Always Under Construction
Last modified:  July 2017

CFC:  Cross-Frequency Coupling and Neurofeedback:

I think an important discovery is being overlooked. In 2010, I predicted that a new type of neurofeedback would up- regulate adaptability and insight. I created a specific neurofeedback instrument to train simultaneous ‘ups and downs’ in the amplitudes of 2 different frequency bands (CFC). For starts I investigated CFC primarily of theta, alpha and gamma EEG. Because CFC is an essential component of global broad band synchronization, I called the process TAG Sync. Five years later my same instrument was independently discovered to measure fluid intelligence [1] through CFC of theta and gamma. 
http://50.0.97.81:8040
General References for this page: [1] Pahor A, et al (2014) - Theta–gamma cross-frequency coupling relates to the level of human intelligence. Intelligence 46 (2014) 283-290. [2] Ray S, et al (2015) - Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit hyperactivity disorder - Rich club organization. Hum Brain Mapp. Dec; 35(12): 6032-6048. p. 11. [3] Chapin TJ, et al (2014) - Neurotherapy and Neurofeedback: Brain-Based Treatment for Psychological and Behavioral Problems. Routledge. pp 144. [4] Florin E, et al (2015) - The brain's resting-state activity is shaped by synchronized cross-frequency coupling of neural oscillations. NeuroImage 111, 26-35 [5] Aru J, et al (2015) - Untangling cross-frequency coupling in neuroscience. Current Opinion in Neurobiology, 31:51–61. [6] Ulrich G (2013) – The Theoretical Interpretation of Electroencephalography. BMed. [7] Varela F, et al (2001) - The brainweb - Phase synchronization and large-scale integration. Nature Reviews Neuroscience, Vol 2, April 2001, p229. [8] Karlsson MP, et al (2012) - Network resets in medial prefrontal cortex mark the onset of behavioral uncertainty. Science Vol 338, 5 Oct 2012. [9] Engel AK, et al (2013) - Intrinsic Coupling Modes - Multiscale Interactions in Ongoing Brain Activity. Neuron 80, Nov 20, 867-886. [10] Kaminski J, et al (2011) - Short-term memory capacity (7 ± 2) predicted by theta to gamma cycle length ratio. Neurobiology of Learning and Memory 95; 19-23 [11] Khalid A, et al (2016) - Gamma oscillation in functional brain networks is involved in the spontaneous remission of depressive behavior induced by chronic restraint stress in mice. BMC Neurosci (2016) 17:4.
2010 - Nexus 2012 - Infiniti 2014 - BioExplorer 2010 - Nexus 2012 - Infiniti 2014 - BioExplorer

TAG Sync Cross Frequency Coupling Envelopes Instrument:

Above you can investigate my instrument # 4, the CFC envelopes instrument showing the coupling over time of the amplitudes of rewards 1 and 2 (which are filtered from the sum of EEG channels 1 and 2). This might be a simple case of amplitude-amplitude coupling except for the fact that amplitudes also reflect the synchronous behavior near the electrode(s). The 10-20 sites used in the TAG Sync General Adaptation Protocol (GAP) include the midline (Fz, Pz) and regions of the right and left fronto-parietal networks (F3,P3 and F4,P4). I call this the “DMN/FPN kernal” but the associated cortical hubs also represent the so-called “rich club” [2]. Please examine instrument #4 which simply displays the amplitude envelopes of rewards 1 and 2, e.g., theta and gamma, over a period of around 6 seconds. Now please look at a similar envelopes instrument adapted from Figure 3 of Pahor & Jaušovec 2014  [1].
In the above graph Pahor & Jaušovec 2014 [1] show the correlation (r = 0.51) between theta and gamma envelopes generated when cognitively intact individuals solve a difficult challenge - Ravens progressive matrices. At rest there is little correlation (r = 0.16) and during a simple RAPM the CFC increases to r = 0.33. Note the gray area in the above graph. An identical appearance (sudden large simultaneous increase) was noted to be accompanied by clinically important insight in my first two alpha-theta synchrony (CFC) patients in 2010. Following a number of initially large synchronous alpha and theta neuronal avalanches, the general coupling between theta and alpha increased throughout the recording. This makes sense because of the 1/f power law distribution of neuronal avalanches. Clinicians with whom I shared this information began observing that general increases of CFC under task (i.e., NFB) are associated with increasing intelligence and maturity. This was described in several TAG Sync case studies in a recent Routledge textbook on neurofeedback [3]. Below, I will address some issues regarding my early use of envelopes to promote self-regulation of broad-band synchronization. The Hailing Channel: My earliest 2010 observations included the fact that it was often necessary to find and “open” a narrow communications channel between two hubs. This frequency was often with 1-2 Hz of the frequency in the spectral display showing the highest amplitude in a particular band. This phenomena appears to have been addressed recently by Florin et al 2015 [4]. Further confirmation that CFC NFB may require individualized treatment was stated earlier this year by Aru et al (2015) who state “... adaptive rather than fixed bandwidths might be necessary when scanning the modulating frequency in explorative analyses." They continue, “... if the bandwidth of the higher frequency component (F2) does not include the side peaks produced by the lower frequency (F1), then CFC cannot be detected even if it is present. [5]"

Cross-Frequency Coupling Neurofeedback - Protocol Selection:

You may want to consult some of the literature below as you implement CFC in your neurofeedback protocols. I prefer not to use the word protocol. I regard the technology-assisted exploration of state changes to be personal and dynamic and work best in what I call a brain-computer-brain interface with a skilled operator. Constant attention is paid to the appearance of paroxysmal fast activity, appearance or disappearance of drowsy or dissipated states [6], as well as shifts in the “hailing frequencies” which we learn to adjust in order to promote awake, adaptive and restorative states. My Nexus and Infiniti Screens include HRV, GSR, Temp & EMG biofeedback during sessions. TAG Sync (as a methodology) carries the cross-frequency coupling all the way to delta, to the 0.1 Hz Mayer wave, to the ultra-low frequencies around 0.01 Hz that are shared with resting state networks. TAG Sync techniques may be applicable to all cortical sites, or those known to be dysfunctional or disconnected through clinical investigations. Here are some clinical reports that may be useful in developing an individual plan. Aging/memory loss - Pinal D, et al (2015) - Stuck in Default Mode - Inefficient Cross-Frequency Synchronization May Lead to Age-Related Short-Term Memory Decline Alzheimer’s Disease - Ittner AA, et al (2014) - p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer’s disease. Acta Neuropathologica Communications, 2:149. Arithmetic Task Processing - Palva JM, et al (2005) - Phase synchrony among neuronal oscillations in the human cortex. The Journal of Neuroscience, April 13, 2005, 25(15):3962-3972. [Free Full Text] Autism - Khan S, et al (2013) - Local and long-range functional connectivity is reduced in concert in autism spectrum disorders. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3107-12. Berman JI, et al (2015) - Alpha-to-Gamma Phase- Amplitude Coupling Methods and Application to Autism Spectrum Disorder. Brain Connect. Apr;5(2):80-90. Depression - Khalid A, et al (2016)  This article shows how the EEGs of traumatized mice change as they spontaneously recover from depression. The brain’s natural treatment for depression appears to be re-immersion in complexity/uncertainty accompanied by global broad band synchronization with primary resolution of delta and gamma CFC [SBeh]. See also  Zheng C, et al (2015) - Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex  pathway in depression. Neuroscience. Feb 12. Epilepsy - Guirgis M, et al (2015) - Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients. J Neural Eng. Mar 13;12(2):026011, Intelligence / memory - Pahor A, et al (2014) - Theta–gamma cross-frequency coupling relates to the level of human intelligence 46 (2014) 283-290.  Roux F, et al (2014) - Working memory and neural oscillations - alpha–gamma versus theta–gamma codes for distinct WM information. Trends in Cognitive Sciences, January 2014, Vol 18, No 1. Xu X, et al (2013) - Reduction in LFP cross-frequency coupling between theta and gamma rhythms associated with impaired STP and LTP in a rat model of brain ischemia. Frontiers in Computational Neuroscience, 05 April. Motivation / Emotion - Schutter DJLG, et al (2011) - Cross-frequency coupling of brain oscillations in studying motivation and emotion. Motiv Emot. [Free Full Text] Near Death Experience / Hospice environment - Borjigin J, et al (2013) - Surge of neurophysiological coherence and connectivity in the dying brain. Proc Nat Acad Sci, Aug 14, 2013. [Full Text]. The EEG exhibits CFC of theta, alpha and gamma plus increased efficiency and directed connectivity. Parkinson’s Disease - Swann NC, et al (2015) - Elevated synchrony in Parkinson disease detected with electroencephalography. Ann Neurol. 2015 Aug 20. Herz DM, et al (2014) - Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson's disease. NeuroImage Vol 90, 15 April, Pages 15-23.  Lopez-Azcarate J, et al (2010) - Coupling between Beta and High-Frequency Activity in the Human Subthalamic Nucleus May Be a Pathophysiological Mechanism in Parkinson's Disease. The Journal of Neuroscience, May 12; 30(19):6667– 6677. Obsessive-Compulsive disorder - Velikova S, et al (2010) - Dysfunctional brain circuitry in obsessive-compulsive disorder - Source and coherence analysis of EEG rhythms. Neuroimage 49; 977-983. Reward/Punishment processing - Cohen MX, et al (2009) - Good Vibrations - Cross-frequency Coupling in the Human Nucleus Accumbens during Reward Processing.  J Cogn Neurosci. May;21(5):875-89. Schizophrenia – Allen EA, et al (2011) - Components of Cross-Frequency Modulation in Health and Disease. Frontiers in Systems Neuroscience; 5:59. Sickness Behavior - Khalid A, et al (2016) - This article shows how the EEGs of traumatized mice change as they spontaneously recover from sickness behavior due to chronic restraint stress. The brain’s natural treatment for depression appears to be re-immersion in complexity/uncertainty accompanied by global broad band synchronization with primary resolution of delta and gamma CFC [SBeh]. Social Anxiety Disorder - Miskovic V, et al (2011) - Changes in EEG cross-frequency coupling during cognitive behavioral therapy for social anxiety disorder. Psychological Science: 22;507.  Knyazev GG (2011) - Cross-frequency coupling of brain oscillations - An impact of state anxiety. Int J Psychophysiology. There is excessive CFC between delta and beta at rest, often relieved by CBT and sometimes testosterone. Tinnitus Adamchic I, et al (2014) - Abnormal cross-frequency coupling in the tinnitus network. Frontiers in Neuroscience, Sept 25. Vascular Dementia - Xu X, et al (2015) - Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus  in Vascular Dementia Rats. Brain Topogr. Mar 14.

More on CFC and EEG Biofeedback:

The phrase “cross-frequency coupling” first appears in the pubmed.gov database in 2002. The number of publications each year dealing with CFC is shown below.
In 2010 I became convinced that it would be adaptive to the brain to be able to regulate alpha-theta phase synchrony on demand in order to facilitate “valid cognition” [7]. It was easy to observe that the larger neuronal avalanches were associated with behavioral changes [8]. With increased training and/or clinical improvement the amplitude envelopes of delta, theta, alpha, and gamma became more correlated. The CFC envelopes instrument became an important part of the feedback sessions. Some clients prefer to train on occasion simply by watching the envelopes instrument and learning to couple the cross-frequency amplitude movements. As we discussed, CFC is easily observed in nature, but can be complicated mathematically. Since, at this time, EEG databases do not advise us with normative inter-site CFC values, we must depend upon theory to guide us. Recently there has been discussion of the significance of such an envelopes instrument. For example, Engel et al 2013 state “We discuss evidence for two distinct types of intrinsic coupling modes which seem to reflect the operation of different coupling mechanisms. One type arises from phase coupling of band-limited oscillatory signals, whereas the other results from coupled aperiodic fluctuations of signal envelopes.” “Several recent studies have applied correlation measures to the amplitude or power envelopes of the recorded signals, rather than to the phase of the underlying oscillations (de Pasquale et al., 2010; Brookes et al., 2011, 2012; Hipp et al., 2012). Analysis of such signal envelopes can be used to capture slow fluctuations similar to what is provided by the BOLD imaging (Laufs et al., 2003; Tagliazucchi et al., 2012a). Both the analysis of envelope correlations in electrophysiological signals and of correlated BOLD fluctuations yield what we designate as envelope ICMs.” (ICM - Intrinsic Coupling Mode). Kaminsky et al 2011 describe CFC in memory, “Envelope traces of those theta and gamma activity bands which had the highest correlation.” [10]  A search for cross-frequency coupling and amplitude envelope correlation provides a wealth of discussion, much of it highly mathematical.
Copyright 2010, 2017 by Douglas Dailey - All Rights Reserved.
Always Under Construction
Last modified:  July  2017

CFC:  Cross-Frequency Coupling and Neurofeedback

In 2010, I predicted that a new type of neurofeedback would up-regulate adaptability and insight. I created a specific neurofeedback instrument to train simultaneous ‘ups and downs’ in the amplitudes of 2 different frequency bands. This is called cross-frequency coupling (CFC). I started by investigating the relation between theta, alpha and gamma. Because CFC is an essential component of global broad band synchronization, I called the process TAG Sync. Below you can see 3 versions of my software. Note in particular instrument #4 - the cross-frequency coupling envelopes instrument. Four years later my same instrument was independently discovered to measure fluid intelligence through CFC of theta and gamma [1].
2010 - Nexus 2012 - Infiniti 2014 - BioExplorer 2010 - Nexus 2012 - Infiniti 2014 - BioExplorer

Cross Frequency Coupling Envelopes Instrument:

In the screen shots above you can see instrument # 4, the CFC envelopes instrument showing the coupling over time of the amplitudes of rewards 1 and 2. This might be a simple case of amplitude-amplitude coupling except for the fact amplitudes also reflect the synchronous activity of neurons underneath and between the electrodes. The 10-20 sites used in the TAG Sync General Adaptation Protocol (GAP) include the midline (Fz, Pz) and regions of the right and left fronto-parietal networks (F3,P3 and F4,P4). I call this collection the “DMN/FPN kernal” but the associated cortical hubs also represent the so-called “rich club” [2]. Please examine my instrument #4 which simply displays the amplitude envelopes of rewards 1 and 2, e.g., theta and gamma, over a period of around 10 seconds. Now please look at a similar envelopes instrument adapted from Figure 3 of Pahor & Jaušovec 2014  [1].
In the above graph Pahor & Jaušovec 2014 [1] show the correlation (r = 0.51) between theta and gamma envelopes generated when cognitively intact individuals solve a difficult challenge - Ravens progressive matrices. At rest there is little correlation (r = 0.16) and during a simple RAPM the CFC increases to r = 0.33.   Note the gray area in the above graph. An identical appearance (sudden large simultaneous increase) was noted to be accompanied by clinically important insight in my first two alpha-theta synchrony (CFC) patients in 2010. Following a number of initially large synchronous alpha and theta neuronal avalanches, the general coupling between theta and alpha increased throughout the sessions. This makes sense because of the 1/f power law distribution of neuronal avalanches. Clinicians with whom I shared this information began observing that general increases of CFC under task (i.e., NFB) are associated with increasing intelligence and maturity. This was described in several TAG Sync case studies in a recent Routledge textbook on neurofeedback [3]. Below, I will address some issues regarding my early use of cross- frequency coupling envelopes to promote self-regulation of broad-band synchronization. The Hailing Channel: My earliest 2010 observations included the fact that it was often necessary to find and “open” a narrow communications channel between two hubs. This frequency was often with 1-2 Hz of the frequency in the spectral display showing the highest amplitude in a particular band. This phenomena appears to have been addressed recently by Florin et al 2015 [4]. Further confirmation that CFC NFB may require individualized treatment was stated earlier this year by Aru et al (2015) who state “... adaptive rather than fixed bandwidths might be necessary when scanning the modulating frequency in explorative analyses." They continue, “... if the bandwidth of the higher frequency component (F2) does not include the side peaks produced by the lower frequency (F1), then CFC cannot be detected even if it is present. [5]"

Cross-Frequency Coupling Neurofeedback - Protocol Selection:

I hesitate to call my CFC NFB a protocol. It is more one of mutual exploration of state changes during the learning of what I call a brain- computer-brain interface. Constant attention is paid to the appearance of paroxysmal fast activity, appearance or disappearance of drowsy or dissipated states [6], as well as shifts in the “hailing frequencies” which we learn to adjust in order to promote awake, adaptive and restorative states. My Nexus and Infiniti screens include HRV, GSR, Temp & EMG biofeedback during sessions. TAG Sync (as a methodology) carries the cross-frequency coupling all the way to delta, to the 0.1 Hz Mayer wave, to the ultra-low frequencies around 0.01 Hz that are shared with resting state networks. TAG Sync techniques may be applicable to all cortical sites, or those known to be dysfunctional or disconnected through clinical investigations. Here are some clinical reports that may be useful in developing an individual plan. Aging/memory loss - Pinal D, et al (2015) - Stuck in Default Mode - Inefficient Cross-Frequency Synchronization May Lead to Age-Related Short-Term Memory Decline Alzheimer’s Disease - Ittner AA, et al (2014) - p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer’s disease. Acta Neuropathologica Communications, 2:149. Arithmetic Task Processing - Palva JM, et al (2005) - Phase synchrony among neuronal oscillations in the human cortex. The Journal of Neuroscience, April 13, 2005, 25(15):3962-3972. [Free Full Text] Autism - Khan S, et al (2013) - Local and long-range functional connectivity is reduced in concert in autism spectrum disorders. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3107-12. Berman JI, et al (2015) - Alpha-to-Gamma Phase-Amplitude Coupling Methods and Application to Autism Spectrum Disorder. Brain Connect. Apr;5(2):80-90. Depression - Zheng C, et al (2015) - Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex  pathway in depression. Neuroscience. Feb 12. Epilepsy - Guirgis M, et al (2015) - Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients. J Neural Eng. Mar 13;12(2):026011, Intelligence / memory - Pahor A, et al (2014) - Theta–gamma cross- frequency coupling relates to the level of human iIntelligence 46 (2014) 283-290.  Roux F, et al (2014) - Working memory and neural oscillations - alpha–gamma versus theta–gamma codes for distinct WM information. Trends in Cognitive Sciences, January 2014, Vol 18, No 1. Xu X, et al (2013) - Reduction in LFP cross-frequency coupling between theta and gamma rhythms associated with impaired STP and LTP in a rat model of brain ischemia. Frontiers in Computational Neuroscience, 05 April. Motivation / Emotion - Schutter DJLG, et al (2011) - Cross-frequency coupling of brain oscillations in studying motivation and emotion. Motiv Emot. [Free Full Text]  Obsessive-Compulsive disorder - Velikova S, et al (2010) - Dysfunctional brain circuitry in obsessive-compulsive disorder - Source and coherence analysis of EEG rhythms. Neuroimage 49; 977-983. Parkinson’s Disease - Swann NC, et al (2015) - Elevated synchrony in Parkinson disease detected with electroencephalography. Ann Neurol. 2015 Aug 20. Herz DM, et al (2014) - Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson's disease. NeuroImage Vol 90, 15 April, Pages 15-23.  Lopez- Azcarate J, et al (2010) - Coupling between Beta and High-Frequency Activity in the Human Subthalamic Nucleus May Be a Pathophysiological Mechanism in Parkinson's Disease. The Journal of Neuroscience, May 12; 30(19):6667– 6677. Reward/Punishment processing - Cohen MX, et al (2009) - Good Vibrations - Cross-frequency Coupling in the Human Nucleus Accumbens during Reward Processing.  J Cogn Neurosci. May;21(5):875-89. Schizophrenia – Allen EA, et al (2011) - Components of Cross-Frequency Modulation in Health and Disease. Frontiers in Systems Neuroscience; 5:59. Social Anxiety Disorder - Miskovic V, et al (2011) - Changes in EEG cross-frequency coupling during cognitive behavioral therapy for social anxiety disorder. Psychological Science: 22;507.  Knyazev GG (2011) - Cross-frequency coupling of brain oscillations - An impact of state anxiety. Int J Psychophysiology. There is excessive CFC between delta and beta at rest, often relieved by CBT and sometimes testosterone. Tinnitus Adamchic I, et al (2014) - Abnormal cross-frequency coupling in the tinnitus network. Frontiers in Neuroscience, Sept 25. Vascular Dementia - Xu X, et al (2015) - Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus  in Vascular Dementia Rats. Brain Topogr. Mar 14.
General References for this page: [1] Pahor A, et al (2014) - Theta–gamma cross-frequency coupling relates to the level of human intelligence. Intelligence 46 (2014) 283-290. [2] Ray S, et al (2015) - Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit hyperactivity disorder - Rich club organization. Hum Brain Mapp. Dec; 35(12): 6032- 6048. p. 11. [3] Chapin TJ, et al (2014) - Neurotherapy and Neurofeedback: Brain- Based Treatment for Psychological and Behavioral Problems. Routledge. pp 144. [4] Florin E, et al (2015) - The brain's resting-state activity is shaped by synchronized cross-frequency coupling of neural oscillations. NeuroImage 111, 26-35 [5] Aru J, et al (2015) - Untangling cross-frequency coupling in neuroscience. Current Opinion in Neurobiology, 31:51–61. [6] Ulrich G (2013) – The Theoretical Interpretation of Electroencephalography. BMed.

More on CFC and EEG Biofeedback:

The phrase “cross-frequency coupling” first appears in the pubmed.gov database in 2002. The number of publications each year dealing with CFC is shown below. The phrase “cross-frequency coupling” first appears in the pubmed.gov database in 2002. The number of publications each year dealing with CFC is shown below.
In 2010 I became convinced that it would be adaptive to the brain to be able to increase alpha-theta phase synchrony on demand in order to facilitate “valid cognition” [7]. It was easy to observe that the larger neuronal avalanches were associated with behavioral changes [8]. With increased training and/or clinical improvement the amplitude envelopes of delta, theta, alpha, and gamma became more correlated. The CFC envelopes instrument became an important part of the feedback sessions. Some clients prefer to train on occasion simply by watching the envelopes instrument and learning to couple the cross-frequency amplitude movements. As we discussed, CFC is easily observed in nature, but can be complicated mathematically. Since, at this time, EEG databases do not advise us with normative inter-site CFC values, we must depend upon theory to guide us. Recently there has been discussion of the significance of such an envelopes instrument. For example, Engel et al 2013 state “We discuss evidence for two distinct types of intrinsic coupling modes which seem to reflect the operation of different coupling mechanisms. One type arises from phase coupling of band-limited oscillatory signals, whereas the other results from coupled aperiodic fluctuations of signal envelopes.” “Several recent studies have applied correlation measures to the amplitude or power envelopes of the recorded signals, rather than to the phase of the underlying oscillations (de Pasquale et al., 2010; Brookes et al., 2011, 2012; Hipp et al., 2012). Analysis of such signal envelopes can be used to capture slow fluctuations similar to what is provided by the BOLD imaging (Laufs et al., 2003; Tagliazucchi et al., 2012a). Both the analysis of envelope correlations in electrophysiological signals and of correlated BOLD fluctuations yield what we designate as envelope ICMs.” (ICM - Intrinsic Coupling Mode). Kaminsky et al 2011 describe CFC in memory, “Envelope traces of those theta and gamma activity bands which had the highest correlation.” [10]  A search for cross-frequency coupling and amplitude envelope correlation provides a wealth of discussion, much of it highly mathematical.
Copyright 2010, 2017 by Douglas Dailey - All Rights Reserved.