Regenerative treatments for scleroderma in cutaneous manifestations of the face: a systematic review.

OBJECTIVES: Scleroderma is a heterogeneous chronic autoimmune disease affecting connective tissue, characterised by chronic inflammation and fibrosis, particularly affecting internal organs and skin. Orofacial involvement is common, leading to facial atrophy, mask-like appearance and difficulties in function that significantly impact patients' quality of life. This systematic review evaluates different autologous regenerative treatments of facial manifestations of scleroderma, aiming to provide comprehensive understanding of their effectiveness in reducing fibrosis, and thereby improving function and skin quality. METHODS: A search in PubMed, Embase, Web of Science Core Collection, Cochrane CENTRAL, and CINAHL was conducted. Studies assessing autologous regenerative treatments in cutaneous manifestations of the face in scleroderma patients were included. Outcomes of interest were treatment characteristics, characterisation of biomaterials, outcome measurements and patient satisfaction. Methodological quality was assessed with the Effective Public Health Practice Project tool. RESULTS: In total 18 studies were included. Methodological quality of studies was weak (n=15) and moderate (n=3). Treatments consisted of autologous fat grafting, platelet-rich plasma, stromal vascular fraction, and adipose-derived stem cells. In general, most studies showed improvements of symptoms, but no treatment was considered superior. CONCLUSIONS: Autologous regenerative treatments hold potential for alleviating cutaneous manifestations of the face in scleroderma. Further clinical trials should be well-designed to improve the quality of clinical evidence.

Mechanical Fractionation of Adipose Tissue-A Scoping Review of Procedures to Obtain Stromal Vascular Fraction.

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.

Morphological Variation of the Mandible in the Orthognathic Population-A Morphological Study Using Statistical Shape Modelling.

The aim of this study was to investigate the value of 3D Statistical Shape Modelling for orthognathic surgery planning. The goal was to objectify shape variations in the orthognathic population and differences between male and female patients by means of a statistical shape modelling method. Pre-operative CBCT scans of patients for whom 3D Virtual Surgical Plans (3D VSP) were developed at the University Medical Center Groningen between 2019 and 2020 were included. Automatic segmentation algorithms were used to create 3D models of the mandibles, and the statistical shape model was built through principal component analysis. Unpaired t-tests were performed to compare the principal components of the male and female models. A total of 194 patients (130 females and 64 males) were included. The mandibular shape could be visually described by the first five principal components: (1) The height of the mandibular ramus and condyles, (2) the variation in the gonial angle of the mandible, (3) the width of the ramus and the anterior/posterior projection of the chin, (4) the lateral projection of the mandible's angle, and (5) the lateral slope of the ramus and the inter-condylar distance. The statistical test showed significant differences between male and female mandibular shapes in 10 principal components. This study demonstrates the feasibility of using statistical shape modelling to inform physicians about mandible shape variations and relevant differences between male and female mandibles. The information obtained from this study could be used to quantify masculine and feminine mandibular shape aspects and to improve surgical planning for mandibular shape manipulations.

A Systematic Review of the Efficacy of Microfocused Ultrasound for Facial Skin Tightening.

Objective: to systematically review the efficacy of microfocused ultrasound (MFU) for facial skin tightening. Methods: A systematic search was performed (Pubmed, Embase) to assess the efficacy of single MFU treatments for facial skin tightening. Eligible studies included randomised controlled trials, controlled trials, cohort studies and case series (n ≥ 10). Objective and subjective outcomes were assessed. Results: A total of 693 studies were identified of which 16 studies were eligible. All the studies involved female patients. MFU is capable of tightening the skin, as observed in studies measuring the results of brow lifts (0.47−1.7 mm) and submental lifts (measured as a 26−45 mm2 reduction in the submental area on lateral photographs). Data from the Global Aesthetic Improvement Scale (GAIS) were pooled, and the day 90 pooled subjective investigator reported scores (IGAIS) (n = 337) showed that 92% of the patients demonstrated an improvement in skin tightening and/or in wrinkle reduction which continued up to one year. Longer-term follow-up data are not available. The patient-reported pooled scores (SGAIS) (n = 81) showed that the skin improvements were mild and continued to increase from 42% (90 days) to 53% (360 days) post-treatment. The MFU treatment was moderately painful and caused transient erythema with or without oedema. Other adverse effects were rare (2%), including dysesthesia (numbness or hypersensitivity), bruising and stinging, mandibular burns, striations and contact dermatitis. Various device settings, treatment protocols and energies were applied. Excessive skin laxity and a BMI > 30 were posed as relative contraindications for MFU treatment because positive results declined with an increase in laxity and BMI. Conclusions: MFU treatment is effective in tightening female patients' mildly to moderately lax facial skin. Future studies should focus on objective treatment outcomes, optimising treatment regimens and male patients.

Effects of Upper Blepharoplasty Techniques on Headaches, Eyebrow Position, and Electromyographic Outcomes: A Randomized Controlled Trial.

The aim of this study was to assess changes in headaches, eyebrow height, and electromyographic (EMG) outcomes of the frontalis and orbicularis oculi muscles, after an upper blepharoplasty with or without resecting a strip of orbicularis oculi muscle. In a randomized controlled trial, 54 patients received an upper blepharoplasty involving either only removing skin (group A) or removing skin with an additional strip of orbicularis muscle (group B). Preoperative, and 6 and 12 months postoperative headache complaints were assessed using the HIT-6 scores and eyebrow heights were measured on standardised photographs. Surface EMG measurements, i.e., electrical activity and muscle fatigue, were assessed for the frontalis and orbicularis oculi muscles preoperatively and 2, 6, and 12 months postoperatively. Significantly fewer headaches were reported following a blepharoplasty. The eyebrow height had decreased, but did not differ between groups. Regarding the surface EMG measurements, only group A's frontalis muscle electrical activity had decreased significantly during maximal contraction 12 months after surgery (80 vs. 39 mV, p = 0.026). Fatigue of both the frontalis and the orbicularis oculi muscles did not change significantly postoperatively compared to baseline. EMG differences between groups were minor and clinically insignificant. The eyebrow height decreased and patients reported less headaches after upper blepharoplasty irrespective of the used technique.

Adjunctive Aesthetic Procedures in Orthognathic Surgery.

An important aesthetic goal in orthognathic planning is to improve facial balance, harmony, volume, and symmetry. It is therefore logical that adjunctive aesthetic procedures become a part of the overall orthognathic treatment plan and that their possibilities are discussed with orthognathic candidates. Such procedures help to improve the final outcome of the orthognathic treatment and enhance patient satisfaction. Training and experience are of utmost importance when offering and performing aesthetic facial surgery. This article discusses various facial aesthetic procedures that can be combined with orthognathic surgery, to the patient's benefit, to help them become the most beautiful version of themselves.

Traditional versus Laterally Extended Upper Blepharoplasty Skin Excisions: Objective and Patient-Reported Outcomes.

BACKGROUND: Different skin excision shapes may result in different aesthetic outcomes after upper blepharoplasty. METHODS: Two skin-only excision shapes were evaluated objectively and subjectively in 28 matched patients with laterally extended skin excision (group A) or traditional elliptical skin excision (group B). The pretarsal show, lateral eyebrow height, amount of scarring (evaluated with the Patient and Observer Scar Assessment Scale), and patient-reported aesthetic results (evaluated using FACE-Q) were scored and compared at 6 and 12 months postoperatively. RESULTS: In both groups, pretarsal show improved significantly after blepharoplasty. The homogeneity of pretarsal show improved significantly in the lateral extension group (group A) together with slightly more pretarsal show (0.5 to 0.8 mm at central pupil region) at 6 and 12 months of follow-up compared with group B ( P = 0.004). A trend was observed in the exocanthion 45-degree measurement, in which group A had 0.6 mm greater pretarsal show 6 months postoperatively. Homogeneity of the pretarsal show had improved significantly in group A, but not in group B, at 12 months after blepharoplasty. No other significant differences were observed between the groups regarding pretarsal show measurements or FACE-Q scores. Both groups showed descent of the lateral eyebrow, but this was only significant in group B. Group B showed 1.4 to 2.0 mm more descent compared with group A. Scarring and adverse effects scores were low in both groups and did not differ. CONCLUSION: Laterally extended skin excision and traditional elliptical skin excision both result in positive aesthetic results, but the laterally extended skin excision technique is accompanied by a slightly more favorable outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Three-dimensional volumetric changes in the airway of growing unilateral complete cleft lip and palate patients after bone-anchored maxillary protraction.

INTRODUCTION: This prospective controlled study evaluates volumetric, length, and average cross-sectional area (aCSA) airway changes in growing patients with unilateral complete cleft lip and palate after 1.5 years of bone-anchored maxillary protraction therapy. METHODS: Thirty-five growing unilateral complete cleft lip and palate patients with maxillary deficiency were included (aged 11.3 ± 0.5 years). Cone-beam computed tomography scans were obtained before bone-anchored maxillary protraction (BAMP) therapy and after 1.5 years. A growing group without cleft (n = 18) patients served as a control group at 1.5 years posttreatment (aged 13.1 ± 1.2 years). Volumetric, length, and aCSA changes of the total airway, nasopharynx (NP), middle pharynx, and inferior pharynx airway were evaluated. RESULTS: After 1.5 years of BAMP therapy, a significant increase was observed in the total airway volume and the NP (P <0.01). The middle and inferior pharynx showed an insignificant tendency of volumetric increase. Compared with the control group, a significantly larger airway volume could be observed in the total airway and NP (P <0.05). The aCSA of the NP increased significantly compared with pretreatment. CONCLUSIONS: The total airway and NP volumes significantly increased in growing subjects with cleft lip and palate after 1.5 years of BAMP therapy to a level comparable to a control group without cleft. Volumetric increase in the NP in the BAMP group is mainly attributed to the increase in its cross-sectional area. BAMP can therefore be recommended as an effective therapy for patients with cleft lip and palate with positive effects on airway development.

Volumetric Effect and Patient Satisfaction after Facial Fat Grafting.

BACKGROUND: Facial fat grafts decrease in volume after transplantation. This observation is based on overall facial three-dimensional analyses, because there is sparse information on volume changes in well-defined aesthetic areas. The authors aimed to assess the overall and, more specifically, the local volumetric effects of facial fat grafting and relate these effects to patient satisfaction up to 1 year after treatment. METHODS: All consecutive adult female patients who were scheduled for facial fat grafting without additional surgical procedures were asked to participate. All patients underwent the same fat grafting method. An algorithm-based personalized aesthetic template was applied to define specific aesthetic areas on the preoperative three-dimensional image. Objective outcome parameters [i.e., three-dimensional volume differences, patient satisfaction (FACE-Q questionnaire)] were measured at baseline and at 6 weeks, 6 months, and 12 months after fat grafting. RESULTS: Of 33 female patients who underwent a facial fat graft procedure, 23 patients had complete three-dimensional data and were eligible for analysis. The highest volume gain was observed 6 weeks after grafting and was followed by a gradual loss thereafter. Overall and in the zygomatic area, a substantial gain in volume was still present 1 year after grafting, whereas this effect was lost in the lip area. FACE-Q scales Satisfaction with Facial Appearance Overall and Satisfaction with Cheeks improved too, whereas scores for Lines: Lips returned to baseline levels. The improvement in FACE-Q scales was in agreement with the objective change in volume. CONCLUSION: Gain in overall and local volumetric effects is accompanied by comparable changes in patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Supplementation of Facial Fat Grafting to Increase Volume Retention: A Systematic Review.

BACKGROUND: For decades, facial fat grafting has been used in clinical practice for volume restoration. The main challenge of this technique is variable volume retention. The addition of supplements to augment fat grafts and increase volume retention has been reported in recent years. OBJECTIVES: The aim of this systematic review was to investigate which supplements increase volume retention in facial fat grafting as assessed by volumetric outcomes and patient satisfaction. METHODS: Embase, Medline, Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to November 30, 2020. Only studies assessing volume after facial fat grafting with supplementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. The quality of the studies was assessed with the Effective Public Health Practice Project tool. RESULTS: After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27 studies were eligible and included for comparison. Supplementation comprised of platelet-rich plasma, platelet-rich fibrin, adipose tissue-derived stromal cells or bone marrow-derived stromal cells, cellular or tissue stromal vascular fraction, or nanofat. In 13 out of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction. The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies, and strong for 1 study. CONCLUSIONS: It remains unclear if additives contribute to facial fat graft retention and there is a need to standardize methodology.

Impact of upper blepharoplasty, with or without orbicularis oculi muscle removal, on tear film dynamics and dry eye symptoms: A randomized controlled trial.

PURPOSE: Upper blepharoplasty may be related to dry eye symptoms since the function of the orbicularis oculi muscle may affect the tear film. We aimed to assess the effect of blepharoplasty with or without the removal of a strip of orbicularis oculi muscle on tear film dynamics and dry eye symptoms. METHODS: A double-blind, randomized, controlled trial comparing upper blepharoplasty without (group A) or with (group B) orbicularis oculi muscle excision was performed on 54 healthy Caucasian patients. Tear film dynamics and dry eye symptoms were evaluated using multiple dry eye parameters, i.e. tear osmolarity, Schirmer test I, corneal/conjunctival staining, tear break-up time (TBUT), Oxford Scheme, Sicca Ocular Staining Score and Ocular Surface Disease Index questionnaire. All the parameters were assessed preoperatively and 6 and 12 months after upper blepharoplasty. All the groups' outcomes were compared. RESULTS: The differences were not significant between the two upper blepharoplasty techniques regarding most of the above-mentioned outcomes. Subjective symptoms of ocular irritation, consistent with dry eye disease and vision-related impairment, were reduced after upper blepharoplasty independent of the type of the technique applied, while the pre and postoperative outcomes of the objective tear dynamics did not differ 12 months after surgery. However, group B demonstrated a significant increase in tear osmolarity and TBUT at the 6-month follow-up visit. CONCLUSION: An upper blepharoplasty alleviates subjective dry eye complaints in the long term, while not changing the tear dynamics. The improvement was independent of the blepharoplasty technique used.

Low Level of Perfectionism as a Possible Risk Factor for Suicide in Adolescents With Attention-Deficit/Hyperactivity Disorder.

Introduction: Suicide is one of the leading causes of death among adolescents. Although it is known that both perfectionism and attention-deficit/hyperactivity disorder ('ADHD') are important risk factors for suicide, there are no studies that have investigated the relationship between suicidal behavior and perfectionism among people with ADHD. Aim: The current study investigates the association between perfectionism and suicide in adolescents with ADHD. Method: Subjects included 88 adolescents with ADHD and 96 non-clinical control adolescents. We used the Multidimensional Perfectionism Scale to evaluate perfectionism as well as its separate traits, and the Mini International Neuropsychologic Interview Kid to evaluate psychiatric disorders and suicidal behavior. Differences between the groups were statistically evaluated using t-tests, a Poisson regression analysis with suicide as a discrete variable, and a logistic regression analysis with suicide as a binary variable. Results: Compared to the control group, the ADHD group showed a significantly lower level on the adaptive 'Organization' trait of perfectionism, but not on any other trait, and a significantly higher level of suicidal behavior. Logistic regression results indicated a significant association for perfectionism in general (OR = 0.93, p = 0.003), and for the 'Personal Standards' trait (OR: 0.82, p = 0.039). Poisson regression analysis also showed a significant association with perfectionism in general (IRR = 0.90; p < 0.001) and with the 'Personal standards' trait model (IRR = 0.81, p = 0.019). Discussion: Our results indicate that a low level of perfectionism, in particular 'Personal standards', may be a risk factor for suicidal behavior in adolescents with ADHD. We recommend that psychoeducation and therapy of adolescents with ADHD should consider focusing on adaptive perfection as a possible risk factor for suicide as well.

Skeletal Changes in Growing Cleft Patients with Class III Malocclusion Treated with Bone Anchored Maxillary Protraction-A 3.5-Year Follow-Up.

This prospective controlled trial aimed to evaluate the skeletal effect of 3.5-years bone anchored maxillary protraction (BAMP) in growing cleft subjects with a Class III malocclusion. SUBJECTS AND METHOD: Nineteen cleft patients (11.4 ± 0.7-years) were included from whom cone beam computed tomography (CBCT) scans were taken before the start of BAMP (T0), 1.5-years after (T1) and 3.5 y after (T2). Seventeen age- and malocclusion-matched, untreated cleft subjects with cephalograms available at T0 and T2 served as the control group. Three dimensional skeletal changes were measured qualitatively and quantitatively on CBCT scans. Two dimensional measurements were made on cephalograms. RESULTS: Significant positive effects have been observed on the zygomaticomaxillary complex. Specifically, the A-point showed a displacement of 2.7 mm ± 0.9 mm from T0 to T2 (p < 0.05). A displacement of 3.8 mm ± 1.2 mm was observed in the zygoma regions (p < 0.05). On the cephalograms significant differences at T2 were observed between the BAMP and the control subjects in Wits, gonial angle, and overjet (p < 0.05), all in favor of the treatment of Class III malocclusion. The changes taking place in the two consecutive periods (ΔT1-T0, ΔT2-T1) did not differ, indicating that not only were the positive results from the first 1.5-years maintained, but continuous orthopedic effects were also achieved in the following 2-years. CONCLUSIONS: In conclusion, findings from the present prospective study with a 3.5-years follow-up provide the first evidence to support BAMP as an effective and reliable treatment option for growing cleft subjects with mild to moderate Class III malocclusion up to 15-years old.

A functional MRI study of presurgical cognitive deficits in glioma patients.

BACKGROUND: The main goal of this functional MRI (fMRI) study was to examine whether cognitive deficits in glioma patients prior to treatment are associated with abnormal brain activity in either the central executive network (CEN) or default mode network (DMN). METHODS: Forty-six glioma patients, and 23 group-matched healthy controls (HCs) participated in this fMRI experiment, performing an N-back task. Additionally, cognitive profiles of patients were evaluated outside the scanner. A region of interest-based analysis was used to compare brain activity in CEN and DMN between groups. Post hoc analyses were performed to evaluate differences between low-grade glioma (LGG) and high-grade glioma (HGG) patients. RESULTS: In-scanner performance was lower in glioma patients compared to HCs. Neuropsychological testing indicated cognitive impairment in LGG as well as HGG patients. fMRI results revealed normal CEN activation in glioma patients, whereas patients showed reduced DMN deactivation compared to HCs. Brain activity levels did not differ between LGG and HGG patients. CONCLUSIONS: Our study suggests that cognitive deficits in glioma patients prior to treatment are associated with reduced responsiveness of the DMN, but not with abnormal CEN activation. These results suggest that cognitive deficits in glioma patients reflect a reduced capacity to achieve a brain state necessary for normal cognitive performance, rather than abnormal functioning of executive brain regions. Solely focusing on increases in brain activity may well be insufficient if we want to understand the underlying brain mechanism of cognitive impairments in patients, as our results indicate the importance of assessing deactivation.

Reproducibility of 3D scanning in the periorbital region.

The reproducibility of scanning in the periorbital region with 3D technology to enable objective evaluations of surgical treatment in the periorbital region was assessed. Facial 3D-scans of 15 volunteers were captured at different time points with a handheld Artec Space Spider structured light scanner. Two scans were made with a one minute interval and repeated after 1 year; for both a natural head position and with the head in a fixation-device. On assessing the area between the eyelashes and eyebrows, the medians of the average deviations between the various cross-sections of the one minute interval 3D-scans ranged from 0.17 to 0.21 mm at baseline, and from 0.10 to 0.11 mm when the minute-interval scanning was repeated one year later. The systematic differences when scanning in a natural head position and fixated position were comparable. The reproducibility of the 3D processing was excellent (intraclass correlation coefficient > 0.9). The repeated scanning deviations (baseline versus one year data) were well within the accepted clinical threshold of 1 mm. Scanning with a hand-held 3D-scanning device (Artec Space Spider) is a promising tool to assess changes in the periorbital region following surgical treatment since the median deviations are well below the clinically accepted 1 mm measuring error, for both the natural head and fixated positions.

Three-dimensional facial volume analysis using algorithm-based personalized aesthetic templates.

Three-dimensional stereophotogrammetry is commonly used to assess volumetric changes after facial procedures. A lack of clear landmarks in aesthetic regions complicates the reproduction of selected areas in sequential images. A three-dimensional volumetric analysis was developed based on a personalized aesthetic template. The accuracy and reproducibility of this method were assessed. Six female volunteers were photographed using the 3dMDtrio system according to a clinical protocol, twice at baseline (T1) and twice after 1year (T2). A styrofoam head was used as control. A standardized aesthetic template was morphed over the baseline images of the volunteers using a coherent point drift algorithm. The resulting personalized template was projected over all sequential images to assess surface area differences, volume differences, and root mean square errors. In 12 well-defined aesthetic areas, mean average surface area and volume differences between the two T1 images ranged from -7.6mm2 to 10.1mm2 and -0.11cm3 to 0.13cm3, respectively. T1 root mean square errors ranged between 0.24mm and 0.62mm (standard deviation 0.18-0.73mm). Comparable differences were found between the T2 images. An increase in volume between T1 and T2 was only observed for volunteers who gained in body weight. Personalized aesthetic templates are an accurate and reproducible method to assess changes in aesthetic areas.

When Right Is on the Left (and Vice Versa): A Case Series of Glioma Patients with Reversed Lateralization of Cognitive Functions.

We report a case series of four patients operated on for a glioma in awake conditions and in whom task-based functional magnetic resonance imaging (fMRI) demonstrated right-dominant activity during a language production task. Language functional sites were identified intraoperatively by electrical stimulations only in the patient with a right-sided lesion. Furthermore, the pre- or postoperative cognitive evaluations in the three patients operated on for a left-sided glioma revealed right spatial neglect and dysexecutive syndrome, hence demonstrating that, in patients with right-dominant activity on language fMRI, the left hemisphere is implicated in spatial consciousness and cognitive control. This study supports the interest of presurgical task-based language fMRI to identify patients with a reversed lateralization of cognitive functions and to make an adequate selection of the battery of intraoperative cognitive tasks to be monitored in those rare outliers.

The effect of response frequency on cognitive brain activity during an alertness task.

A required response forces the brain to react overtly on a stimulus. This may be a factor that influences cognitive activity during a task, as it could facilitate for instance alertness, especially in tasks that are relatively easy. In the current article, we therefore tested the hypothesis that response frequency affects cognitive brain activity in an alertness task. In this 3T functional MRI study, healthy volunteers performed a continuous performance task with three conditions with increasing response frequency. Only scans during presentation of non-targets were analyzed, to exclude activity related to the change in frequency in response selection and motor responses between conditions. To evaluate changes in cognitive brain activity, a network analysis was performed based on two main networks including regions with task-induced activation and task-induced deactivation. We tested for differences in brain activity as an effect of target frequency. Performance results indicated no effect of target frequency on accuracy or reaction time. During non-targets, we found significant signal changes in TID for all three conditions, whereas TIA showed no significant signal changes in any condition. Target frequency did not have a significant effect on the level of signal change at network level, as well as at individual region level. Our study showed predominantly deactivation during non-responses in all three task conditions. Furthermore, our results indicate that response frequency does not influence brain activity during an alertness task. Our results provide additional information relevant for the understanding of the neurophysiological implementation of cognitive control or alertness.

Brain Activity Associated With Expected Task Difficulty.

Previous research shows that people can use a cue to mentally prepare for a cognitive challenge. The response to a cue has been defined as phasic alertness which is reflected in faster responses and increased activity in frontal, parietal, thalamic, and visual brain regions. We examine if and how phasic alertness can be tuned to the expected difficulty of an upcoming challenge. If people in general are able to tune their level of alertness, then an inability to tune may be linked to disease. Twenty-two healthy volunteers performed a cued visual perception task with two levels of task difficulty. Performance and brain activity were compared between these two levels. Performance was lower for difficult stimuli than for easy stimuli. For both cue types, participants showed activation in a network associated with central executive function and deactivation in regions of the default mode network (DMN) and visual cortex. Deactivation was significantly stronger for cues signaling difficult stimuli than for cues signaling easy stimuli. This effect was most prominent in medial prefrontal gyrus, visual, and temporal cortices. Activation did not differ between the cues. Our study shows that phasic alertness is represented by activated as well as deactivated brain regions. However only deactivated brain regions tuned their level of activity to the expected task difficulty. These results suggest that people, in general, are able to tune their level of alertness to an upcoming task. Cognition may be facilitated by a brain-state coupled to expectations about an upcoming cognitive challenge. Unique identifier = 842003004.