FRIEND Engine Framework: a real time neurofeedback client-server system for neuroimaging studies.

In this methods article, we present a new implementation of a recently reported FSL-integrated neurofeedback tool, the standalone version of "Functional Real-time Interactive Endogenous Neuromodulation and Decoding" (FRIEND). We will refer to this new implementation as the FRIEND Engine Framework. The framework comprises a client-server cross-platform solution for real time fMRI and fMRI/EEG neurofeedback studies, enabling flexible customization or integration of graphical interfaces, devices, and data processing. This implementation allows a fast setup of novel plug-ins and frontends, which can be shared with the user community at large. The FRIEND Engine Framework is freely distributed for non-commercial, research purposes.

Grey matter changes associated with deficit awareness in mild cognitive impairment: a voxel-based morphometry study.

Reduced awareness of cognitive deficits in mild cognitive impairment (MCI) is associated with poorer outcomes although little is known about the anatomical correlates of this. We examined the association of insight and grey matter volume using a voxel-based morphometry approach in 65 volunteers with MCI and 55 healthy age-matched controls. Participants with MCI had multiple areas of subtle grey matter volume loss compared with controls, although these did not survive correction for multiple comparisons. These were predominantly in the temporal and anterior portions of the brain. Individuals with MCI did not differ from each other on a number of demographic and cognitive variables according to level of insight. Reduced awareness of cognitive deficits was associated with few differences in grey matter volume apart from a subtle loss of grey matter in the medial frontal gyri. Given the modest nature of these findings, the routine assessment of insight in non-clinical populations of individuals with MCI is therefore not supported. Prospective data in larger samples, however, would be helpful to clarify this further and determine if impaired insight predicts brain atrophy and cognitive decline.

Memory networks in tinnitus: a functional brain image study.

UNLABELLED: Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. METHODS: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the "Tinnitus Handicap Inventory" (THI). The images were processed and analyzed using "Statistical Parametric Mapping" (SPM8). RESULTS: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. CONCLUSION: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.

Real-time fMRI pattern decoding and neurofeedback using FRIEND: an FSL-integrated BCI toolbox.

The demonstration that humans can learn to modulate their own brain activity based on feedback of neurophysiological signals opened up exciting opportunities for fundamental and applied neuroscience. Although EEG-based neurofeedback has been long employed both in experimental and clinical investigation, functional MRI (fMRI)-based neurofeedback emerged as a promising method, given its superior spatial resolution and ability to gauge deep cortical and subcortical brain regions. In combination with improved computational approaches, such as pattern recognition analysis (e.g., Support Vector Machines, SVM), fMRI neurofeedback and brain decoding represent key innovations in the field of neuromodulation and functional plasticity. Expansion in this field and its applications critically depend on the existence of freely available, integrated and user-friendly tools for the neuroimaging research community. Here, we introduce FRIEND, a graphic-oriented user-friendly interface package for fMRI neurofeedback and real-time multivoxel pattern decoding. The package integrates routines for image preprocessing in real-time, ROI-based feedback (single-ROI BOLD level and functional connectivity) and brain decoding-based feedback using SVM. FRIEND delivers an intuitive graphic interface with flexible processing pipelines involving optimized procedures embedding widely validated packages, such as FSL and libSVM. In addition, a user-defined visual neurofeedback module allows users to easily design and run fMRI neurofeedback experiments using ROI-based or multivariate classification approaches. FRIEND is open-source and free for non-commercial use. Processing tutorials and extensive documentation are available.

Brain and mood changes over 2 years in healthy controls and adults with heart failure and ischaemic heart disease.

AIMS: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow-up period of 2 years. METHODS AND RESULTS: This was a 24-month longitudinal study of 19 participants with systolic HF, 43 with IHD, and 45 controls. Subjects were older than 45 years and free of cognitive impairment at the start of follow-up. We acquired magnetic resonance images and used Statistical Parametric Mapping version 8 (SPM8) to investigate changes in the distribution of cerebral grey matter volume over time. We used the Cambridge Cognitive Examination of the Elderly (CAMCOG) and the Hospital Anxiety and Depression Scale (HADS) to assess 2-year changes in cognitive function and mood. Changes in total grey matter volume and cognitive function were similar across the three study groups, but participants with HF showed evidence of increasing severity of anxiety and depressive symptoms. HF was associated with subtle regional loss of grey matter in the right and left thalamus, left caudate, left and right posterior cingulate, left and right parahippocampal gyri, left superior and middle temporal gyri, and right inferior parietal lobule compared with controls and, to a lesser extent, participants with IHD. CONCLUSION: HF and IHD are not associated with a disproportional loss of cerebral grey matter or cognitive decline over 2 years compared with cardiologically healthy controls. Adults with HF experience increasing symptoms of anxiety and depression over 2 years compared with controls, and this increased vulnerability is associated with a relative loss of grey matter in brain regions that are important for the modulation of emotions.

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease.

BACKGROUND: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. METHODS: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. RESULTS: Participants with high tHcy (≥15 µmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. CONCLUSIONS: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal.

Cognitive and brain changes associated with ischaemic heart disease and heart failure.

AIMS: It is unclear whether the cognitive dysfunction associated with heart failure (HF) is due to HF or comorbid conditions such as ischaemic heart disease (IHD). This study aimed to determine whether, compared with controls with and without IHD, adults with systolic HF show evidence of cognitive impairment and cerebral grey matter (GM) loss. METHODS AND RESULTS: Cross-sectional study of 35 participants with HF, 56 with IHD, and 64 controls without either HF or IHD. Subjects were older than 45 years and free of overt cognitive impairment. We acquired magnetic resonance images and used SPM8 to determine regional differences in cerebral GM volume. Participants with HF had lower scores than controls without IHD on immediate memory, long delay recall and digit coding, whereas those with IHD had lower long delay recall scores than controls without IHD. Compared with controls without IHD, participants with HF showed evidence of GM loss in the left cingulate, the right inferior frontal gyrus, the left middle and superior frontal gyri, the right middle temporal lobe, the right and left anterior cingulate, the right middle frontal gyrus, the inferior and pre-central frontal gyri, the right caudate, and occipital-parietal regions involving the left precuneus. The loss of GM followed a similar, less extensive, pattern when we compared participants with HF and IHD. CONCLUSION: Adults with HF have worse immediate and long-term memory and psychomotor speed than controls without IHD. Heart failure is associated with changes in brain regions that are important for demanding cognitive and emotional processing.

24-month effect of smoking cessation on cognitive function and brain structure in later life.

BACKGROUND: Observational studies investigating the association between smoking, cognitive decline and dementia have produced conflicting results. We completed this trial to determine if smoking cessation decreases the progression of cognitive decline in later life. METHODS: We recruited older smokers (n=229) and never smokers (n=98) and invited smokers to join a smoking cessation trial. The primary outcome of interest was change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) scores over 24 months. Secondary measures included the Logical Memory test and changes in gray matter density. Successful smoking cessation was defined as a minimum of 547 smoking free days during follow up. RESULTS: The ADAS-cog scores of unsuccessful quitters (UQ) increased (i.e., became worse) 1.1±0.3 and 1.2±0.4 points more than the scores of never smokers (NS) (p=0.001) and successful quitters (SQ) (p=0.006) respectively over the 24 months of follow up. Similarly, the scores of UQ declined (i.e., became worse) relative to NS on measures of immediate (p=0.004) and delayed recall (p=0.029). All analyses were adjusted for age, years of education, baseline cognitive performance, alcohol use, depression scores, and the presence of chronic respiratory disease. Thirty-six NS, 18 SQ and 48 UQ completed the imaging substudy. Compared with NS, UQ showed a disproportional loss of gray matter density in the right thalamus, right and left inferior semi-lunar lobule, as well as left superior and inferior parietal lobule over 24 months. SQ showed loss of gray matter compared with NS in the right middle and inferior occipital gyri, right and left culmen, and the left superior frontal gyrus. We did not find any brain regions in which UQ had lost more gray matter than SQ over 2 years. CONCLUSION: These results are consistent with the hypothesis that smoking causes cognitive decline and loss of gray matter tissue in the brain over time.

Psychopathy as a disorder of the moral brain: fronto-temporo-limbic grey matter reductions demonstrated by voxel-based morphometry.

Major advances have been made in the understanding of the neurobiology of psychopathy in the past years, yet the distribution and extent of neuroanatomical abnormalities underlying the disorder are still poorly known. It is also unclear if different dimensions of the construct of psychopathy (e.g., emotional callousness, antisocial behavior) correspond to structural abnormalities in distinct regions of the brain. We tested the following hypotheses: (1) psychopathy is related to grey matter reductions in regions of the brain that underlie moral conduct and (2) the severity of psychopathy is related to the degree of structural abnormalities. Optimized voxel-based morphometry and the screening version of the Psychopathy Checklist (PCL: SV) were employed to investigate a matched sample of 15 community psychiatric patients with high PCL: SV scores, and 15 healthy normal volunteers. The analyses controlled for total grey matter, white matter and cerebrospinal fluid volumes. Grey matter reductions were observed in the frontopolar, orbitofrontal and anterior temporal cortices, superior temporal sulcus region, and insula of the patients. The degree of structural abnormalities was significantly related to the interpersonal/affective dimension of psychopathy. The pattern of grey matter reductions in patients with high psychopathy scores comprised a distributed fronto-temporal network which plays a critical role in moral sensibility and behavior.

Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease.

OBJECTIVES: The results of observational studies suggest that smoking increases the risk of Alzheimer disease (AD). The authors designed this study to determine if older people who smoke have decreased gray matter density in brain regions associated with incipient AD. METHODS: The authors recruited 39 pairs (N = 78) of smokers/never-smokers 70 to 83 years of age who were matched for age, sex, education, and handedness. Participants were free of clinically significant cognitive impairment, depression, stroke, or other serious medical conditions. Gray matter density was determined by voxel-based morphometry using statistical parametric mapping of T1-weighted magnetic resonance images. RESULTS: Smokers had decreased gray matter density in the posterior cingulum and precuneus (bilateral), right thalamus, and frontal cortex (bilateral) compared with never-smokers. CONCLUSIONS: Smoking is associated with decreased gray matter density in brain regions previously associated with incipient AD. Longitudinal investigations are required to clarify whether these changes are progressive in nature.

The self as a moral agent: linking the neural bases of social agency and moral sensitivity.

The human brain is inherently able to understand the world in moral ways, endowing most of us with an intuitive sense of fairness, concern for others, and observance of cultural norms. We have argued that this moral sensitivity ability depends on a sophisticated integration of cognitive, emotional, and motivational mechanisms, which are modulated by individual experience in different cultural milieus. Different lines of investigation on agency and morality have pointed to overlapping neural systems. Therefore, understanding the relationships between morality and agency may provide key insights into the mechanisms underlying human behavior in several clinical and societal settings. We used functional MRI to investigate the contribution of agency and of specific moral emotions to brain activation using action scripts. Results showed that emotionally neutral agency recruited neural networks previously associated with agency, intentionality and moral cognition, encompassing ventral and subgenual sectors of the medial prefrontal cortex (PFC), insula, anterior temporal cortex and superior temporal sulcus (STS). Compared to emotionally neutral agency, different categories of moral emotions led to distinct activation patterns: (1) prosocial emotions (guilt, embarrassment, compassion) activated the anterior medial PFC and STS, with (2) empathic emotions (guilt and compassion) additionally recruiting the mesolimbic pathway; (3) other-critical emotions (disgust and indignation) were associated with activation of the amygdala-parahippocampal and fusiform areas. These findings indicate that agency related to norm-abiding social behaviors of emotionally neutral scripts share neural substrates both with the "default mode" of brain function and with the moral sensitivity network. Additional activation in specific components of this network is elicited by different classes of moral emotions, in agreement with recent integrative models of moral cognition and emotion.

Dopamine transporter density by [99mTc]-TRODAT-1 SPECT and neurocognitive performance - a preliminary pilot study

Introducción: los déficits cognitivos están relacionados con el deterioro funcional y con la baja calidad de vida en la enfermedad de Parkinson (EP). El sistema dopaminérgico de los ganglios basales es importante para el funcionamiento cognitivo y motor. Radiomarcadores de transportador de Dopamina (TAD) han sido utilizados para calcular la pérdida neuronal dopaminérgica en humanos. Objetivos: estudiar la relación entre el deterioro cognitivo y la pérdida neuronal dopaminérgica estriatal en pacientes con EP. Métodos: quince pacientes fueron escaneados con [99mTc]-TRODAT-1 y SPECT. El estriado (STR) y el lóbulo occipital (BKG) fueron definidos como regiones de interés (RIs) para la obtención del potencial de ligación (PL = [STR - BKG] / BKG). Exámenes neurocognitivos fueron aplicados, incluyendo el Rey Auditory Verbal Learning Test (RAVLT), Wisconsin Card Sorting Test (WCST), Ravens Progressive Matrices, Digit Span y Tavis 3. Resultados: El PL fue correlacionado negativamente con los exámenes de RAVLT 4 y 5, que evalúan el aprendizaje verbal. El PL también fue correlacionado negativamente con el artículo de aprendizaje de WCST y los artículos de Tavis 3, el error de acción y el número de aciertos. Conclusiones: este estudio indica que la pérdida de TAD estriatal está asociada con un desempeño mas pobre en tareas de flexibilidad cognitiva y aprendizaje verbal. Estos resultados están de acuerdo con un estudio previo con participantes sanos que encontró una relación entre la densidad de TAD del caudado y el desempeño en tareas de aprendizaje verbal. La segmentación del caudado/putamen en una muestra mayor está en desarrollo y podrá proveer más información sobre déficits cognitivos y pérdida de TAD estriatal.