1 00:00:00,000 --> 00:00:09,200 Welcome to From the Spectrum Podcast. This is a podcast about autism. It is my 2 00:00:09,200 --> 00:00:16,480 goal to explain what is autism. I intend to use a mixture of scientific 3 00:00:16,480 --> 00:00:24,840 literature, personal experience, and opinion. With opinion I will explain why 4 00:00:24,840 --> 00:00:32,000 I feel the way I do and give examples. I will provide links to various 5 00:00:32,000 --> 00:00:39,160 references for each episode. For each episode we will discuss various aspects 6 00:00:39,160 --> 00:00:47,080 of autism. For today's episode we will discuss biological aspects implicating 7 00:00:47,080 --> 00:00:55,360 the excitation and inhibition balance. The EI balance is a worthy discussion 8 00:00:55,360 --> 00:01:03,360 with autism and a lengthy discussion. Today's episode is part 2 of a two-part 9 00:01:03,360 --> 00:01:11,920 series covering the EI balance. Notice not all of the topics covered are a 10 00:01:11,920 --> 00:01:20,560 cause of all the cases of autism. Autism is a genetic patchwork. It is not one 11 00:01:20,560 --> 00:01:28,320 gene and not all gene implications reach autistics in the same manner. The 12 00:01:28,320 --> 00:01:36,720 cause of all autistic phenotypes are unknown. I want to warn you, you need to 13 00:01:36,720 --> 00:01:43,600 know some literature and even some literature I have shared on autism are 14 00:01:43,600 --> 00:01:51,240 attempts to create pharmacological help. This has concerns. This has concerns 15 00:01:51,240 --> 00:01:57,240 because of our medical paradigm which likes and maybe even prefers 16 00:01:57,240 --> 00:02:03,520 prescriptions as the first line, as something that gets lots of financial 17 00:02:03,520 --> 00:02:14,200 backing and it isn't hard to know why. I want you to understand autism and I want 18 00:02:14,200 --> 00:02:21,200 you to make informed decisions. For today's episode we will cover metabolic 19 00:02:21,200 --> 00:02:30,880 demands, glutamate and GABA, some neuromodulators like serotonin, dopamine, 20 00:02:30,880 --> 00:02:39,800 epinephrine and nor epinephrine, remember that's adrenaline and acetylcholine. Also 21 00:02:39,800 --> 00:02:50,160 N-methyl deaspartate which is NMDA and AMPA. Remember feel free to look up the 22 00:02:50,160 --> 00:02:58,520 nomenclature to AMPA. We will also discuss a couple of brain networks, the 23 00:02:58,520 --> 00:03:06,560 thalamocortical and the medial prefrontal cortex. Also learning and memory, 24 00:03:06,560 --> 00:03:12,760 remember neuroplasticity. Remember this is essentially occurring in the 25 00:03:12,760 --> 00:03:20,960 background as certain cells are firing and making us more of what we are. This is 26 00:03:20,960 --> 00:03:29,960 the basis of who we are. So the excitation inhibition creates a noisy and 27 00:03:29,960 --> 00:03:39,920 metabolic demanding condition. This can create crash or burnout or avoidance. 28 00:03:39,920 --> 00:03:48,240 This could mean the interaction if chosen or when it cannot be avoided is very 29 00:03:48,240 --> 00:03:58,960 demanding or more accurately it could be or it likely will be demanding. This 30 00:03:58,960 --> 00:04:08,680 explains a lot of criteria A. That alone helps explain a lot about autism. 31 00:04:08,680 --> 00:04:16,480 Metabolic demands keeping up with the demanding outside world, paying attention 32 00:04:16,480 --> 00:04:23,600 and making sense of everything and consider that rate of information we 33 00:04:23,600 --> 00:04:31,920 previously discussed, that fire hose of information. We keep track at least our 34 00:04:31,920 --> 00:04:40,080 brain or body does of our metabolic account. We meaning our brains, we 35 00:04:40,080 --> 00:04:47,080 meaning people. Lisa Feldman Barrett compares it to a bank account. Do I have 36 00:04:47,080 --> 00:04:55,560 enough resources to cover whatever task or environmental demand I am navigating? 37 00:04:55,560 --> 00:05:05,280 Or will that task demand cause me a metabolic deficit? Will I overdraw my 38 00:05:05,280 --> 00:05:15,640 metabolic account? My metabolic resources. Excitation is demanding. It works the 39 00:05:15,640 --> 00:05:23,600 sympathetic nervous system, the get up and go side. Inhibition is calming and 40 00:05:23,600 --> 00:05:32,080 quieting. Remember it shuts systems down. It works the parasympathetic side, the 41 00:05:32,080 --> 00:05:40,840 inactivating and relaxing side. Remember glutamate is excitation, GABA is 42 00:05:40,840 --> 00:05:50,920 inhibition. In autism, glutamate is more behavioral symptoms and GABA is more 43 00:05:50,920 --> 00:06:01,520 sensory processing and not limited to just those. Criteria A and B are 44 00:06:01,520 --> 00:06:12,400 downstream of these conditions, meaning a result of or a response to. Because of the 45 00:06:12,400 --> 00:06:22,360 excitation inhibition, we get criteria A and B. Possibly a sequela of the 46 00:06:22,360 --> 00:06:33,160 abnormal brain development. Whatever that looks like for the autistic. NMDA, N 47 00:06:33,160 --> 00:06:40,600 methyl D aspartate. NMDA increases signaling between cells. It excites 48 00:06:40,600 --> 00:06:49,720 cells and connections. It is common. NMDA and AMPA have spatial relationships, 49 00:06:49,720 --> 00:06:56,040 meaning they are often close and work alongside each other for the overall go 50 00:06:56,040 --> 00:07:08,640 and intentions of the cell. Which in this case is excitation or activation. NMDA 51 00:07:08,640 --> 00:07:17,000 and AMPA are excitation receptors for glutamate. Dopamine modulates glutamate 52 00:07:17,000 --> 00:07:24,760 release. Remember dopamine has many functions in the human body. Much more 53 00:07:24,760 --> 00:07:33,520 than most know. Here dopamine starts glutamate. Remember to activate and 54 00:07:33,520 --> 00:07:39,520 glutamate carries out several physiological responses in the nervous 55 00:07:39,520 --> 00:07:48,120 system. Symnaptic plasticity is the basis for learning and memory. Remember 56 00:07:48,120 --> 00:07:56,600 essentially this is neuroplasticity. Becoming who we are. Our old friend the 57 00:07:56,600 --> 00:08:03,600 striatum is a region of interest. Remember the striatum and the ventral 58 00:08:03,600 --> 00:08:10,000 striatum is the nucleus of compass. Think of it as a subdivision within a 59 00:08:10,000 --> 00:08:17,640 larger community. The striatum is where motor movements essentially begin and 60 00:08:17,640 --> 00:08:28,120 decision-making. Go directed task, social behaviors, habit and emotions. So once 61 00:08:28,120 --> 00:08:38,840 again we uncovered many bases of autism symptomology. The data on AMPA shows 62 00:08:38,840 --> 00:08:47,160 social implications. Further the data show AMPA dysfunction does not affect 63 00:08:47,160 --> 00:08:56,320 repetitive behaviors and cognitive deficits. In autism AMPA can have hyper 64 00:08:56,320 --> 00:09:03,720 or hypo excitatory transmission. Again hinting on the spectrum and the ability 65 00:09:03,720 --> 00:09:10,360 to navigate certain environments differently. For repetitive type symptoms 66 00:09:10,360 --> 00:09:19,680 this looks to be more NMDA. Additionally and on the theme of neuroplasticity 67 00:09:19,680 --> 00:09:31,600 and or a synaptic plasticity. AMPA receptors are crucial for memory. When BDNF 68 00:09:31,600 --> 00:09:42,680 from our previous episode, NMDA and or AMPA are inhibited, massive impairments 69 00:09:42,680 --> 00:09:52,160 occur. The EI imbalance occurs. Remember that is not limited to autism but 70 00:09:52,160 --> 00:10:02,360 certainly a factor in autism. Neuromodulators. Okay we discussed aromatic 71 00:10:02,360 --> 00:10:11,800 amino acids, tryptophan and tyrosine. These two special proteins account for 72 00:10:11,800 --> 00:10:19,880 the synthesis of most neuromodulators. Remember neuromodulators are slightly 73 00:10:19,880 --> 00:10:27,040 more complex than neurotransmitters even though they are essentially the same. 74 00:10:27,040 --> 00:10:36,000 Neuromodulators are serotonin, dopamine, epinephrine and nor epinephrine and 75 00:10:36,000 --> 00:10:44,080 acetylcholine. These are crucial for the functioning of the human body and the 76 00:10:44,080 --> 00:10:53,360 nervous system. With that deficiencies of these are not, are not necessarily 77 00:10:53,360 --> 00:11:03,000 related to autism. Directly. However remember dopamine in the human body is 78 00:11:03,000 --> 00:11:10,560 much, much more than the wanting, the pursuit, the craving we think of and 79 00:11:10,560 --> 00:11:17,920 serotonin is likely the most studied neuromodulator within this class for 80 00:11:17,920 --> 00:11:30,240 autism. Dating back to the 1960s. Remember the 16p11.2 discussion. Serotonin is 81 00:11:30,240 --> 00:11:37,920 about having and helps determine active coping versus passive coping. In other 82 00:11:37,920 --> 00:11:49,680 words how you respond to events perceived as unwanted or aversive. A subregion of 83 00:11:49,680 --> 00:11:56,960 the thalamus is involved here too. The lateral habinula and lots is going on 84 00:11:56,960 --> 00:12:06,400 here with avoidance, feelings, social behaviors so more of that and adapting 85 00:12:06,400 --> 00:12:15,640 sensory integration and perhaps even more larger system integration. So 86 00:12:15,640 --> 00:12:23,720 consider that on the superpower to super deficit spectrum. Mainly with 87 00:12:23,720 --> 00:12:31,400 neuromodulators each modulator kind of owns a piece of brain real estate. For 88 00:12:31,400 --> 00:12:42,240 serotonin remember having is the raffae an area in the brainstem. Dopamine is the 89 00:12:42,240 --> 00:12:49,600 substantia nigra and also melanin is huge here from a previous discussion and in 90 00:12:49,600 --> 00:12:57,120 the ventral tegmental area epinephrine and nor epinephrine remember brain 91 00:12:57,120 --> 00:13:05,480 adrenaline is the locus ceruleus and acetylcholine used for focus it modulates 92 00:13:05,480 --> 00:13:14,080 focus is the basal for brain or specifically the subdivision nucleus 93 00:13:14,080 --> 00:13:23,160 basalis. Remember these things activate and inactivate whole systems or regions 94 00:13:23,160 --> 00:13:30,560 of the nervous system. The topic with autism is those modulators and those 95 00:13:30,560 --> 00:13:37,480 specific regions implicate the cell activity and subsequent glutamate and 96 00:13:37,480 --> 00:13:45,000 GABA and the cortical and sub cortical communication because in large part 97 00:13:45,000 --> 00:13:53,080 autism has the implications and connection possibly through myelin or 98 00:13:53,080 --> 00:14:00,080 axonal impairment, synaptic impairments, any of the developmental regions of 99 00:14:00,080 --> 00:14:06,920 interest that we have discussed. The list and discussion on these incredible 100 00:14:06,920 --> 00:14:16,400 neuromodulators is no way near exhaustive. One thing to note and I did not 101 00:14:16,400 --> 00:14:24,560 specifically search for any data but acetylcholine and muscle movement is 102 00:14:24,560 --> 00:14:36,120 this implicated in autism. I don't know but acetylcholine controls muscles and 103 00:14:36,120 --> 00:14:45,120 the reason why I wonder is of the motor movement symptoms with autism. Lastly the 104 00:14:45,120 --> 00:14:54,720 nicotinetic receptors for acetylcholine are not only excitable but considered a 105 00:14:54,720 --> 00:15:04,040 rapid excitation. It's like giving the car extra gas for acceleration. 106 00:15:04,040 --> 00:15:13,880 Acetylcholine is used for our focus, how and where we will use our metabolic 107 00:15:13,880 --> 00:15:24,120 energy. A crucial area in the brain is the medial prefrontal cortex. The medial 108 00:15:24,120 --> 00:15:33,560 prefrontal helps determine how we feel, our mood in real time or during thought, 109 00:15:33,560 --> 00:15:43,080 or planning. Remember we run models of how we will feel and do as we navigate 110 00:15:43,080 --> 00:15:52,760 the world. All of us do, autistics or not. A buzzword in neuroscience is the 111 00:15:52,760 --> 00:16:01,320 default mode network. Briefly because it will be too much for this episode, the 112 00:16:01,320 --> 00:16:08,640 default mode network is a state of being during periods of no task demands. Well 113 00:16:08,640 --> 00:16:17,240 for autistics we have plenty of tasks. Remember the criteria B. We have tasks and 114 00:16:17,240 --> 00:16:24,280 interest. In other words how others experience this state of a lack of 115 00:16:24,280 --> 00:16:34,440 demands. Autistics being isolated to ourselves. We can thrive in this time and 116 00:16:34,440 --> 00:16:42,960 because of neuroplasticity we can prefer this time. The medial prefrontal 117 00:16:42,960 --> 00:16:53,000 cortex uses glutamate and GABA. Of course especially GABA to quiet the body during 118 00:16:53,000 --> 00:17:02,080 planning. Recently it was found by Nolan Williams. The medial prefrontal cortex 119 00:17:02,080 --> 00:17:08,440 sends signals down to the heart and slows the heart down during those 120 00:17:08,440 --> 00:17:17,960 excitable states, during those unwanted states. Anyway high excitation 121 00:17:17,960 --> 00:17:27,200 impairs information processing. In the medial prefrontal cortex especially 122 00:17:27,200 --> 00:17:36,760 social and cognition. GABA sets corresponding thalamocortical circuits. 123 00:17:36,760 --> 00:17:43,760 Here we are talking about those connections and communications. Cells 124 00:17:43,760 --> 00:17:53,320 traveling and activating and inactivating systems. Remember the thalamus is the 125 00:17:53,320 --> 00:18:03,040 hotspot. A hotspot for the senses and sensory processing. The thalamocortical 126 00:18:03,040 --> 00:18:13,920 is the pass from the thalamus to the cortex. It relayes sensory information and 127 00:18:13,920 --> 00:18:23,880 integrates it with appropriate systems. The medial generates social responses, 128 00:18:23,880 --> 00:18:34,880 behavioral flexibility and ambition of responses and attention and emotion. 129 00:18:34,880 --> 00:18:43,320 Remember two things. Don't consider a singular area to be the only place or 130 00:18:43,320 --> 00:18:54,200 thing responsible. Such as attention or emotion is the medial prefrontal. Nothing 131 00:18:54,200 --> 00:19:03,800 in the human body is singular. Two, the medial prefrontal is very 132 00:19:03,800 --> 00:19:13,880 metabolically demanding. It requires a lot of energy and resources. Remember the 133 00:19:13,880 --> 00:19:26,280 CNT NAP2 discussion. A lack of inhibitory responses complicates socialness and 134 00:19:26,280 --> 00:19:36,360 cognitive flexibility. And you can see this with traits of autism. So right 135 00:19:36,360 --> 00:19:45,360 there that's criteria A and B. We just highlighted key components for each 136 00:19:45,360 --> 00:19:55,840 criteria. In the background the foot soldiers of our brain and nervous 137 00:19:55,840 --> 00:20:05,800 system are those neuromodulators such as serotonin. Remember vast for socialness 138 00:20:05,800 --> 00:20:14,200 and active versus passive coping. And dopamine. Where do we want to provide 139 00:20:14,200 --> 00:20:23,880 energy for our pursuits? Sapolsky says dopamine isn't about the pursuit of 140 00:20:23,880 --> 00:20:34,040 happiness. Dopamine is about the happiness of pursuit. And I challenge you to 141 00:20:34,040 --> 00:20:41,280 explain it any better than that on the cellular level of wanting. Dopamine is 142 00:20:41,280 --> 00:20:51,480 wanting. Serotonin is having. This is a healthy balance. Many things in our 143 00:20:51,480 --> 00:20:58,440 biology can be seen on that seesaw. Remember the seesaw with the glutamate 144 00:20:58,440 --> 00:21:08,200 and GABA. And remember as a response to those neuromodulators glutamate and GABA 145 00:21:08,200 --> 00:21:17,640 are also constantly running in the background. All the while neuroplasticity 146 00:21:17,640 --> 00:21:26,440 is occurring. Strengthening of connections at the synaptic level. 147 00:21:26,440 --> 00:21:35,280 Strengthening those synaptic connections. A crucial consideration especially with 148 00:21:35,280 --> 00:21:45,600 autism. A crucial consideration is more sensory input equals faster firing rates 149 00:21:45,600 --> 00:21:55,840 of the items discussed today. That is a normal EI balance. So in other words to 150 00:21:55,840 --> 00:22:04,080 repeat more sensory input equals faster firing rates of the items discussed 151 00:22:04,080 --> 00:22:15,480 today. This is a condition with a normal EI balance. Now imagine when the 152 00:22:15,480 --> 00:22:25,960 EI is imbalanced. Imagine the firing rates now. Today's discussion and the 153 00:22:25,960 --> 00:22:31,040 previous episode highlights opportunities for superpowers and 154 00:22:31,040 --> 00:22:41,760 super deficits. Now you, you don't get to determine this. It is the responsibility 155 00:22:41,760 --> 00:22:50,400 of others to help people with autism to find their superpowers. Nobody controls 156 00:22:50,400 --> 00:22:59,400 the rate of information autistics have. Nobody controls what superpowers each 157 00:22:59,400 --> 00:23:10,960 autistic will receive. In addition it is also up to the autistic when possible to 158 00:23:10,960 --> 00:23:20,200 find their superpowers. However delay public and the surrounding people cannot 159 00:23:20,200 --> 00:23:29,440 and should not limit people with autism. One of the best things you can do for 160 00:23:29,440 --> 00:23:39,520 autism is just delete everything you know about autism and then relearn it. 161 00:23:39,520 --> 00:23:48,600 Learn what autism is actually and whenever I say delete just go ahead and 162 00:23:48,600 --> 00:23:56,160 wipe it out. But don't worry our memory in the human brain is often like the 163 00:23:56,160 --> 00:24:01,840 memory on our computer. You're not actually going to delete it completely out. It 164 00:24:01,840 --> 00:24:07,520 will still be there in the background. You can still retrieve it. My point is 165 00:24:07,520 --> 00:24:17,200 don't limit your capacity to think. Don't be offended by people asking you to 166 00:24:17,200 --> 00:24:24,800 think differently. To expand your critical thinking especially on this autism 167 00:24:24,800 --> 00:24:32,480 phenomena. Don't try to change an autistic person because they are 168 00:24:32,480 --> 00:24:38,760 different than you or different than others. Don't let that offend your 169 00:24:38,760 --> 00:24:46,360 beliefs and capacity to apply critical thinking in life. If you are listening 170 00:24:46,360 --> 00:24:51,680 and enjoy the episode, if you enjoy the podcast please feel free to leave a 171 00:24:51,680 --> 00:25:00,960 review and or rating. In podcasting reviews and or ratings are huge and I 172 00:25:00,960 --> 00:25:06,400 very much appreciate your feedback. If you would like to contact me please 173 00:25:06,400 --> 00:25:19,680 email me at info.fromthespectrum.atgmail.com. Thank you for listening to 174 00:25:19,680 --> 00:25:35,000 From the Spectrum podcast.