Jane Neumann

Involvement of the Inferior Frontal Junction in Cognitive Control: Meta-Analyses of Switching and Stroop Studies

There is growing evidence that a specific region in the posterior frontolateral cortex is involved intimately in cognitive control processes. This region, located in the vicinity of the junction of the inferior frontal sulcus and the inferior precentral sulcus, was termed the inferior frontal junction (IFJ). The IFJ was shown to be involved in the updating of task representations and to be activated commonly in a within‐subject investigation of a task‐switching paradigm, the Stroop task, and a verbal n‐back task. Here, we investigate the involvement of the IFJ in cognitive control by employing a meta‐analytic approach. Two quantitative meta‐analyses of functional magnetic resonance imaging (fMRI) studies were conducted. One meta‐analysis included frontal activations from task‐switching, set‐shifting, and stimulus–response (S–R) reversal studies, the other included frontal activations from color–word Stroop studies. Results showed highly significant clustering of activations in the IFJ in both analyses. These results provide strong evidence for the consistent involvement of the IFJ in both switching and Stroop paradigms. Furthermore, they support our concept of areal specialization in the frontolateral cortex, which posits that it is not only the middorsolateral part that plays an important role in cognitive control, but also the IFJ. Finally, our results demonstrate how quantitative meta‐analyses can be used to test hypotheses about the involvement of specific brain regions in cognitive control. Hum Brain Mapp 25:22–34, 2005.

Striatum and pre-SMA facilitate decision-making under time pressure

Human decision-making almost always takes place under time pressure. When people are engaged in activities such as shopping, driving, or playing chess, they have to continually balance the demands for fast decisions against the demands for accurate decisions. In the cognitive sciences, this balance is thought to be modulated by a response threshold, the neural substrate of which is currently subject to speculation. In a speed decision-making experiment, we presented participants with cues that indicated different requirements for response speed. Application of a mathematical model for the behavioral data confirmed that cueing for speed lowered the response threshold. Functional neuroimaging showed that cueing for speed activates the striatum and the pre-supplementary motor area (pre-SMA), brain structures that are part of a closed-loop motor circuit involved in the preparation of voluntary action plans. Moreover, activation in the striatum is known to release the motor system from global inhibition, thereby facilitating faster but possibly premature actions. Finally, the data show that individual variation in the activation of striatum and pre-SMA is selectively associated with individual variation in the amplitude of the adjustments in the response threshold estimated by the mathematical model. These results demonstrate that when people have to make decisions under time pressure their striatum and pre-SMA show increased levels of activation.

The extended language network: A meta-analysis of neuroimaging studies on text comprehension

Language processing in context requires more than merely comprehending words and sentences. Important subprocesses are inferences for bridging successive utterances, the use of background knowledge and discourse context, and pragmatic interpretations. The functional neuroanatomy of these text comprehension processes has only recently been investigated. Although there is evidence for right‐hemisphere contributions, reviews have implicated the left lateral prefrontal cortex, left temporal regions beyond Wernickes area, and the left dorso‐medial prefrontal cortex (dmPFC) for text comprehension. To objectively confirm this extended language network and to evaluate the respective contribution of right hemisphere regions, meta‐analyses of 23 neuroimaging studies are reported here. The analyses used replicator dynamics based on activation likelihood estimates. Independent of the baseline, the anterior temporal lobes (aTL) were active bilaterally. In addition, processing of coherent compared with incoherent text engaged the dmPFC and the posterior cingulate cortex. Right hemisphere activations were seen most notably in the analysis of contrasts testing specific subprocesses, such as metaphor comprehension. These results suggest task dependent contributions for the lateral PFC and the right hemisphere. Most importantly, they confirm the role of the aTL and the fronto‐medial cortex for language processing in context. Hum Brain Mapp 2008.

Neural correlates of error awareness

Error processing results in a number of consequences on multiple levels. The posterior frontomedian cortex (pFMC) is involved in performance monitoring and signalling the need for adjustments, which can be observed as post-error speed-accuracy shifts at the behavioural level. Furthermore autonomic reactions to an error have been reported. The role of conscious error awareness for this processing cascade has received little attention of researchers so far. We examined the neural correlates of conscious error perception in a functional magnetic resonance imaging (fMRI) study. An antisaccade task known to yield sufficient numbers of aware and unaware errors was used. Results from a metaanalysis were used to guide a region of interest (ROI) analysis of the fMRI data. Consistent with previous reports, error-related activity in the rostral cingulate zone (RCZ), the pre-supplementary motor area (pre-SMA) and the insular cortex bilaterally was found. Whereas the RCZ activity did not differentiate between aware and unaware errors, activity in the left anterior inferior insular cortex was stronger for aware as compared to unaware errors. This could be due to increased awareness of the autonomic reaction to an error, or the increased autonomic reaction itself. Furthermore, post-error adjustments were only observed after aware errors and a correlation between post-error slowing and the hemodynamic activity in the RCZ was revealed. The data suggest that the RCZ activity alone is insufficient to drive error awareness. Its signal appears to be useful for post-error speed-accuracy adjustments only when the error is consciously perceived.

Cortico-striatal connections predict control over speed and accuracy in perceptual decision making

When people make decisions they often face opposing demands for response speed and response accuracy, a process likely mediated by response thresholds. According to the striatal hypothesis, people decrease response thresholds by increasing activation from cortex to striatum, releasing the brain from inhibition. According to the STN hypothesis, people decrease response thresholds by decreasing activation from cortex to subthalamic nucleus (STN); a decrease in STN activity is likewise thought to release the brain from inhibition and result in responses that are fast but error-prone. To test these hypotheses—both of which may be true—we conducted two experiments on perceptual decision making in which we used cues to vary the demands for speed vs. accuracy. In both experiments, behavioral data and mathematical model analyses confirmed that instruction from the cue selectively affected the setting of response thresholds. In the first experiment we used ultra-high-resolution 7T structural MRI to locate the STN precisely. We then used 3T structural MRI and probabilistic tractography to quantify the connectivity between the relevant brain areas. The results showed that participants who flexibly change response thresholds (as quantified by the mathematical model) have strong structural connections between presupplementary motor area and striatum. This result was confirmed in an independent second experiment. In general, these findings show that individual differences in elementary cognitive tasks are partly driven by structural differences in brain connectivity. Specifically, these findings support a cortico-striatal control account of how the brain implements adaptive switches between cautious and risky behavior.

Neural correlates of Alzheimer's disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients

Alzheimers disease is the most common form of dementia. Its prodromal stage amnestic mild cognitive impairment is characterized by deficits of anterograde episodic memory. The development of standardized imaging inclusion criteria has to be regarded as a prerequisite for future diagnostic systems. Moreover, successful treatment requires isolating imaging markers predicting the disease. Accordingly, we conducted a systematic and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimers disease and its prodromal stage. To prevent any a priori assumptions and enable a data-driven approach only studies applying quantitative automated whole brain analysis were included. Finally, 40 studies were identified involving 1351 patients and 1097 healthy control subjects reporting either atrophy or decreases in glucose utilization and perfusion. The currently most sophisticated and best-validated of coordinate-based voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis reveals that early Alzheimers disease affects structurally the (trans-)entorhinal and hippocampal regions, functionally the inferior parietal lobules and precuneus. Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably the progression from amnestic mild cognitive impairment to Alzheimers disease, whereas changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed Alzheimers disease involved additionally a frontomedian-thalamic network. In conclusion, the meta-analysis characterizes the prototypical neural substrates of Alzheimers disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive markers it enables successful treatment strategies in the future and contributes to standardized imaging inclusion criteria for Alzheimers disease as suggested for future diagnostic systems.

Mapping the depressed brain: A meta-analysis of structural and functional alterations in major depressive disorder

BACKGROUND Depression has a lifetime prevalence of up to 20%. Neuroimaging methods have revealed various structural and functional changes that occur in a human brain during a depressive episode. However, we still lack information concerning the extent to which structural and functional changes co-occur in a depressed brain. Furthermore, it is difficult to evaluate from a merely qualitative literature review what regional brain changes in volume and activation are robust across depressed patient samples and consistent across imaging centers. METHODOLOGY AND PRINCIPLE FINDINGS This study is a meta-analysis from 10 selected studies published previously. We applied the statistical anatomical/activation likelihood estimate method (ALE) in a total of 176 depressed patients and 175 controls for the MRI modality and in a total of 102 depressed patients and 94 controls for the PET modality to quantitatively identify those brain regions that show concordant alteration in the midst of a depressive episode across imaging modalities and study sites. We find a convergent change in the limbic-cortical brain circuit in depression compared to controls of both Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data. The specific changes include lower gray matter volumes in the amygdala, the dorsal frontomedian cortex, and the right paracingulate cortex, as well as increases in glucose metabolism in the right subgenual and pregenual anterior cingulate cortices. CONCLUSIONS/SIGNIFICANCE Our current findings represent an important first step towards a more focused approach to neuroimaging unipolar depression. The regions identified could serve as a specific region-of-interest-for-disease template for both individual in vivo imaging studies and postmortem histopathologic exploration.

Dopamine DRD2 Polymorphism Alters Reversal Learning and Associated Neural Activity

In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIa polymorphism is associated with reduced expression of dopamine (DA) D2 receptors in the striatum. Recently, it was observed that carriers of the A1 allele (A1+ subjects) showed impaired learning from negative feedback in a reinforcement learning task. Here, using functional MRI (fMRI), we investigated carriers and noncarriers of the A1 allele while they performed a probabilistic reversal learning task. A1+ subjects showed subtle deficits in reversal learning. In particular, these deficits consisted of an impairment in sustaining the newly rewarded response after a reversal and in a generally decreased tendency to stick with a rewarded response. Both genetic groups showed increased fMRI signal in response to negative feedback in the rostral cingulate zone (RCZ) and anterior insula. Negative feedback that incurred a change in behavior additionally engaged the ventral striatum and a region of the midbrain consistent with the location of dopaminergic cell groups. The response of the RCZ to negative feedback increased as a function of preceding negative feedback. However, this graded response was not observed in the A1+ group. Furthermore, the A1+ group also showed diminished recruitment of the right ventral striatum and the right lateral orbitofrontal cortex (lOFC) during reversals. Together, these results suggest that a genetically driven reduction in DA D2 receptors leads to deficient feedback integration in RCZ. This, in turn, was accompanied by impaired recruitment of the ventral striatum and the right lOFC during reversals, which might explain the behavioral differences between the genetic groups.

Characterizing acupuncture stimuli using brain imaging with fMRI: A systematic review and meta-analysis of the literature

Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies.

Neural networks in frontotemporal dementia - A meta-analysis

OBJECTIVE Frontotemporal dementia is the most common form of frontotemporal lobar degeneration. It is characterized by deep alterations in behavior and personality. We conducted a systematic and quantitative meta-analysis to examine its neural correlates and place the disease in a framework of cognitive neuropsychiatry. METHODS MedLine and Current Contents search engines were used to identify imaging studies investigating frontotemporal dementia between 1980 and 2005. Nine studies were identified reporting either atrophy or decreases in glucose utilization. Finally, the analysis involved 132 patients and 166 controls. A quantitative meta-analysis was performed. Maxima of the studies resulted in activation likelihood estimates. RESULTS The meta-analysis revealed a particularly frontomedian network impaired in frontotemporal dementia. Additionally, right anterior insula, and medial thalamus were identified. CONCLUSIONS Our study specifies frontotemporal dementia as the frontomedian variant of frontotemporal lobar degeneration. The disease affects neural networks enabling self-monitoring, theory of mind capabilities, processing/evaluation of internal mental states, perception of pain and emotions, and sustaining personality and self. Our study contributes to placing frontotemporal dementia in cognitive neuropsychiatry.