Subregions Of Prefrontal Cortex Research Articles

Structural brain changes with lifetime trauma and re-experiencing symptoms is 5-HTTLPR genotype-dependent

ABSTRACT Background: Findings on structural brain alterations following trauma are inconsistent due probably to heterogeneity in imaging studies and population, clinical presentations, genetic vulnerability, and selection of controls. This study examines whether trauma and re-experiencing symptoms are associated with specific alterations in grey matter volumes and if this varies according to 5-HTTLPR genotype. Methods: Structural MRI was used to acquire anatomical scans from 377 community-dwelling older adults. Quantitative regional estimates of 22 subregional volumes were derived using FreeSurfer software. Lifetime trauma was assessed using the validated Watson’s PTSD inventory, which evaluates the most severe trauma experienced according to DSM criteria. Analyses adjusted for age, sex, total brain volume, head injury, and comorbidities. Results: Of the 212 participants reporting lifetime trauma, 35.4% reported re-experiencing symptoms and for 1.9%, this was severe enough to meet criteria for full threshold PTSD. In participants with the SS 5-HTTLPR genotype only, re-experiencing symptoms were associated with smaller volumes in middle and superior temporal, frontal (lateral orbital, rostral and caudal middle) and parietal (precuneus, inferior and superior) regions. The trauma-exposed participants without re-experiencing symptoms were not significantly different from the non-trauma-exposed participants except for smaller precuneus and superior parietal region in traumatized participants and a larger amygdala in traumatized women specifically. Conclusions: In the non-clinical sample, lifetime trauma and re-experiencing symptoms were associated with smaller volume in prefrontal, temporal and parietal cortex subregions, and this varied according to serotonergic genetic vulnerability, 5-HTTLPR SS individuals being most susceptible.

Modulation of value-based decision making behavior by subregions of the rat prefrontal cortex

RationaleDuring value-based decision-making, organisms make choices on the basis of reward expectations, which have been formed during prior action-outcome learning. Although it is known that neuronal manipulations of different subregions of the rat prefrontal cortex (PFC) have qualitatively different effects on behavioral tasks involving value-based decision-making, it is unclear how these regions contribute to the underlying component processes.ObjectivesAssessing how different regions of the rodent PFC contribute to component processes of value-based decision-making behavior, including reward (or positive feedback) learning, punishment (or negative feedback) learning, response persistence, and exploration versus exploitation.MethodsWe performed behavioral modeling of data of rats in a probabilistic reversal learning task after pharmacological inactivation of five PFC subregions, to assess how inactivation of these different regions affected the structure of responding of animals in the task.ResultsOur results show reductions in reward and punishment learning after PFC subregion inactivation. The prelimbic, infralimbic, lateral orbital, and medial orbital PFC particularly contributed to punishment learning, and the prelimbic and lateral orbital PFC to reward learning. In addition, response persistence depended on the infralimbic and medial orbital PFC. As a result, pharmacological inactivation of the infralimbic and lateral orbitofrontal cortex reduced the number of reversals achieved, whereas inactivation of the prelimbic and medial orbitofrontal cortex decreased the number of rewards obtained. Finally, using simulated data, we explain discrepancies with a previous study and demonstrate complex, interacting relationships between conventional measures of probabilistic reversal learning performance, such as win-stay/lose-switch behavior, and component processes of value-based decision-making.ConclusionsTogether, our data suggest that distinct components of value-based learning and decision-making are generated in medial and orbital PFC regions, displaying functional specialization and overlap, with a prominent role of large parts of the PFC in negative feedback processing.

Functional dissociations between subregions of the medial prefrontal cortex on the rodent touchscreen continuous performance test (rCPT) of attention.

Converging evidence in humans, monkeys, and rodents suggests a functional dissociation of cognitive function along the dorso-ventral axis of the prefrontal cortex (PFC). Previous studies of attention suggest that the anterior cingulate cortex (ACC) plays a role in target detection, whereas the prelimbic (PL) cortex is important for tests requiring the combined detection and discrimination of signals. We investigated the effect of discrete, quinolinic acid-induced lesions of subregions of the rat medial PFC (mPFC)-ACC, PL cortex, and infralimbic (IL) cortex-on attentional performance on the recently developed rodent touchscreen continuous performance test (rCPT). Rats were tested under a range of behavioral conditions involving stimulus duration (SD), flanker distraction, temporal predictability, and event rate. Rats with lesions of the PL cortex demonstrated the most persistent attentional impairment under conditions of reduced and variable SD and high event rate (lower discrimination sensitivity [d'] and hit rate), and flanker distraction (lower hit rate). Rats with lesions of the ACC exhibited a profound but transient attentional impairment (lower d' and hit rate) in the early stages of behavioral testing, which ameliorated with repeated testing. Rats with lesions of the IL cortex showed no impairments on response control measures. The PL cortex plays a greater role than the ACC in the detection and discrimination of a complex visual stimulus among multiple nontarget stimuli in the rCPT. The findings support evidence for a functional dissociation of attentional performance along the dorso-ventral axis of the mPFC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Prefrontal Cortex Regulates Chronic Stress-Induced Cardiovascular Susceptibility.

BackgroundThe medial prefrontal cortex is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs medial prefrontal cortex function and prefrontal‐dependent behaviors. Additionally, chronic stress induces sympathetic predominance, contributing to health detriments associated with autonomic imbalance. Previous studies identified a subregion of rodent prefrontal cortex, infralimbic cortex (IL), as a key regulator of neuroendocrine‐autonomic integration after chronic stress, suggesting that IL output may prevent chronic stress‐induced autonomic imbalance. In the current study, we tested the hypothesis that the IL regulates hemodynamic, vascular, and cardiac responses to chronic stress.Methods and ResultsA viral‐packaged small interfering RNA construct was used to knockdown vesicular glutamate transporter 1 (vGluT1) and reduce glutamate packaging and release from IL projection neurons. Male rats were injected with a vGluT1 small interfering RNA‐expressing construct or GFP (green fluorescent protein) control into the IL and then remained as unstressed controls or were exposed to chronic variable stress. IL vGluT1 knockdown increased heart rate and mean arterial pressure reactivity, while chronic variable stress increased chronic mean arterial pressure only in small interfering RNA‐treated rats. In another cohort, chronic variable stress and vGluT1 knockdown interacted to impair both endothelial‐dependent and endothelial‐independent vasoreactivity ex vivo. Furthermore, vGluT1 knockdown and chronic variable stress increased histological markers of fibrosis and hypertrophy.ConclusionsKnockdown of glutamate release from IL projection neurons indicates that these cells are necessary to prevent the enhanced physiological responses to stress that promote susceptibility to cardiovascular pathophysiology. Ultimately, these findings provide evidence for a neurobiological mechanism mediating the relationship between stress and poor cardiovascular health outcomes.

Supplemental Material for Functional Dissociations Between Subregions of the Medial Prefrontal Cortex on the Rodent Touchscreen Continuous Performance Test (rCPT) of Attention

Supplemental Material for Functional Dissociations Between Subregions of the Medial Prefrontal Cortex on the Rodent Touchscreen Continuous Performance Test (rCPT) of Attention

Prefrontal cortex alterations in glia gene expression in schizophrenia with and without suicide

BackgroundPatients with schizophrenia (SCZ) run a lifelong risk of suicide. Alterations in glia activities in the prefrontal cortex (PFC) have been reported in relation to suicide in patients with SCZ. While immune processes in the CNS have been related to the susceptibility and course of SCZ, there are hardly any direct comparisons between individuals with SCZ, both those who died of natural causes and those that committed suicide, and healthy controls. Materials and methodsWe compared mRNA expression using real time qPCR of 16 glia-related genes in the dorsal lateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) between 35 patients with SCZ (7 suicide completers and 28 patients who died of natural causes) and 34 well-matched controls without psychiatric or neurological diseases. ResultsWe found an increased expression of the astrocytic gene aldehyde dehydrogenase-1 family member L1 (ALDH1L1) mRNA, a marker involved in dopaminergic activity, in SCZ versus controls. Excluding individuals with SCZ that committed suicide resulted in an elevated expression in the DLPFC of both ALDH1L1 and glutamine synthetase (GS) genes in patients with SCZ, compared to suicide completers and non-psychiatric controls. Regarding microglia genes: in the ACC, homeostatic markers such as chemokine (C-X3-C motif) ligand 1 (CX3CR1) mRNA expression was increased in SCZ without suicide as compared to suicide completers, while no change was found when compared to controls. Another, purinergic receptor 12 (P2RY12) mRNA was exclusively elevated in the ACC of suicide completers, compared to either other group. Triggering receptor expressed on myeloid cells 2 (TREM2) expression, which maintains microglial metabolism, was reduced in non-suicide patients with SCZ, compared to suicide victims and control subjects. ConclusionsDifferential changes are found in astrocyte and microglia genes in the PFC subregions in relation to SCZ and suicide, indicating possible disturbances of glia homeostasis in these conditions.

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Background: Echium amoenum (E. amoenum) is an Iranian medicinal plant with mood-enhancing effects. Objectives: This study was designed to investigate the effect of standardized E. amoenum hydroalcoholic extract on restraint stress (RS)-evoked anxiety- and- depressive-like behaviors in mice. Methods: This experimental study was conducted at the Tabriz University of Medical Sciences, Tabriz, Iran, in 2018. Doses of the hydroalcoholic extract of E. amoenum were optimized for rosmarinic acid (> %2 w/w) concentration of the extract. Other phytochemical indices, including total phenolic and flavonoid contents and radical scavenging activity, were also measured. For behavioral studies, 65 mice were randomly assigned into five groups (n = 13) of control, RS, RS + E75, RS + E150, and RS + E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups received E. amoenum extract (75, 150, and 300 mg/kg, p.o.) concomitantly with RS exposure. Anxiety-like behaviors were assessed by Elevated Plus Maze (EPM) and Open Field Test (OFT). Depression was assessed by the forced swim test (FST) and Tail Suspension Test (TST). Western blotting was performed to determine the protein levels of IL-1β, NF-κB, TNF-α, and IL-6 in the prefrontal cortex (PFC) and hippocampus (HIP). The concentrations of corticosterone, alanine aminotransferase, aspartate aminotransferase, and alanine phosphatase were also measured in serum. Results: Moderate and high doses of the extract ameliorated RS-induced anxiety- (P < 0.05 in OFT and EPM) and depressive-like (P < 0.05 and P < 0.01 in FST; P < 0.01 and P < 0.001 in TST) behaviors. These results were approved by decreased serum corticosterone levels (P < 0.05 and P < 0.001). Furthermore, E. amoenum reduced the protein expression of neuroinflammatory markers in the HIP and PFC subregions (significant at least at P < 0.05 for IL-1β, NF-κB, and TNF-α). Although RS slightly increased the serum levels of liver enzymes, no histopathological changes were seen in the liver of the RS or E. amoenum-treated groups. Conclusions: E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated inflammation and behavioral changes.

Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence.

A number of training interventions have been designed to improve executive functions and inhibitory control (IC) across the lifespan. Surprisingly, no study has investigated the structural neuroplasticity induced by IC training from childhood to late adolescence, a developmental period characterized by IC efficiency improvement and protracted maturation of prefrontal cortex (PFC) subregions involved in IC. The aim of the present study was to investigate the behavioral and structural changes induced by a 5-week computerized and adaptive IC training in school-aged children (10-year-olds) and in adolescents (16-year-olds). Sixty-four children and 59 adolescents were randomly assigned to an IC (i.e. Color-Word Stroop and Stop-Signal tasks) or an active control (AC) (knowledge- and vocabulary-based tasks) training group. In the pre- and posttraining sessions, participants performed the Color-Word Stroop and Stop-signal tasks, and an anatomical resonance imaging (MRI) was acquired for each of them. Children's IC efficiency improved from the pre- to the posttraining session in boys but not in girls. In adolescents, IC efficiency did not improve after IC training. Similar to the neuroplastic mechanisms observed during brain maturation, we observed IC training-related changes in cortical thickness and cortical surface area in several PFC subregions (e.g. the pars opercularis, triangularis, and orbitalis of the inferior frontal gyri) that were age- and gender-specific. Because no correction for multiple comparisons was applied, the results of our study provide only preliminary evidence of the complex structural neuroplastic mechanisms at the root of behavioral changes in IC efficiency from pre- to posttraining in school-aged children and adolescents.

Executive Function Performance And Cortical Activation When Cycling On An Active Workstation In Young Adults

BACKGROUND: Previous studies suggested that exercise on an active workstation while working may be a promising intervention strategy for reducing sedentary time at workplace. The influence of active workstation on cognitive function are not well studied and the existing studies yielded mixed findings. OBJECTIVE: To investigate the effects of cycling on an active workstation on executive function and cortical activation in young adults. METHODS: In a cross-over study design, 35 young adults (mean age = 21.4 ± 2.6 years, 45.7% females) were randomly assigned the following two task conditions separated by 48 hours: performing cognitive tests while sitting (SIT) and performing cognitive tests while self-paced cycling on an active workstation (ACTIVE). Executive function was assessed by a task-switching paradigm and Stroop Color and Word Test (SCWT) programed using E-Prime 2 professional (Psychology Software Tools, Inc., Sharpsburg, PA, USA), respectively. Global switch costs, local switch costs and Stroop effects were derived and used as the behavioral outcomes of the two tasks. Cortical activation during the two conditions was monitored using a 38-channel fNIRS (NIRx Medical Technologies LLC, USA). RESULTS: There were no significant differences on Stroop effects (136.25 ± 125.67 vs. 101.61 ± 137.10, p = 0.19) between SIT and ACTIVE conditions. The global switch costs (463.19 ± 206.86 vs. 452.77 ± 167.05, p = 0.73) and local switch costs (-6.14 ± 147.22 vs. 9.97 ± 156.08, p = 0.70) also did not differ. For the fNIRS results, ACTIVE condition led to greater cortical activity in left-dorsolateral prefrontal cortex (left-DLPFC) related to Stroop effects (0.88 ± 17.75 vs. 13.85 ± 19.44 a.u, p = 0.02). For the task switch test, there were no significant differences in cortical activation between SIT and ACTIVE conditions. CONCLUSION: The results suggests that the performances on Stroop task and task-switching were not impaired by self-paced cycling on a workstation. Importantly, cycling led to greater recruitment of sub-region of prefrontal cortex indicated by a greater cortical activation related to Stroop effects in the left-DLPFC.

Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial

BackgroundTranscranial direct current stimulation (tDCS) is a promising intervention for major depression. However, its clinical effects are heterogeneous. We investigated, in a subsample of the randomized, clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECT-TDCS), whether the volumes of left and right prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were associated with prefrontal tDCS response. MethodsBaseline structural T1 weighted MRI data were analyzed from 52 patients (15 males). Patients were randomized to the following conditions: escitalopram 20 mg/day, bifrontal tDCS (2 mA, 30min, 22 sessions), or placebo. Antidepressant outcomes were assessed over a treatment period of 10 weeks. Voxel-based gray matter volumes of PFC and ACC were determined using state-of-the-art parcellation approaches. ResultsAccording to our a priori hypothesis, in the left dorsal PFC, larger gray matter volumes were associated with depression improvement in the tDCS group (n = 15) compared to sham (n = 21) (Cohen's d = 0.3, 95% confidence interval [0.01; 0.6], p = 0.04). Neither right PFC nor ACC volumes were associated with depression improvement. Exploratory analyses of distinct PFC subregions were performed, but no area was associated with tDCS response after correction for multiple comparisons. ConclusionLeft PFC baseline gray matter volume was associated with tDCS antidepressant effects. This brain region and its subdivisions should be investigated further as a potential neurobiological predictor for prefrontal tDCS treatment in depression and might be correlated with tDCS antidepressant mechanisms of action.

Temporal evolution of cortical ensembles promoting remote memory retrieval.

Memories of fearful events can last a lifetime. The prelimbic (PL) subregion of prefrontal cortex plays a critical role in fear memory retrieval over time. Most studies have focused on acquisition, consolidation, and retrieval of recent memories, but much less is known about the neural mechanisms of remote memory. Using a new knock-in mouse for activity-dependent genetic labeling (TRAP2), we demonstrate that neuronal ensembles in PL are dynamic. PL neurons TRAPed during later memory retrievals are more likely to be reactivated and make larger behavioral contributions to remote memory retrieval compared to those TRAPed during learning or early memory retrieval. PL activity during learning is required to initiate this time-dependent reorganization in PL ensembles underlying memory retrieval. Finally, while neurons TRAPed during earlier and later retrievals have similar broad projections throughout the brain, PL neurons TRAPed later have a stronger functional recruitment of cortical targets.

Triple dissociation of attention and decision computations across prefrontal cortex.

Naturalistic decision-making typically involves sequential deployment of attention to choice alternatives to gather information before a decision is made. Attention filters how information enters decision circuits, implying attentional control may shape how decision computations unfold. We recorded neuronal activity from three subregions of prefrontal cortex (PFC) while monkeys performed an attention-guided decision-making task. From the first saccade to decision-relevant information, a triple dissociation of decision- and attention-related computations emerged in parallel across PFC subregions. During subsequent saccades, orbitofrontal cortex activity reflected value comparison between currently and previously attended information. By contrast, anterior cingulate cortex carried several signals reflecting belief updating in light of newly attended information, integration of evidence to a decision bound, and an emerging plan for what action to choose. Our findings show how anatomically dissociable PFC representations evolve during attention-guided information search, supporting computations critical for value-guided choice.

Weighted Stochastic Block Models of the Human Connectome across the Life Span

The human brain can be described as a complex network of anatomical connections between distinct areas, referred to as the human connectome. Fundamental characteristics of connectome organization can be revealed using the tools of network science and graph theory. Of particular interest is the network’s community structure, commonly identified by modularity maximization, where communities are conceptualized as densely intra-connected and sparsely inter-connected. Here we adopt a generative modeling approach called weighted stochastic block models (WSBM) that can describe a wider range of community structure topologies by explicitly considering patterned interactions between communities. We apply this method to the study of changes in the human connectome that occur across the life span (between 6–85 years old). We find that WSBM communities exhibit greater hemispheric symmetry and are spatially less compact than those derived from modularity maximization. We identify several network blocks that exhibit significant linear and non-linear changes across age, with the most significant changes involving subregions of prefrontal cortex. Overall, we show that the WSBM generative modeling approach can be an effective tool for describing types of community structure in brain networks that go beyond modularity.

Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets.

The neurobiology of fear memory and extinction has been the subject of extensive research efforts that have increased our understanding of the brain regions, circuitry, and the cellular and molecular determinants of fear memory processes. However, the inability to access and directly study the brains of PTSD patients has made it difficult to translate the rodent fear memory studies to understand the neurobiological underpinnings of PTSD. The formation of a PTSD brain repository has recently been undertaken to address this issue. This will allow for high throughput gene expression and proteome analysis that can be coupled with epigenetic and genomic approaches to characterize the molecular alterations underlying PTSD. Preliminary studies using next generation RNA sequencing have identified PTSD specific gene expression alterations in the prefrontal cortex (PFC). The approaches used for transcriptome analysis and early findings regarding two glucocorticoid regulated genes of interest, FKBP5 and SGK1 are discussed, and the consequences of altered SGK1 are presented. Altered SGK1 could contribute to synaptic alterations in PFC subregions that could contribute to loss of inhibitory control and extinction of fear memories. Based on these findings, we discuss new studies demonstrating that ketamine can increase synapse number in the PFC and enhance the extinction of fear memory in rodent models and improve symptoms in PTSD patients. Continued molecular and cellular characterization of postmortem brain tissue of PTSD subjects will further define the neurobiology of PTSD and identify novel targets for safe and more efficacious treatments.

Basolateral amygdalar inactivation blocks chronic stress-induced lamina-specific reduction in prefrontal cortex volume and associated anxiety-like behavior

Chronic exposure to stress causes cognitive deficits, anxiety and depression. Earlier studies have suggested that the prefrontal cortex (PFC) and basolateral amygdala (BLA) can differentially modulate the stress-induced alterations either by their action on HPA axis or via direct reciprocal connections between them. The PFC dysfunction and BLA hypertrophy following stress are known to cause anxiety and affective symptoms. Recent studies indicate that inactivation of BLA projections to PFC remarkably decreases anxiety. However, the effect of BLA inactivation on stress-induced anxiety and associated volume loss in prelimbic (PrL) and anterior cingulate (ACC) subregions of PFC is not known. Accordingly, we evaluated the effect of BLA lesion or inactivation during chronic immobilization stress (CIS) on an approach-avoidance task and associated volume loss in the PFC. The stressed rats showed a significant volumetric reduction in layer I and II of the PrL and ACC. Interestingly, BLA lesion prior to stress prevented the volume loss in PrL and ACC. Further, BLA lesion blocked the anxiety-like behavior in stressed rats. However, in the absence of stress, BLA lesion increased the number of shocks as compared to controls. As BLA lesion produced an anticonflict effect, we performed temporary inactivation of BLA specifically during stress. Similar to BLA lesion, lidocaine-induced inactivation prevented the stress-induced volume loss and anxiety-like behavior. We demonstrate that inactivation of BLA during stress prevents CIS-induced anxiety and associated structural correlates in the PFC. The present study extends the hypothesis of amygdalar silencing as a possible management strategy for stress and associated disorders.

Solving the Credit Assignment Problem With the Prefrontal Cortex.

In naturalistic multi-cue and multi-step learning tasks, where outcomes of behavior are delayed in time, discovering which choices are responsible for rewards can present a challenge, known as the credit assignment problem. In this review, I summarize recent work that highlighted a critical role for the prefrontal cortex (PFC) in assigning credit where it is due in tasks where only a few of the multitude of cues or choices are relevant to the final outcome of behavior. Collectively, these investigations have provided compelling support for specialized roles of the orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal (dlPFC) cortices in contingent learning. However, recent work has similarly revealed shared contributions and emphasized rich and heterogeneous response properties of neurons in these brain regions. Such functional overlap is not surprising given the complexity of reciprocal projections spanning the PFC. In the concluding section, I overview the evidence suggesting that the OFC, ACC and dlPFC communicate extensively, sharing the information about presented options, executed decisions and received rewards, which enables them to assign credit for outcomes to choices on which they are contingent. This account suggests that lesion or inactivation/inhibition experiments targeting a localized PFC subregion will be insufficient to gain a fine-grained understanding of credit assignment during learning and instead poses refined questions for future research, shifting the focus from focal manipulations to experimental techniques targeting cortico-cortical projections.

Are ventrolateral and dorsolateral prefrontal cortices involved in the computerized Corsi block-tapping test execution? An fNIRS study.

The Corsi block-tapping test (CBT) is an old neuropsychological test that, requiring the storage and the reproduction of spatial locations, assesses spatial working memory (WM). Despite its wide use in clinical practice, the specific contribution of prefrontal cortex (PFC) subregions during CBT execution has not been clarified yet. Considering the importance of spatial WM in daily life and the well-known role of ventrolateral-PFC/dorsolateral-PFC (VLPFC/DLPFC) in WM processes, the present study was aimed at investigating, by a 20-channel functional near-infrared spectroscopy (fNIRS) system (including four short-separation channels), the hemodynamic response of the VLPFC/DLPFC during a computerized version of the CBT. Thirty-nine university students were asked to perform CBT standard version (CBTs), block-suppression CBT (CBTb), and control task (CBTc). A VLPFC activation during CBTs and a DLPFC activation during CBTb were hypothesized. The results of the Bayesian analysis have not shown a delineated specific activation of VLPFC/DLPFC during either CBTs or CBTb. These results together with the related ones obtained by others using fMRI are not sufficient to definitively state the role of the PFC subregions during CBT execution. The adoption of high-density diffuse optical tomography would be helpful in further exploration of the PFC involvement in spatial WM tasks.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

ABSTRACTAmyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS.Objective:To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS.Methods:21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales.Results:Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05).Conclusion:Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

Emotion and the prefrontal cortex: An integrative review.

The prefrontal cortex (PFC) plays a critical role in the generation and regulation of emotion. However, we lack an integrative framework for understanding how different emotion-related functions are organized across the entire expanse of the PFC, as prior reviews have generally focused on specific emotional processes (e.g., decision making) or specific anatomical regions (e.g., orbitofrontal cortex). Additionally, psychological theories and neuroscientific investigations have proceeded largely independently because of the lack of a common framework. Here, we provide a comprehensive review of functional neuroimaging, electrophysiological, lesion, and structural connectivity studies on the emotion-related functions of 8 subregions spanning the entire PFC. We introduce the appraisal-by-content model, which provides a new framework for integrating the diverse range of empirical findings. Within this framework, appraisal serves as a unifying principle for understanding the PFC's role in emotion, while relative content-specialization serves as a differentiating principle for understanding the role of each subregion. A synthesis of data from affective, social, and cognitive neuroscience studies suggests that different PFC subregions are preferentially involved in assigning value to specific types of inputs: exteroceptive sensations, episodic memories and imagined future events, viscero-sensory signals, viscero-motor signals, actions, others' mental states (e.g., intentions), self-related information, and ongoing emotions. We discuss the implications of this integrative framework for understanding emotion regulation, value-based decision making, emotional salience, and refining theoretical models of emotion. This framework provides a unified understanding of how emotional processes are organized across PFC subregions and generates new hypotheses about the mechanisms underlying adaptive and maladaptive emotional functioning. (PsycINFO Database Record

Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional Specialization and Long-Range Interactions.

The ability to select information that is relevant to current behavioral goals is the hallmark of voluntary attention and an essential part of our cognition. Attention tasks are a prime example to study at the neuronal level, how task related information can be selectively processed in the brain while irrelevant information is filtered out. Whereas, numerous studies have focused on elucidating the mechanisms of visual attention at the single neuron and population level in the visual cortices, considerably less work has been devoted to deciphering the distinct contribution of higher-order brain areas, which are known to be critical for the employment of attention. Among these areas, the prefrontal cortex (PFC) has long been considered a source of top-down signals that bias selection in early visual areas in favor of the attended features. Here, we review recent experimental data that support the role of PFC in attention. We examine the existing evidence for functional specialization within PFC and we discuss how long-range interactions between PFC subregions and posterior visual areas may be implemented in the brain and contribute to the attentional modulation of different measures of neural activity in visual cortices.