Left Prefrontal Areas Research Articles

Multiple modes of clearing one's mind of current thoughts: Overlapping and distinct neural systems

This study used the power of neuroimaging to identify the neural systems that remove information from working memory, a thorny issue to examine because it is difficult to confirm that individuals have actually modified their thoughts. To overcome this problem, brain activation as measured via fMRI was assessed when individuals had to clear their mind of all thought (global clear), clear their mind of a particular thought (targeted clear), or replace the current thought (replace), relative to maintaining an item in working memory. The pattern of activity in posterior sensory regions across these conditions confirmed compliance with task demands. A hierarchy of brain regions involved in cognitive control, including parietal, dorsolateral prefrontal and frontopolar regions, were engaged to varying degrees depending on the manner in which information was removed from working memory. In addition, individuals with greater difficulty in controlling internal thoughts exhibited greater activity in prefrontal brain regions associated with cognitive control, as well as in left lateral prefrontal areas including Broca's area, which is associated with inner speech.

Anodal transcranial direct current stimulation (tDCS) increases frontal–midline theta activity in the human EEG: A preliminary investigation of non-invasive stimulation

Rhythmical brain activity in the range between four and eight Hz acquired over frontal–midline EEG recording sites – so called frontal–midline theta activity – is regarded as one of the most prominent neural signatures of sustained attention. It is reported to parametrically increase with cognitive load and is thought to be generated in medial prefrontal cortex. Here we explored the possibility of using anodal transcranial direct current stimulation over frontal sites to enhance frontal–midline theta activity and to increase sustained attention performance. We used a small preliminary sample to test a novel direct current stimulation electrode configuration by which we were able to significantly increase frontal–midline theta amplitude in a resting condition after the end of the stimulation period. Using standardised low resolution electromagnetic tomography analysis the effect in the surface EEG was localised to right prefrontal and left medial prefrontal brain areas. Transcranial direct current stimulation did, however, not have any impact on behavioural performance during a sustained attention task. This most likely was due to a very fast washout of the stimulation’s after effect on theta activity. Although these are only preliminary results from a rather small sample, this study demonstrates that transcranial direct current stimulation can be used to rather selectively enhance frontal–midline theta amplitude.

Does co-morbid obsessive-compulsive disorder modify the abnormal language processing in schizophrenia patients? An FMRI study.

Background: Impaired language processing is one of the most replicated findings in functional brain studies of schizophrenia (SCH). This is demonstrated by reduced activations in left prefrontal language areas (i.e., BA44/45, the inferior frontal gyrus, IFG) presented as decreased language lateralization. This finding was documented both in chronic as well as in first-episode SCH patients, arguing for a neurobiological marker for SCH. In a previous study, we demonstrated the specificity of this finding to SCH patients when compared to obsessive–compulsive disorder (OCD) patients in whom language processing was similar to healthy controls. Since a sizable proportion of SCH patients also meet DSM-IV criteria for OCD, we further sought to elucidate whether OCD attenuates abnormal prefrontal language lateralization in this unique group of schizo-obsessive patients compared to their non-OCD-SCH counterparts.Methods: We used functional magnetic resonance imaging (fMRI) to investigate regional activation and language lateralization in the left and right IFG and inter-hemispheric functional connectivity (FC) during a language task of auditory verb generation in 14 SCH patients with OCD, compared to 17 SCH patients without OCD, 13 OCD patients and 14 healthy controls.Results: No between-group differences were found in the behavioral measurements of word generation. However, while OCD patients were indistinguishable from healthy volunteers, a similarly reduced lateralization in the IFG and diminished inter-hemispheric FC was noted in the two SCH groups with and without OCD.Conclusion: The co-occurrence of OCD in SCH does not attenuate abnormal processing of language as reflected by regional IFG activity and FC. These results further support the notion that these language processing abnormalities are characteristic of SCH and that SCH–OCD combined psychopathology is more akin to SCH than to OCD.

Dopaminergic modulation of resting‐state functional connectivity in de novo patients with Parkinson's disease

Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine-dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP-CIT positron emission tomography imaging and resting-state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine-dependent functional networks. The major finding is that the patterns of dopamine-dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine-dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine-dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine-dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine-dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian-related motor and cognitive performance.

EEG mean frequency changes in healthy subjects during prefrontal transcranial direct current stimulation

In this pilot study we evaluated electroencephalographic (EEG) mean frequency changes induced by prefrontal transcranial direct current stimulation (tDCS) and investigated whether they depended on tDCS electrode montage. Eight healthy volunteers underwent tDCS for 15 min during EEG recording. They completed six tDCS sessions, 1 wk apart, testing left and right direct current (DC) dipole directions with six different montages: four unipolar montages (one electrode on a prefrontal area, the other on the opposite wrist) and two bipolar montages (both electrodes on prefrontal areas), and a single sham session. EEG power spectra were assessed from four 1-min EEG epochs, before, during, and after tDCS. During tDCS the outcome variable, brain rate (fb), changed significantly, and the changes persisted for minutes after tDCS ended. With the DC dipole directed to the left (anode on the left prefrontal area or wrist), fb increased, and with the DC dipole directed to the right (anode on the right prefrontal area or wrist), fb decreased, suggesting asymmetric prefrontal cortex functional organization in the normal human brain. Anodal and cathodal effects were opposite but equally large. Gender left these effects unchanged.

A large scale (N=102) functional neuroimaging study of error processing in a Go/NoGo task.

We report a functional magnetic resonance imaging (fMRI) study of 102 healthy participants who completed a demanding Go/NoGo task. The primary purpose of this study was to delineate the neural systems underlying responses to errors in a large sample. We identified a number of regions engaged during error processing including the anterior cingulate, left lateral prefrontal areas and bilateral inferior frontal gyrus, and the subthalamic nucleus. The power afforded by the large cohort enabled identification of regions not consistently measured during Go/NoGo tasks thus helping to incrementally refine our understanding of the neural correlates of error processing. With the present fMRI results, in combination with our previous exploration of response inhibition (Steele et al.), we outline a comprehensive set of regions associated with both response inhibition and error processing.

Neurofeedback As a Treatment for Major Depressive Disorder – A Pilot Study

BackgroundThere is growing interest in neurofeedback as a treatment for major depressive disorder. Reduction of asymmetry of alpha-activity between left and right prefrontal areas with neurofeedback has been postulated as effective in earlier studies. Unfortunately, methodological shortcomings limit conclusions that can be drawn from these studies. In a pilot-study, we investigated the effectiveness of reduction of asymmetry of alpha-activity with neurofeedback in depressed participants with the use of a stringent methodological approach.MethodsNine participants meeting DSM-IV criteria for major depressive disorder were treated with a maximum of 30 neurofeedback-sessions, aimed at reducing asymmetry of alpha-activity, over a 10-week period. No changes in the use of antidepressants were allowed 6 weeks before and during the intervention. Changes in depressive symptomatology were assessed with the Quick Inventory of Depressive Symptoms, self-report version.ResultsWe observed response in 1 and remission in 4 out of a total of 9 participants. The effectiveness appeared largest in female participants. The mean asymmetry of alpha-activity decreased significantly over sessions in a quadratic fashion. This decrease was associated with clinical response.ConclusionsThis pilot study suggests that neurofeedback aimed at a reduction of frontal asymmetry of alpha-activity may be effective as a treatment for depression. However, this was an open label pilot study. Non-specific effects of the procedure and/or a beneficial natural course may have confounded the results. Randomized controlled trials will have to establish the efficacy of neurofeedback for depression.Trial RegistrationNederlands Trial Register NTR1629

Individual differences in general/fluid intelligence are evoked by functional integration and the efficiency of long-distance connections in the brain

Here white matter fibers connecting several brain regions were obtained with deterministic and probabilistic tractography in a sample of 104 healthy young adults. The properties of the computed connectivity matrices were studied from two distinguishable perspectives. The first was based on global and nodal standard graph theory metrics, whereas the second relied on exploratory factor analysis (EFA) for selecting potentially relevant sub-networks. A broad set of cognitive constructs was considered: general (g), fluid, crystallized, and spatial intelligence, working memory capacity, attention, and processing speed. The findings show that graph metrics change depending on the applied tractography, and only the probabilistic method yielded factorable connectivity matrices. Secondly, EFA reveals structural networks underlying variability in intelligence factors and cognitive processes. Thirdly, variability in g and Gf was predicted by functional integration–segregation and predominant long-distance structural connections in the brain, playing a key role the left inferior parietal and prefrontal areas.

Pseudo-continuous arterial spin labeling MRI study of schizophrenic patients

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a novel noninvasive technique that can measure regional cerebral blood flow (rCBF). To our knowledge, few studies have examined rCBF in patients with schizophrenia by ASL-MRI. Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in schizophrenic patients, taking the regional cerebral gray matter volume into account. The subjects were 36 patients with schizophrenia and 42 healthy volunteers who underwent 3-tesla MRI, diffusion tensor imaging (DTI), and pCASL. We evaluated the gray matter volume imaging, DTI, and pCASL imaging data in a voxel-by-voxel statistical analysis. The schizophrenia patients showed reduced rCBF in the left prefrontal and bilateral occipital cortices compared to the healthy volunteers. There was a significant reduction of gray matter volume in the left inferior frontal cortex in the schizophrenia patients. With respect to the fractional anisotropy (FA) values in the DTI, there were significant FA reductions in the left superior temporal, left external capsule, and left inferior prefrontal regions in the patients compared to the controls. ConclusionOur pCASL study with partial volume effect correction together with volumetry and DTI data demonstrated hypoactivity in the left prefrontal area beyond structural abnormalities in schizophrenia patients. There were also hypofunction areas in bilateral occipital cortices, although structural abnormalities were not apparent.

Task-dependent Activity and Connectivity Predict Episodic Memory Network-based Responses to Brain Stimulation in Healthy Aging

BackgroundTranscranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. ObjectivesTo evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. MethodsWe applied a paradigm of repetitive TMS – intermittent theta-burst stimulation – over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. ResultsIn the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. ConclusionsThe results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches.

Verification of Kando Requirements in the Kando Understanding Support Process Using DOE and Bioinstrumentation

Understanding customer requirements is most important for a conceptual design. Successful companies are providing the highest quality service by which customer receives a satisfaction through the Kando experience. Thus, an element of customer satisfaction is necessary for the great success in business. Therefore, authors have proposed the Idea Creation Support System (ICSS) — for an idea creation to the Kando understanding process through WOM (Word Of Mouth) effectiveness. In this paper, we propose an assessment system of the Kando understanding support process through the V-model with V&V (Verification & Validation) of this process for ICSS. We confirmed the desirable process for drawing the Kando requirement and the activation of a left side prefrontal area showed the positive expectation for a scene which assumed from a Kando requirement through the V-model with V&V as the assessment system.

Different perception of musical stimuli in patients with monolateral and bilateral cochlear implants.

The aim of the present study is to measure the perceived pleasantness during the observation of a musical video clip in a group of cochlear implanted adult patients when compared to a group of normal hearing subjects. This comparison was performed by using the imbalance of the EEG power spectra in alpha band over frontal areas as a metric for the perceived pleasantness. Subjects were asked to watch a musical video clip in three different experimental conditions: with the original audio included (Norm), with a distorted version of the audio (Dist), and without the audio (Mute). The frontal EEG imbalance between the estimated power spectra for the left and right prefrontal areas has been calculated to investigate the differences among the two populations. Results suggested that the perceived pleasantness of the musical video clip in the normal hearing population and in the bilateral cochlear implanted populations has similar range of variation across the different stimulations (Norm, Dist, and Mute), when compared to the range of variation of video clip's pleasantness for the monolateral cochlear implanted population. A similarity exists in the trends of the perceived pleasantness across the different experimental conditions in the mono- and bilaterally cochlear implanted patients.

Navigated transcranial magnetic stimulation in rehabilitation of traumatic frontal lobes injury

Traumatic injury of frontal lobes has severe impact on social adaptation due to alterations in cognitive function and behavior. Considering the low efficacy of conventional rehabilitation methods, the development of complementary approaches is needed. Rhythmic transcranial magnetic stimulation (rTMS) is known to improve short and long-term memory, processing speed, problem solving in dementia. However, the trials show conflicting results that might be caused by lack of individualization as the target of stimulation is defined exclusively on the base of anatomy. We used fMRI-guided rTMS of the left dorsolateral prefrontal area to ameliorate consequences of traumatic injury of the frontal lobes. Case report demonstrating the efficacy of this method is presented. Significant improvement was observedafter 15 sessions of rTMS in patient with severe traumatic brain injury who gained an increase in cognitive speed, development of ability to summarize and acquire experience, improvement in planning, control and error correction.

Transcranial magnetic stimulation modulates left premotor cortex activity in facial expression recognition as a function of anxiety level

AbstractRecognition of emotional facial expressions is based on simulation and mirroring processes, and the premotor cortex is supposed to support this simulation mechanism. The role of this prefrontal area in processing emotional faces with different valence (anger, fear, happiness and neutral) was explored taking into account the effect of the lateralization model (more right-side activation for negative emotions; more left-side activation for positive emotions) of face processing and anxiety level (high vs low). High-frequency repetitive transcranial magnetic stimulation (rTMS, 10 Hz) was applied to the left prefrontal area to induce an increased activation response within the left premotor cortex. Twenty-nine subjects, who were divided into two different groups depending on their anxiety level (high/low anxiety; State-Trait-Anxiety Inventory (STAI), were asked to detect emotion / no emotion. Accuracy (AcI) and response times (RTs) were considered in response to the experimental conditions. A general significant increased performance was found in response to positive emotions in the case of left-side stimulation. Moreover, whereas high-anxiety subjects revealed a significant negative-valence bias in absence of stimulation, they showed a more significant AcI increasing and RTs decreasing in response to positive emotions in case of left premotor brain activation. The present results highlight the role of the premotor system for facial expression processing as a function of emotional type, supporting the existence of a valence-specific lateralized system within the prefrontal area. Finally, a sort of “restoring effect” induced by TMS was suggested for high-anxiety subjects.

P300 in obsessive–compulsive disorder: Source localization and the effects of treatment

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.

P 46. Featural and Configural processing of faces are dissociated in the dorsolateral prefrontal cortex: A TMS study

Facial recognition relies on distinct and parallel types of processing: featural processing focuses on the individual components of a face (e.g., the shape or the size of the eyes), whereas configural (or “relational”) processing considers the spatial interrelationships among the single facial components (e.g., distance of the mouth from the nose). Previous neuroimaging evidence has suggested that featural and configural processes may rely on different brain circuits. By using rTMS, here we show for the first time a double dissociation in dorsolateral prefrontal cortex for different aspects of face processing. Twelve participants were asked to perform a same-different judgment task (“Jane faces” task, Mondloch et al., 2002, Perception 31:553–66) on two shortly consecutive presented faces. Two sets of stimuli (faces differing either for featural or configural aspects) were run separately to allow time for each style of processing to emerge. Triple-pulse TMS was delivered between 100 and 150 ms after the onset of the second face stimulus over the left middle frontal gyrus, the right middle frontal gyrus, or the vertex, in addition to a condition where no TMS was administered. TMS over the left middle frontal gyrus selectively disrupted featural processing, whereas TMS over the right frontal gyrus selectively interfered with configural processing of faces. By establishing a causal link between activation in left and right prefrontal areas and different modes of face processing, our data extend previous neuroimaging evidence and may have important implications in the study of face-processing deficits, such as those manifested in prosopagnosia and autistic spectrum disorders.

Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson's disease

BackgroundParkinson's disease with mild cognitive impairment (PD-MCI) is a heterogeneous entity in terms of cognitive profiles and conversion to dementia. However, the risk factors for ongoing cognitive decline in patients...

Default Mode Network Connectivity in Stroke Patients

The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 ‘first-ever’ stroke patients. Patients were scanned 9–12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in ‘first-ever’ stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.

Akinetic Mutism Without a Structural Prefrontal Lesion

Akinetic mutism is characterized by profound apathy and a lack of verbal and motor output for action, despite preserved alertness. The condition usually follows bilateral damage to the medial frontal subcortical circuits. We report a 59-year-old right-handed woman who was admitted to the neurology ward with sudden-onset akinetic mutism. Her medical history included an ischemic stroke 3 years earlier, with residual anomia and mild agraphia but no motor dysfunction. On this admission, a cranial computed tomography scan disclosed an acute left superior cerebellar infarction embracing the vermis, and a prior left inferior parietal infarct. Electroencephalogram showed bilateral frontal delta-wave activity. Four weeks later, we performed a technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (Tc-HMPAO SPECT) scan to study the patient's frontal lobe function. The SPECT scan revealed the causative bifrontal hypoperfusion, more prominent on the right, while the structurally evident cerebellar infarction was predictably masked by subacute hyperperfusion phenomenon. Contralateral frontal diaschisis is an established sequela of cerebellar infarction. Because this patient also had lesions in the left parietal region, her left prefrontal area was critically deprived of its major reciprocally connected cortical counterparts (right prefrontal and left parietal), and also became dysfunctional. Her resulting bilateral frontal dysfunction is a common cause of akinetic mutism.

Dysfunctional Cortical Connectivity During the Auditory Oddball Task in Patients with Schizophrenia

Background:We studied the imaginary coherence (IC) of gamma frequency oscillations between brain regions of male schizophrenia patients during an auditory oddball task using magnetoencephalography (MEG) and electroencephalography (EEG).Methods:Subjects were 10 right-handed male schizophrenia patients, evaluated by the positive and negative symptom scale (PANSS), and 10 healthy controls. Functional connectivity during the auditory oddball task was reconstructed in low (30-50 Hz) and high (50-100 Hz) gamma bands, and represented by imaginary coherence (IC) based on significant oscillatory power changes. We calculated correlations between PANSS scores and IC.Results:In the high gamma band, IC between left occipital and right prefrontal lobe areas during the time window 750-1000 ms from stimulus onset showed negative correlations with total negative scores, total positive scores, the sum of positive and negative scores in PANSS, conceptual disorganization, and social avoidance scores. In the low gamma band, IC between the same areas from 250-500 ms also showed a negative correlation with the conceptual disorganization score. In the same time window, IC between left occipital and right frontoparietal lobe areas in the low gamma band showed a positive correlation with hallucinatory behavior; IC between right temporal pole and left prefrontal lobe areas showed a positive correlation with delusion scores, although these ICs were decreased relative to controls.Conclusions:Functional disconnection of high and low gamma bands in auditory oddball task may play an important role in the auditory processing in schizophrenia patients.