Functional connectivity profile of the human inferior frontal junction: involvement in a cognitive control network

Background: The human inferior frontal junction area (IFJ) is critically involved in three main component processes of cognitive control (working memory, task switching and inhibitory control). As it overlaps with several areas in established anatomical labeling schemes, it is considered to be underreported as a functionally distinct location in the neuroimaging literature. While recent studies explicitly focused on the IFJ´s anatomical organization and functional role as a single brain area, it is usually not explicitly denominated in studies on cognitive networks. However based on few analyses in small datasets constrained by specific a priori assumptions on its functional specialization, the IFJ has been postulated to be part of a cognitive control network. Goal of this meta-analysis was to establish the IFJ’s connectivity profile on a high formal level of evidence by aggregating published implicit knowledge about its co-activations. We applied meta-analytical connectivity modeling (MACM) based on the activation likelihood estimation (ALE) method without specific assumptions regarding functional specialization on 180 (reporting left IFJ activity) and 131 (right IFJ) published functional neuroimaging experiments derived from the BrainMap database. This method is based on coordinates in stereotaxic space, not on anatomical descriptors. Results: The IFJ is significantly co-activated with areas in the dorsolateral and ventrolateral prefrontal cortex, anterior insula, medial frontal gyrus / pre-SMA, posterior parietal cortex, occipitotemporal junction / cerebellum, thalamus and putamen as well as language and motor areas. Results are corroborated by an independent resting-state fMRI analysis. Conclusions: These results support the assumption that the IFJ is part of a previously described cognitive control network. They also highlight the involvement of subcortical structures in this system. A direct line is drawn from works on the functional significance of brain activity located at the IFJ and its anatomical definition to published results related to distributed cognitive brain systems. The IFJ is therefore introduced as a convenient starting point to investigate the cognitive control network in further studies

Towards literature-based feature selection for diagnostic classification: A meta-analysis of resting-state fMRI in depression

Information derived from functional magnetic resonance imaging (fMRI) during wakeful rest has been introduced as a candidate diagnostic biomarker in unipolar major depressive disorder (MDD). Multiple reports of resting state fMRI in MDD describe group effects. Such prior knowledge can be adopted to pre-select potentially discriminating features for diagnostic classification models with the aim to improve diagnostic accuracy. Purpose of this analysis was to consolidate spatial information about alterations of spontaneous brain activity in MDD, primarily to serve as feature selection for multivariate pattern analysis techniques (MVPA). Thirty two studies were included in final analyses. Coordinates extracted from the original reports were assigned to two categories based on directionality of findings. Meta-analyses were calculated using the non-additive activation likelihood estimation approach with coordinates organized by subject group to account for non-independent samples. Converging evidence revealed a distributed pattern of brain regions with increased or decreased spontaneous activity in MDD. The most distinct finding was hyperactivity/hyperconnectivity presumably reflecting the interaction of cortical midline structures (posterior default mode network components including the precuneus and neighboring posterior cingulate cortices associated with self-referential processing and the subgenual anterior cingulate and neighboring medial frontal cortices) with lateral prefrontal areas related to externally-directed cognition. Other areas of hyperactivity/hyperconnectivity include the left lateral parietal cortex, right hippocampus and right cerebellum whereas hypoactivity/hypoconnectivity was observed mainly in the left temporal cortex, the insula, precuneus, superior frontal gyrus, lentiform nucleus and thalamus. Results are made available in two different data formats to be used as spatial hypotheses in future studies, particularly for diagnostic classification by MVPA

Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia

Background: The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG. Methods: This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders (n = 30) or non-responders (n = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated. Results: SVM did not reach sufficient overall predictive accuracies (38.0–54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by post hoc univariate comparisons. Conclusion: In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique

Probing the relevance of the hippocampus for conflict-induced memory improvement

The hippocampus plays a key role for episodic memory. In addition, a small but growing number of studies has shown that it also contributes to the resolution of response conflicts. It is less clear how these two functions are related, and how they are affected by hippocampal lesions in patients with mesial temporal lobe epilepsy (MTLE). Previous studies suggested that conflict stimuli might be better remembered, but whether the hippocampus is critical for supporting this interaction between conflict processing and memory formation is unknown. Here, we tested 19 patients with MTLE due to hippocampal sclerosis and 19 matched healthy controls. Participants performed a face-word Stroop task during functional magnetic resonance imaging (fMRI) followed by a recognition task for the faces. We tested whether memory performance and activity in brain regions implicated in long-term memory were modulated by conflict during encoding, and whether this differed between MTLE patients and controls. In controls, we largely replicated previous findings of improved memory for conflict stimuli. While MTLE patients showed response time slowing during conflict trials as well, they did not exhibit a memory benefit. In controls, neural activity of conflict resolution and memory encoding interacted within a hippocampal region of interest. Here, left hippocampal recruitment was less efficient for memory performance in incongruent trials than in congruent trials, suggesting an intrahippocampal competition for limited resources. They also showed an involvement of precuneus and posterior cingulate cortex during conflict resolution. Both effects were not observed in MTLE patients, where activation of the precuneus and posterior cingulate cortex instead predicted later memory. Further research is needed to find out whether our findings reflect widespread functional reorganization of the episodic memory network due to hippocampal dysfunction

Lack of Association Between Shape and Volume of Subcortical Brain Structures and Restless Legs Syndrome

ObjectivePrevious studies on patients with restless legs syndrome (RLS) yielded inconclusive results in the magnetic resonance imaging (MRI)-based analyses of alterations of subcortical structures in the brain. The aim of this study was to compare volumes as well as shapes of subcortical structures and the hippocampus between RLS cases and controls. Additionally, the associations between the genetic risks for RLS and subcortical volumes were investigated.MethodsWe compared volumetric as well as shape differences assessed by 3 T MRI in the caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus in 39 RLS cases versus 117 controls, nested within a population-based sample. In a subsample, we explored associations between known genetic risk markers for RLS and the volumes of the subcortical structures and the hippocampus.ResultsNo significant differences between RLS cases and controls in subcortical and hippocampal shapes and volumes were observed. Furthermore, the genetic risk for RLS was unrelated to any alterations of subcortical and hippocampal gray matter volume.InterpretationWe conclude that neither RLS nor the genetic risk for the disease give rise to changes in hippocampal and subcortical shapes and gray matter volumes

Tackling frontal lobe-related functions in PKU through functional brain imaging: a Stroop task in adult patients.

BACKGROUND: Profound mental retardation in phenylketonuria (PKU) can be prevented by a low phenylalanine (Phe) diet. However, even patients treated early have inconsistently shown deficits in several frontal lobe-related neuropsychological tasks such as the widely accepted Stroop task. The goal of this study was to investigate whether adult patients exhibit altered brain activation in Stroop-related locations in comparison to healthy controls and if an acute increase in blood Phe levels in patients has an effect on activation patterns. METHODS: Seventeen male, early-treated patients with classic PKU (mean ± SD age: 31.0 ± 5.2 years) and 15 male healthy controls (32.1 ± 6.4 years) were compared using a color-word matching Stroop task in a functional magnetic resonance imaging (fMRI) study at 3T. Participants were scanned twice, and an oral Phe load (100 mg/kg body weight) was administered to patients prior to one of the fMRI sessions (placebo-controlled). Activity in brain regions that are known to be involved in Stroop tasks was assessed. RESULTS: PKU patients exhibited poorer accuracy in incongruent trials. Reaction times were not significantly different. There were no consistent differences in BOLD activations in Stroop-associated brain regions. The oral Phe administration had no significant effect on brain activity. CONCLUSIONS: Neither a generally slower task performance nor distinctively altered functioning of brain networks involved in a task representing a subset of dopamine-dependent executive functions could be proven. Decreased accuracy and inconsistent findings in posterior areas necessitate further study of frontal-lobe functioning in PKU patients in larger study samples

Image_6_Effects of acute ischemic stroke on binaural perception.JPEG

Stroke-induced lesions at different locations in the brain can affect various aspects of binaural hearing, including spatial perception. Previous studies found impairments in binaural hearing, especially in patients with temporal lobe tumors or lesions, but also resulting from lesions all along the auditory pathway from brainstem nuclei up to the auditory cortex. Currently, structural magnetic resonance imaging (MRI) is used in the clinical treatment routine of stroke patients. In combination with structural imaging, an analysis of binaural hearing enables a better understanding of hearing-related signaling pathways and of clinical disorders of binaural processing after a stroke. However, little data are currently available on binaural hearing in stroke patients, particularly for the acute phase of stroke. Here, we sought to address this gap in an exploratory study of patients in the acute phase of ischemic stroke. We conducted psychoacoustic measurements using two tasks of binaural hearing: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. The location of the stroke lesion was established by previously acquired MRI data. An additional general assessment included three-frequency audiometry, cognitive assessments, and depression screening. Fifty-five patients participated in the experiments, on average 5 days after their stroke onset. Patients whose lesions were in different locations were tested, including lesions in brainstem areas, basal ganglia, thalamus, temporal lobe, and other cortical and subcortical areas. Lateralization impairments were found in most patients with lesions within the auditory pathway. Lesioned areas at brainstem levels led to distortions of lateralization in both hemifields, thalamus lesions were correlated with a shift of the whole auditory space, whereas some cortical lesions predominantly affected the lateralization of stimuli contralateral to the lesion and resulted in more variable responses. Lateralization performance was also found to be affected by lesions of the right, but not the left, basal ganglia, as well as by lesions in non-auditory cortical areas. In general, altered lateralization was common in the stroke group. In contrast, deficits in tone-in-noise detection were relatively scarce in our sample of lesion patients, although a significant number of patients with multiple lesion sites were not able to complete the task.</p

Image_8_Effects of acute ischemic stroke on binaural perception.PNG

Stroke-induced lesions at different locations in the brain can affect various aspects of binaural hearing, including spatial perception. Previous studies found impairments in binaural hearing, especially in patients with temporal lobe tumors or lesions, but also resulting from lesions all along the auditory pathway from brainstem nuclei up to the auditory cortex. Currently, structural magnetic resonance imaging (MRI) is used in the clinical treatment routine of stroke patients. In combination with structural imaging, an analysis of binaural hearing enables a better understanding of hearing-related signaling pathways and of clinical disorders of binaural processing after a stroke. However, little data are currently available on binaural hearing in stroke patients, particularly for the acute phase of stroke. Here, we sought to address this gap in an exploratory study of patients in the acute phase of ischemic stroke. We conducted psychoacoustic measurements using two tasks of binaural hearing: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. The location of the stroke lesion was established by previously acquired MRI data. An additional general assessment included three-frequency audiometry, cognitive assessments, and depression screening. Fifty-five patients participated in the experiments, on average 5 days after their stroke onset. Patients whose lesions were in different locations were tested, including lesions in brainstem areas, basal ganglia, thalamus, temporal lobe, and other cortical and subcortical areas. Lateralization impairments were found in most patients with lesions within the auditory pathway. Lesioned areas at brainstem levels led to distortions of lateralization in both hemifields, thalamus lesions were correlated with a shift of the whole auditory space, whereas some cortical lesions predominantly affected the lateralization of stimuli contralateral to the lesion and resulted in more variable responses. Lateralization performance was also found to be affected by lesions of the right, but not the left, basal ganglia, as well as by lesions in non-auditory cortical areas. In general, altered lateralization was common in the stroke group. In contrast, deficits in tone-in-noise detection were relatively scarce in our sample of lesion patients, although a significant number of patients with multiple lesion sites were not able to complete the task.</p

Image_2_Effects of acute ischemic stroke on binaural perception.jpg

Stroke-induced lesions at different locations in the brain can affect various aspects of binaural hearing, including spatial perception. Previous studies found impairments in binaural hearing, especially in patients with temporal lobe tumors or lesions, but also resulting from lesions all along the auditory pathway from brainstem nuclei up to the auditory cortex. Currently, structural magnetic resonance imaging (MRI) is used in the clinical treatment routine of stroke patients. In combination with structural imaging, an analysis of binaural hearing enables a better understanding of hearing-related signaling pathways and of clinical disorders of binaural processing after a stroke. However, little data are currently available on binaural hearing in stroke patients, particularly for the acute phase of stroke. Here, we sought to address this gap in an exploratory study of patients in the acute phase of ischemic stroke. We conducted psychoacoustic measurements using two tasks of binaural hearing: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. The location of the stroke lesion was established by previously acquired MRI data. An additional general assessment included three-frequency audiometry, cognitive assessments, and depression screening. Fifty-five patients participated in the experiments, on average 5 days after their stroke onset. Patients whose lesions were in different locations were tested, including lesions in brainstem areas, basal ganglia, thalamus, temporal lobe, and other cortical and subcortical areas. Lateralization impairments were found in most patients with lesions within the auditory pathway. Lesioned areas at brainstem levels led to distortions of lateralization in both hemifields, thalamus lesions were correlated with a shift of the whole auditory space, whereas some cortical lesions predominantly affected the lateralization of stimuli contralateral to the lesion and resulted in more variable responses. Lateralization performance was also found to be affected by lesions of the right, but not the left, basal ganglia, as well as by lesions in non-auditory cortical areas. In general, altered lateralization was common in the stroke group. In contrast, deficits in tone-in-noise detection were relatively scarce in our sample of lesion patients, although a significant number of patients with multiple lesion sites were not able to complete the task.</p

Image_4_Effects of acute ischemic stroke on binaural perception.JPEG

Stroke-induced lesions at different locations in the brain can affect various aspects of binaural hearing, including spatial perception. Previous studies found impairments in binaural hearing, especially in patients with temporal lobe tumors or lesions, but also resulting from lesions all along the auditory pathway from brainstem nuclei up to the auditory cortex. Currently, structural magnetic resonance imaging (MRI) is used in the clinical treatment routine of stroke patients. In combination with structural imaging, an analysis of binaural hearing enables a better understanding of hearing-related signaling pathways and of clinical disorders of binaural processing after a stroke. However, little data are currently available on binaural hearing in stroke patients, particularly for the acute phase of stroke. Here, we sought to address this gap in an exploratory study of patients in the acute phase of ischemic stroke. We conducted psychoacoustic measurements using two tasks of binaural hearing: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. The location of the stroke lesion was established by previously acquired MRI data. An additional general assessment included three-frequency audiometry, cognitive assessments, and depression screening. Fifty-five patients participated in the experiments, on average 5 days after their stroke onset. Patients whose lesions were in different locations were tested, including lesions in brainstem areas, basal ganglia, thalamus, temporal lobe, and other cortical and subcortical areas. Lateralization impairments were found in most patients with lesions within the auditory pathway. Lesioned areas at brainstem levels led to distortions of lateralization in both hemifields, thalamus lesions were correlated with a shift of the whole auditory space, whereas some cortical lesions predominantly affected the lateralization of stimuli contralateral to the lesion and resulted in more variable responses. Lateralization performance was also found to be affected by lesions of the right, but not the left, basal ganglia, as well as by lesions in non-auditory cortical areas. In general, altered lateralization was common in the stroke group. In contrast, deficits in tone-in-noise detection were relatively scarce in our sample of lesion patients, although a significant number of patients with multiple lesion sites were not able to complete the task.</p