A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor Neurochemical Enhancement of Conscious Error Awareness Time-response analysis of the effect of stimulant medication on the learning ability of children referred for hyperactivity. Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain A Randomized Controlled Trial Investigating the Effects of Neurofeedback, Methylphenidate, and Physical Activity on Event-Related Potentials in Children with Attention-Deficit/Hyperactivity Disorder. The specificity of the effects of stimulant medication on classroom learning-related measures of cognitive processing for Attention Deficit Disorder children A randomized, controlled study of behavioral intervention for chemotherapy distress in children with cancer. A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD. Cognitive enhancing effects of modafinil in healthy volunteers Cognitive Functioning During Methadone and Buprenorphine Treatment: Results of a Randomized Clinical Trial Neurofeedback Treatment for Attention-Deficit/Hyperactivity Disorder in Children: A Comparison with Methylphenidate Modafinil, but not escitalopram, improves working memory and sustained attention in long-term, high-dose cocaine users Early markers of cognitive enhancement: developing an implicit measure of cognitive performance Modafinil combined with cognitive training is associated with improved learning in healthy volunteers – A randomised controlled trial Cognitive rehabilitation for early post-surgery inpatients affected by primary brain tumor: a randomized, controlled trial
Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients . An open-label , r and omized , pilot trial examined both the general and differential efficacy of 4 weeks of methylpheni date ( MPH ) and modafinil ( MOD ) in 24 brain tumor patients . Participants completed cognitive tests and self-report measures of fatigue , sleep disturbance , mood and quality of life at baseline and after 4 weeks . Following stimulant treatment , there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention . Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy . Inconsistent , differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD . There was also evidence of a general beneficial effect on patient-reported measures of fatigue , mood , and quality of life , with no statistically significant differences between treatment arms in these measures over time . The results from this small pilot study should be interpreted with caution , but appear to warrant additional research , in larger study sample s , targeting fatigue , processing speed and executive function , and exploring different doses of stimulants . Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience . Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes ( e.g. , attention deficit hyperactivity disorder , drug addiction ) . These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing , but our underst and ing of the neurochemical drivers of these processes is limited . We conducted a r and omized , double-blind , placebo-controlled , cross-over design of the influence of methylpheni date , atomoxetine , and citalopram on error awareness in 27 healthy participants . The error awareness task , a go/no-go response inhibition paradigm , was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition . A single dose of methylpheni date , but not atomoxetine or citalopram , significantly improved the ability of healthy volunteers to consciously detect performance errors . Furthermore , this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylpheni date condition for errors made with versus without awareness . Our results have implication s for the underst and ing of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors This report introduces a method for obtaining behavioral time-response information for a short-acting psychotropic drug ( methylpheni date [ Ritalin ] ) that is widely used to treat behaviorally hyperactive children . We used a laboratory learning task to document that between one and two hours after the administration of a single dose of methylpheni date , the drug exerts its maximum effect on performance in a learning task in the laboratory . This effect on cognitive performance dissipates within the same day . This rapid and transient effect of methylpheni date makes it possible to classify patients in a single day into those who respond favorably and those who respond adversely to the drug in terms of its effect on cognitive behavior PURPOSE Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness . These are caused both by the effects of the disease and the effects of radiation and chemotherapy . We sought to determine whether methylpheni date treatment would improve these patients ' neurobehavioral functioning despite their expected neurologic deterioration . PATIENTS AND METHODS Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylpheni date .  Ability to function in activities of daily living and magnetic resonance imaging ( MRI ) findings were also documented . Patients were assessed on 10 , 20 , and 30 mg of methylpheni date twice daily . RESULTS Significant improvements in cognitive function were observed on the 10-mg twice-daily dose . Functional improvements included improved gait , increased stamina and motivation to perform activities , and in one case , increased bladder control . Adverse effects were minimal and immediately resolved when treatment was discontinued . There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose . Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects . CONCLUSION This study demonstrated improved patient function in the setting of a progressive neurologic illness . Methylpheni date should be more widely considered as adjuvant brain tumor therapy Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence The indirect catecholamine agonist methylpheni date ( Ritalin ) is the drug treatment of choice in attention deficit/hyperactivity disorder ( AD/HD ) , one of the most common behavioral disorders of childhood ( DSM-IV ) , although symptoms may persist into adulthood . Methylpheni date can enhance cognitive performance in adults and children diagnosed with AD/HD ( Kempton et al. , 1999 ; Riordan et al. , 1999 ) and also in normal human volunteers on tasks sensitive to frontal lobe damage , including aspects of spatial working memory ( SWM ) performance ( Elliott et al. , 1997 ) . The present study investigated changes in regional cerebral blood flow ( rCBF ) induced by methylpheni date during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug . The results show that the methylpheni date -induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex . The beneficial effects of methylpheni date on working memory were greatest in the subjects with lower baseline working memory capacity . This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for underst and ing the treatment of AD/HD OBJECTIVE Electroencephalographic ( EEG ) neurofeedback ( NF ) is considered a nonpharmacological alternative for medication in attention-deficit/hyperactivity disorder ( ADHD ) . Comparisons of the behavioral efficacy of NF and medication have produced inconsistent results . EEG measures can provide insight into treatment mechanisms , but have received little consideration . In this r and omized controlled trial ( RCT ) , effects of NF were compared with methylpheni date ( MPH ) , and physical activity ( PA ) in children with ADHD on event-related potential ( ERP ) indices of response inhibition , which are involved in ADHD psychopathology . METHODS Using a multicenter three way parallel group RCT design , 112 children with a Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) ( American Psychiatric Association 1994 ) diagnosis of ADHD , between 7 and 13 years of age , were initially included .  NF training consisted of 30 sessions of theta/beta training at Cz over a 10 week period . PA training was a semiactive control group , matched in frequency and duration . MPH was titrated using a double-blind placebo controlled procedure in 6 weeks , followed by a stable dose for 4 weeks . ERP measures of response inhibition , N2 and P3 , were available for 81 children at pre- and postintervention ( n = 32 NF , n = 25 MPH , n = 24 PA ) . RESULTS Only the medication group showed a specific increase in P3 amplitude compared with NF ( partial eta-squared [ ηp(2 ) ] = 0.121 ) and PA ( ηp(2 ) = 0.283 ) , which was related to improved response inhibition . Source localization of medication effects on P3 amplitude indicated increased activation primarily in thalamic and striatal nuclei . CONCLUSIONS This is the first study that simultaneously compared NF with stimulant treatment and a semiactive control group . Only stimulant treatment demonstrated specific improvements in brain function related to response inhibition . These results are in line with recent doubts on the efficacy and specificity of NF as treatment for ADHD . CLINICAL TRIALS REGISTRATION Train Your Brain ? Exercise and Neurofeedback Intervention for ADHD , https:// clinical trials.gov/show/NCT01363544 , Ref . No. NCT01363544 There appear to be beneficial effects of stimulant medication on daily classroom measures of cognitive functioning for Attention Deficit Disorder ( ADD ) children , but the specificity and origin of such effects is unclear . Consistent with previous results , 0.3 mg/kg methylpheni date improved ADD children 's  performance on a classroom reading comprehension measure . Using the Posner letting-matching task and four additional measures of phonological processing , we attempted to isolate the effects of methylpheni date to parameter estimates of ( a ) selective attention , ( b ) the basic cognitive process of retrieving name codes from permanent memory , and ( c ) a constant term that represented nonspecific aspects of information processing . Responses to the letter-matching stimuli were faster and more accurate with medication compared to placebo . The improvement in performance was isolated to the parameter estimate that reflected nonspecific aspects of information processing . A lack of medication effect on the other measures of phonological processing supported the Posner task findings in indicating that methylpheni date appears to exert beneficial effects on academic processing through general rather than specific aspects of information processing Fifty-four pediatric cancer patients were studied to determine the relative efficacy of two forms of behavioral intervention for reducing chemotherapy-related distress . Following baseline assessment , subjects were r and omly assigned to receive either hypnosis , non-hypnotic distraction/relaxation , or attention placebo ( control ) during the subsequent identical chemotherapy course . Observational and interview measures of anticipatory and postchemotherapy nausea , vomiting , distress , and functional disruption served as outcome data . Results indicated that treatment condition was the single best predictor of change from baseline to intervention , with children in the hypnosis group reporting the greatest reduction of both anticipatory and postchemotherapy symptoms . The cognitive distraction/relaxation intervention appeared to have a maintenance effect in which symptoms did not get much worse or much better , while children in the control group had symptoms that consistently became worse over time . Emetic potential of the chemotherapy and the prophylactic use of antiemetics each appeared to contribute to the overall severity of symptoms . While the efficacy of hypnosis in the management of chemotherapy distress is supported , the complexities of interacting biologic and psychologic factors are highlighted PURPOSE To evaluate the efficacy of combined methylpheni date and EEG feedback treatment for children with ADHD . METHODS Forty patients with ADHD were r and omly assigned to the combination group ( methylpheni date therapy and EEG feedback training ) or control group ( methylpheni date therapy and non-feedback attention training ) in a 1:1 ratio using the double-blind method . These patients , who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years , had obtained optimal therapeutic effects by titrating the methylpheni date dose prior to the trial . The patients were assessed using multiple parameters at baseline , after 20 treatment sessions , after 40 treatment sessions , and in 6-month follow-up studies . RESULTS Compared to the control group , patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions . CONCLUSION The combination of EEG feedback and methylpheni date treatment is more effective than methylpheni date alone . The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Cognitive impairment in drug-dependent patients receiving methadone ( MMP ) maintenance treatment has been reported previously . We assessed cognitive functioning after at least 14 days of stable substitution treatment with buprenorphine ( BUP ) or MMP and after 8 to 10 weeks . We performed a r and omized , nonblinded clinical trial in 59 drug-dependent patients receiving either BUP or MMP maintenance treatment and healthy normal controls ( n = 24 ) matched for sex , age , and educational level . Thirteen patients dropped out of the study before the second testing was performed  ( BUP , n = 22 ; MMP , n = 24 ) . A neuropsychological test battery was used to measure selective attention , verbal memory , motor/cognitive speed , and cognitive flexibility . In addition , subjective perceived stress was assessed with a question naire . Patients in both treatment groups performed equally well in all of the cognitive domains tested . Both BUP and MMP patients showed significantly improved concentration and executive functions after 8 to 10 weeks of stable substitution treatment . The control group achieved better results than the BUP and MMP groups in most cognitive domains , indicating cognitive impairment in the patients . Perceived stress did not show any significant change after 8 to 10 weeks of treatment , and no major differences were detected between the 3 groups . No effects of perceived stress on cognitive function were found . Our results indicate a cognitive impairment in patients receiving maintenance treatment with BUP  or  MMP  compared with healthy controls . Selective attention improved in both patient groups during treatment . We propose that the improvement of attention may facilitate rehabilitation of drug-dependent patients Clinical trials have suggested that neurofeedback may be efficient in treating attention-deficit/hyperactivity disorder ( ADHD ) . We compared the effects of a 3-month electroencephalographic feedback program providing reinforcement contingent on the production of cortical sensorimotor rhythm ( 12–15 Hz ) and beta1 activity ( 15–18 Hz ) with stimulant medication . Participants were N = 34 children aged 8–12 years , 22 of which were assigned to the neurofeedback group and 12 to the methylpheni date group according to their parents ' preference . Both neurofeedback and methylpheni date were associated with improvements on all subscales of the Test of Variables of Attention , and on the speed and accuracy measures of the d2 Attention Endurance Test . Furthermore , behaviors related to the disorder were rated as significantly reduced in both groups by both teachers and parents on the IOWA-Conners Behavior Rating Scale . These findings suggest that neurofeedback was efficient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment OBJECTIVE The purpose of the present study was to determine the effects of modafinil , escitalopram , and modafinil + escitalopram administration on neurocognition in a sample of long-term , high-dose cocaine users . METHOD Sixty-one cocaine-dependent individuals were r and omly assigned to receive placebo ( n = 14 ) , modafinil , 200 mg , once daily ( n = 16 ) , escitalopram , 20 mg , once daily ( n = 16 ) , or modafinil and escitalopram , once daily ( n = 15 ) , for five days on an inpatient basis . Urin analysis was used to confirm abstinence from cocaine on the day of admission and the next five days . Baseline neurocognitive assessment , which included measures of attention/information processing , episodic memory , and working memory , was conducted immediately after the washout phase and prior to the administration of modafinil . The follow-up assessment was conducted after participants had received modafinil or placebo for five days . RESULTS Repeated- measures , mixed model analysis of variance showed that modafinil administration was associated with significantly improved performance on two measures of working memory span ( mean n-back span , maximum n-back span ) and a trend toward significant improvement on a measure of visual working memory ( visual accuracy ) and two measures of sustained attention , consistency of response time ( Variability ) and reduced impulsivity ( Perseveration ) . Modafinil administration did not modulate performance on measures of information processing speed or episodic memory .  Escitalopram did not modulate performance on measures of cognition , either alone or in combination with modafinil . CONCLUSIONS This study provides initial data showing that , in a sample of long-term , high-dose cocaine users , administration of psychotropic medications , such as modafinil , can improve performance on measures of working memory . Moreover , it confirms the utility of study ing the interactive effects of psychotropic medications to confirm the manner in which the c and i date medications independently and interactively affect neurocognition . These effects are likely relevant in the treatment of cocaine dependence , in which the remediation of impaired working memory may be associated with improved treatment outcomes . This article is part of a Special Issue entitled ' Cognitive Enhancers ' There is intense interest in the development of effective cognitive enhancing drugs which would have therapeutic application across a number of neurological and psychological disorders including dementia , schizophrenia and depression . However , development in this area has been limited by the absence of sensitive biomarkers which can be used to detect and refine therapeutic-like action in phase 1 clinical studies . The aim of the present study was therefore to develop a measure of cognition relevant to the action of c and i date cognitive enhancers which might be sensitive to pharmacological manipulation in healthy volunteers . Healthy volunteers ( n = 34 ) were r and omised to receive a single dose of modafinil ( 100 mg ) or placebo . Five hours post dose , attentional flexibility in learning was assessed using a novel implicit learning task . Volunteers also completed an auditory digit span task and visual analogue scales ( VAS ) . Modafinil increased alertness as measured by the VAS . In the implicit learning task , modafinil enhanced learning rates in terms of both accuracy and reaction time , suggesting an increase in implicit rule learning . These results suggest that the novel learning task should be explored as a biomarker of early cognitive improvement which could be more sensitive than conventional measures Improving cognition in people with neuropsychiatric disorders remains a major clinical target . By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition . In the present study we tested a recently-proposed methodology to combine CT with a ' cognitive-enhancing ' drug to improve cognitive test scores and exp and ed on previous approaches by delivering combination drug and CT , over a long intervention of repeated sessions , and used multiple tasks to reveal the cognitive processes being enhanced . We also aim ed to determine whether gains from this combination approach generalised to untrained tests . In this proof of principle r and omised-controlled trial thirty-three healthy volunteers were r and omised to receive either modafinil or placebo combined with daily cognitive training over two weeks . Volunteers were trained on tasks of new- language learning , working memory and verbal learning following 200 mg modafinil or placebo for ten days . Improvements in trained and untrained tasks were measured . Rate of new- language learning was significantly enhanced with modafinil , and effects were greatest over the first five sessions . Modafinil improved within-day learning rather than between-day retention . No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning . Gains in all tasks were retained post drug-administration , but transfer effects to broad cognitive abilities were not seen . This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients and exerts a deep negative impact on quality of life interfering with familiar , social and career-related activities . To test the effectiveness of early cognitive rehabilitation treatment for in patients affected by primary brain tumors . Out of 109 consecutive patients enrolled in the study , 58 patients were r and omly assigned to a rehabilitation group or to a control group . The rehabilitation consisted of 16 one-hour individual sessions of therapist-guided cognitive training , spread over 4 weeks , combining computer exercises and metacognitive training . Patients in the control group received usual care without cognitive training . All patients were evaluated by means of a comprehensive neuropsychological battery at the admission ( T0 ) and after 4 weeks ( T1 ) . Patients in the rehabilitation group showed a significant improvement of cognitive functions . In particular , the domains that benefited most from the training were visual attention and verbal memory . The control group exhibited only a slightly , not statistically relevant , enhancement of cognitive performances .  Cognitive rehabilitation for neuro-oncological in patients result ed in a significant enhancement of cognitive performances after the training , also providing a foundation for early administration . Future research should be aim ed to clarify the patients ’ characteristics that predict neuropsychological improvement , to identify the most effective elements in rehabilitative programs and to study the effects of treatment extension to everyday life
Based on a systematic review and meta- analysis we show that expectations regarding the effectiveness of these drugs exceed their actual effects , as has been demonstrated in single- or double-blind r and omised controlled trials .
For methylpheni date an improvement of memory was found , but no consistent evidence for other enhancing effects was uncovered .
Modafinil on the other h and , was found to improve attention for well-rested individuals , while maintaining wakefulness , memory and executive functions to a significantly higher degree in sleep deprived individuals than did a placebo .
However , repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation though maintaining wakefulness and possibly even inducing overconfidence in a person 's own cognitive performance
The term neuroenhancement refers to improvement in the cognitive , emotional and motivational functions of healthy individuals through , inter alia , the use of drugs .
Of known interventions , psychopharmacology provides readily available options , such as methylpheni date and modafinil .
Both drugs are presumed to be in widespread use as cognitive enhancers for non-medical reasons .