Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial

McDonald, Brenna C.; Flashman, Laura A.; Arciniegas, David B.; Ferguson, Robert J.; Li, Xing; Harezlak, Jaroslaw; Sprehn, Gwen C.; Hammond, Flora M.; Maerlender, Arthur C.; Kruck, Carrie L.; Gillock, Karen L.; Frey, Kim; Wall, Rachel; Saykin, Andrew J.; McAllister, Thomas W.

doi:10.1038/npp.2016.261

Cited by 44 publications

(24 citation statements)

References 39 publications

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“…Ramasubbu and Goodyear (2008) carried out a study in a cohort of stroke patients which involved periodic fMRI scanning with two cognitive tasks during a 3-day course of MPh administration and they found increases in activation in the patient WM networks. McDonald et al (2016) found that TBI patients who received a dose of MPh in conjunction with a neurocognitive rehabilitation programme demonstrated improvements in several cognitive domains including WM. Future TBI studies designed to have a daily dose of MPh, periodic cognitive testing and serial MRI scans would add to the current knowledge of the longer term neural activation patterns and pharmacological action of MPh.…”

Section: Discussionmentioning

confidence: 99%

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Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate

Manktelow

Menon

Sahakian

et al. 2017

Front. Behav. Neurosci.

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Traumatic brain injury (TBI) often results in cognitive impairments for patients. The aim of this proof of concept study was to establish the nature of abnormalities, in terms of activity and connectivity, in the working memory network of TBI patients and how these relate to compromised behavioral outcomes. Further, this study examined the neural correlates of working memory improvement following the administration of methylphenidate. We report behavioral, functional and structural MRI data from a group of 15 Healthy Controls (HC) and a group of 15 TBI patients, acquired during the execution of the N-back task. The patients were studied on two occasions after the administration of either placebo or 30 mg of methylphenidate. Between group tests revealed a significant difference in performance when HCs were compared to TBI patients on placebo [F(1, 28) = 4.426, p < 0.05, ηp2 = 0.136]. This difference disappeared when the patients took methylphenidate [F(1, 28) = 3.665, p = 0.66]. Patients in the middle range of baseline performance demonstrated the most benefit from methylphenidate. Changes in the TBI patient activation levels in the Left Cerebellum significantly and positively correlated with changes in performance (r = 0.509, df = 13, p = 0.05). Whole-brain connectivity analysis using the Left Cerebellum as a seed revealed widespread negative interactions between the Left Cerebellum and parietal and frontal cortices as well as subcortical areas. Neither the TBI group on methylphenidate nor the HC group demonstrated any significant negative interactions. Our findings indicate that (a) TBI significantly reduces the levels of activation and connectivity strength between key areas of the working memory network and (b) Methylphenidate improves the cognitive outcomes on a working memory task. Therefore, we conclude that methylphenidate may render the working memory network in a TBI group more consistent with that of an intact working memory network.

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Section: Discussionmentioning

confidence: 99%

“…They also found an improvement in RTs for this group but only in the WM task. More recently, improvements in WM, episodic memory and attention were demonstrated in a TBI patient population in a study which combined MPh with a structured metacognitive rehabilitation programme (McDonald et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate

Manktelow

Menon

Sahakian

et al. 2017

Front. Behav. Neurosci.

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“…In the search for novel 'pro-cognitive' agents, one 'known' or reference drug for attention-enhancing effects is the psychostimulant, amphetamine. Acutely, amphetamine and other psychostimulants are known to have positive effects on specific neurocognitive measures in both healthy subjects (HS) and in individuals with a variety of disabling brain conditions including, among others, attention-deficit hyperactivity disorder (Rapoport et al, 1980), SZ (Barch, 2010;Barch and Carter, 2005;Goldberg et al, 1991;Pietrzak et al, 2010), and traumatic brain injury (Kim et al, 2006;McDonald et al, 2017). Interestingly, procognitive effects of amphetamine (20 mg, po) were not detected among a large cohort of adult HS using the MATRICS Consensus Cognitive Battery (MCCB), a gold standard for detecting procognitive drug effects (Nuechterlein et al, 2008); however, subgroups characterized by low baseline MCCB scores, higher age, and specific personality dimensions did exhibit amphetamineassociated gains in MCCB performance (Chou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of Amphetamine on Sensorimotor Gating and Neurocognition in Antipsychotic-Medicated Schizophrenia Patients

Swerdlow

Bhakta

Talledo

et al. 2017

Neuropsychopharmacol.

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Prepulse inhibition (PPI) of startle is being explored both as an indicator of target engagement for, and a biomarker predicting the sensitivity to, procognitive effects of drugs. We now report the effects of the pro-attentional drug, d-amphetamine, on PPI and neurocognition in antipsychotic-medicated schizophrenia patients and healthy subjects (HS) who were also tested in a targeted cognitive training (TCT) module. 44 HS and 38 schizophrenia patients completed a double-blind, placebo-controlled crossover study of the effects of a single dose of amphetamine (10 mg po) on PPI and MATRICS Consensus Cognitive Battery (MCCB) performance; TCT results were previously reported from 60 of these subjects. Moderators predicting AMPH sensitivity were assessed, including the rs4680 single-nucleotide polymorphism for catechol-O-methyltransferase (COMT). After placebo, patients exhibited PPI deficits with 60 ms prepulse intervals; these deficits were 'rescued' by amphetamine. The magnitude of amphetamine-enhanced PPI was greater in patients than in HS (p<0.032), and was associated with positive symptoms (p<0.007), antipsychotic load (p<0.015), hedonic effects of AMPH (p<0.003), and with the presence of at least one methionine allele in rs4680 (p<0.008). No significant effects of amphetamine on MCCB performance were detected in either group, though pro-attentional effects of amphetamine in patients were associated with greater amphetamine-enhanced TCT learning. Amphetamine acutely 'normalized' PPI in antipsychotic-medicated schizophrenia patients; no concurrent acute neurocognitive changes were detected by the MCCB. Findings suggest that in the context of appropriate antipsychotic medication, a low dose of amphetamine enhances brain processes associated with higher function in schizophrenia patients, without accompanying changes in MCCB performance.

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“…PC levels decrease again to normal levels in fly brains after cocaine removal, or after MPH treatment. In addition to ADHD patients, cognitive enhancement following MPH has also been reported for patients with traumatic brain injury as well as depression after stroke (36)(37)(38). Moreover, Goldstein's group showed that the use of a low dose of MPH improved cognitive tasks in cocaine abusers (39).…”

Section: Discussionmentioning

confidence: 95%

Mass Spectrometry Imaging of Cocaine, Drug Removal and Methylphenidate Alter Phospholipids in Drosophila Brain

Philipsen

Phan

Fletcher

et al. 2020

Preprint

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Cocaine dependence displays a broad impairment in cognitive performance including attention, learning and memory. To obtain a better understanding of the action of cocaine in the nervous system, and the relation between phospholipids and memory, we have investigated whether phospholipids recover in the brain following cocaine removal using the fly model, Drosophila. In addition, the effects of methylphenidate, a substitute medication for cocaine dependence, on fly brain lipids after cocaine abuse are also determined to see if it can rescue the lipid changes caused by cocaine. Time of flight secondary ion mass spectrometry with a (CO2)6000+ gas cluster ion beam was used to detect intact phospholipids. We show that cocaine has persistent effects, both increasing and decreasing the levels of specific phosphatidylethanolamines and phosphatidylinositols. These changes remain after cocaine withdrawal and are not rescued by methylphenidate. Cocaine is again shown to generally increase the levels of phosphatidylcholines in the fly brain; however, after drug withdrawal the abundance of these lipids returns to the original level and methylphenidate treatment of the flies following cocaine exposure enhances the reversal of the lipid level reducing them below the original control. The study provides insight into the molecular effects of cocaine and methylphenidate on brain lipids. We suggest that phosphatidylcholine could be a potential target for the treatment of cocaine abuse, as well as be a significant hallmark of cognition and memory loss with cocaine.

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Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial

Cited by 44 publications

References 39 publications

Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate

Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate

Effects of Amphetamine on Sensorimotor Gating and Neurocognition in Antipsychotic-Medicated Schizophrenia Patients

Mass Spectrometry Imaging of Cocaine, Drug Removal and Methylphenidate Alter Phospholipids in Drosophila Brain

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