Showing papers on "Superior frontal gyrus published in 2014"

Cognitive control and its impact on recovery from aphasic stroke

Abstract: Aphasic deficits are usually only interpreted in terms of domain-specific language processes. However, effective human communication and tests that probe this complex cognitive skill are also dependent on domain-general processes. In the clinical context, it is a pragmatic observation that impaired attention and executive functions interfere with the rehabilitation of aphasia. One system that is important in cognitive control is the salience network, which includes dorsal anterior cingulate cortex and adjacent cortex in the superior frontal gyrus (midline frontal cortex). This functional imaging study assessed domain-general activity in the midline frontal cortex, which was remote from the infarct, in relation to performance on a standard test of spoken language in 16 chronic aphasic patients both before and after a rehabilitation programme. During scanning, participants heard simple sentences, with each listening trial followed immediately by a trial in which they repeated back the previous sentence. Listening to sentences in the context of a listen–repeat task was expected to activate regions involved in both language-specific processes (speech perception and comprehension, verbal working memory and pre-articulatory rehearsal) and a number of task-specific processes (including attention to utterances and attempts to overcome pre-response conflict and decision uncertainty during impaired speech perception). To visualize the same system in healthy participants, sentences were presented to them as three-channel noise-vocoded speech, thereby impairing speech perception and assessing whether this evokes domain general cognitive systems. As expected, contrasting the more difficult task of perceiving and preparing to repeat noise-vocoded speech with the same task on clear speech demonstrated increased activity in the midline frontal cortex in the healthy participants. The same region was activated in the aphasic patients as they listened to standard (undistorted) sentences. Using a region of interest defined from the data on the healthy participants, data from the midline frontal cortex was obtained from the patients. Across the group and across different scanning sessions, activity correlated significantly with the patients’ communicative abilities. This correlation was not influenced by the sizes of the lesion or the patients’ chronological ages. This is the first study that has directly correlated activity in a domain general system, specifically the salience network, with residual language performance in post-stroke aphasia. It provides direct evidence in support of the clinical intuition that domain-general cognitive control is an essential factor contributing to the potential for recovery from aphasic stroke.

Resting state networks in major depressive disorder.

Abstract: Resting state functional magnetic resonance imaging (fMRI) examines the spontaneous low frequency neural activity of the brain to reveal networks of correlated neural activity. A number of different methodologies, each with its own advantages and disadvantages, have been used to examine networks of neural activity that may be related to clinical presentation. Major depressive disorder (MDD) research has largely focused on the default mode network (DMN), which is most active at rest and may relate to negative rumination. However, other networks can be discerned in the resting state such as salience and affective and cognitive control networks, all of which may be relevant to MDD psychopathology. This article reviews the rapidly increasing literature on resting state networks. A number of state- and trait-dependent abnormalities have been reported in MDD in a wide variety of regions including the cerebellum, lingual gyrus, anterior cingulate cortex (ACC), middle frontal gyrus (MFG), dorsolateral prefrontal cortex (dlPFC), amygdala and insula. Current and chronic medication is often a potential confound. Few trials have examined the immediate or delayed effects of antidepressants on resting state networks. This article presents a novel approach to the analysis of drug effects, the identification of signatures of efficacy, and thus for drug development.

An 8‐month randomized controlled exercise trial alters brain activation during cognitive tasks in overweight children

Abstract: Objective: Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children. Design and Methods: Participants included 43 unfit, overweight (BMI 85th percentile) children 8- to 11-years old (91% Black), who were randomly divided into either an aerobic exercise (n 524) or attention control group (n 519). Each group was offered a separate instructor-led after-school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker. Results: Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus. Conclusions: Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children.

Structural Changes Induced by Daily Music Listening in the Recovering Brain after Middle Cerebral Artery Stroke: A Voxel-Based Morphometry Study

Abstract: Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (nD 49) who either listened to their favorite music [music group (MG), nD 16] or verbal material [audio book group (ABG), nD 18] or did not receive any listening material [control group (CG), nD 15] during the 6month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood.This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

Introspection, attention or awareness? The role of the frontal lobe in binocular rivalry.

Abstract: Bistable stimuli are one of the most popular approaches to studying the neural mechanism of conscious visual perception. Such stimuli contain conflicting information, which the visual system cannot integrate into a unified percept. This causes the perceptual state of the observer to change every few seconds between the two interpretations while the physical stimulus remains the same. Binocular rivalry is an example of such perceptual phenomena with ambiguity achieved by presenting one image to one eye and a different image to the other eye. Perceptual changes during binocular rivalry are particularly vivid, and closely resemble a physical image exchange. The study of neural mechanisms of bistable perception and binocular rivalry revealed the involvement of multiple areas across different levels of the visual hierarchy (Sterzer et al., 2009). While the activated stimulus-selective temporal lobe areas depend on the stimulus category that produces ambiguity, activity in the parietal and frontal lobe seems to be common to all stimuli and increases specifically during transition periods between the two percepts. The activation of the frontal lobe areas is particularly intriguing. It suggests that the mechanisms of conscious vision might involve typical higher-level frontal lobe functions such as attention, motivation and decision-making. Previous studies of bistable perception relied on participants' explicit reports of their conscious state (most commonly button presses). Under certain conditions, however, perceptual states can be inferred objectively, without self-report. An example recent study by Frassle et al. (2014) took advantage of two ocular reflexes, optokinetic nystagmus and the pupillary light reflex, and designed binocular rivalry stimuli that selectively drive these reflexes. Simple eye tracking measures provided the authors with objective information about their subjects' perceptual changes over time. The authors used fMRI to monitor brain activity when observers experienced either genuine binocular rivalry or a “replay” (a control condition which simulates rivalry-like perceptual alterations by physically switching the stimulus presented to both eyes). These conditions were performed while subjects either actively reported their perceptual state or just passively viewed the stimuli. Such experimental design allowed Frassle et al. to make an important observation. Comparison of rivalry with replay in the passive viewing condition showed less activation in the frontal cortex compared to active report condition. The most prominent decrease was observed in the left superior and bilateral middle frontal gyri. According to the authors, decrease of frontal activity implies that frontal lobe areas play a role in introspection and motor response generation, but not in perceptual changes per se. Frontal lobe takes about one third of the cortical volume, and is comprised of multiple architectonically and functionally distinct areas (Stuss, 2011). Given this diversity it is important to ask, which frontal lobe regions are typically active during perceptual transitions in bistable perception, and how they relate to the regions reported by Frassle et al. as showing reduced activation during passive viewing. Previous studies comparing perceptual changes in rivalry with replay frequently reported activation in the inferior frontal cortex (IFC), middle frontal gyrus (MFG) and superior frontal gyrus (SFG) (Lumer et al., 1998; Zaretskaya et al., 2010; Knapen et al., 2011; Frassle et al., 2014), located mostly in the right hemisphere (Figure ​(Figure1,1, green). Frassle et al. on the other hand, report decreased activity around the bilateral MFG and bilateral SFG only (Figure 3 and Table 2 in Frassle et al., 2014, Figure ​Figure1,1, red). Moreover, their right superior frontal activation is relatively far from the locations reported previously. Thus, the two activation maps in the frontal lobe overlap only partially, namely around the right MFG, and perhaps also the left SFG. Activity of other rivalry-related frontal nodes, in particular the right superior frontal and the right inferior frontal ones, did not decrease significantly. The latter areas may therefore continue to play an important role in perceptual changes even without active motor report. Figure 1 Rivalry-related brain network. Locations reported to be more active in rivalry compared to instantaneous replay based on observer's button presses in previous studies (green) are plotted together with locations that were less active during passive viewing ... Besides, passive viewing involves not only less self-monitoring, but also less attention. Attention, in turn, is linked to increased activity in frontal, but also parietal and extrastriate areas. The reduction of activity at multiple non-frontal brain locations (Table 2 in Frassle et al., 2014, Figure ​Figure1)1) is in our view compatible with a more general attention effect. Difference in median dominance durations between active and passive conditions further support an attentional explanation. The authors report that, at least in the case of the pupil size-based analyses, median dominance durations were longer in the passive viewing condition. It is known that not only unreported but also unattended rivalry can lead to longer dominance durations (Paffen and Alais, 2011). In sum some of the fMRI effects are difficult to disentangle from attentional modulation. Besides singling out the effects of self-monitoring from those of attention during passive viewing, it is important to dissociate the effects of self-monitoring and those of motor response. The ability to report one's conscious experience is not a prerequisite for conscious perception, but this may not hold for self-monitoring and introspection. Can we be sure that we are aware of something without reflecting about it? In fact, several approaches to consciousness define self-awareness as its essential component (Van Gulick, 2014). This raises some more philosophical questions about the nature of conscious experience that are beyond the scope of this review. In any case, we think that future studies could benefit from better segregation of different processes that accompany self-report and equating attentional demands between different conditions. Almost two decades ago Crick and Koch (1995) proposed that extrastriate projections to the frontal cortex are necessary for conscious perception, thus putting the frontal lobes front and center in the study of neural correlates of consciousness. Indeed, experimental findings on bistable perception over the years supported the important role of frontal areas in generating perceptual changes (e.g., Sterzer and Kleinschmidt, 2007; Weilnhammer et al., 2013). The study of Frassle et al. does point to a possible confound of active motor report in perception-related activity of some frontal lobe sites. However, it does not rule out the possibly important role of other frontal lobe areas in generating conscious visual experience.

Irritable bowel syndrome in female patients is associated with alterations in structural brain networks.

Abstract: Alterations in gray matter (GM) density/volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with differing chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at University of California, Los Angeles, Los Angeles, CA, USA, between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 healthy controls [HCs], 30 ± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between the group with IBS and the HC group. Relative to HCs, the IBS group had lower volumes in the bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found in the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for the Early Trauma Inventory global score, with the exception of the right amygdala and the left postcentral gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, in patients with IBS, the right cingulate gyrus and right thalamus were identified as being significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in patients with IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks.

Losing the rose tinted glasses: Neural substrates of unbiased belief updating in depression

Abstract: Recent evidence suggests that a state of good mental health is associated with biased processing of information that supports a positively skewed view of the future. Depression, on the other hand, is associated with unbiased processing of such information. Here, we use brain imaging in conjunction with a belief update task administered to clinically depressed patients and healthy controls to characterize brain activity that supports unbiased belief updating in clinically depressed individuals. Our results reveal that unbiased belief updating in depression is mediated by strong neural coding of estimation errors in response to both good news (in left inferior frontal gyrus and bilateral superior frontal gyrus) and bad news (in right inferior parietal lobule and right inferior frontal gyrus) regarding the future. In contrast, intact mental health was linked to a relatively attenuated neural coding of bad news about the future. These findings identify a neural substrate mediating the breakdown of biased updating in major depression disorder, which may be essential for mental health.

Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis.

Abstract: Background Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research. Method To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants. Results The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression. Conclusions Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

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

Abstract: 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.

Functional connectivity changes between parietal and prefrontal cortices in primary insomnia patients: evidence from resting-state fMRI

Abstract: Primary insomnia can severely impair daytime function by disrupting attention and working memory and imposes a danger to self and others by increasing the risk of accidents. We speculated that the neurobiological changes impeding working memory in primary insomnia patients would be revealed by resting-state functional MRI (R-fMRI), which estimates the strength of cortical pathways by measuring local and regional correlations in blood oxygen level dependent (BOLD) signs independent of specific task demands. We compared the R-fMRI activity patterns of 15 healthy controls to 15 primary insomnia patients (all 30 participants were right-handed) using a 3.0 T MRI scanner. The SPM8 and REST1.7 software packages were used for preprocessing and analysis. Activity was expressed relative to the superior parietal lobe (SPL, the seed region) to reveal differences in functional connectivity to other cortical regions implicated in spatial working memory. In healthy controls, bilateral SPL activity was associated with activity in the posterior cingulate gyrus, precuneus, ventromedial prefrontal cortex, and superior frontal gyrus, indicating functional connectivity between these regions. Strong functional connectivity between the SPL and bilateral pre-motor cortex, bilateral supplementary motor cortex, and left dorsolateral prefrontal cortex was observed in both the control group and the primary insomnia group. However, the strength of several other functional connectivity pathways to the SPL exhibited significant group differences. Compared to healthy controls, connectivity in the primary insomnia group was stronger between the bilateral SPL and the right ventral anterior cingulate cortex, left ventral posterior cingulate cortex, right splenium of the corpus callosum, right pars triangularis (right inferior frontal gyrus/Broca’s area), and right insular lobe, while connectivity was weaker between the SPL and right superior frontal gyrus (dorsolateral prefrontal cortex). Primary insomnia appears to alter the functional connectivity between the parietal and frontal lobes, cortical structures critical for spatial and verbal working memory.

Negative emotion modulates prefrontal cortex activity during a working memory task: a NIRS study

Abstract: This study investigated the neural processing underlying the cognitive control of emotions induced by the presentation of task-irrelevant emotional pictures before a working memory task Previous studies have suggested that the cognitive control of emotion involves the prefrontal regions Therefore, we measured the hemodynamic responses that occurred in the prefrontal region with a 16-channel near-infrared spectroscopy (NIRS) system In our experiment, participants observed two negative or two neutral pictures in succession immediately before a 1-back or 3-back task Pictures were selected from the International Affective Picture System (IAPS) We measured the changes in the concentration of oxygenated hemoglobin (oxyHb) during picture presentation and during the n-back task The emotional valence of the picture affected the oxyHb changes in anterior parts of the medial prefrontal cortex (MPFC) (located in the left and right superior frontal gyrus) and left inferior frontal gyrus during the n-back task; the oxyHb changes during the task were significantly greater following negative rather than neutral stimulation As indicated in a number of previous studies, and the time courses of the oxyHb changes in our study, activation in these locations is possibly led by cognitive control of emotion, though we cannot deny it may simply be emotional responses There were no effects of emotion on oxyHb changes during picture presentation or on n-back task performance Although further studies are necessary to confirm this interpretation, our findings suggest that NIRS can be used to investigate neural processing during emotional control

Symptom dimensions are associated with reward processing in unmedicated persons at risk for psychosis

Abstract: There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio- and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.

Altered Amygdala Connectivity Within the Social Brain in Schizophrenia

Abstract: Background: Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. Methods: We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. Results: While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. Discussion: We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

Abstract: OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients.

Pituitary adenylate cyclase–activating polypeptide is reduced in Alzheimer disease

Abstract: Objectives: There is growing evidence that pituitary adenylate cyclase–activating polypeptide (PACAP) is associated with Alzheimer disease (AD) pathology in animal models, but human studies are needed. Methods: We studied the brains of patients with pathologically confirmed late-onset AD and age-matched cognitively normal (CN) subjects to investigate the expression of PACAP messenger RNA (34 AD and 14 CN) and protein (12 AD and 11 CN) in a case-control study. Results: We report that PACAP levels are reduced in multiple brain regions, including the entorhinal cortex, the middle temporal gyrus, the superior frontal gyrus, and the primary visual cortex. This reduction is correlated with higher amyloid burden (CERAD plaque density) in the entorhinal cortex and superior frontal gyrus but not in the primary visual cortex, a region spared in most cases of AD. PACAP expression is lower in advanced Braak stages (V and VI) than in moderate stages (III and IV). Increased PACAP levels are associated with decreased scores on the Dementia Rating Scale, a global cognitive measure. Finally, CSF levels paralleled brain levels in AD but not in Parkinson dementia or frontotemporal dementia brains. Conclusions: The close relationship between PACAP reduction and the severity of AD pathology suggests that downregulation of PACAP may contribute to AD pathogenesis.

Idiopathic-generalized epilepsy shows profound white matter diffusion-tensor imaging alterations.

Abstract: Objectives Idiopathic-generalized epilepsy (IGE) is currently considered to be a genetic disease without structural alterations on conventional MRI. However, voxel-based morphometry has shown abnormalities in IGE. Another method to analyze the microstructure of the brain is diffusion-tensor imaging (DTI). We sought to clarify which structural alterations are present in IGE and the most frequent subsyndrome juvenile myoclonic epilepsy (JME). Experimental design We studied 25 patients (13 IGE and 12 JME) and 44 healthy controls with DTI. Fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity (AD/RD) were calculated and group differences were analyzed using tract-based spatial statistics (TBSS). Additionally we performed a target-based classification of TBSS results based on the Freesurfer cortical regions. Principle observations TBSS showed widespread FA reductions as well as MD and RD increases in patients compared to controls. Affected areas were corpus callosum, corticospinal tract, superior and inferior longitudinal fasciculus and supplementary motor regions. No significant differences were found between JME and IGE subgroups. The target-based classification confirmed a particular involvement of the superior frontal gyrus (mesiofrontal area) in IGE/ME. Conclusions IGE and JME patients showed clear microstructural alterations in several large white matter tracts. Similar findings have been reported in rodent models of IGE. Previous, region-of-interest-based DTI studies may have under-estimated the spatial extent of structural loss associated with generalized epilepsy. The comparison of clinically defined JME and IGE groups revealed no significant DTI differences in our cohort. Hum Brain Mapp 35:3332–3342, 2014. © 2013 Wiley Periodicals, Inc.

The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate-precuneus pathway.

Abstract: Introduction Perturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus. Methods Using functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting-state functional connectivity analysis using the anterior cingulate cortex as a seed. Results Independent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed-based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60–0.76; P < 0.05). Conclusions In concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting-state functional connectivity in this pathway increases during nicotine withdrawal in correlation with the intensity of withdrawal-induced craving. These findings suggest that smoking triggers structural and functional neural adaptations in the brain that support withdrawal-induced craving.

Altered Brain Activation Patterns Under Different Working Memory Loads in Patients With Type 2 Diabetes

Abstract: OBJECTIVE Type 2 diabetes mellitus (T2DM) has important effects on cognition and the risk for Alzheimer disease (AD). Working memory (WM) is a susceptible cognitive domain of mild cognitive impairment and AD. Thus, the identification of brain activation patterns under different WM loads can potentially enhance our understanding of the mechanisms underlying cognitive dysfunction in T2DM. RESEARCH DESIGN AND METHODS The current study assessed the effects of T2DM on cognitive performance and explored the related neuronal damage through a visual n -back task and functional magnetic resonance imaging. RESULTS We found that patients with T2DM exhibited worse executive and memory abilities than control subjects. Furthermore, the patterns of brain activation changed under different WM loads in the T2DM patients, who exhibited reduced activation in the left inferior frontal gyrus under low loads and reduced activation in the left middle frontal gyrus and superior frontal gyrus (SFG) under high loads. Thus, more regions of diminished activation were seen in the frontal cortex with increasing task difficulty. Furthermore, we found that lower SFG activation was associated with worse cognitive function. CONCLUSIONS The findings demonstrate deficient WM in patients with T2DM and the relation between cognitive function and degree of neuronal activity and their relevance to AD risk. Further longitudinal studies are needed to replicate these results and to evaluate the clinical value of brain imaging methods in the prediction of disease progress in these patients.

Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients

Abstract: Background Apolipoprotein E ɛ4 (ApoE4) has been associated with an increased risk of Alzheimer9s disease (AD), amyloid deposition and hypometabolism. ApoE4 is less prevalent in non-amnestic AD variants suggesting a direct effect on the clinical phenotype. However, the impact of ApoE4 on amyloid burden and glucose metabolism across different clinical AD syndromes is not well understood. We aimed to assess the relationship between amyloid deposition, glucose metabolism and ApoE4 genotype in a clinically heterogeneous population of AD patients. Methods 52 patients with probable AD (National Institute on Aging-Alzheimer9s Association) underwent [ 11 C]Pittsburgh compound B (PIB) and [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. All patients had positive PIB-PET scans. 23 were ApoE4 positive (ApoE4+) (14 heterozygous and 9 homozygous) and 29 were ApoE4 negative (ApoE4−). Groups consisted of language-variant AD, visual-variant AD and AD patients with amnestic and dysexecutive deficits. 52 healthy controls were included for comparison. FDG and PIB uptake was compared between groups on a voxel-wise basis and in regions of interest. Results While PIB patterns were diffuse in both patient groups, ApoE4− patients showed higher PIB uptake than ApoE4+ patients across the cortex. Higher PIB uptake in ApoE4− patients was particularly significant in right lateral frontotemporal regions. In contrast, similar patterns of hypometabolism relative to controls were found in both patient groups, mainly involving lateral temporoparietal cortex, precuneus, posterior cingulate cortex and middle frontal gyrus. Comparing patient groups, ApoE4+ subjects showed greater hypometabolism in bilateral medial temporal and right lateral temporal regions, and ApoE4− patients showed greater hypometabolism in cortical areas, including supplementary motor cortex and superior frontal gyrus. Conclusions ApoE4+ AD patients showed lower global amyloid burden and greater medial temporal hypometabolism compared with matched ApoE4− patients. These findings suggest that ApoE4 may increase susceptibility to molecular pathology and modulate the anatomic pattern of neurodegeneration in AD.

Multimodal Brain Connectivity Analysis in Unmedicated Late-Life Depression

Abstract: Late-life depression (LLD) is a common disorder associated with emotional distress, cognitive impairment and somatic complains. Structural abnormalities have been suggested as one of the main neurobiological correlates in LLD. However the relationship between these structural abnormalities and altered functional brain networks in LLD remains poorly understood. 15 healthy elderly comparison subjects from the community and 10 unmedicated and symptomatic subjects with geriatric depression were selected for this study. For each subject, 87 regions of interest (ROI) were generated from whole brain anatomical parcellation of resting state fMRI data. Whole-brain ROI-wise correlations were calculated and compared between groups. Group differences were assessed using an analysis of covariance after controlling for age, sex and education with multiple comparison correction using the false discovery rate. Structural connectivity was assessed by tract-based spatial statistics (TBSS). LLD subjects had significantly decreased connectivity between the right accumbens area (rA) and the right medial orbitofrontal cortex (rmOFC) as well as between the right rostral anterior cingulate cortex (rrACC) and bilateral superior frontal gyrus (bsSFG). Altered connectivity of rrACC with the bsSFG was significantly correlated with depression severity in depressed subjects. TBSS analysis showed a 20% reduction in fractional anisotropy (FA) in the right Forceps Minor (rFM) in depressed subjects. rFM FA values were positively correlated with rA-rmOFC and rrACC-bsFG functional connectivity values in our total study sample. Coordinated structural and functional impairment in circuits involved in emotion regulation and reward pathways play an important role in the pathophysiology of LLD.

Task switching in traumatic brain injury relates to cortico-subcortical integrity.

Abstract: Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico-subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract-based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico-subcortical loops with the (pre-)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal-subcortical projections in TBI, which is associated with task switching impairments.