Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. (2015)

tDCS is showing promise: “…improved such that [schizophrenia] patients were indistinguishable from healthy control subjects”…

Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. (2015)

Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.

“The ability to exert control over our behavior is fundamental to human cognition, and is impaired in many neuropsychiatric disorders. Here, we show evidence for the neural mechanisms of adaptive control that distinguish healthy people from people who have schizophrenia. We found that the noninvasive electrical stimulation phase aligns low-frequency brain rhythms and enhances functional connectivity. This brain stimulation modulated the temporal structure of low-frequency oscillations and synchrony, improving adaptive control. Moreover, we found that causal changes in the low-frequency oscillations improved behavioral responses to errors and long-range connectivity at the single-trial level. These results implicate theories of executive control and cortical dysconnectivity, and point to the possible development of nonpharmacological treatment alternatives for neuropsychiatric conditions.”

“The present study has important implications for translating these findings from the laboratory into the real world. The treatment of cognitive deficits has traditionally been the domain of pharmacology; however, there are several encouraging signs that transcranial electrical stimulation may offer a safe alternative or adjunct approach. For patients with schizophrenia, atypical antipsychotic drugs (e.g., clozapine, risperidone, olanzapine) can ameliorate some aspects of cognitive deficits. However, there are adverse side effects, such as obesity and diabetes, and some patients develop resistance. Therefore, there is a dire need for effective and noninvasive treatment options without the side effects. Over the past decade, tDCS has come into the spotlight, showing some promise as a drug-free intervention for neuropsychiatric illnesses, such as schizophrenia. Compelling rationales for using tDCS in schizophrenia include the fact that NMDA receptor dysfunction is implicated in schizophrenia pathophysiology and NMDA antagonists abolish tDCS effects, whereas NMDA agonists enhance tDCS effects. Second, schizophrenia is associated with deficits in neuroplasticity, specifically brain-derived neurotropic factor (BDNF)-dependent synaptic plasticity, and research has shown that dc stimulation promotes BDNF-dependent plasticity. Third, compared with other noninvasive stimulation methods, such as transcranial magnetic stimulation (TMS), tDCS is cost-effective, easy to use, portable, and safe, making this technique an attractive candidate as a supplementary neurointervention for people with severe neuropsychiatric conditions such as schizophrenia, which places a heavy personal and societal burden, reportedly costing more than $62.7 billion per year in the United States.”

“In summary, our findings demonstrate that the posterror slowing deficit of adaptive control in schizophrenia is governed, in part, by dysfunctional processes indexed by theta-band phase dynamics, which are abnormally decoupled from frontolateral oscillations important for the implementation of cognitive control. However, by stimulating medial-frontal cortex, considered by many to represent a fulcrum for the action-monitoring network, we were able to improve the behavioral and neural signatures of adaptive control in schizophrenia temporarily.”

See also:

Transcranial direct current stimulation as a treatment for auditory hallucinations. (2015)

The effect of transcranial Direct Current Stimulation on gamma activity and working memory in schizophrenia

Stimulating the aberrant brain: Evidence for increased cortical hyperexcitability from a transcranial direct current stimulation (tDCS) study of individuals predisposed to anomalous perceptions

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3 thoughts on “Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. (2015)

  1. The processing of an appropriate control group wasn’t clear to me from reading the supplementary material. The subject patients were diagnosed with schizophrenia and took psychoactive medication which the researchers equated to chlorpromazine dosages. The control group subjects had neither the condition nor were prescribed the medications.

    How did the researchers differentiate the influences of psychoactive medications on the experimental results from those of the subject patients’ conditions? Were there were some numerical calculations not shown in the supplementary material? To be sure that the zapping was effective for the subject patients’ conditions, though, wouldn’t the control group subjects need to take the same medications so that the experimental data reflected only the schizophrenia differences?

    The researchers also asserted that “..causal changes in the low-frequency oscillations improved behavioral responses to errors and long-range connectivity at the single-trial level.” In my opinion, brain waves can’t be termed causes. Other studies have clearly established that brain waves are effects of underlying causes. Was there something that stopped the researchers of this study from investigating the underlying causes?

    http://surfaceyourrealself.com/2015/07/16/what-is-an-appropriate-experimental-control-group-surfaceyourrealself/

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  2. Thanks for your comments. Scrutinising articles isn’t my forte and I’m not an expert in this area so I appreciate your thoughts. To me, ‘…outpatients with schizophrenia and demographically matched healthy controls’ is a reasonable start for this type of study. There may be a better control group but as I see it, attempting to normalise a deficit induced by schizophrenia using patients (with deficits in adaptive control) relative to healthy people is a vital step forward.

    How did the researchers differentiate the influences of psychoactive medications on the experimental results from those of the subject patients’ conditions? Were there were some numerical calculations not shown in the supplementary material? To be sure that the zapping was effective for the subject patients’ conditions, though, wouldn’t the control group subjects need to take the same medications so that the experimental data reflected only the schizophrenia differences?

    The authors do cover part of this:

    “…it is unlikely that medication of the patients with schizophrenia can explain the results. Atypical antipsychotics have been shown to produce modest but significant benefits for cognitive deficits in schizophrenia. Given our within-subjects design, any medication effects would apply equally across stimulation conditions. However, we observed significant neural and behavioral effects following active tDCS relative to sham in patients with schizophrenia, and we found no significant subject-wise correlations between the medication dose (i.e., chlorpromazine dose equivalent) and the primary outcome measures (r17 < 0.323, P > 0.191 across all measures). Thus, it is unlikely that the effects we observed are simply due to the presence of antipsychotic medication. However, further work is needed to better determine the specific effects of antipsychotic medications on posterror behavioral adjustments.”

    On potential differences related to the particular medication used, see here

    Clearly, administering antipsychotics to healthy controls would further complicate results, likely inducing deficits in healthy populations, rather than more accurately reflecting only ‘schizophrenia differences’:

    “Only a few reports describe effects of antipsychotic drugs on cognition in healthy subjects. Decreased cognitive performance related to attention, response time and information processing have been reported for subjects given up to five doses of the typical antipsychotic drug haloperidol (Ramaekers et al., 1999; Saeedi et al., 2006; Vernaleken et al., 2006). Studies of atypical antipsychotics have shown impairments (Ramaekers et al., 1999; Morrens et al., 2007; amisulpride and olanzapine, respectively), no effect (Chung et al., 2012; aripiprazole) or improvement (Chung et al., 2012; amisulpride) on cognitive functioning.” [1]

    The full text does state the following:

    “Although these findings are consistent with the hypothesis that impaired medial-frontal theta activity explains the adaptive control deficits in schizophrenia, these findings are correlational in nature. We next sought to provide the first test of this hypothesis in the human brain to elucidate the potential causal mechanism…”

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    • Thanks, Nick!

      As you said, giving the same psychoactive medication to the control group subjects would likely cause cognitive deficits in healthy people. So it’s just fun with numbers that the researchers stated “..it is unlikely that the effects we observed are simply due to the presence of antipsychotic medication” in my view.

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