Effort-cost decision-making associated with negative symptoms in schizophrenia and bipolar disorder.

Motivational deficits and reduced goal-directed behavior for external rewards have long been considered an important features of negative symptoms in patients with schizophrenia (SCZ). Negative symptoms have also a high prevalence in bipolar disorder (BP). We used a transdiagnostic approach in order to examine association between negative symptoms and effort allocation for monetary rewards. 41 patients with SCZ and 34 patients with BP were enrolled in the study along with 41 healthy controls (HC). Effort-Expenditure for Rewards Task (EEfRT) was used to measure subjects' effort allocation for monetary rewards. Generalized estimating equation models were used to analyze EEfRT choice behavior. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). SCZ and BP groups expended lower effort to obtain a monetary rewards compared to HC. Severity of negative symptoms was negatively correlated with EEfRT performance in both diagnostic groups. Each diagnostic group showed lower effort allocation for monetary rewards compared to HC suggesting reduced motivation for monetary rewards. In addition, our results suggest that abnormal effort-based decision-making might be a transdiagnostic factor underlying negative symptoms.

Clinical predictors of Alzheimer's disease-like brain atrophy in individuals with memory complaints.

OBJECTIVES: The definition and assessment methods for subjective cognitive decline (SCD) vary among studies. We aimed to investigate which features or assessment methods of SCD best predict Alzheimer's disease (AD)-related structural atrophy patterns. METHODS: We assessed 104 individuals aged 55+ with memory complaints but normal cognitive screening. Our research questions were as follows: To improve the prediction of AD related morphological changes, (1) Would the use of a standardized cognitive screening scale be beneficial? (2) Is conducting a thorough neuropsychological evaluation necessary instead of relying solely on cognitive screening tests? (3) Should we apply SCD-plus research criteria, and if so, which criterion would be the most effective? (4) Is it necessary to consider medical and psychiatric comorbidities, vitamin deficiencies, vascular burden on MRI, and family history? We utilized Freesurfer to analyze cortical thickness and regional brain volume meta-scores linked to AD or predicting its development. We employed multiple linear regression models for each variable, with morphology as the dependent variable. RESULTS: AD-like morphology was associated with subjective complaints in males, individuals with advanced age, and higher education. Later age of onset for complaints, complaints specifically related to memory, excessive deep white matter vascular lesions, and using medications that have negative implications for cognitive health (according to the Beers criteria) were predictive of AD-related morphology. The subjective cognitive memory questionnaire scores were found to be a better predictor of reduced volumes than a single-question assessment. It is important to note that not all SCD-plus criteria were evaluated in this study, particularly the APOE genotype, amyloid, and tau status, due to resource limitations. CONCLUSIONS: The detection of AD-related structural changes is impacted by demographics and assessment methods. Standardizing SCD assessment methods can enhance predictive accuracy.

Neural correlates of mental state decoding and mental state reasoning in schizophrenia.

Theory of mind skills are disrupted in schizophrenia. However, various theory of mind tasks measure different neurocognitive domains. This multimodal neuroimaging study aimed to investigate the neuroanatomical correlates of mental state decoding and reasoning components of theory of mind in schizophrenia and healthy controls (HCs) using T1-weighted and diffusion-weighted (DTI) magnetic resonance imaging (MRI). Sixty-two patients with schizophrenia and 34 HCs were included. The Reading the Mind in the Eyes (RMET) and Hinting tests were used to evaluate mental state decoding and reasoning, respectively. Correlations between social cognition and cortical parameters (thickness, volume, surface area), or DTI scalars (fractional anisotropy, axial diffusivity, radial diffusivity) were cluster-based corrected for multiple comparisons. In schizophrenia, RMET scores showed positive correlations in 3 clusters, including left insula thickness, right superior-temporal thickness, left superior-temporal-sulcus volume, and DTI analysis revealed that fractional anisotropy showed positive correlations in 3 clusters, including right inferior-fronto-occipital fasciculus, left forceps-major, left inferior-fronto-occipital fasciculus. In schizophrenia, Hinting test scores showed positive correlations in 3 clusters in T1-weighted MRI, including left superior-temporal-sulcus volume, left superior-temporal-sulcus surface area, left pars-orbitalis volume. In conclusion, this study provided evidence for the involvement of particular cortical regions and white matter tracts in mental state decoding and reasoning.

Abnormal Structural Network Communication Reflects Cognitive Deficits in Schizophrenia.

Schizophrenia has long been thought to be a disconnection syndrome and several previous studies have reported widespread abnormalities in white matter tracts in individuals with schizophrenia. Furthermore, reductions in structural connectivity may also impair communication between anatomically unconnected pairs of brain regions, potentially impacting global signal traffic in the brain. Therefore, we used different communication models to examine direct and indirect structural connections (polysynaptic) communication in large-scale brain networks in schizophrenia. Diffusion-weighted magnetic resonance imaging scans were acquired from 62 patients diagnosed with schizophrenia and 35 controls. In this study, we used five network communication models including, shortest paths, navigation, diffusion, search information and communicability to examine polysynaptic communication in large-scale brain networks in schizophrenia. We showed less efficient communication between spatially widespread brain regions particulary encompassing cortico-subcortical basal ganglia network in schizophrenia group relative to controls. Then, we also examined whether reduced communication efficiency was related to clinical symptoms in schizophrenia group. Among different measures of communication efficiency, only navigation efficiency was associated with global cognitive impairment across multiple cognitive domains including verbal learning, processing speed, executive functions and working memory, in individuals with schizophrenia. We did not find any association between communication efficiency measures and positive or negative symptoms within the schizophrenia group. Our findings are important for improving our mechanistic understanding of neurobiological process underlying cognitive symptoms in schizophrenia.

Reduced sensitivity but intact motivation to monetary rewards and reversal learning in obesity.

BACKGROUND: Obesity has been linked to altered reward processing but little is known about which components of reward processing including motivation, sensitivity and learning are impaired in obesity. We examined whether obesity compared to healthy weight controls is associated with differences in distinct subdomains of reward processing. To this end, we used two established paradigms, namely the Effort Expenditure for Rewards task (EEfRT) and the Probabilistic Reversal Learning Task (PRLT). METHODS: 30 individuals with obesity (OBS) and 30 healthy weight control subjects (HC) were included in the study. Generalized estimating equation models were used to analyze EEfRT choice behavior. PRLT data was analyzed using both conventional behavioral variables of choices and computational models. RESULTS: Our findings from the different tasks speak in favor of a hyposensitivity to non-food rewards in obesity. OBS did not make fewer overall hard task selections compared to HC in the EEfRT suggesting generally intact non-food reward motivation. However, in highly rewarding trials (i.e.,trials with high reward magnitude and high reward probability),OBSmadefewer hard task selections compared to normal weight subjects suggesting decreased sensitivity to highly rewarding non-food reinforcers. Hyposensitivity to non-food rewards was also evident in OBS in the PRLT as evidenced by lower win-stay probability compared to HC. Our computational modelling analyses revealed decreased stochasticity but intact reward and punishment learning rates in OBS. CONCLUSIONS: Our findings provide evidence for intact reward motivation and learning in OBS but lower reward sensitivity which is linked to stochasticity of choices in a non-food context. These findings might provide further insight into the mechanism underlying dysfunctional choices in obesity.

Negative symptoms are associated with modularity and thalamic connectivity in schizophrenia.

Negative symptoms, including avolition, anhedonia, asociality, blunted affect and alogia are associated with poor long-term outcome and functioning. However, treatment options for negative symptoms are limited and neurobiological mechanisms underlying negative symptoms in schizophrenia are still poorly understood. Diffusion-weighted magnetic resonance imaging scans were acquired from 64 patients diagnosed with schizophrenia and 35 controls. Global and regional network properties and rich club organization were investigated using graph analytical methods. We found that the schizophrenia group had higher modularity, clustering coefficient and characteristic path length, and lower rich connections compared to controls, suggesting highly connected nodes within modules but less integrated with nodes in other modules in schizophrenia. We also found a lower nodal degree in the left thalamus and left putamen in schizophrenia relative to the control group. Importantly, higher modularity was associated with greater negative symptoms but not with cognitive deficits in patients diagnosed with schizophrenia suggesting an alteration in modularity might be specific to overall negative symptoms. The nodal degree of the left thalamus was associated with both negative and cognitive symptoms. Our findings are important for improving our understanding of abnormal white-matter network topology underlying negative symptoms in schizophrenia.

Computational analysis of probabilistic reversal learning deficits in male subjects with alcohol use disorder.

Background: Alcohol use disorder is characterized by perseverative alcohol use despite negative consequences. This hallmark feature of addiction potentially relates to impairments in behavioral flexibility, which can be measured by probabilistic reversal learning (PRL) paradigms. We here aimed to examine the cognitive mechanisms underlying impaired PRL task performance in patients with alcohol use disorder (AUDP) using computational models of reinforcement learning. Methods: Twenty-eight early abstinent AUDP and 27 healthy controls (HC) performed an extensive PRL paradigm. We compared conventional behavioral variables of choices (perseveration; correct responses) between groups. Moreover, we fitted Bayesian computational models to the task data to compare differences in latent cognitive variables including reward and punishment learning and choice consistency between groups. Results: AUDP and HC did not significantly differ with regard to direct perseveration rates after reversals. However, AUDP made overall less correct responses and specifically showed decreased win-stay behavior compared to HC. Interestingly, AUDP showed premature switching after no or little negative feedback but elevated proneness to stay when accumulation of negative feedback would make switching a more optimal option. Computational modeling revealed that AUDP compared to HC showed enhanced learning from punishment, a tendency to learn less from positive feedback and lower choice consistency. Conclusion: Our data do not support the assumption that AUDP are characterized by increased perseveration behavior. Instead our findings provide evidence that enhanced negative reinforcement and decreased non-drug-related reward learning as well as diminished choice consistency underlie dysfunctional choice behavior in AUDP.

Cortical thickness and surface area in patients with obsessive compulsive disorder and their unaffected siblings.

Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.

Fronto-striatal structures related with model-based control as an endophenotype for obsessive-compulsive disorder.

Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive-compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD > SIB > HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.

Resting state functional connectivity in adolescent synthetic cannabinoid users with and without attention-deficit/hyperactivity disorder.

OBJECTIVE: Synthetic cannabinoids (SCs) have become increasingly popular in recent years, especially among adolescents. The first aim of the current study was to examine resting-state functional connectivity (rsFC) in SC users compared to controls. Our second aim was to examine the influence of comorbid attention-deficit/hyperactivity disorder (ADHD) symptomatology on rsFC changes in SC users compared to controls. METHODS: Resting-state functional magnetic resonance imaging (fMRI) analysis included 25 SC users (14 without ADHD and 11 with ADHD combined type) and 12 control subjects. RESULTS: We found (i) higher rsFC between the default mode network (DMN) and salience network, dorsal attention network and cingulo-opercular network, and (ii) lower rsFC within the DMN and between the DMN and visual network in SC users compared to controls. There were no significant differences between SC users with ADHD and controls, nor were there any significant differences between SC users with and without ADHD. CONCLUSIONS: We found the first evidence of abnormalities within and between resting state networks in adolescent SC users without ADHD. In contrast, SC users with ADHD showed no differences compared to controls. These results suggest that comorbidity of ADHD and substance dependence may show different rsFC alterations than substance use alone.

White matter microstructure and connectivity in patients with obsessive-compulsive disorder and their unaffected siblings.

OBJECTIVE: We aimed to examine white matter microstructure and connectivity in individuals with obsessive-compulsive disorder (OCD) and their unaffected siblings, relative to healthy controls. METHODS: Diffusion-weighted magnetic resonance imaging (dMRI) scans were acquired in 30 patients with OCD, 21 unaffected siblings, and 31 controls. We examined white matter microstructure using measures of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Structural networks were examined using network-based statistic (NBS). RESULTS: Compared to controls, OCD patients showed significantly reduced FA and increased RD in clusters traversing the left forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and cingulum. Furthermore, the OCD group displayed significantly weaker connectivity (quantified by the streamline count) compared to controls in the right hemisphere, most notably in edges connecting subcortical structures to temporo-occipital cortical regions. The sibling group showed intermediate streamline counts, FA and RD values between OCD and healthy control groups in connections found to be abnormal in patients with OCD. However, these reductions did not significantly differ compared to controls. CONCLUSION: Therefore, siblings of OCD patients display intermediate levels in dMRI measures of microstructure and connectivity, suggesting white matter abnormalities might be related to the familial predisposition for OCD.

Structural dysconnectivity in offspring of individuals with bipolar disorder: The effect of co-existing clinical-high-risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) might be associated in disturbances in brain networks. However, little is known about the abnormalities in structural brain connectivity which might be related to vulnerability to BD and predictive of the emergence of manic symptoms. No previous study has investigated the effect of subthreshold syndromes on structural dysconnectivity in offspring of parents with BD (BDoff). METHODS: We investigated diffusion weighted images of 70 BDoff and 48 healthy controls (HC). Nineteen of the 70 BDoff had presented with subthreshold syndromes indicating a clinical high-risk (BDoff-CHR) and other 51 BDoff had no such history (BDoff-non-CHR). Global and regional network properties, rich club organization and inter-regional connectivity in BDoff and healthy controls were investigated using graph analytical methods and network-based-statistics (NBS). RESULTS: Global properties of WM networks appeared to be intact in BDoff-CHR and BDoff-non-CHR. However, decreased regional connectivity in right occipito-parietal areas and cerebellum was a common feature of both BDoff groups. Importantly, decreased interregional connectivity between nodes in right and left prefrontal regions, nodes in right prefrontal lobe and right temporal lobe and nodes in left occipital area and left cerebellum were evident in BDoff-CHR but not BDoff-non-CHR. LIMITATIONS: The cross-sectional nature of the study was the main consideration. CONCLUSION: Decreased regional connectivity in right posterior brain regions might be related to vulnerability to BD. On the other hand, interregional dysconnectivity in anterior frontal and limbic regions and left posterior brain regions might be evident in individuals genetically at risk for developing BD who had experienced subthreshold mood symptoms.

Structural connectivity in adolescent synthetic cannabinoid users with and without ADHD.

Synthetic cannabinoids (SC) have become increasingly popular in the last few years, especially among adolescents. Given ADHD is overrepresented in patients with substance use across adolescents compared to the general population, the current study aims were two-fold: i) examine structural brain network topology in SC users compared to healthy controls and, ii) examine the influence of ADHD on network topology in SC users. Diffusion-weighted magnetic resonance imaging scans were acquired from 27 SC users (14 without ADHD and 13 with ADHD combined type) and 13 controls. Structural networks were examined using network-based statistic and connectomic analysis. We found that SC users without ADHD had significantly weaker connectivity compared to controls in bilateral hemispheres, most notably in edges connecting the left parietal and occipital regions. In contrast, SC users with ADHD showed stronger structural connectivity compared to controls. In addition, adolescent SC users with ADHD, but not without ADHD, displayed reduced network organization, indicated by lower clustering coefficient and modularity, suggesting that poor structural network segregation and preserved structural network integration. These results suggest that comorbidity of ADHD and substance dependence may show different structural connectivity alterations than substance use alone. Therefore, future connectivity studies in the substance use population should account for the presence of ADHD in their samples, which may be associated with disparate connectivity profiles.

Cortical Thickness and Subcortical Volumes in Adolescent Synthetic Cannabinoid Users with or Without ADHD: a Preliminary Study.

INTRODUCTION: Synthetic cannabinoids (SCs) have become increasingly popular in the last few years, especially among adolescents. Given Attention deficit/hyperactivity disorder (ADHD) is over represented in patients with substance use across adolescents compared to the general population, the current study aims were two-fold: i) examine cortical thickness, surface area and subcortical volumes in SC users compared to controls, ii) examine the influence of ADHD on cortical thickness, surface area and subcortical volumes in SC users. METHODS: Structural magnetic resonance imaging scans were acquired from 28 SC users (15 without ADHD and 13 with ADHD combined type) and 13 controls. RESULTS: We found that SC users both with and without ADHD groups have significantly reduced cortical thickness compared to controls in areas of the left caudal middle frontal and left superior frontal. In addition, SC users with ADHD also showed reduced cortical thickness in the right precentral and postcentral gyruses. We also found increased right nucleus accumbens volume in SC users without ADHD, but not with ADHD, compared to controls. CONCLUSION: These results suggest that similar to cannabis use, SC use has also negative effects on brain morphology and comorbidity of ADHD and substance dependence may show different cortical thickness and subcortical volume alterations than substance use alone.

Rich club and reward network connectivity as endophenotypes for alcohol dependence: a diffusion tensor imaging study.

We aimed to examine the whole-brain white matter connectivity and local topology of reward system nodes in patients with alcohol use disorder (AUD) and unaffected siblings, relative to healthy comparison individuals. Diffusion-weighted magnetic resonance imaging scans were acquired from 18 patients with AUD, 15 unaffected siblings of AUD patients and 15 healthy controls. Structural networks were examined using network-based statistic and connectomic analysis. Connectomic analysis showed a significant ordered difference in normalized rich club organization (AUD < Siblings < Controls). We also found rank ordered differences (Control > Sibling > AUD) for both nodal clustering coefficient and nodal local efficiency in reward system nodes, particularly left caudate, right putamen and left hippocampus. Network-based statistic analyses showed that AUD group had significantly weaker connectivity than controls in the right hemisphere, mostly in the edges connecting putamen and hippocampus with other brain regions. Our results suggest that reward system network abnormalities, especially in subcortical structures, and impairments in rich-club organization might be related to the familial predisposition for AUD.

The comparison of risky and ambiguity decision making and cool executive functions between patients with obsessive compulsive disorder and healthy controls

Abstract Background: Executive functioning has been evaluated in obsessive compulsive disorder (OCD). Cool and hot executive functioning discrimination provided a different way of conceptualising executive functions. Objectives: The aim of this study was to compare ambiguity and risky decision-making and cool executive functions in an OCD and a healthy control group. The relationship between decision-making and cool executive functioning was investigated. Methods: Sixty-two OCD patients and 48 healthy control participants were compared. Decision-making was measured using the Iowa Gambling Task. The cool executive functioning was assessed using the Stroop Test and the Wisconsin Card Sorting Task (WCST). Results: The OCD group completed the WCST and the Stroop Test statistically significantly with a lower score than that of the control group. The OCD group had impaired response inhibition and set-shifting that indicate impaired cool executive functioning. In contrast to a lack of a statistically significant difference, the risky decision-making performance was worse in the OCD group than in the healthy control group and in the unmedicated OCD patients than in the medicated OCD patients. Discussion: The OCD patients had a poorer performance in risky decision-making and cool executive functioning. There was a link between risky decision-making performance and impaired cool executive functions.

Longitudinal assessment of gray matter volumes and white matter integrity in patients with medication-overuse headache.

Background Medication-overuse headache is a common clinical entity, but neuroimaging studies investigating volumetric and microstructural alterations of the brain in medication-overuse headache are rare. Therefore, in the current longitidunal study we evaluated gray matter volume and white matter integrity in patients with medication-overuse headache before and after drug withdrawal. Methods A prospective study evaluated 27 patients with medication-overuse headache and 27 age-, sex-, and education-matched healthy adults. High-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging were obtained from the control group and medication-overuse headache patients before and six months after drug withdrawal. Tract-based spatial statistics of multiple diffusivity indices and voxel-based morphometry were employed to investigate white and gray matter abnormalities. Results No correlation was found between age, gender, education and smoking status in both groups. The most commonly overused medications were simple analgesics (96.3%) and combined analgesics (3.7%). The mean duration of the history of medication overuse and headaches was 56.7 ± 63.5 months. White matter diffusional and gray matter morphological alterations including volume, fractional anisotropy, radial diffusivity, and axial diffusivity analyses showed no significant relationship in the patients before and six months after withdrawal of analgesics. Also no difference was observed between the patients versus controls. Conclusion Our data demonstrated no structural alterations within the brain in medication-overuse headache.

Impulsivity, Sensation Seeking, and Decision-Making in Long-Term Abstinent Cannabis Dependent Patients.

INTRODUCTION: In contrast to several studies that examined different domains of neurocognitive functions in long-term abstinent cannabis users, there are few studies examined impulsivity in cannabis users with prolonged abstinence. The aim of this study was to test whether impulsivity and sensation seeking traits and impulsive decision-making are transient or enduring in patients with cannabis dependence who were abstinent for at least 1 month. METHODS: The study included 30 patients with cannabis dependence (CDP) who had been abstinent for at least 1 month and 30 healthy controls. All the participants were male and the two groups were matched for age and duration of education. RESULTS: As a result of Iowa Gambling Task (IGT) evaluation, there was no significant group (CDP vs. control) by block interaction in IGT performance (p=0.680). CDP showed significantly higher Barratt Impulsiveness Scale-11 (BIS-11) total (p=0.006), BIS-11 non-planning (p=0.006) and Zuckerman Sensation Seeking Scale experience seeking subscale (p=0.001) scores compared with controls. CONCLUSIONS: This is the first study to investigate decision-making, self-report impulsivity and sensation seeking in long-term abstinent CDP. Our findings suggest that both self-report impulsivity and experience seeking may reflect a stable trait in CDP but not deficits on decision-making. This suggestion is consistent with the hypothesis that elevated impulsivity and sensation seeking traits may lead to addiction when they occur together rather than alone.

Empathy, and its relationship with cognitive and emotional functions in alcohol dependency.

BACKGROUND: Empathy can be defined as the ability to understand the other's thoughts and feelings. It contains both cognitive and emotional components. AIMS: The aim of this study was to investigate the empathy ability of patients with alcohol dependency in association with cognitive and emotional functions, after acute detoxification and during long-term abstinence. METHODS: Thirty-three alcohol dependent inpatients that completed a detoxification process and stayed abstinent throughout the study, and 33 healthy comparison subjects that matched the patients for age, gender, and education level were included in the study. All the participants were administered the Facial Emotion Identification Test (FEIT), Facial Emotion Discrimination Test (FEDT), Trail Making Test (TMT), Digit Span Test (DST), Auditory Consonant Trigram Test (ACT), and Empathy Quotient Scale (EQS). All the tests were repeated after 3 months of abstinence. RESULTS: At the first evaluation conducted after detoxification, patients performed significantly worse than healthy comparisons in almost all tests. At the second evaluation, which was conducted after 3 months of abstinence, the patients improved significantly in all measures, and no significant differences were detected between the patient and comparison groups. There were significant correlations between the test scores and EQS score. CONCLUSIONS: Alcohol dependency has deleterious effects on empathy ability, and cognitive and emotional functions. Those impairments can improve with abstinence. Empathy ability has strong relationships with cognitive and emotional functions.