Prefrontal Cognitive Function Research Articles

A randomised crossover trial of nitrate and breakfast on prefrontal cognitive and haemodynamic response functions

It remains unknown whether dietary nitrate and breakfast may enhance working memory (WM) performance by augmenting physiological mechanisms and subjective psychological well-being. We performed a 3-arm randomised within-subject crossover study, with pretest-posttest comparisons, to test whether nitrate consumption via breakfast with a beetroot juice shot or regular breakfast compared to no breakfast improved WM (measured with n-back tests) and cognitive task-related changes in prefrontal cortical haemodynamic response (oxygenated- and deoxygenated-haemoglobin derived from functional near-infrared spectroscopy). In addition, effects on peripheral vascular function and self-reported psychological factors were assessed. In 60 adolescents (13–15 years old; 66% girls), WM improved in all conditions, with no intervention effects. Intervention effects were seen for oxygenated-haemoglobin changes, such that it increased after the breakfast with a nitrate shot during the WM tests and decreased after the regular breakfast. Thus, different neurophysiological mechanisms may be at play to preserve WM in adolescents depending on their breakfast composition. The trial was registered in the ISRCTN registry (ISRCTN16596056) on 21/02/2022.

Effects of partial sleep deprivation on prefrontal cognitive functions in adolescents.

The effect of sleep deprivation on cognitive functions associated with the frontal lobe, such as attention, executive functions, and working memory, is not well known. This study aimed to investigate the effect of partial sleep deprivation in adolescents on the cognitive tasks of the frontal lobe, including visuospatial working memory, processing speed, sustained attention, executive functions, and short-term visual memory. Participants were recruited from voluntary students of Çukurova University. Eighteen adolescents underwent four consecutive nights of monitored sleep restriction (6-6.5h/night) and four nights of sleep extension (10-10.5h/night) in a counterbalanced order and separated by a washout period. Following each sleep period, the cognitive performance was assessed, at a fixed morning time, using a computerized neuropsychological test battery based on frontal lobe functions tasks, which was a timed test providing both accuracy and reaction time outcome measures. Only the spatial working memory performance of cognitive tasks was found to be statistically lower in the restricted-sleep condition than in the extended-sleep condition (p < 0.05). No significant difference was found in the performance of cognitive tasks evaluating simple attention, constant attention, executive functions, and cognitive flexibility. The findings of this study indicated that partial sleep restriction negatively affects specifically working memory and strategic thinking skills among cognitive functions based on the frontal lobe. Especially the visuospatial working memory and strategic thinking skills of adolescents might be susceptible to chronic partial sleep deprivation.

Superior frontal regions reflect the dynamics of task engagement and theta band-related control processes in time-on task effects

Impairment of cognitive performance is often observed in time-on tasks. Theoretical considerations suggest that especially prefrontal cortex cognitive control functions is affected by time-on-task effects, but the role of effort/task engagement is not understood. We examine time-on-task effects in cognitive control on a neurophysiological level using a working-memory modulated response inhibition task and inter-relate prefrontal neuroanatomical region-specific theta-band activity with pupil diameter data using EEG-beamforming approaches. We show that task performance declines with time-on tasks, which was paralleled by a concomitant decreases of task-evoked superior frontal gyrus theta-band activity and a reduction in phasic pupil diameter modulations. A strong relation between cognitive control-related superior frontal theta-band activity and effort/task engagement indexed by phasic pupil diameter modulations was observed in the beginning of the experiment, especially for tasks requiring inhibitory controls and demanding high working memory. This strong relation vanished at the end of the experiment, suggesting a decoupling of cognitive control resources useable for a task and effort invested that characterizes time-on-task effects in prefrontal cortical structures.

Aerobic Exercise Combined With Transcranial Direct Current Stimulation Over the Prefrontal Cortex in Parkinson Disease: Effects on Cortical Activity, Gait, and Cognition

Background Since people with Parkinson disease (PD) rely on limited prefrontal executive resources for the control of gait, interventions targeting the prefrontal cortex (PFC) may help in managing PD-related gait impairments. Transcranial direct current stimulation (tDCS) can be used to modulate PFC excitability and improve prefrontal cognitive functions and gait. Objective We investigated the effects of adding anodal tDCS applied over the PFC to a session of aerobic exercise on gait, cognition, and PFC activity while walking in people with PD. Methods A total of 20 people with PD participated in this randomized, double-blinded, sham-controlled crossover study. Participants attended two 30-minute sessions of aerobic exercise (cycling at moderate intensity) combined with different tDCS conditions (active- or sham-tDCS), 1 week apart. The order of sessions was counterbalanced across the sample. Anodal tDCS (2 mA for 20 minutes [active-tDCS] or 10 s [sham-tDCS]) targeted the PFC in the most affected hemisphere. Spatiotemporal gait parameters, cognitive functions, and PFC activity while walking were assessed before and immediately after each session. Results Compared with the pre-assessment, participants decreased step time variability (effect size: −0.4), shortened simple and choice reaction times (effect sizes: −0.73 and −0.57, respectively), and increased PFC activity in the stimulated hemisphere while walking (effect size: 0.54) only after aerobic exercise + active-tDCS. Conclusion The addition of anodal tDCS over the PFC to a session of aerobic exercise led to immediate positive effects on gait variability, processing speed, and executive control of walking in people with PD.

Neuropsychological Outcomes after Surgery for Olfactory Groove Meningiomas.

Simple SummaryOlfactory groove meningiomas account for 9% of all meningiomas, present with unique molecular characteristics and are standardly treated by surgical removal. Due to their location (in direct contact with cortical structures exerting key-role functions in cognition), olfactory groove meningiomas might negatively impact cognitive abilities. However, little is known about the effects of both their presence and surgical removal on patients’ neuropsychological functions. In this retrospective study, we analyze the evolution of neuropsychological abilities in 17 patients benefitting from surgical removal of an olfactory groove meningioma. We observed that those patients already presented with preoperative deficits in pre-frontal cortex cognitive functions, more pronounced in the domain of cognitive flexibility, followed by attention. After an initial postoperative worsening, patients tended to improve in the majority of cognitive aspects, with attention and flexibility remaining impaired at one-year follow-up.Background: In recent years, several studies have reported abnormal pre- and postoperative neuropsychological functioning in patients with meningiomas located in the prefrontal cortex (notably the ventromedial region). In the case of olfactory groove meningiomas, the tumor is in direct contact with the inferior aspect of the prefrontal cortex, a cortical region with crucial roles in decision-making, cognition and memory functions, potentially negatively impacting neuropsychological functions. Materials and Methods: We retrospectively compared pre- and post-operative neuropsychological testing of 17 patients undergoing surgical removal of olfactory groove meningiomas in our institution between January 2013 and December 2018. Neuropsychological results were obtained from the patients’ medical history and normalized as z-scores of their respective cognitive functions. Results: Assessment of cognitive follow-up showed an important heterogeneity among patients. Pre-operative cognitive impairment was observed in most patients, particularly in cognitive flexibility (mean z-score: −1.35). Immediate post-operative cognitive status showed an overall impairment in all domains of cognition, significant for the domains of attention (p = 0.0273) and flexibility (p = 0.0234) and almost significant for the domain of language (p = 0.0547). The late follow-up at one year showed a trend towards general improvement, although attention and flexibility remained impaired. Discussion: Olfactory groove meningiomas impact pre-frontal cortex cognitive functions, particularly in the domain of cognitive flexibility. After an initial postoperative worsening, patients tended to improve in most aspects after one year, aside from cognitive flexibility and attention.

A Frontal Neuropsychological Profile in Fitness to Drive

Traffic accidents are a global concern due to the elevated mortality rates of both drivers and pedestrians. The World Health Organization declared 2011-2020 as the Decade of Action for Road Safety, endorsing initiatives to reduce traffic-related deaths. Yet, despite these incentives, fatal accidents still occur. Different studies have linked deficits in executive functions to risky driving attitudes and crashes. The present study focuses on demographic, cognitive and personality factors, related to the prefrontal cortex, that are characteristic of drivers prone to risky behavior behind the wheel. The penalty Points System was used to classify drivers as “safe”, with no point loss over a two-year period, or “risky”, with full point loss during the same interval. A neuropsychological assessment of prefrontal cognitive functions was carried out on each group to identify variables associated with safe and risky behavior. Neuropsychological indexes were obtained from a continuous performance task without cue (Simple Attention), a continuous performance task with cue (Conditioned Attention), the Tower of Hanoi test and the Neurologically-related Changes in Personality Inventory (NECHAPI). A Discriminant Analysis (DA) found that education level, reaction times in Simple and Conditioned Attention, learning errors in the Tower of Hanoi and vulnerability in the personality test, best predicted whether drivers were likely to be in the safe or risky group. Finally, a cross-validation analysis performed on the same sample correctly classified 87.5% of the drivers. These data suggest that prefrontal dysfunction contributes to risky behavior behind the wheel. The inclusion of cognitive programs to identify and train drivers with this propensity could reduce risky driving, and consequently, save lives on the road.

Seeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy

Cortical α-synuclein pathology plays a role in the development of cognitive dysfunction in both Parkinson's disease and dementia with Lewy bodies, although the causative cellular lesions have remained unclear. We aimed to address causal links between α-synuclein-driven pathology in the cerebral cortex and the development of cognitive impairments using new experimental models. Neuronal overexpression of human α-synuclein was induced in the rat medial prefrontal cortex using viral vectors. This was combined with inoculations of preformed fibrils of human α-synuclein in some animals. Rats were evaluated with tests probing prefrontal cognitive functions (delayed matching/nonmatching to position and 5-choice serial reaction time task). Patterns of neuropathology were characterized immunohistochemically. Neither α-synuclein overexpression nor the fibril seeds alone yielded any behavioral phenotype. In contrast, combining the 2 approaches produced significant impairments in working memory, attention, and inhibitory control. All animals injected with α-synuclein vectors exhibited high immunoreactivity for human α-synuclein in the medial prefrontal cortex and its primary projection targets. However, only when this overexpression was combined with fibril inoculations did animals exhibit large, proteinase K-resistant and Ser129 -phosphorylated α-synuclein intraneuronal inclusions in the medial prefrontal cortex and its closely interconnected brain regions. The inclusions were associated with distorted dendritic morphologies and partial neuronal loss in the targeted cortical areas. Cortical overexpression of human α-synuclein is not sufficient to produce cognitive dysfunction, whereas combining this overexpression with fibril seeds yields both cognitive and histopathological phenotypes that are relevant to human Lewy body disease. © 2019 International Parkinson and Movement Disorder Society.

Effects of COMT polymorphism on the cortical processing of vocal pitch regulation.

Recent evidence has shown that auditory-motor integration for speech production is influenced by cognitive functions such as working memory and attention, suggesting that speech motor control is likely modulated by mechanisms mediated by prefrontal regions. Catechol-O-methyltransferase (COMT) gene plays an important role in dopamine breakdown in the prefrontal cortex and has been associated with a variety of prefrontal cognitive functions. The present event-related potential study investigated the association between COMT ValMet polymorphism and auditory-motor processing of vocal feedback errors. A sample of 131 Chinese young female adults was genotyped for rs4680 and produced sustained vowels while hearing their voice unexpectedly shifted down in pitch by 50 or 200 cents. The behavioral results showed no effects of COMT ValMet on vocal compensations for pitch perturbations. However, individuals with the Met allele produced significantly larger P2 responses to -200 cents perturbations than individuals with the Val/Val genotype. These results suggest the existence of a relationship between COMT ValMet polymorphism and self-monitoring of speech feedback errors, and they provide insights into our understanding of the top-down modulations of speech motor control mediated by prefrontal regions.

Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency

BackgroundThe aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment.MethodsA randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of − 2 to − 1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires.ResultsData from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor.ConclusionsThe adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor.Trial registrationThis study is registered with ClinicalTrials.gov, number NCT01877512.

F236. CLONIDINE NORMALIZES MMN IN SCHIZOPHRENIA PATIENTS ON STABLE MEDICATION

BackgroundSchizophrenia is a severe brain disorder with profound deficits in prefrontal cortical cognitive functioning. These cognitive deficits form a core feature in schizophrenia for which treatment has been proven to be clinically challenging. One of the key neurotransmitters involved in cognitive functioning is noradrenaline. Previous research has demonstrated disrupted noradrenergic activity in schizophrenia while several studies report improvements in prefrontal cognitive functioning by a selective α2-agonist. Clonidine is such a selective α2A-agonist and previous research in our lab has demonstrated that a (range of) single dosage(s) of clonidine normalize(s) sensory gating in chronically ill, yet stably medicated patients with schizophrenia. Currently, we investigated if clonidine also normalizes Mismatch Negativity (MMN) deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with negative symptoms and cognitive functioning in schizophrenia.MethodsIn a pseudo-randomized, double-blind, placebo-controlled experiment twenty chronically ill, yet stably medicated, male patients with schizophrenia were tested with the MMN paradigm from the Copenhagen Psychophysiological Test-Battery (CPTB) on 5 different occasions, each separated by a week. Four hours prior to testing patients were randomized administered either a placebo (non psycho-active compound) or a single dose of 25, 50, 75 or 150 μg of clonidine (Catapresan) on top of their usual medication on each occasion, in such a way that each patient received every dose once. Patients were matched on age and gender with 20 healthy controls (HC), who did not receive any treatment. The MMN paradigm consisted of 1800 stimuli with 4 types of stimuli: 1 standard (1000 Hz, 50 ms) presented 82% of the time and 3 types of deviants, based on either frequency (FreqMMN: 1200 Hz, 50 ms), duration (DurMMN: 1000 Hz, 100 ms) or their combination (FreqDurMMN: 1200 Hz, 100 ms) each with a probability of 6%. All stimuli had an intensity of 75dB and were presented with an interstimulus interval randomized between 300 and 500 ms. Subjects were requested to ignore all stimuli and were therefore watching a (muted) nature documentary.ResultsIn the placebo condition, patients had significantly reduced DurMMN and FreqDurMMN amplitude compared to HC, whereas FreqMMN did not show significant group differences. Furthermore, all doses of clonidine normalized FreqDurMMN amplitude in such a way that it was not significantly different anymore from the HC, while DurMMN only normalized with the highest dose (150ug).DiscussionOur results indicate disrupted MMN amplitude in chronically ill patients with schizophrenia in spite of the fact that they were stable on their medical treatment. In addition, our data provide evidence that a single dose of clonidine is able to normalize MMN amplitude in these patients. Furthermore, patients could not distinguish between the placebo and the treatment conditions or reported any side effects of these low doses of clonidine. Together with our previous reports indicating normalized sensory and sensorimotor gating in these patients following administration of clonidine, our results could be of potential high clinical relevance in the treatment of schizophrenia. Future studies should therefore focus on longer trial periods to investigate if clonidine, besides normalizing MMN amplitude and sensory(motor) gating, can also ameliorate negative symptoms and cognitive functioning in schizophrenia.

Cognición social y funciones cognitivas en pacientes con epilepsia tratados con acetato de eslicarbacepina

Epilepsy is accompanied by cognitive disorders, frequently aggravated by the use of antiepileptic drugs, which can affect social empathy. To analyse the impact of treatment with eslicarbazepine acetate (ESL) on social cognition and prefrontal cognitive functions in adults with focal epilepsy. We conducted a prospective single-centre study with patients aged between 18 and 65 years with focal seizures treated with ESL. The patients were evaluated in their baseline visit and at six months after starting ESL treatment by means of tasks designed for theory of mind, executive and attentional functions, auditory-verbal memory, quality of life, and anxiety and depression. Forty-one patients were treated with ESL, and 30 completed the follow-up. A significant improvement was observed in the theory of mind tasks. In the analysis stratified by sex, the men showed greater improvement. A cognitive improvement was observed in the Wisconsin Card Sorting Test, Symbol Digit, Backward Digit Span and Stroop tests. No differences were found in the Quality of Life in Epilepsy-31 Inventory or in the Hospital Anxiety and Depression Scale. These results were independent of the reduction in the number of seizures and the ESL dosage. Treatment with ESL could improve some aspects of theory of mind in patients with epilepsy, especially in men and independently of the control of seizures, with no changes in quality of life, anxiety or depression.

Social cognition and prefrontal cognitive function in patients with epilepsy treated with eslicarbazepine acetate

Purpose: The purpose of this study was to evaluate the impact of treatment with eslicarbazepine acetate (ESL) on social cognition and prefrontal cognitive function in adults with partial onset seizures.

Lack of Associations between Female Hormone Levels and Visuospatial Working Memory, Divided Attention and Cognitive Bias across Two Consecutive Menstrual Cycles.

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability.Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects).Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle.Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.

116.2 Discovery and Development of Novel M1 and M4 PAMs for the Treatment of Schizophrenia.

Abstract Background: Multiple lines of evidence indicate that development of selective positive allosteric modulators (PAMs) of the M1 and M4 muscarinic acetylcholine receptor subtypes (mAChR) represent important novel therapeutic approaches for the complex symptoms associated schizophrenia. Over the last decade, Dr. Jones and colleagues at the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) have disclosed the discovery of several, selective mAChR PAMs, as represented by the M1 PAM VU6004256 and M4 PAM VU0467154. This presentation will focus on recent findings demonstrating the ability of M1 and M4 PAMs to reverse abnormalities in prefrontal cortical-mediated physiology, behaviors, and/or cognitive functions observed across preclinical models of N-methyl-D-aspartate subtype of the glutamate receptor (NMDAR) hypofunction, which are thought to underlie many of the symptoms observed in schizophrenia. Methods: Medicinal chemistry and high throughput screening methods were utilized to identify two different series of selective M1 and M4 PAMs, represented by VU6004256 and VU0467154. Disposition was determined in mouse and rat pharmacokinetic studies using LC/MS/MS quantitation. In vivo efficacy was determined across several mouse and rat models predictive of antipsychotic-like activity and enhancement of cognitive function, in particular using the genetic mouse model of global reduction in the NR1 subunit of the NMDAR (NR1 knockdown [KD]). Results: In vitro both VU6004256 and VU0467154 exhibit low nanomolar potency at M1 or M4, respectively, with no activity at the other mAChR subtypes up to 30 μM or significant off target activity at other GPRCs at 10 µM. These ligands are also highly brain penetrant with suitable pharmacokinetic properties for in vivo dosing. Both VU6004256 and VU0467154 produced dose-dependent reductions in preclinical models predictive of antipsychotic-like activity, including reversal of hyperlocomotion in the NR1 KD mice. In addition, the M1 PAM VU6004256 decreased excessive pyramidal neuron firing in layer V of the prefrontal cortex (PFC) in awake, freely moving NR1 KD mice, as well as reversed impairments in two PFC-mediated learning tasks observed in these mice. Interestingly, the M4 PAM VU0467154 also enhanced performance in preclinical models of associative learning and memory functions after acute and chronic dosing and induced state-dependent alterations in sleep architecture and arousal. Conclusion: Collectively, these findings indicate that VU6004256 and VU0467154 represent highly optimized M1 and M4 PAM tool compounds for the evaluation of the respective roles of these mAChR subtypes in vivo and provide further validation for the development of selective M1 and M4 PAMs for the treatment of the psychotic symptoms and cognitive impairments observed in schizophrenia.

Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients with Very Mild Clinical Disability.

Cognitive dysfunction affects 40–65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated. Our results show that 51.1% of MS patients have cognitive dysfunction compared to HC. An impairment of verbal and visual memory, working memory, and executive functions was found in the RRMS group. After subgrouping RRMS by EDSS, group 1 (EDSS ≤ 1.5) showed involvement of verbal memory and executive functions; moreover, group 2 (2 ≤ EDSS ≤ 2.5) patients were also impaired in information processing speed and visual memory. Our results show that utilizing a comprehensive neuropsychological assessment, approximately half of MS patients with very mild physical disability exhibit cognitive impairment with a primary involvement of prefrontal cognitive functions. Detecting impairment of executive functions at an early clinical stage of disease could be useful to promptly enroll MS patients in targeted rehabilitation.

Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex.

The prefrontal cortex (PFC) regulates cognitive processes critical for goal-directed behavior. PFC cognitive dysfunction is implicated in multiple psychopathologies, including attention deficit hyperactivity disorder (ADHD). Although it has long been known that corticotropin-releasing factor (CRF) and CRF receptors are prominent in the PFC, the cognitive effects of CRF action within the PFC are poorly understood. The current studies examined whether CRF receptor activation in the PFC modulates cognitive function in rats as measured in a delayed response task of spatial working memory. CRF dose-dependently impaired working memory performance when administered either intracerebroventricularly (ICV) or directly into the PFC. The working memory actions of CRF in the PFC were topographically organized, with impairment observed only following CRF infusions into the caudal dorsomedial PFC (dmPFC). Additional studies examined whether endogenous CRF modulates working memory. Both ICV and intra-dmPFC administration of the nonselective CRF antagonist, D-Phe-CRF, dose-dependently improved working memory performance. To better assess the translational potential of CRF antagonists, we examined the cognitive effects of systemic administration of the CRF1 receptor selective antagonist, NBI 35965. Similar procognitive actions were observed in these studies. These results are the first to demonstrate that CRF acts in the PFC to regulate PFC-dependent cognition. Importantly, the ability of CRF antagonists to improve working memory is identical to that seen with all approved treatments for ADHD. These observations suggest that CRF antagonists may represent a novel approach for the treatment of ADHD and other disorders associated with dysregulated prefrontal cognitive function.

Cognitive enhancement by transcranial laser stimulation and acute aerobic exercise.

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation and acute aerobic exercise on the same cognitive tasks. We examined whether transcranial infrared laser stimulation of the prefrontal cortex, acute high-intensity aerobic exercise, or the combination may enhance performance in sustained attention and working memory tasks. Sixty healthy young adults were randomly assigned to one of the following four treatments: (1) low-level laser therapy (LLLT) with infrared laser to two forehead sites while seated (total 8min, 1064nm continuous wave, 250mW/cm(2), 60J/cm(2) per site of 13.6cm(2)); (2) acute exercise (EX) of high-intensity (total 20min, with 10-min treadmill running at 85-90% VO2max); (3) combined treatment (LLLT + EX); or (4) sham control (CON). Participants were tested for prefrontal measures of sustained attention with the psychomotor vigilance task (PVT) and working memory with the delayed match-to-sample task (DMS) before and after the treatments. As compared to CON, both LLLT and EX reduced reaction time in the PVT [F(1.56) = 4.134, p = 0.01, η (2) = 0.181] and increased the number of correct responses in the DMS [F(1.56) = 4.690, p = 0.005, η (2) = 0.201], demonstrating a significant enhancing effect of LLLT and EX on cognitive performance. LLLT + EX effects were similar but showed no significantly greater improvement on PVT and DMS than LLLT or EX alone. The transcranial infrared laser stimulation and acute aerobic exercise treatments were similarly effective for cognitive enhancement, suggesting that they augment prefrontal cognitive functions similarly.

Guanfacine promotes neuronal survival in medial prefrontal cortex under hypobaric hypoxia

High altitude hypobaric hypoxia (HH) affects prefrontal cognitive and executive functions. Guanfacine, alpha 2A adrenoceptor agonist ameliorates the neurological outcomes of high altitude exposure and associated prefrontal neurodegeneration. However, the molecular mechanism underlying the neuroprotective effect of guanfacine following HH remains elusive. Altered balance of pro and anti-apoptotic proteins have been implicated in the beneficial effect of guanfacine to enhance neuronal survival. We examined the effects of guanfacine on expression of some key neurotropic and cytoskeletal proteins following HH. Male rats were exposed to simulated altitude of 7620m and received an intramuscular injection of either saline or guanfacine at a dose of 1mg/kg for 7 consecutive days. Differential expression of desired proteins was evaluated in layer II of medial prefrontal cortex (PFC) by biochemical and immunohistochemical assays. Guanfacine treatment significantly increased the expression of BDNF in layer II of the medial PFC during normoxia and HH. Moreover, there was a negative correlation of this neurotropic factor with neurodegeneration of pyramidal cells present in this layer of medial PFC. We found a significant decrease in Caspase3 and Bax while a significant increase in Bcl2 with guanfacine treatment during HH. Further, change in Bax to Bcl2 ratio was in correlation with Caspase3 expression in layer II of the medial PFC, indicating that Caspase3 is responsible for Bcl2 cleavage and hence modulation of apoptosis. Guanfacine treatment induced a marked and significant increase in MAP2 and Spinophilin expression in dendritic arbors and spines respectively. Interestingly, alteration in these cytoskeletal proteins was accompanied by simultaneous changes in morphological parameters of dendrites in layer II of medial PFC. Guanfacine modulates the neurotropic, cytoskeletal, pro and anti-apoptotic protein expression in medial PFC under HH and therefore serve as a countermeasure in the amelioration of HH induced alteration in these proteins.

Cognitive Function in Patients Before and After Micro-neurosurgical Resection of Frontal Brain Tumors

Patients with lesions of the prefrontal cortex as a result of frontal brain tumors (intra- and extra-axial) can show impairments of executive functions 1 2 3 4. Although there are a large number of psychological tests, the detection of impairments of relevant everyday executive functions in these patients is still extremely difficult. In 30 patients with lesions of the prefrontal cortex, the executive functions were tested with the Behavioral Assessment of Dysexecutive Syndrome (BADS) and 21 patients were also followed up postoperatively. Additionally, if possible, the Wisconsin Card Sorting Test (WCST), a widely used executive function test, and the Wechsler Adult Intelligence Scale (WAIS) for general cognitive performance were conducted. Pre- and postoperatively, a total of 16 patients were followed up with all three tests. The aim was to investigate the neuropsychological assessment pre- and postoperatively, to evaluate it in terms of deficits and changes in performance and to ensure that no new relevant everyday cognitive deficits arose. Preoperatively, only one patient, who could not be tested post-surgery, showed a reduced overall profile value in the BADS. In all tested patients, there was no evidence of deterioration of cognitive status 8 - 12 weeks postoperatively. Further investigations using fMRI should be used to clarify whether the results obtained should be interpreted as neuroplastic adaptations of prefrontal cognitive functions or as a failure to detect deficits due to a lack of sensitivity of the tests used.

Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study

BackgroundNeuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. ObjectiveInvestigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. MethodsNineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. p<0.05 was deemed statistically significant. ResultsThe sleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. ConclusionsIncreased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated.