The role of oscillatory alpha activity (8-13 Hz) in cognitive processing remains an open question. It has been debated whether alpha activity plays a direct role in the neuronal processing required for a given task or whether it reflects idling and/or functional inhibition. Recent electroencephalography (EEG) studies have demonstrated that alpha activity increases parametrically with load during retention in working memory paradigms. While it is known that the parieto-occipital cortex is involved in the generation of the spontaneous alpha oscillations, it remains unknown where the sources of the memory-dependent alpha activity are located. We recorded brain activity using magnetoencephalography (MEG) from human subjects performing a Sternberg memory task where faces were used as stimuli. Spectral analysis revealed a parametric increase in alpha activity with memory load over posterior brain areas. We then applied a source reconstruction technique that allowed us to map the parametric increase in alpha activity to the anatomical magnetic resonance (MR) images of the subject. The primary sources of the memory-dependent alpha activity were in the vicinity of the parieto-occipital sulcus. This region is not directly involved in working memory maintenance of faces. Our findings are consistent with the notion that alpha activity reflects disengagement or inhibition of the visual dorsal stream. We propose that the disengagement reflected in alpha power serves to suppress visual input in order to devote resources to structures responsible for working memory maintenance.

Neuronal oscillations support cognitive processing. Modern views suggest that neuronal oscillations do not only reflect coordinated activity in spatially distributed networks, but also that there is interaction between the oscillations at different frequencies. For example, invasive recordings in animals and humans have found that the amplitude of fast oscillations (>40 Hz) occur non-uniformly within the phase of slower oscillations, forming the so-called cross-frequency coupling (CFC). However, the CFC patterns might be influenced by features in the signal that do not relate to underlying physiological interactions. For example, CFC estimates may be sensitive to spectral correlations due to non-sinusoidal properties of the alpha band wave morphology. To investigate this issue, we performed CFC analysis using experimental and synthetic data. The former consisted in a double-blind magnetoencephalography pharmacological study in which participants received either placebo, 0.5 or 1.5 mg of lorazepam (LZP; GABAergic enhancer) in different experimental sessions. By recording oscillatory brain activity with during rest and working memory (WM), we were able to demonstrate that posterior alpha (8–12 Hz) phase was coupled to beta-low gamma band (20–45 Hz) amplitude envelope during all sessions. Importantly, bicoherence values around the harmonics of the alpha frequency were similar both in magnitude and topographic distribution to the cross-frequency coherence (CFCoh) values observed in the alpha-phase to beta-low gamma coupling. In addition, despite the large CFCoh we found no significant cross-frequency directionality (CFD). Critically, simulations demonstrated that a sizable part of our empirical CFCoh between alpha and beta-low gamma coupling and the lack of CFD could be explained by two-three harmonics aligned in zero phase-lag produced by the physiologically characteristic alpha asymmetry in the amplitude of the peaks relative to the troughs. Furthermore, we showed that periodic signals whose waveform deviate from pure sine waves produce non-zero CFCoh with predictable CFD. Our results reveal the important role of the non-sinusoidal wave morphology on state of the art CFC metrics and we recommend caution with strong physiological interpretations of CFC and suggest basic data quality checks to enhance the mechanistic understanding of CFC.

GABAergic interneurons are strongly implicated in the generation of gamma and alpha oscillations in human occipital cortex where drug-induced power modulations predicted WM performance. Our findings bring us an important step closer to linking neuronal dynamics to behavior by embracing established animal models.

The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with high-functioning-autism and 23 matched controls participated. Participants were presented with two-syllable words embedded in various auditory backgrounds (pink noise, moving ripple, amplitude-modulated pink noise, amplitude-modulated moving ripple) to assess speech-in-noise-reception thresholds. The gain in signal perception of pink noise with temporal dips relative to pink noise without temporal dips was smaller in children with autism (p = 0.008). Thus, the autism group was less able to integrate auditory information present in temporal dips in background sound, supporting the complexity-specific perceptual account.

Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in patients with attention deficit hyperactivity disorder. However, the cognitive-enhancing effects of such 'smart drugs' in the healthy population are still unclear. Here, we investigated effects of methylphenidate (Ritalin, 20  mg) on reward and punishment learning in healthy students (N=19) in a within-subject, double-blind, placebo-controlled cross-over design. Results revealed that methylphenidate effects varied both as a function of task demands and as a function of baseline working memory capacity. Specifically, methylphenidate improved reward vs punishment learning in high-working memory subjects, whereas it impaired reward vs punishment learning in low-working memory subjects. These results contribute to our understanding of individual differences in the cognitive-enhancing effects of methylphenidate in the healthy population. Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research.

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A balance has to be struck between supporting distractor-resistant representations in working memory and allowing those representations to be updated. Catecholamine, particularly dopamine, transmission has been proposed to modulate the balance between the stability and flexibility of working memory representations. However, it is unclear whether drugs that increase catecholamine transmission, such as methylphenidate, optimize this balance in a task-dependent manner or bias the system toward stability at the expense of flexibility (or vice versa). Here we demonstrate, using pharmacological fMRI, that methylphenidate improves the ability to resist distraction (cognitive stability) but impairs the ability to flexibly update items currently held in working memory (cognitive flexibility). These behavioral effects were accompanied by task-general effects in the striatum and opposite and task-specific effects on neural signal in the pFC. This suggests that methylphenidate exerts its cognitive enhancing and impairing effects through acting on the pFC, an effect likely associated with methylphenidate's action on the striatum. These findings highlight that methylphenidate acts as a double-edged sword, improving one cognitive function at the expense of another, while also elucidating the neurocognitive mechanisms underlying these paradoxical effects.

These results open up the possibility to further study the underlying mechanisms of ADHD by examining how differences in the fronto-striatal network might explain different abilities in modulating the alpha band activity.