Frontal Brain Areas Research Articles

Two distinct networks for encoding goals and forms of action: An effective connectivity study

Goal-directed actions are characterized by two main features: the content (i.e., the action goal) and the form, called vitality forms (VF) (i.e., how actions are executed). It is well established that both the action content and the capacity to understand the content of another's action are mediated by a network formed by a set of parietal and frontal brain areas. In contrast, the neural bases of action forms (e.g., gentle or rude actions) have not been characterized. However, there are now studies showing that the observation and execution of actions endowed with VF activate, in addition to the parieto-frontal network, the dorso-central insula (DCI). In the present study, we established-using dynamic causal modeling (DCM)-the direction of information flow during observation and execution of actions endowed with gentle and rude VF in the human brain. Based on previous fMRI studies, the selected nodes for the DCM comprised the posterior superior temporal sulcus (pSTS), the inferior parietal lobule (IPL), the premotor cortex (PM), and the DCI. Bayesian model comparison showed that, during action observation, two streams arose from pSTS: one toward IPL, concerning the action goal, and one toward DCI, concerning the action vitality forms. During action execution, two streams arose from PM: one toward IPL, concerning the action goal and one toward DCI concerning action vitality forms. This last finding opens an interesting question concerning the possibility to elicit VF in two distinct ways: cognitively (from PM to DCI) and affectively (from DCI to PM).

A Study on the Correlation of Various Factors in Patients With Severe Traumatic Brain Injuries.

Traumatic brain injury (TBI), ranging from minor impacts to severe cases, affects temporal and frontal brain areas, contributing to mortality and disability worldwide. The Glasgow Coma Scale (GCS) evaluates consciousness levels, aiding in prioritizing emergency care, while the Disability Rating Score (DRS) assesses overall function, particularly in severe cases, with greater sensitivity than GCS for clinical changes in TBI patients. To correlate various factors with each other in patients presented with severe TBIs. The retrospective study analyzed data from patients with severe TBIsadmitted to the hospital from February 2023to April 2024. Patients' demographic and clinical data, including GCSand DRSscores, were collected. Statistical analysis, including logistic regression, assessed mortality predictors. The study revealed significant correlations (p<0.05) between age and marital status (p=0.002) and surgery (p=0.003). Surgery also correlated significantly with the mechanism of injury (p<0.001). Furthermore, a negative correlation was found between GCS after 24 hours and change in GCS (p<0.001), while a positive correlation existed between DRS after 24 hoursand DRS on the 14th day (p<0.001). These findings highlight the complex interplay between demographic factors, medical interventions, and clinical outcomes in TBI patients. The study found that older individuals, particularly those involved in road traffic accidents, had poorer recovery outcomes and higher rates of surgery, with a strong correlation between changes in GCSand DRSscores.

Quantitative assessment of traumatic brain injury risk in diverse age groups of females: Insights from computational biomechanics

Traumatic Brain Injury (TBI) stands as a multifaceted health concern, exhibiting varying influences across human population. This study delves into the biomechanical complexities of TBI within gender-specific contexts, focusing on females. Our primary objective is to investigate distinctive injury mechanisms and risks associated with females, emphasizing the imperative for tailored investigations within this cohort.By employing Fluid-Structure Interaction (FSI) Analysis, we conducted simulations to quantify biomechanical responses to traumatic forces across diverse age groups of females. The study utilized a scaling technique to create finite element models (FEMs). The young female FEM, based on anthropometric data, showcased a 15 % smaller head geometry compared to the young male FEM. Moreover, while the elderly female FEM closely mirrored the young female FEM in most structural aspects, it showed distinctive features such as brain atrophy and increased cerebrospinal fluid (CSF) layer thickness. Notably, the child female FEM (ages 7–11 years) replicated around 95 % of the young female FEM's geometry. These structural distinctions meticulously captured age-specific variations across our modeled female age groups. It's noteworthy that identical conditions, encompassing impact intensity, loading type, and boundary conditions, were maintained across all FEMs in this biomechanical finite element analysis, ensuring comparative results.The findings unveiled significant variations in frontal and occipital pressures among diverse age groups, highlighting potential age-related discrepancies in TBI susceptibility among females. These variations were primarily linked to differences in anatomical features, including brain volume, CSF thickness, and brain condition, as the same material properties were used in the FEMs. These results were approximately 4.70, 6.33 and 6.43 % in frontal area of brain in diverse age groups of females (young, elderly, and child) respectively compared to young male FEM. Comparing the FEM results between the young female and the elderly female, we observed a decrease in occipital brain pressure at the same point, reducing from 171,993 to 167,793 Pa, marking an approximate 2.5 % decrease. While typically the elderly exhibit greater brain vulnerability compared to the young, our findings showcase a reduction in brain pressure. Notably, upon assessing the relative movement between the brain and the skull at the point located in occipital area, we observed greater relative movement in the elderly (1.8 mm) compared to the young female (1.04 mm). Therefore, brain atrophy increases the range of motion of the brain within the cranial space. The study underscores the critical necessity for nuanced TBI risk assessment tailored to age and gender, emphasizing the importance of age-specific protective strategies in managing TBIs across diverse demographics. Future research employing individual modeling techniques and exploring a wider age spectrum holds promise in refining our understanding of TBI mechanisms and adopting targeted approaches to mitigate TBI in diverse groups.

Multi-modal Neuroimaging Phenotyping of Mnemonic Anosognosia in the Aging Brain

BackgroundUnawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer’s Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging.MethodsAmyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups.ResultsIndividuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition.ConclusionsUnawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.

The neural networks of touch observation

Abstract Studies have consistently demonstrated that the mere observation of touch engages our own somatosensory cortices. However, a systematic evaluation of the involved networks is missing. Here, we present results of a meta-analytic connectivity modeling (MACM) approach based on clusters revealed by activation likelihood estimation (ALE) combined with resting-state analysis to detect networks subserving our ability to empathize with tactile experiences of other people. ALE analysis revealed 8 clusters in frontal, temporal, and parietal brain areas, which behavioral domain profiles predominantly refer to cognition and perception. The MACM analysis further identified distinct networks that are subserved by subcortical structures, revealed that all clusters involved in touch observation are connected to dorso-medial frontal and anterior cingulate cortex control regions, and showed that medial temporal lobe memory structures do not inform network activation during touch observation (confirmed by post hoc resting-state connectivity analyses). Our data highlight the importance of higher-level control areas and suggest only a minor role for past bodily experiences in the ad hoc perception of other people’s experiences.

Exploring EEG resting state as a function of boredom proneness in pre-adolescents and adolescents.

Boredom is a prominent experience commonly reported in school settings and associated with poor academic achievement. Little is known, however, about the age-related trajectory of boredom. Here we examined self-reported ratings of boredom in a cross-sectional sample of 8 to 15-year olds (n = 185) as a function of resting state EEG. Results indicated that reports of boredom in school rose as a function of age. Resting state EEG showed a decrease in theta power with age perhaps reflective of increased control. While no effects were evident in beta and alpha bands, we did observe an interaction between boredom and age for frontal asymmetry such that for those higher in boredom, the asymmetry increased with age. Finally, for theta to beta ratios there were main effects of age (i.e., a decrease in theta/beta ratio with age) and boredom such that those higher in boredom had higher theta/beta ratios over frontal and central brain areas. The results are discussed in the context of prior work on school-related boredom and provide several important avenues for further research.

Emotion recognition in relation to tumor characteristics in patients with low-grade glioma.

Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favorable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location, laterality, tumor volume, and histopathological characteristics in patients with LGG, postsurgery, and before start of adjuvant therapy. A total of 121 patients with LGG were matched with 169 healthy controls (HC). Tumor location [including (frontal) subregions; insula, anterior cingulate cortex, lateral prefrontal cortex (LPFC), orbitofrontal-ventromedial PFC] and tumor volume were determined on MRI scans. Emotion recognition was measured with the Ekman 60 faces test of the Facial Expressions of Emotion-Stimuli and Tests (FEEST). Patients with LGG performed significantly lower on the FEEST than HC, with 33.1% showing impairment compared to norm data. Emotion recognition was not significantly correlated to frontal tumor location, laterality, and histopathological characteristics, and significantly but weakly with general cognition and tumor volume. Emotion recognition is impaired in patients with LGG but not (strongly) related to specific tumor characteristics or general cognition. Hence, measuring SC with individual neuropsychological assessment of these patients is crucial, irrespective of tumor characteristics, to inform clinicians about possible impairments, and consequently offer appropriate care.

An MR spectroscopy study of temporal areas excluding primary auditory cortex and frontal regions in subjective bilateral and unilateral tinnitus

Previous studies indicate changes in neurotransmission along the auditory pathway in subjective tinnitus. Most authors, however, investigated brain regions including the primary auditory cortex, whose physiology can be affected by concurrent hearing deficits. In the present MR spectroscopy study we assumed increased levels of glutamate and glutamine (Glx), and other Central Nervous System metabolites in the temporal lobe outside the primary auditory cortex, in a region involved in conscious auditory perception and memory. We studied 52 participants with unilateral (n = 24) and bilateral (n = 28) tinnitus, and a control group without tinnitus (n = 25), all with no severe hearing losses and a similar hearing profile. None of the metabolite levels in the temporal regions of interest were found related to tinnitus status or laterality. Unexpectedly, we found a tendency of increased concentration of Glx in the control left medial frontal region in bilateral vs unilateral tinnitus. Slightly elevated depressive and anxiety symptoms were also shown in participants with tinnitus, as compared to healthy individuals, with the bilateral tinnitus group marginally more affected. We discuss no apparent effect in the temporal lobes, as well as the role of frontal brain areas, with respect to hearing loss, attention and psychological well-being in chronic tinnitus. We furthermore elaborate on the design-related and technical obstacles of MR spectroscopy.

Neuroanatomical correlates of aggressiveness: a case-control voxel- and surface-based morphometric study.

Aggression occurs across the population ranging on a symptom continuum. Most previous studies have used magnetic resonance imaging in clinical/forensic samples, which is associated with several confounding factors. The present study examined structural brain characteristics in two healthy samples differing only in their propensity for aggressive behavior. Voxel- and surface-based morphometry (SBM) analyses were performed on 29 male martial artists and 32 age-matched male controls. Martial artists had significantly increased mean gray matter volume in two frontal (left superior frontal gyrus and bilateral anterior cingulate cortex) and one parietal (bilateral posterior cingulate gyrus and precuneus) brain clusters compared to controls (whole brain: p < 0.001, cluster level: family-wise error (FWE)-corrected). SBM analyses revealed a trend for greater gyrification indices in martial artists compared to controls in the left lateral orbital frontal cortex and the left pars orbitalis (whole brain: p < 0.001, cluster level: FWE-corrected). The results indicate brain structural differences between martial artists and controls in frontal and parietal brain areas critical for emotion processing/inhibition of emotions as well as empathic processes. The present study highlights the importance of studying healthy subjects with a propensity for aggressive behavior in future structural MRI research on aggression.

Common hyper-entropy patterns identified in nicotine smoking, marijuana use, and alcohol use based on uni-drug dependence cohorts.

Substance use disorders present similar behaviors and psychopathologies related to impaired decision making/inhibition control and information processing, suggesting common alterations in frontal and limbic brain areas. To test this hypothesis, we identified three uni-substance use cohorts with dependence to only one type of substance from the Human Connectome Project: marijuana dependence, nicotine dependence, and alcohol dependence. Fifty-nine marijuana uses, 34 nicotine smokers, 35 alcohol drinkers, and their age and sex-matched non-substance use controls were identified. We used brain entropy mapping to probe brain alterations in substance use disorders. Compared to non-substance use individuals, all three substance use disorder cohorts had increased brain entropy. Marijuana dependence and nicotine dependence showed overlapped hyper-brain entropy in bilateral dorso-lateral prefrontal cortex, anterior cingulate cortex, and right insula. Hyper-brain entropy in marijuana dependence and alcohol dependence overlap in left insula, left doso-lateral prefrontal cortex, and posterior cingulate. Hyper-brain entropy in nicotine dependence and alcohol dependence overlap only in left dorso-lateral prefrontal cortex. Hyper-brain entropy in those areas was correlated with increased impulsivity or reduced inhibition control in substance use disorder but not in controls. Drug dependence is associated with hyper-brain entropy in the prefrontal cortex and the meso-limbic system, independent of a specific addictive drug. Brain entropy in this circuit provides a sensitive marker to detect brain and behavioral alterations in substance user disorders.

Major depressive disorder diagnosis from electroencephalogram data and potential treatment with dimethyltryptamine

In recent times, there has been increasing interest in utilizing EEG-based techniques for studying Major Depressive Disorder as a dynamic method. Although it is frequently used for identifying depression, the method is still difficult to interpret. The conventional treatment of MDD involves medications such as Selective Serotonin Reuptake Inhibitors, which often have adverse effects. On the other hand, the use of dimethyltryptamine to stimulate brain activity in regions where MDD patients show lower activity has demonstrated promising results. This study analyzed resting-state EEG signals from MDD patients, DMT users, and healthy controls to evaluate and validated a computer-aided approach. The brain activity of DMT users was recorded and compared with MDD individuals and healthy controls. Using Welch's method, the power of several frequency bands was analyzed from the EEG dataset for comparison and diagnosis. The extracted EEG data underwent noise removal and feature extraction. The features from all controls were concatenated to form a data matrix. Furthermore, the data matrix was standardized using the Z-score standardization method. The classifier model logistic regression was employed to train and test the extracted features. The results of the investigations have demonstrated the most important features, such as signal power of the EEG data from the frontal, temporal, parietal, and occipital brain areas, to be significant.

Engaging learners with games-Insights from functional near-infrared spectroscopy.

The use of game elements in learning tasks is thought to facilitate emotional and behavioral responses as well as learner engagement. So far, however, little is known about the underlying neural mechanisms of game-based learning. In the current study, we added game elements to a number line estimation task assessing fraction understanding and compared brain activation patterns to a non-game-based task version. Forty-one participants performed both task versions in counterbalanced order while frontal brain activation patterns were assessed using near-infrared spectroscopy (within-subject, cross-sectional study design). Additionally, heart rate, subjective user experience, and task performance were recorded. Task performance, mood, flow experience, as well as heart rate did not differ between task versions. However, the game-based task-version was rated as more attractive, stimulating and novel compared to the non-game-based task version. Additionally, completing the game-based task version was associated with stronger activation in frontal brain areas generally involved in emotional and reward processing as well as attentional processes. These results provide new neurofunctional evidence substantiating that game elements in learning tasks seem to facilitate learning through emotional and cognitive engagement.

Neural Substrates of Psychomotor Speed Deficits in Cerebral Small Vessel Disease: A Brain Disconnectome Mapping Study.

It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed performance, the effect that different locations and volumes of WMH may have on cSVD-related cognitive impairment remains unclear. Therefore, we aimed to explore (1) whether global WMH, deep WMH (DWMH), and periventricular (PVWMH) volumes display different psychomotor speed associations; (2) whether tract-specific WMH volume shows stronger cognitive associations compared with global measures of WMH volume; (3) whether specific patterns of WMH location lead to different degrees of disconnectivity. Using the BCBToolkit, we investigated which pattern of distribution and which locations of WMH lesion result in impaired psychomotor speed in a well-characterized sample (n = 195) of cSVD patients without dementia. Two key findings emerge from our study. First, global (and not tract-specific) measures of WMH volume were associated with psychomotor speed performance. Second, disconnection maps revealed the involvement of callosal tracts, association and projection fibers, and frontal and parietal cortical brain areas related to psychomotor speed, while the lesion location influenced such associations. In conclusion, psychomotor deficits are affected differently by WMH burden and topographic distribution through brain disconnection in non-demented cSVD patients.

Increased Cortical Activity in Novices Compared to Experts During Table Tennis: A Whole-Brain fNIRS Study Using Threshold-Free Cluster Enhancement Analysis

There is a growing interest to understand the neural underpinnings of high-level sports performance including expertise-related differences in sport-specific skills. Here, we aimed to investigate whether expertise level and task complexity modulate the cortical hemodynamics of table tennis players. 35 right-handed table tennis players (17 experts/18 novices) were recruited and performed two table tennis strokes (forehand and backhand) and a randomized combination of them. Cortical hemodynamics, as a proxy for cortical activity, were recorded using functional near-infrared spectroscopy, and the behavioral performance (i.e., target accuracy) was assessed via video recordings. Expertise- and task-related differences in cortical hemodynamics were analyzed using nonparametric threshold-free cluster enhancement. In all conditions, table tennis experts showed a higher target accuracy than novices. Furthermore, we observed expertise-related differences in widespread clusters compromising brain areas being associated with sensorimotor and multisensory integration. Novices exhibited, in general, higher activation in those areas as compared to experts. We also identified task-related differences in cortical activity including frontal, sensorimotor, and multisensory brain areas. The present findings provide empirical support for the neural efficiency hypothesis since table tennis experts as compared to novices utilized a lower amount of cortical resources to achieve superior behavioral performance. Furthermore, our findings suggest that the task complexity of different table tennis strokes is mirrored in distinct cortical activation patterns. Whether the latter findings can be useful to monitor or tailor sport-specific training interventions necessitates further investigations.

The Neural Correlates of Exact Calculation in Word and Numerical Formats in Low And High Math Performers: A fNIRS Study

The representation format of math problems can manifest dissimilarly in people with varying levels of math performance. The aim of this study was to investigate the neurocognitive underpinnings of two-digit exact calculation tasks in different formats: numerical and word. Fifty-three students were divided into groups with high and low levels of math performance based on their ability to solve math problems. They were asked to calculate addition problems with two-digit numbers and to read math problems that did not require calculations. Brain activation was recorded using functional near-infrared spectroscopy (fNIRS). General linear model (GLM) analysis revealed that reading math problems without calculation led to increased activation in the inferior temporal and fusiform gyri in a group of high-level performers, while a group of low-level performers demonstrated increased activation in Broca’s area and the inferior frontal gyrus in the same experimental condition, as well as during solving arithmetic problems in a word format of the exact calculation task. Analysis after bootstrapping revealed similar activation patterns in both groups. Both domain-specific and domain-general regions of the frontal and parietal brain areas were involved in the calculations. Right and left hemisphere activation was found both in low and high math performers. Comparing experimental conditions with resting state revealed significant activation in Broca’s area in all conditions in a group of high-level performers and in a word format of arithmetic problems in a group of low-level performers. Thus, the observed brain patterns suggest the involvement of complex sentence comprehension, especially in high-performing students. These results could be used in future to improve educational practice for students with varying levels of math competence.

Natural Oscillatory Frequency Slowing in the Premotor Cortex of Early-Course Schizophrenia Patients: A TMS-EEG Study.

Despite the heavy burden of schizophrenia, research on biomarkers associated with its early course is still ongoing. Single-pulse Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) has revealed that the main oscillatory frequency (or "natural frequency") is reduced in several frontal brain areas, including the premotor cortex, of chronic patients with schizophrenia. However, no study has explored the natural frequency at the beginning of illness. Here, we used TMS-EEG to probe the intrinsic oscillatory properties of the left premotor cortex in early-course schizophrenia patients (<2 years from onset) and age/gender-matched healthy comparison subjects (HCs). State-of-the-art real-time monitoring of EEG responses to TMS and noise-masking procedures were employed to ensure data quality. We found that the natural frequency of the premotor cortex was significantly reduced in early-course schizophrenia compared to HCs. No correlation was found between the natural frequency and age, clinical symptom severity, or dose of antipsychotic medications at the time of TMS-EEG. This finding extends to early-course schizophrenia previous evidence in chronic patients and supports the hypothesis of a deficit in frontal cortical synchronization as a core mechanism underlying this disorder. Future work should further explore the putative role of frontal natural frequencies as early pathophysiological biomarkers for schizophrenia.

Triangulating causality between childhood obesity and neurobehavior: Behavioral genetic and longitudinal evidence.

Childhood obesity is a serious health concern that is not yet fully understood. Previous research has linked obesity with neurobehavioral factors such as behavior, cognition, and brain morphology. The causal directions of these relationships remain mostly untested. We filled this gap by using the Adolescent Brain Cognitive Development study cohort comprising 11,875 children aged 9-10. First, correlations between the age- and sex-specific 95th BMI percentile (%BMIp95) and neurobehavioral measures were cross-sectionally analyzed. Effects were then aggregated by neurobehavioral domain for causal analyses. Behavioral genetic Direction of Causation modeling was used to test the direction of each relationship. Findings were validated by longitudinal cross-lagged panel modeling. %BMIp95 correlated with impulsivity, motivation, psychopathology, eating behavior, and cognitive tests (executive functioning, language, memory, perception, working memory). Greater %BMIp95 was also associated with reduced cortical thickness in frontal and temporal brain areas but with increased thickness in parietal and occipital areas. Similar although weaker patterns emerged for cortical surface area and volume. Behavioral genetic modeling suggested causal effects of %BMIp95 on eating behavior (β=0.26), cognition (β=0.05), cortical thickness (β=0.15), and cortical surface area (β=0.07). Personality/psychopathology (β=0.09) and eating behavior (β=0.16) appeared to influence %BMIp95. Longitudinal evidence broadly supported these findings. Results regarding cortical volume were inconsistent. Results supported causal effects of obesity on brain functioning and morphology. The present study highlights the importance of physical health for brain development and may inform interventions aimed at preventing or reducing pediatric obesity. RESEARCH HIGHLIGHTS: A continuous measure related to obesity, %BMIp95, has correlations with various measures of brain functioning and structure Behavioral genetic and longitudinal modeling suggest causal links from personality, psychopathology, and eating behavior to %BMIp95 Results also indicate directional links from %BMIp95 to eating behavior, cognition, cortical thickness, and cortical surface area Obesity may play a role for healthy brain development during childhood.

Neuroanatomical correlates of genetic risk for obesity in children

Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

Functional MRI markers for treatment-resistant depression: Insights and challenges.

Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation in TRD as well as potential targets for treatment interventions. This chapter provides an overview of the main findings of studies using three imaging modalities: structural magnetic resonance imaging (MRI), functional MRI (fMRI), and magnetic resonance spectroscopy (MRS). Decreased connectivity and metabolite concentrations in frontal brain areas appear to characterize TRD, although results are not consistent across studies. Treatment interventions, including rapid-acting antidepressants and transcranial magnetic stimulation (TMS), have shown some efficacy in reversing these changes while alleviating depressive symptoms. However, comparatively few TRD imaging studies have been conducted, and these studies often have relatively small sample sizes or employ different methods to examine a variety of brain areas, making it difficult to draw firm conclusions from imaging studies about the pathophysiology of TRD. Larger studies with more unified hypotheses, as well as data sharing, could help TRD research and spur better characterization of the illness, providing critical new targets for treatment intervention.

Persistent depressive symptoms are associated with frontal regional atrophy in patients with Alzheimer's disease.

Depression in individuals with Alzheimer's disease (AD) is common, difficult to treat and inadequately understood. Previous studies have identified possible differences in regional brain atrophy in individuals with AD and depression, but the results have been inconsistent and some studies had less robust definitions of depression. We aimed to examine regional brain atrophy in two large dementia focused cohorts. We used data from Alzheimer's disease neuroimaging initiative (ADNI) and the National Alzheimer's Co-ordinating Center (NACC), for those with data from at least one MRI scan. Depression ratings were available using the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI). Intermittent depressive symptoms were defined as one episode above threshold (≥8 on GDS, ≥6 on NPI depression subscale and ≥2 on the Neuropsychiatric Inventory version Q depression sub-scale) and persistent as ≥2 episodes. Derived regional volumetric data was available from ADNI and the NACC. Data was available from 698 individuals with AD in NACC and from 666 individuals in ADNI. We found no evidence of between group differences in regional brain volume at baseline, or of differential atrophy in NACC. In ADNI we found evidence of increased brain atrophy in several frontal brain areas. Because this study was limited to those with MRI data, the numbers in some analyses were low. MRI parcellation differed between studies making direct comparison difficult. For some individuals only the NPI was used to rate depression. We have found mixed evidence of increased regional atrophy in depression in AD, mainly in frontal brain regions. We found no evidence to support a vascular basis for depression in AD.