I retired last July from academics but still have a backlog of publications and data that seem to pop-up now and then in the medical literature. Hopefully, I will complete my bucket list and publish a pending book about brain augmentation with Springer. The same was a joint effort with Ioan Opris, who unfortunately died last year. I have tried to fill the shoes of my friend Ioan and make his last effort come to fruition. I will keep the readers informed of that venture. In the meanwhile, I have worked with ASCOPAS from Costa Rica in translating into Spanish a lot of practical autism related information that I had originally written in English. I hope that this book, Autismo Actualizado, will fill a knowledge gap for the Hispanic speaking community.

My last clinical trial on transcranial magnetic stimulation (TMS) is now available online. It may be the last article that I write as first author for the medical literature. Many of the reader of this blog know of my love for electronics. Doing neuromodulation as part of my medical career has therefore been an exhilarating hobby for me. In this particular article I had the idea of analyzing brainwaves the same way we do in electronic communications. I loved the results and sometimes read and reread the paragraphs trying to relive my euphoria for the findings. The full article is available by clicking this link. At the top of the page you will find a tab for the «full-text available».

Noteworthy points are the following:

In addition to the normal metrics of event-related gamma potentials, our study is the first to quantitate the envelope and settling time of gamma oscillations. Measurements of the ringing decay were significantly different when comparing autistics and neurotypical controls. In autism, baseline levels of gamma oscillations showed a shortened period of ringing decay. Short ringing times implies a system with lower sensitivity (Silver & Tiede-mann, 1978); one that makes synchronization and integration of information among different neuronal networks imprecise or inefficient. The inhibitory deficit evidenced in neuropathological studies of ASD thus translates into a low sensitivity system seemingly overwhelmed by the background level of noise. In a previous study, modeling such a system gave rise to stochastic resonance; a phenomenon where a neural network embedded in a noisy back-ground acquired, counterintuitively, enhanced sensitivity (Casanova et al., 2014). The phenomenon serves to explain the autistic emphasis for sameness (i.e., an adaptation to an optimal noise level) and the sensory peculiarities (hypo- and hypersensitivity) characteristic of the condition.

In modeling the activity of excitable membranes, resonance is achieved by the combined action of inductive and capacitive reactance (Gutfreund et al., 1995). These are intrinsic properties of passive elements within the membrane that serve to oppose the flow of current. The interaction of capacitance and inductance allows the membrane to act as an electrical resonator, one that preferentially oscillates at the circuit’s resonant frequency. In biological systems, a resonant peak in the frequency domain implies a dampened oscillation in the time domain (Gutfreund et al., 1995). Some systems may have multiple, distinct resonance frequencies. The greatest response or amplitude is achieved for the least amount of dampening. Following an excitatory phase, wherein the system is stimulated into resonance, a free ring-ing decay ensues which provides a measure of impedance (Brewer, 2012). For brainwave forms, interneurons provide the resistive element necessary to elicit gamma oscillations. Detailed computational models of cortical circuitry have shown how downregulation of PV cells disinhibit networks and alter gamma oscillations in response to stimulation (Volman et al., 2011). Indeed, optogenetically inhibiting the action of PV cells suppresses gamma oscillations in vivo while activating these interneurons generates gamma oscillations (Sohal et al., 2009). In the end, excitation and inhibition of appropriate power alternate in order to establish the cyclic behavior of brainwave oscillations (Buzsáki & Wang, 2012). During this cyclic behavior excitation and amplification mark the time period to peak amplitude while inhibition characterizes the settling pace of the ensuing decay curve.—In essence we described a biomarker for the level of excitation and for inhibition in the brain that can be used as outcome measure when following patients!
(PDF) Ringing Decay of Gamma Oscillations and Transcranial Magnetic Stimulation Therapy in Autism Spectrum Disorder. Available from: https://www.researchgate.net/publication/351008295_Ringing_Decay_of_Gamma_Oscillations_and_Transcranial_Magnetic_Stimulation_Therapy_in_Autism_Spectrum_Disorder#fullTextFileContent [accessed Apr 22 2021].

The complete abstract of the article reads as follows:

Research suggest that in autism spectrum disorder (ASD) a disturbance in the coordinated interactions of neurons within local networks gives rise to abnormal patterns of brainwave activity in the gamma bandwidth. Low frequency transcranial magnetic stimulation (TMS) over the dorsolateral prefrontal cortex (DLPFC) has been proven to normalize gamma oscillation abnormalities, executive functions, and repetitive behaviors in high functioning ASD individuals. In this study, gamma frequency oscillations in response to a visual classification task (Kanizsa figures) were analyzed and compared in 19 ASD (ADI-R diagnosed, 14.2 ± 3.61 years old, 5 girls) and 19 (14.8 ± 3.67 years old, 5 girls) age/gender matched neurotypical individuals. The ASD group was treated with low frequency TMS (1.0 Hz, 90% motor threshold, 18 weekly sessions) targeting the DLPFC. In autistic subjects, as compared to neurotypicals, significant differences in event-related gamma oscillations were evident in amplitude (higher) pre-TMS. In addition, recordings after TMS treatment in our autistic subjects revealed a significant reduction in the time period to reach peak amplitude and an increase in the decay phase (settling time). The use of a novel metric for gamma oscillations. i.e., envelope analysis, and measurements of its ringing decay allowed us to characterize the impedance of the originating neuronal circuit. The ringing decay or dampening of gamma oscillations is dependent on the inhibitory tone generated by networks of interneurons. The results suggest that the ringing decay of gamma oscillations may provide a biomarker reflective of the excitatory/inhibitory balance of the cortex and a putative outcome measure for interventions in autism.

I am enthused by the reported findings and hope that the medical community pursues the practical aspects of our research. My best regards to all of my collaborators over the years. Loved all of our conjoint efforts and discussions which kept me young at heart. I will always be indebted to all of you.