Changes In Dorsolateral Prefrontal Cortex Research Articles

Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial

AbstractHypnotizability, one’s ability to experience cognitive, emotional, behavioral and physical changes in response to suggestions in the context of hypnosis, is a stable neurobehavioral trait associated with improved treatment outcomes from hypnosis-based therapy. Increasing hypnotizability in people who are low-to-medium hypnotizable individuals could improve both the efficacy and effectiveness of therapeutic hypnosis as a clinical intervention. Hypnotizability is associated with dorsolateral prefrontal cortex (DLPFC) functions and connectivity with the salience network, yet there is conflicting evidence as to whether unilateral inhibition of the DLPFC changes hypnotizability. We hypothesized that using personalized neuroimaging-guided targeting to non-invasively stimulate the left DLPFC with transcranial magnetic stimulation (TMS) would temporarily increase hypnotizability. In a preregistered, double-blinded, randomized controlled trial, we recruited a sample of 80 patients with fibromyalgia syndrome, a functional pain disorder for which hypnosis has been a demonstrated beneficial non-pharmacological treatment option. All participants were TMS-naive. Participants were randomly assigned to active or sham continuous theta-burst stimulation over a personalized neuroimaging-derived left-DLPFC target, a technique termed SHIFT (Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation). We tested our hypothesis using the hypnotic induction profile scores, a standardized measure of hypnotizability. Pre-to-post SHIFT change in the hypnotic induction profile scores was significantly greater in the active versus sham group after 92 s of stimulation (P = 0.046). Only the active SHIFT group showed a significant increase in hypnotizability following stimulation (active: P < 0.001; sham: P = 0.607). As such, modulation of trait hypnotizability is possible in humans using non-invasive neuromodulation. Our findings support a relationship between the inhibition of the left DLPFC and an increase in hypnotizability. Dose–response optimization of spaced SHIFT should be explored to understand the optimal dose–response relationship. ClinicalTrials.gov registration: NCT02969707.

Modulating the activity in the dorsolateral prefrontal cortex changes gain–loss framing effect of intertemporal choice: A transcranial direct current stimulation study.

Modulating the activity in the dorsolateral prefrontal cortex changes gain–loss framing effect of intertemporal choice: A transcranial direct current stimulation study.

Plasticity changes in dorsolateral prefrontal cortex associated with procedural sequence learning are hemisphere-specific

Corticocortical neuroplastic changes from higher-order cortices to primary motor cortex (M1) have been described for procedural sequence learning. The dorsolateral prefrontal cortex (DLPFC) plays critical roles in cognition, including in motor learning and memory. However, neuroplastic changes in the DLPFC and their influence on M1 and on motor learning are not well understood. The present study examined bilateral DLPFC–M1 changes in plasticity induced by procedural motor sequence learning in a serial reaction time task. DLPFC plasticity induced by procedural sequence learning was examined by comparing before vs. after training assessments of ipsilateral/contralateral DLPFC–M1 interactions between sequence order and random order trials performed using either the left or right hand. Intra-hemispheric (inter-stimulus interval [ISI] = 10 ms) and inter-hemispheric (ISI = 10 or 50 ms) DLPFC–M1 interactions and single-pulse motor-evoked potentials (MEPs) were measured with transcranial magnetic stimulation (TMS). The reaction times of participants measured during motor training were faster for sequence learning than for random learning with either hand. Paired-pulse TMS induced DLPFC–M1 interactions that were disinhibited after motor sequence learning, especially for left DLPFC–left M1 interactions with right hand task performance and for left DLPFC–right M1 interactions with left hand task performance. These findings indicate that motor sequence learning induces neuroplastic changes to enhance DLPFC–M1 interactions. This manifestation of plasticity showed hemispheric specificity, favoring the left DLPFC. DLPFC plasticity may be a useful index of DLPFC function and may be a treatment target for enhancing DLPFC function and motor learning.

Increased prefrontal activity during usual walking in aging

Executive functions are important for successful accomplishment of walking tasks, particularly during a dual task. Over the past few years, several studies investigated prefrontal cortex activity under different walking conditions in older adults with functional near infrared spectroscopy (fNIRS). However, little is known about changes in dorsolateral prefrontal cortex (DLPFC) activity during walking in the early stages of aging. The main objective of this study was to compare changes in DLPFC activity during simple and dual task walking across three different age groups. Twenty-five young (age range = 18–37), twenty-five youngest-old (age range = 55–65), and twenty-five older adults (age range = 67–87) participated in this study. Main results showed that, during simple task walking, older adults had increased DLPFC activity with equivalent walking performance. This increased mainly concerned the right hemisphere. During dual task walking, older adults had increased right DLPFC activity but seemed to have enough resources to maintain their performance during DT walking. This result supports the idea that compensation mechanisms, due to loss of automaticity of walking in aging, appear already during simple task walking. Measuring cortical activity with fNIRS during a simple task walking might be used as valuable indicator for identifying individuals at risk of falling.

Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microdeletion syndrome establishes CRLF3 as a critical regulator of neurogenesis.

SUMMARYNeurodevelopmental disorders are often caused by chromosomal microdeletions comprising numerous contiguous genes. A subset of neurofibromatosis type 1 (NF1) patients with severe developmental delays and intellectual disability harbors such a microdeletion event on chromosome 17q11.2, involving the NF1 gene and flanking regions (NF1 total gene deletion [NF1-TGD]). Using patient-derived human induced pluripotent stem cell (hiPSC)-forebrain cerebral organoids (hCOs), we identify both neural stem cell (NSC) proliferation and neuronal maturation abnormalities in NF1-TGD hCOs. While increased NSC proliferation results from decreased NF1/RAS regulation, the neuronal differentiation, survival, and maturation defects are caused by reduced cytokine receptor-like factor 3 (CRLF3) expression and impaired RhoA signaling. Furthermore, we demonstrate a higher autistic trait burden in NF1 patients harboring a deleterious germline mutation in the CRLF3 gene (c.1166T>C, p.Leu389Pro). Collectively, these findings identify a causative gene within the NF1-TGD locus responsible for hCO neuronal abnormalities and autism in children with NF1.

The Relationship Between Brain Metabolites Alterations and Neuropsychological Deficits in Patients with Methamphetamine Use Disorder: A Proton Magnetic Resonance Spectroscopy Study.

Chronic use of methamphetamine induces neuropsychological deficits and neurochemical changes in frontostriatal regions. This study aimed to examine the relationship between brain metabolites alterations in frontostriatal regions and neuropsychological deficits in patients with methamphetamine use disorder. A total of 30 methamphetamine users and 20 control participants were selected and a battery of standardized executive function, attention, and memory tasks, including the Wisconsin Card Sorting Test, Stroop Test, and Wechsler Memory Scale, was administered to them. Proton-Magnetic resonance spectroscopy (H-MRS) of N-Acetylaspartate/Creatine (NAA/Cr), Choline/Creatine (Cho/Cr), and glutamate + glutamine/creatine (Glx/Cr) in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and basal ganglia (BG) were also undertaken. Current findings indicated that there were significant differences between two groups in metabolite ratios including NAA/Cr, Cho/Cr, and Glx/Cr in three areas, except for Glx/Cr in BG. Moreover, compared to healthy controls, methamphetamine users showed poorer performance in all neuropsychological tests. Finally, a significant relationship was found between regional metabolites alterations, particularly in the ACC, and neuropsychological deficits in methamphetamine users. In addition to neurochemical changes and neuropsychological deficits in patients with methamphetamine use disorder, current results highlighted the relationship between these changes in DLPFC, ACC, and BG with cognitive deficits in methamphetamine users.

Changes in Prefrontal Cortical Activity During Walking and Cognitive Functions Among Patients With Parkinson's Disease

Background: Walking becomes more and more degraded as Parkinson's Disease (PD) progresses. Previous research examined factors contributing to this deterioration. Among them, changes in brain cortical activity during walking have been less studied in this clinical population.Objectives: This study aimed to: (1) investigate changes in dorsolateral prefrontal cortex (DLPFC) activation during usual walking and dual-task walking conditions in patients with PD; (2) examine the association between cortical activity and behavioral/cognitive outcomes; and (3) explore which factors best predict increased activation of the DLPFC during usual walking.Methods: Eighteen patients with early stage PD and 18 controls performed 4 conditions: (1) standing while subtracting, (2) usual walking, (3) walking while counting forward, and (4) walking while subtracting. Cortical activity in DLPFC, assessed by changes in oxy-hemoglobin (ΔHbO2) and deoxy-hemoglobin (ΔHbR), was measured using functional near infrared spectroscopy (fNIRS). Gait performance was recorded using wearables sensors. Cognition was also assessed using neuropsychological tests, including the Trail Making Test (TMT).Results: DLPFC activity was higher in patients compared to controls during both usual walking and walking while subtracting conditions. Patients had impaired walking performance compared to controls only during walking while subtracting task. Moderate-to-strong correlations between ΔHbO2 and coefficients of variation of all gait parameters were found for usual walking and during walking while counting forward conditions. Part-B of TMT predicted 21% of the variance of ΔHbO2 during usual walking after adjustment for group status.Conclusions: The increased DLPFC activity in patients during usual walking suggests a potential compensation for executive deficits. Understanding changes in DLPFC activity during walking may have implications for rehabilitation of gait in patients with PD.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

IntroductionCognitive symptoms from Parkinson’s disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson’s disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3–8 Hz) and/or beta (10–30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

BDNF polymorphism in non-veridical decision making and differential effects of rTMS.

Making decisions when an objectively correct option is not obvious, involves different neurobiological mechanisms than "veridical" decision making. The dorsolateral prefrontal cortex (DLPFC) exhibits a distinct pattern of prefrontal activation in non-veridical cognition, but little is known about the role of underlying neurobiological endophenotypes. A functional polymorphism in the brain-derived neurotrophic factor (BDNF) gene, causing a valine (Val) to methionine (Met) amino acid substitution at codon 66, has been shown to be associated with structural and functional changes in DLPFC and affect veridical decision making. We hypothesized that the BDNF genotype may be related to non-veridical cognition. We explored whether the BDNF Val66Met polymorphism affected preferences in a cognitive task devoid of intrinsically correct or false choice, using the Cognitive Bias Task (CBT). We also studied if manipulating the right DLPFC with rTMS stimulation changes non-veridical preferences. Sixteen healthy adults, including 9 Val/Val and 7 Val/Met subjects, participated in the study. Participants with Val/Met genotype expressed a more context-independent, internally driven choice selection preference. Val/Val subjects' selection was more dependent on the context, driven by the properties of external stimuli. rTMS stimulation enhanced a preexisting bias in choice preferences. In Val/Val subjects, TMS stimulation shifted the non-veridical preference bias towards greater dependence on external context, while in Val/Met subjects the CBT score became more context-independent. Our study showed that BDNF genotype is associated with a bias in non-veridical preferences and that Val/Val and Val/Met subjects respond differently to right DLPFC rTMS stimulation, further enhancing their preexisting selection biases.

Bilateral Transcranial Magnetic Stimulation on DLPFC Changes Resting State Networks and Cognitive Function in Patients With Bipolar Depression.

Introduction: Bipolar patients have abnormalities in cognitive functions and emotional processing. Two resting state networks (RSNs), the default mode network (DMN) and the sensorimotor network (SMN), play a decisive role in these two functions. Dorsolateral prefrontal cortex (DLPFC) is one of the main areas in the central executive network (CEN), which is linked to the activities of each of the two networks. Studies have found DLPFC abnormalities in both hemispheres of patients with bipolar depression. We hypothesized that the bilateral repetitive transcranial magnetic stimulation (rTMS) of DLPFC would produce changes in the activity of both the SMN and DMN as well as relevant cognitive function in patients with bipolar depression that responded to treatment.Methods: 20 patients with bipolar depression underwent 10 sessions of 1 Hz rTMS on right DLPFC with subsequent 10 Hz rTMS on left DLPFC. Changes in electroencephalography resting networks between pre and post rTMS were evaluated utilizing low-resolution electromagnetic tomography (eLORETA). Depression symptom was assessed using the Beck Depression Inventory (BDI-II) and cognitive function was assessed by Verbal Fluency Test (VFT), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, and Wisconsin Card Sorting Test (WCST).Results: Responders to rTMS showed significantly lower DMN activity at baseline and a significant decrease in SMN connectivity after treatment. Non-responders did not significantly differ from the control group at the baseline and they showed higher activity in the SMN, visual network, and visual perception network compared to control group following treatment. Bilateral rTMS resulted in significant changes in the executive functions, verbal memory, and depression symptoms. No significant changes were observed in selective attention and verbal fluency.Conclusion: Bilateral stimulation of DLPFC, as the main node of CEN, results in changes in the activity of the SMN and consequently improves verbal memory and executive functions in patients with bipolar depression.

Erratum to: The relationship between dorsolateral prefrontal activation and speech performance-based social anxiety using functional near infrared spectroscopy.

Functional near-infrared (fNIR) spectroscopy is a promising new technology that has demonstrated utility in the study of normal human cognition. We utilized fNIR spectroscopy to examine the effect of social anxiety and performance on hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC). Socially phobic participants and non-clinical participants with varying levels of social anxiety completed a public speaking task in front of a small virtual audience while the DLPFC was being monitored by the fNIR device. The relationship between anxiety and both blood volume (BV) and deoxygenated hemoglobin (Hb) varied significantly as a function of speech performance, such that individuals with low social anxiety who performed well showed an increase in DLPFC activation relative to those who did not perform well. This result suggests that effortful thinking and/or efficient top-down inhibitory control may have been required to complete an impromptu speech task with good performance. In contrast, good performers who were highly socially anxious showed lower DLPFC activation relative to good performers who were low in social anxiety, suggesting autopilot thinking or less-effortful thinking. In poor performers, slight increases in DLPFC activation were observed from low to highly anxious individuals, which may reflect a shift from effortless thinking to heightened self-focused attention. Heightened self-focused attention, poor inhibitory control resulting in excessive fear or anxiety, or low motivation may lower performance. These results suggest that there can be different underlying mechanisms in the brain that affect the level of speech performance in individuals with varying degrees of social anxiety. This study highlights the utility of the fNIR device in the assessment of changes in DLPFC in response to exposure to realistic phobic stimuli, and further supports the potential utility of this technology in the study of the neurophysiology of anxiety disorders.

P192 Investigating the role of the parietal and prefrontal cortices in spatial working memory using transcranial direct current stimulation

Question Working memory involves the temporary storage, processing, and manipulation of information. Previous studies have suggested that the posterior parietal cortex (PPC), and dorsolateral prefrontal cortex (DLPFC) are involved in spatial working memory, and spatial and object working memory, respectively. The aim of the present pilot study was to investigate whether modulation of the activity of the left PPC and the left DLPFC changes spatial, and object working memory performance. Transcranial direct current stimulation (tDCS) was used for this purpose. Based on past literature we expected to see improvement of both spatial and object working memory after tDCS of the left DLPFC as well as improvement of spatial working memory after tDCS of the left PPC. Methods Participants ( n = 12) attended three experimental sessions with different stimulation conditions. Fifteen minutes of 1.5 mA anodal tDCS was applied over either the left PPC, left DLPFC or occipital lobe as control condition, beginning five minutes before the task. Participants were required to perform a 2-back spatial and object working memory task; i.e., they were required to pay attention to both objects and their location. Abstract objects were presented on either of an eight locations placed on a virtual circle around the centre of the screen. In addition to a 2-back object working memory task, occasionally participants were asked to indicate the location of the object they saw two screens previously. Performance in three different conditions was measured for analysis: (1) 2-back working memory task for the cases in which both cue and target objects were presented in the same location (OWM-same), (2) in different location (OWM-different) and (3) spatial working memory (SWM). Results Preliminary results showed that performance in the OWM-different condition was lower than OWM-same. There, however, was no significant different between different stimulation conditions. Conclusions These results suggest that anodal tDCS to the left PPC and left DLPFC might not be able to modulate spatial, and object working memory performance. Further studies are needed to investigate the differential role(s) of the DLPFC and PPC in spatial and working memory.

The relationship between dorsolateral prefrontal activation and speech performance-based social anxiety using functional near infrared spectroscopy

Functional near-infrared (fNIR) spectroscopy is a promising new technology that has demonstrated utility in the study of normal human cognition. We utilized fNIR spectroscopy to examine the effect of social anxiety and performance on hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC). Socially phobic participants and non-clinical participants with varying levels of social anxiety completed a public speaking task in front of a small virtual audience while the DLPFC was being monitored by the fNIR device. The relationship between anxiety and both blood volume (BV) and deoxygenated hemoglobin (Hb) varied significantly as a function of speech performance, such that individuals with low social anxiety who performed well showed an increase in DLPFC activation relative to those who did not perform well. This result suggests that effortful thinking and/or efficient top-down inhibitory control may have been required to complete an impromptu speech task with good performance. In contrast, good performers who were highly socially anxious showed lower DLPFC activation relative to good performers who were low in social anxiety, suggesting autopilot thinking or less-effortful thinking. In poor performers, slight increases in DLPFC activation were observed from low to highly anxious individuals, which may reflect a shift from effortless thinking to heightened self-focused attention. Heightened self-focused attention, poor inhibitory control resulting in excessive fear or anxiety, or low motivation may lower performance. These results suggest that there can be different underlying mechanisms in the brain that affect the level of speech performance in individuals with varying degrees of social anxiety. This study highlights the utility of the fNIR device in the assessment of changes in DLPFC in response to exposure to realistic phobic stimuli, and further supports the potential utility of this technology in the study of the neurophysiology of anxiety disorders.

Aberrant Gray Matter Structure Associated with Sleep Disturbance in the Drug Naïve Subjects with Alzheimer’s Disease

Background and ObjectiveaaAlthough the sleep disturbances are very common and serious behavioral symptoms in Alzheimer’s disease (AD), the neuronal substrate of the gray matter structures associated with sleep disturbances in AD were not clear. The aim of this study is to investigate distinctive correlation patterns between the gray matter volume and sleep disturbances in AD. MethodsaaThirty drug-naive patients with AD and 30 group-matched healthy control subjects underwent 3T magnetic resonance imag ing scanning, and the whole brain gray matter volumes were measured using voxel based morphometry. We explored the correlation pattern between the gray matter volumes and the sleep disturbances in AD using the sleep disturbance subscale of Neuropsychiatric Inventory (NPI). ResultsaaSignificant negative correlations were observed between left dorsolateral prefrontal cortex (DLPFC) and hypothalamus vol umes and sleep disturbance subscale of NPI (false discovery rate corrected for multiple comparisons p < 0.05). ConclusionsaaThis study was the first to explore the relationships between whole brain gray matter volumes and sleep disturbances of drug-naive patients with AD. These structural changes in DLPFC and hypothalamus might be the core of the underlying neurobiological mechanisms of sleep disturbances in AD.

Stimulation in the dorsolateral prefrontal cortex changes subjective evaluation of percepts.

Nelson and Narens have proposed a metacognition model that dissociates the objective processing of information (object-level) and the subjective evaluation of the performance (i.e., the metalevel). Neurophysiological evidence also indicates that the prefrontal cortices (PFC) are the brain areas which perform the metalevel function [1]–[3]. A corresponding neural mechanism of Nelson and Narens’s model, called dynamic filtering theory [4], [5], indicates that object-level processing is distributed in the posterior cortices and regulated by the prefrontal cortices with a filtering or gating mechanism to select appropriate signals and suppress inappropriate signals and noise. Based on this model, a hypothesis can be developed that, in the case of uncertainty or overloading of object-level processing, the prefrontal cortices will become more active in order to modulate signals and noise. This hypothesis is supported by a recent fMRI study [6] showing that the PFC (Brodmann area 9, BA9) was activated when subjects were overloaded in a bimodal attentional task, compared to a unimodal task. Here, we report a study showing that applying repetitive transmagnetic stimulation (rTMS) over the BA9 in order to interfere with its functional activity resulted in significant increas in guessed responses, compared to three other control conditions (i.e., no-TMS, sham TMS on BA9, and rTMS on Cz). The results are compatible with the dynamic filtering theory and suggest that a malfunction of the PFC would weaken the quality of meta-cognitive percepts and increase the number of guessed responses.

Changes in cortical morphology resulting from long-term amygdala damage

The amygdala's contribution to emotion, cognition and behavior depends on its interactions with subcortical and cortical regions. Amygdala lesions result in altered functional activity in connected regions, but it is not known whether there might be long-term structural sequelae as well. We hypothesized that developmental bilateral amygdala lesions would be associated with specific gray matter morphometric abnormalities in the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and the ventral visual stream. We conducted regions of interest and vertex-based analyses of structural MRI data acquired in two patients with long-standing focal bilateral amygdala lesions (S.M. and A.P.), compared to gender- and age-matched healthy comparison subjects. Both patients showed significant proportional increases in gray matter volume of the vmPFC. Cortical thickness was increased in the vmPFC and ACC and decreased in the ventral visual stream. There were no morphometric changes in dorsolateral prefrontal cortex or dorsal visual stream cortices. These findings support the hypothesis that cortical regions strongly connected with the amygdala undergo morphometric changes with long-standing amygdala damage. This is the first evidence in humans of the remote alteration of brain morphology in association with amygdala lesions, and will help in interpreting the structural and functional consequences of amygdala pathology in neuropsychiatric disorders.

Neural correlates of STN DBS-induced cognitive variability in Parkinson disease

BackgroundAlthough deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function, it has variable effects on working memory (WM) and response inhibition (RI) performance. The purpose of this study was to determine the neural correlates of STN DBS-induced variability in cognitive performance. MethodsWe measured bilateral STN DBS-induced blood flow changes (PET and [15O]-water on one day) in the supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and right inferior frontal cortex (rIFC) as well as in exploratory ROIs defined by published meta-analyses. STN DBS-induced WM and RI changes (Spatial Delayed Response and Go-No-Go on the next day) were measured in 24 PD participants. On both days, participants withheld PD medications overnight and conditions (OFF vs. ON) were administered in a counterbalanced, double-blind manner. ResultsAs predicted, STN DBS-induced DLPFC blood flow change correlated with change in WM, but not RI performance. Furthermore, ACC blood flow change correlated with change in RI but not WM performance. For both relationships, increased blood flow related to decreased cognitive performance in response to STN DBS. Of the exploratory regions, only blood flow changes in DLPFC and ACC were correlated with performance. ConclusionsThese results demonstrate that variability in the effects of STN DBS on cognitive performance relates to STN DBS-induced cortical blood flow changes in DLPFC and ACC. This relationship highlights the need to further understand the factors that mediate the variability in neural and cognitive response to STN DBS.

A lasting post-stimulus activation on dorsolateral prefrontal cortex is produced when processing valence and arousal in visual affective stimuli

This paper introduces a new paradigm in the study of emotional processes through functional neuroimaging. We study whether the valence and arousal of visual stimuli influence neuroimaging of the evoked hemodynamic changes. Using functional near-infrared spectroscopy (fNIRS), we investigate evoked-cerebral blood oxygenation (CBO) changes in dorsolateral prefrontal cortex (DLPFC) during direct exposure to different emotion-eliciting stimuli ('on' period), and during the period directly following stimulus cessation ('off' period). We hypothesize that the evoked-CBO, rather than return to baseline after stimulus cessation, would show either overshoot or undershoot. The study includes 30 healthy subjects and a total of 9 stimuli, which consist of video-clips with different emotional content. The total sample of trials studied (270) is classified according to the valence and arousal ratings given by the subjects. Results show a more robust activation in DLPFC during the 'off' period than during the 'on' period, depending on the subjective degree of arousal given to the stimulus. Our findings provide the first fNIRS evidence showing that an increment in subjective arousal leads to activation in DLPFC which persists after stimulus cessation and this does not occur with non-arousing stimuli. Neuroimaging studies must consider the duration and affective dimensions of the stimulus as well as the duration of the scanning to specify how much of the recorded response is analyzed. Not accounting for this difference may contribute to confusion in the data interpretation.

Working memory effects on semantic processing: Priming differences in pars orbitalis

Both working memory (WM) and controlled (attention-mediated) semantic processing functions have been thought to operate as limited capacity systems, but the possible link between these processes has not been investigated. We found that increased WM load attenuated semantic priming (i.e., reduced the response time advantage for semantically primed relative to unprimed items) and changed fMRI signal intensities in brain regions usually associated with both WM (dorsolateral prefrontal cortex) and controlled semantic retrieval (inferior frontal gyrus [IFG], pars orbitalis). fMRI signal changes in dorsolateral prefrontal cortex were negatively correlated with signal changes in pars orbitalis. The findings suggest that controlled semantic processing and working memory share neural system resources.

Activation in dorsolateral prefrontal cortex in response to maternal criticism and praise in recovered depressed and healthy control participants

High family levels of expressed emotion reliably predict relapse in patients with schizophrenia and mood disorders; however, the neural mechanisms linking expressed emotion and relapse are unexplored. Dysfunctional activity in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of depression. Functional magnetic resonance imaging (fMRI) was used to assess focal activation changes in DLPFC in response to a novel psychosocial challenge stimulus developed from the expressed emotion construct. Healthy control subjects and fully remitted unipolar depressed participants completed blood oxygen level-dependent fMRI while they heard their own mothers making critical and praising comments about them. Relative to control subjects, participants with a history of depression failed to activate DLPFC when they heard critical remarks. There were no differences between the two groups in their DLPFC responses to maternal praise. Even if fully well at the time of testing, participants with a known vulnerability to depression respond differently to the psychosocial challenge of being criticized. These findings might have implications for our understanding of vulnerability to depression and to depressive relapse.