circuits or in other brain regions even if they did not have any cognitive impairment according to the test batteries. We hypothesized that brain activation patterns in patients at a very early stage of the disease at very low EDSS-Score would not differ from healthy subjects.

Methods

We examined 13 patients at an early stage of MS matched with 13 healthy controls with a detailed psychometric test battery and an fMRI working memory paradigm.

Results

Patients and healthy controls did not differ in psychometric test batteries. In both groups those cortex areas typically involved in working memory processes like dorso-lateral prefrontal (DLPFC), ventro-lateral-prefrontal (VLPFC), fronto-medial and parietal cortex areas (Brodmann 6, 7, 8, 9, 10, 32, 40, 45, 46, 47) were equally activated.

Conclusion

In contrast to former studies we found no differences in activation patterns in the fMRI scanning measuring working memory tasks between psychometrically tested homogenous groups of patients in early stages of MS and control subjects.