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Cocaine addiction is characterized by overwhelming craving for the substance, which drives its escalating use despite adverse consequences. Animal models suggest a disrupted glutamate homeostasis in the nucleus accumbens to underlie addiction-like behavior. After chronic administration of cocaine, rodents show decreased levels of accumbal glutamate, whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, due to technical obstacles, the role of disturbed glutamate homeostasis for cocaine addiction in humans remains only partially understood, and accordingly, no approved pharmacotherapy exists. Here, we applied a tailored proton magnetic resonance spectroscopy protocol that allows glutamate quantification within the human nucleus accumbens. We found significantly reduced basal glutamate concentrations in the nucleus accumbens in cocaine-addicted (N= 26) compared with healthy individuals (N= 30), and increased glutamate levels during cue-induced craving in cocaine-addicted individuals compared with baseline. These glutamatergic alterations, however, could not be significantly modulated by a short-term challenge of N-acetylcysteine (2400 mg/day on 2 days). Taken together, our findings reveal a disturbed accumbal glutamate homeostasis as a key neurometabolic feature of cocaine addiction also in humans. Therefore, we suggest the glutamatergic system as a promising target for the development of novel pharmacotherapies, and in addition, as a potential biomarker for a personalized medicine approach in addiction.

Although the beneficial effects of opioid substitution for the reduction of heroin use are well established, its effect on other substance use is unclear. We aimed to evaluate short-term and long-term changes in substance use in opioid-dependent patients on opioid substitution therapy. We focused on frequent use of heroin, cocaine, benzodiazepines, and alcohol under naturalistic conditions (ie, with non-selected patients and clinical practice as usual) over 17 years.

Natural and behaviorally relevant sounds are characterized by temporal modulations of their waveforms, which carry important cues for sound segmentation and communication. Still, there is little consensus as to how this temporal information is represented in auditory cortex. Here, by using functional magnetic resonance imaging (fMRI) optimized for studying the auditory system, we report the existence of a topographically ordered spatial representation of temporal sound modulation rates in human auditory cortex. We found a topographically organized sensitivity within auditory cortex to sounds with varying modulation rates, with enhanced responses to lower modulation rates (2 and 4 Hz) on lateral parts of Heschl's gyrus (HG) and faster modulation rates (16 and 32 Hz) on medial HG. The representation of temporal modulation rates was distinct from the representation of sound frequencies (tonotopy) that was orientated roughly orthogonal. Moreover, the combination of probabilistic anatomical maps with a previously proposed functional delineation of auditory fields revealed that the distinct maps of temporal and spectral sound features both prevail within two presumed primary auditory fields hA1 and hR. Our results reveal a topographically ordered representation of temporal sound cues in human primary auditory cortex that is complementary to maps of spectral cues. They thereby enhance our understanding of the functional parcellation and organization of auditory cortical processing.