In methamphetamine users, the choice for methamphetamine images was comparable to neutral images; in controls, it was comparable to unpleasant images. Thus, methamphetamine users chose to view more drug-related images than controls on the probabilistic task with a similar trend on the explicit task that requires verification in future studies; see the Supplementary Information.
Although at first blush it may seem unexpected or problematic that the methamphetamine images appeared to be of modest value to methamphetamine users, our prior work in cocaine use disorder has similarly revealed high ambivalence about choosing drug-related images Moeller et al, In this way, it becomes less likely that drugs and related cues are chosen for lack of other, more attractive options Ahmed, Of greater importance, methamphetamine users exhibited a consistent pattern of correlations between choice and BP ND on both tasks: the more that methamphetamine choice exceeded pleasant choice—or, alternatively, the closer methamphetamine choice came to exceeding pleasant choice—the lower was the D2-type BP ND in the lateral OFC.
A potential contribution of lateral OFC to drug-related choice behavior is not unexpected, given that this extended region contributes to multiple functions relevant to choice behavior and decision-making. Studies have also implicated the PFC including the OFC in modulating risky decision-making, and such modulation of PFC activation in turn has been correlated with D2-type receptor availability in striatum Kohno et al, ; methamphetamine users, who had striatal D2-type receptor deficits, did not exhibit significant modulation of PFC activation by risk Kohno et al, More recently, theory and evidence point to the OFC as constructing a latent or abstract representation about the task environment Schuck et al, , perhaps encoding the moment-to-moment value of task-relevant stimuli, choices, or actions based on current internal states Rudebeck and Murray, This study also had several unexpected or null findings.
First, it was somewhat surprising that we did not find BP ND correlations in ventral or dorsal striatal regions, which a priori were main regions of interest.
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However, we note that the lack of a specific association in methamphetamine users between drug-related choice and striatal D2-type BP ND is consistent with an earlier study that examined choice for real cocaine administration over receiving an alternative reinforcer merchandise voucher Martinez et al, Future studies could explore the possibility of differential connectivity between striatal and OFC regions. One hypothesis is that drug-biased choice could result from the interplay of drug-associated abnormalities in striatal reward circuitry and respective abnormalities in OFC functioning London et al, ; Volkow and Fowler, Second, a previous study reported that striatal D1-type BP ND negatively correlated with the choice for real cocaine over merchandise vouchers Martinez et al, , whereas we did not find correlations between striatal D1-type BP ND and drug-related choice.
Rather, differences between the studies could involve the potential neurotoxicity of the two drugs Schmitt and Reith, , or recency of drug use, which may have affected choice in addition to the receptors assayed. In the prior cocaine studies, PET scans were performed following 14 days of abstinence, and the cocaine self-administration sessions were performed 2—3 days after [ 11 C]raclopride or [ 11 C]NNC PET scans.
In contrast, methamphetamine users studied here were more recently abstinent 4—7 days. Differences between hypothetical and real rewards could also be an influencing factor Camerer and Mobbs, For these reasons, and in conjunction with non-human animal studies showing that decision-making eg, during risk is modulated by both D1-type Stopper et al, and D2-type receptors Simon et al, ; Zalocusky et al, , additional work is required to dissect the common and distinct roles of D1- vs D2-type receptors in drug-relevant decision-making in methamphetamine dependence.
Nevertheless, our findings that correlations emerged between drug-choice and BP ND for D2-type receptors is largely consistent with available evidence specifying an important role of D2-type receptors in the pathophysiology of stimulant addiction Ashok et al, ; London et al, —although it should be noted that prior studies have concentrated on D2 receptors in striatal regions. Furthermore, insofar as our drug-choice tasks are associated with OFC D2-type dopamine receptor availability and with methamphetamine craving, future studies can test the validity of these tasks in potentially interrogating OFC functioning in clinical contexts.
Indeed, task associations with clinical outcomes previously have been observed in cocaine addiction Moeller et al, a , and deficient dopamine neurotransmission—albeit again in striatal regions—has predicted poorer treatment outcomes in cocaine and methamphetamine addiction Martinez et al, ; Wang et al, Limitations of this study include the following.
First, the relatively small sample size limits statistical power, particularly in the D1-type BP ND analyses. Second, we acknowledge some inconsistency in behavior on the two choice tasks ie, significant interaction for the probabilistic task as expected, but not for the explicit task. The lack of interaction for the explicit task may be partially attributable to the button pressing demands of the task.
Although we controlled for the total number of presses, the variability in pressing was high. Third, there was a time gap between the choice tasks and D1-type but not D2-type assessments, although this choice-D1 time gap did not correlate with our main dependent variables and so is unlikely to have influenced these null results.
Fourth, the ligands used in the present study have imperfect selectivity. In conclusion, D2-type, but not D1-type, receptor availability in the lateral OFC was correlated with, and possibly underlies, the choice to view drug-related images over affectively pleasant images in chronic methamphetamine users.
By providing support for cortical involvement, these findings refine our understanding of a central research question in addiction concerning how dopamine deficits contribute to drug-biased decision-making. Results also support the important idea that a greater preference for drug rewards in the presence of similarly attractive non-drug rewards provides important markers of addiction severity and extent of underlying neurobiological abnormalities Goldstein and Volkow, The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The authors declare no conflict of interest. Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC in humans: validation and reproducibility. J Cereb Blood Flow Metab 20 : — Ahmed SH Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction.
Sonata No. 4 Hob.VI:D2 Sheet Music by Franz Joseph Haydn
Neurosci Biobehav Rev 35 : — A fully automatic multimodality image registration algorithm. J Comput Assist Tomogr 19 : — Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: a systematic review and meta-analysis. JAMA Psychiatry 74 : — Int J Neuropsychopharmacol 18 : pyu Neuroimage 76 : — Pleasure systems in the brain.
Neuron 86 : — Camerer C, Mobbs D Differences in behavior and brain activity during hypothetical and real choices. Trends Cogn Sci 21 : 46— Mol Imag Biol 9 : — Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci 12 : — Effect of experimental analogs of contingency management treatment on cocaine seeking behavior. Drug Alcohol Depend : — J Nuclear Mede 39 : — Hogarth L, Chase HW Parallel goal-directed and habitual control of human drug-seeking: implications for dependence vulnerability.
Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17 : — Jenkinson M, Smith S A global optimisation method for robust affine registration of brain images. Med Image Anal 5 : — Cereb Cortex 25 : — Risky decision making, prefrontal cortex, and mesocorticolimbic functional connectivity in methamphetamine dependence. JAMA Psychiatry 71 : — Simplified reference tissue model for PET receptor studies. Neuroimage 4 : — Technical Report A J Neurosci 29 : — Orbitofrontal cortex and human drug abuse: functional imaging.
Cereb Cortex 10 : — Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging. Brain Res : — Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior. Neuropsychopharmacology 29 : — Nevertheless Stein introduces a degree of tempo and dynamic arching from E17 and E, like Monod creating the sense that each section thaws a little as it continues; more puzzlingly, he also abbreviates E19, creating the kind of apparently arbitrary nuance familiar from Stadlen's recording, and does the same at the corresponding point of A2 E And there are conventional rallentandi at the end of A1 and A2.
Stein takes the B section substantially slower than Monod 31 as against 36 , so he faces more pressing problems of coherence.
String Duo in B-flat major, Hob.VI:3 (Haydn, Joseph)
He too decelerates as he approaches the terminal dyads of each of the groups, though unlike Monod, to whose handling of these dyads I shall return, Stein gives them all equal weight: this parses the groups clearly enough but offers little interpretation of the relationships between them. Once more like Monod, he creates the sense that E91— is a single group with an interruption at E From E91 to E the only significant inflection is the prolongation of E99, coinciding, as it happens, with Webern's annotation of Stadlen's score; this is one case where the apparent mobility indicated by the tempo graph does not translate into listening experience — probably through lack of coordination with other parameters such as dynamics and articulation — and at this tempo the demisemiquavers acquire a chugging quality they do not have in Monod's recording.
Finally, like Monod, Stein embraces E— within a sustained rallentando, with a caesura before the A2 section that is much more modest than Stadlen's gargantuan silence at this point but still unmistakably rhetorical. Literalism, then, is relative. But it is less through its inherent properties than through its background that Stein's recording adds to the emerging picture of Op.
But while Stein did not study with Webern, he was studying with Webern's teacher at the very time when Op.
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This provides a further perspective from which to approach his recording though we must remember that it was by that time eleven years old. In a chapter on Webern's Piano Variations, Stein , p.
But he provides little guidance on how exactly this is to be done. You only have to compare Stadlen's and Stein's recordings of Op. Perhaps unsurprisingly, then, there is at times a disconnect between what Stein says and what he does, between his explicit and tacit knowledge.
This is E53—56, which, as we saw, Webern parsed — implicitly in his original score, and explicitly in Stadlen's — as the first four notes of a group that terminates with E Stein's parsing reflects a mathematical conception that is expressed through visual symmetry, whereas Webern's is based on a more traditional sense of motion towards a cadential point. And the point is that, in his recording, Stein plays it Webern's way. I imagine he did the same when he played Op. What is most revealing about Stein's thesis, however, is the evidence it provides that — more than a decade after his recording — he was still thinking of Op.
He divides movements into sections, periods, phrases and groups, which he relates to the forms and processes of Classical music, in much the same way as Leibowitz or — more particularly — the composer, theorist and Webern pupil Leopold Spinner, whose very traditional analytical contribution to the Webern issue of Die Reihe rubs shoulders awkwardly with the articles by Boulez, Stockhausen and Pousseur. And in this way, the most ostensibly literal of all recordings of Op.
Jacobs's recording might be seen as the first clear sign of a crossing over between the hitherto distinct styles initiated in the recorded repertoire by Stadlen and Monod. The element of crossing over comes in the tempos of the A sections, which at respective averages of 29 and 25 are close to Stadlen's 28 and Jacobs's performance of the B section resembles Monod's — which I imagine he listened to — not only in its tempo and overall shaping but also in a telltale detail: the handling of the terminal dyads of the paired groups, at E52 and E57, E67 and E72, and E85 and E We have seen that, in his coaching sessions with Stadlen, Webern clarified the parsing — with the dyads terminating each group — and that Stein also played the music this way, even though the diagram in his thesis parsed it differently.
But parsing is not all that is at issue. Stein expresses the parsing by prolonging the terminal dyads: as I said, his playing is clear, but the groups remain disconnected. Monod, by contrast, has a more subtle approach. He consistently prolongs the note that precedes each dyad but shortens the dyad itself: this makes the parsing equally clear but means that each group presses on into the next. Jacobs's strategy is identical to Monod's, and the effect is that much more articulate at his slightly slower tempo.
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As for Loriod's recording, it is in some ways a compendium of Darmstadt pianism. And on Sonic Visualiser the tempo and dynamic profiles of the B section exhibit the familiar arching for each group from E46 to E90, the same sustained tempo from E91 to relieved by the piano passages from E— and E—, the same slight tearing off at E and the same decelerando and diminuendo to the section break after E But all this is thrown into the shade by the clipped articulation, lack of pedal and aggressively dry recording acoustic that perhaps led Borio , p.
At the beginning of both A1 and A2 Loriod consistently plays the third and fourth pitches of each group staccato, breaking up the residual sense of more or less legato melody that is present in almost all the other recordings I have discussed: in doing this she is of course disregarding Webern's slurs.
The lack of flow is enhanced by the fact that — like Stein rather than Monod or Jacobs — she prolongs the terminal dyads rather than the notes preceding them. In short, Loriod intensifies the effect of literalism that Mathew complained of in Monod, and like Monod she achieves it through deviating from literal execution. For Hill and others, the dry, apparently disengaged pointillism of Loriod's recording makes it the paradigm of Darmstadt pianism.
The odd thing about this is the date, given on the record label as May This, after all, is long after the moment of what Bailey , p. If the term is not clearly focused in terms of time, it is hardly more so in terms of place. Darmstadt is in central Germany, but, as the international nature of the Ferienkurse might lead one to expect, recordings of Op. The one recording actually made in Darmstadt was Stadlen's — of all the recordings the most conspicuously opposed to Darmstadt pianism — while of the three recordings from the s that are most often associated with it Monod, Stein and Jacobs , one was made by a French pianist in America, one by an American pianist in America, and one by an American pianist in France.
A fourth, made for radio in Canada and probably dating from , 21 21Nancy Canning's Gould discography places it in , apparently based on examination of the Canadian Broadcasting Corporation archives, but the 1 January date looks like a placeholder Canning , pp. The date is taken from Bazzana , p. And though Gould could always have heard Monod's recording, there are no particularly compelling links for example, his treatment of the telltale dyads in the B section is not like Monod's.
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And this pattern of geographical dispersal continued. It is remarkable that Germany comes in with just two: Franzpeter Goebels , whose playing carries echoes of Stadlen's, and Christian Zacharias All this means that, if the idea of Darmstadt pianism is to stand for anything, it must be a way of playing or the aesthetic ideology that informed it. Some common features among the recordings of Monod, Stein, Jacob and Loriod can be identified, most of which are also found in Gould's. Tempos tend to be fast though that is not true of Stein's performance of the B section, or Jacobs's of the A sections, while the fastest come from Gould — especially the live recording he made in at the Moscow Conservatory.
There is a general quality of understatement, though even at its most extreme it does not preclude traditional rhetorical features such as caesurae or tempo modification, particularly in the B section: the effect ranges from the cool expressivity of Jacobs's performance to the alienating dryness of Loriod's.
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It may be more productive, then, to identify key features of the Darmstadt aesthetic and map them onto the recordings. In her book Serial Music, Serial Aesthetics , Grant locates a fundamental characteristic of Darmstadt serialism in the swerve away from thematicism that is exemplified by Klammer who, as we saw, complained about the vestiges of thematic thinking in Webern and Boucourechliev who insisted that his music was free from any such taint.
An early advocate was Leibowitz , p. This idea was taken up by Eimert, Boulez and Pousseur, thus becoming part of Darmstadt orthodoxy. And on this basis Grant , p.
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It is only Loriod's recording to which this applies, however, and as I have said, such effects — created primarily by articulation — run alongside a quite traditional concern for parsing, pacing, the balancing of elements and the creation of direction. It is however the series of live recordings made by Gould between the s and the s that best illustrates these concerns and strategies in action.
In the article I have already mentioned, I trace the stages through which his interpretation developed by focusing on the telltale dyads in the B section. In Gould played them like Stein, parsing the groups but offering no interpretation of the relationships between them.