Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial

Author(s):  
Krishna T. Patel ◽  
Michael C. Stevens ◽  
Amanda Dunlap ◽  
Alana Gallagher ◽  
Stephanie S. O’Malley ◽  
...  
2021 ◽  
Vol 89 (9) ◽  
pp. S303-S304
Author(s):  
Jack Kaufman ◽  
Joseph Kim ◽  
Anna Bradford ◽  
Jacob Germain ◽  
Victor Patron ◽  
...  

NeuroImage ◽  
2020 ◽  
Vol 207 ◽  
pp. 116368 ◽  
Author(s):  
Isha Dhingra ◽  
Sheng Zhang ◽  
Simon Zhornitsky ◽  
Thang M. Le ◽  
Wuyi Wang ◽  
...  

2015 ◽  
Vol 146 ◽  
pp. e151
Author(s):  
Jane Joseph ◽  
X. Zhu ◽  
C. Benca ◽  
G. Baik ◽  
F. Davies ◽  
...  

2016 ◽  
Vol 22 (6) ◽  
pp. 1576-1589 ◽  
Author(s):  
Liam J Nestor ◽  
Anna Murphy ◽  
John McGonigle ◽  
Csaba Orban ◽  
Laurence Reed ◽  
...  

2013 ◽  
Vol 74 (7) ◽  
pp. 529-537 ◽  
Author(s):  
Krishna T. Patel ◽  
Michael C. Stevens ◽  
Shashwath A. Meda ◽  
Christine Muska ◽  
Andre D. Thomas ◽  
...  

2021 ◽  
Author(s):  
◽  
Vera Christine Deppert

Increased intraindividual variability of reaction time is a main cognitive feature of Attention Deficit Hyperactivity Disorder. It is associated with deficits in sustained attention. While traditionally, mean and variance were used to characterize reaction time distributions, the ex-gaussian distributional model allows a more sophisticated analysis of reaction time series. Reaction time distributions are separated in a normal and an exponential component. The present study investigates the impact of incentives on reaction time variability in a sample of adult ADHD patients. ADHD is associated with increased Tau, the output parameter of the ex-gaussian model characterizing the exponential part of the distribution. Tau is linked to “lapses of attention”, which are more frequent in ADHD patients. It is known that tau can be modulated in ADHD Patients. It was therefore postulated that tau would be higher in ADHD Patients in a paradigm where quick answers were required but could be modulated by monetary incentives. In addition, the effect of “delay discounting”, which is more distinct in ADHD patients, on reaction time variability was investigated. Eventually, the association of variability measures with strength of ADHD symptoms was tested. To this end, reaction time distributions of 62 adult ADHD patients and 45 healthy controls from two different reaction time paradigms were analyzed. The monetary incentive delay task, by comprehending a control – and a win condition, allows an investigation of the effect of incentives on reaction times. Subjects had to react as fast as possible by keypress to a stimulus, after a cue signaled a possible monetary reward. During the Delay-Discounting-Task, subjects had to choose between sooner, but smaller, and higher delayed monetary rewards, during which they could use as much time for consideration as desired. Results show that an increased Tau in the control condition of the monetary- incentive-delay-task could be replicated, while a distinct influence of the win condition emerged. Subjects with ADHD showed an improvement of Tau in the win condition even below the level of healthy controls. However, they showed increased variability of the “regular” responses around the mean of the normal component of the distribution, represented by sigma. Moreover, it was indicated by trend a higher reaction time variability in ADHD patients during choices of delayed rewards. Tau was associated the current symptom strength as well as with the strength of ADHD-Symptoms during childhood, assessed by questionnaire. While the present results could have implications for etiological models of the disease, they may also contribute to the development of novel diagnostic methods. In advanced studies, neural correlates of sophisticated measures of reaction time variability should be investigated. Furthermore, they should be associated with genetic risk factors with regard to possible endophenotypes. Possible implications for clinical handling of patients should be explored.


2007 ◽  
Vol 26 (05) ◽  
pp. 381-386
Author(s):  
G. Juckel ◽  
J. Wrase ◽  
J. Gallinat ◽  
A. Heinz ◽  
F. Schlagenhauf

ZusammenfassungEine Störung des dopaminergen Belohnungssystems bei schizophrenen Patienten wurde wiederholt postuliert. Ein solcher Zusammenhang liegt aufgrund der bei schizophrenen Störungen bekannten dopaminergen Dysfunktion und der klinischen Phänomenologie vor allem der Negativsymptomatik nahe. Der Artikel berichtet die Ergebnisse zweier Studien mit funktioneller Magnetresonanztomografie (fMRT), in denen dieser Zusammenhang untersucht wurde. Es wurden zum einen unmedizierte schizophrene Patienten und zum anderen Patienten unter Behandlung mit typischen und atypischen Neuroleptika sowie gesunde Kontrollen mit einem motivationalen Paradigma (Monetary Incentive Delay Task, MID) untersucht. Im Vergleich zu den gesunden Kontrollpersonen zeigten unbehandelte schizophrene Patienten eine signifikant reduzierte Aktivierung des ventralen Striatums inklusive des Nucleus accumbens, einer Kernregion des Belohnungssystems, bei der Antizipation von Gewinn. Je niedriger die individuelle Aktivierung im ventralen Striatum ausfiel, desto höher war die Negativsymptomatik der unbehandelten Patienten. Ähnlich wie bei unbehandelten Patienten zeigten Patienten mit typischer neuroleptischer Medikation keine signifikante Aktivierung des ventralen Striatums und wiederum eine Assoziation mit der Negativsymptomatik, während Patienten mit atypischer neuroleptischer Medikation eine mäßiggradige Aktivierung des ventralen Striatums aufwiesen, die nicht mit der Schwere der Negativsymptomatik korrelierte. Diese Beobachtungen weisen darauf hin, dass sowohl unbehandelte Patienten wie Patienten mit hochgradiger Blockade der Dopaminrezeptoren durch typische Neuroleptika eine Beeinträchtigung des Belohnungssystems aufweisen. Die Erfassung der direkten Interaktion zwischen der Funktion des Belohungssystems und der dopaminergen Neurotransmission ist Gegenstand laufender Studien.


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