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The Neurobiology of Stress: Gray Matters

(Editor’s note:  below you have part 2 of the 6-part The Neu­ro­bi­ol­o­gy of Stress series. If you are join­ing the series now, you can read the pre­vi­ous part Here.)

Stayin’ Alive

Under­stand­ing the Human Brain and How It Responds to Stress

Gray Mat­ters

The term gray mat­ter usu­al­ly evokes an image of the cor­tex, because that ’ s the part most vis­i­ble in pic­tures of the brain.  In fact, gray mat­ter makes up not only the cere­bral cor­tex but also the cen­tral por­tion of the spinal cord and areas called the cere­bel­lar cor­tex and the hip­pocam­pal cor­tex.  This dense tis­sue is packed full of neu­ronal cells, their den­drites (branch­ing, root — like end­ings), axon ter­mi­nals (the oth­er end), and those sticky glial cells I men­tioned ear­li­er. The cor­tex is the area of the brain where the actu­al pro­cess­ing of infor­ma­tion takes place.  Because of its rel­a­tive size and com­plex­i­ty, it ’ s easy to under­stand why it plays a key role in mem­o­ry, atten­tion, per­cep­tu­al aware­ness, thought, lan­guage, and con­scious­ness.

A Divi­sion of Labor

A cen­tral groove, or fis­sure, runs from the front to back of the cor­tex, divid­ing it into right and left hemi­spheres. In gen­er­al, the left hemi­sphere con­trols func­tions on the right side of the human body and the right hemi­sphere con­trols the left side, but there are sig­nif­i­cant excep­tions and much sophis­ti­cat­ed inter­ac­tion between the two hemi­spheres. This com­mu­ni­ca­tion between the left and right hemi­spheres is facil­i­tat­ed by the cor­pus cal­lo­sum, a wide, fl at bun­dle of axons locat­ed in the cen­ter of the brain, beneath the cor­tex. Think of it as the Lin­coln Tun­nel, con­nect­ing Man­hat­tan and Jer­sey City. (I ’ ll leave it to you to decide which one rep­re­sents which hemi­sphere.)

The cor­pus cal­lo­sum makes up the largest area of so — called white mat­ter in the brain. White mat­ter is made of bun­dles of axons each encased in a sheath of myelin. These nerve bun­dles lead into and out of the cor­tex and the cere­bel­lum, and branch to the “ old brain, ” the hip­pocam­pus. About 40 per­cent of the human brain is made up of gray mat­ter, and the oth­er 60 per­cent is white mat­ter. It’s the white mat­ter that facil­i­tates com­mu­ni­ca­tion between dif­fer­ent gray mat­ter areas and between the gray mat­ter and the rest of the body. White mat­ter is the Inter­net of our brains. (Al Gore did not invent it.)

Evo­lu­tion, tem­pered by expe­ri­ence, has employed gray mat­ter to build what might be con­sid­ered very well — devel­oped “ cog­ni­tive con­dos ” that sit above the hip­pocam­pus. This arrange­ment is very impor­tant to a dis­cus­sion of stress. Our old or prim­i­tive brain was primed for sur­vival in our ances­tors ’ envi­ron­ment. It’s inter­est­ing to note that the brains of low­er ver­te­brates like fish and amphib­ians have their white mat­ter on the out­side of their brain. We are blessed (and cursed) with lots of gray mat­ter that gives us the abil­i­ty to think things through (espe­cial­ly if we are anx­ious). Frogs and sala­man­ders and their pond — side friends don’t think about dan­ger so much — they just get out of its way! (And while I can ’ t be sure, I don ’ t think that they have night­mares about giant human chil­dren armed with nets.)

How do you feel about that? In case you ever get this ques­tion on Jeop­ardy or in a game of Triv­ial Pur­suit, the lim­bic sys­tem is made up of the amyg­dala, the hip­pocam­pus, the cin­gu­late gyrus, for­ni­cate gyrus, hypo­thal­a­mus, mam­mil­lary body, epi­thal­a­mus, nucle­us accum­bens, orbitofrontal cor­tex, parahip­pocam­pal gyrus, and thal­a­mus. These struc­tures work togeth­er to process emo­tions, moti­va­tion, the reg­u­la­tion of mem­o­ries, the inter­face between emo­tion­al states and mem­o­ry of events, the reg­u­la­tion of breath­ing and heart rate, the pro­duc­tion of hor­mones, the “ fight or flight ” response, sex­u­al arousal, cir­ca­di­an rhythms, and some deci­sion — mak­ing sys­tems. Pret­ty impres­sive job descrip­tion, eh? The word lim­bic comes from the Latin word lim­bus, which trans­lates to “ belt ” or “ bor­der, ” because this sys­tem forms the inner bor­der of the cor­tex. The lim­bic sys­tem is part of the old brain and devel­oped first, fol­lowed by the new brain: the cor­tex, which is some­times referred to as the neo­cor­tex. Put very sim­ply, the lim­bic sys­tem feels and remem­bers; the cor­tex acts and reacts. And they com­mu­ni­cate with each oth­er. Why is this impor­tant? The lim­bic sys­tem fig­ures promi­nent­ly in what ’ s called the stress response, which is a cen­tral play­er in this book.

These days, both our old and new brains are acti­vat­ed when we ’ re under stress. The prim­i­tive part, the lim­bic sys­tem (notably the hip­pocam­pus), sniffs out dan­ger well before the new brain (the neo­cor­tex) actu­al­ly process­es it. The old brain responds first, act­ing as a sort of fi re alarm sys­tem. It is the neo­cor­tex, and in par­tic­u­lar, the frontal lobe (the pre-frontal cor­tex), that helps us make sense of the alarms.

The cor­tex is made up of four major sec­tions, arranged from the front to the back. These are called the frontal, pari­etal, occip­i­tal, and tem­po­ral lobes. Each of the four lobes is found in both hemi­spheres, and each is respon­si­ble for dif­fer­ent, spe­cial­ized cog­ni­tive func­tions. For exam­ple, the occip­i­tal lobe con­tains the pri­ma­ry visu­al cor­tex, and the tem­po­ral lobe (locat­ed by the tem­ples, and close to the ears) con­tains the pri­ma­ry audi­to­ry cor­tex.

The frontal lobes are posi­tioned at the front most region of the cere­bral cor­tex and are involved in move­ment, deci­sion mak­ing, prob­lem solv­ing, and plan­ning. There are three main divi­sions of the frontal lobes. They are the pre­frontal cor­tex, the pre­mo­tor area, and the motor area. The frontal lobe of the human brain con­tains areas devot­ed to abil­i­ties that are enhanced in or unique to humans. The pre­frontal cor­tex is respon­si­ble for plan­ning com­plex cog­ni­tive behav­iors, the expres­sion of per­son­al­i­ty, deci­sion mak­ing, and social behav­ior, as well as the orches­tra­tion of thoughts and actions nec­es­sary for a per­son to car­ry out goals. A spe­cial­ized area known as the ven­tro­lat­er­al pre-frontal cor­tex has pri­ma­ry respon­si­bil­i­ty for the pro­cess­ing of com­plex lan­guage. It is more com­mon­ly called Bro­ca ’ s area, named for a nine­teenth — cen­tu­ry French physi­cian who deter­mined its role.

In humans and oth­er pri­mates, an area locat­ed at the for­ward part of the pre­frontal cor­tex is called the orbitofrontal cor­tex. It gets its name from its posi­tion imme­di­ate­ly above the orbits, the sock­ets in which the eyes are locat­ed. The orbitofrontal cor­tex is very involved in inter­pret­ing rewards, deci­sion mak­ing, and pro­cess­ing social and emo­tion­al infor­ma­tion. For this rea­son, some con­sid­er it to be a part of the lim­bic sys­tem.

The amyg­dala, a part of the lim­bic sys­tem, is a brain struc­ture that is respon­si­ble for decod­ing emo­tions, espe­cial­ly those the brain per­ceives as threats. As we evolved as a species, many of our alarm cir­cuits have been grouped togeth­er in the amyg­dala. Not sur­pris­ing­ly, many regions of the brain send neu­rons into the amyg­dala. As a result, lots of sen­so­ry mes­sages trav­el instan­ta­neous­ly to the amyg­dala to inform it of poten­tial dan­gers lurk­ing in our neigh­bor­hood. The amyg­dala is our guard dog.

The amyg­dala is direct­ly wired to the hip­pocam­pus, also a part of the lim­bic sys­tem. Since the hip­pocam­pus is involved in stor­ing and retriev­ing explic­it mem­o­ries, it feeds the amyg­dala with strong emo­tions trig­gered by these rec­ol­lec­tions. Why is this impor­tant? If a child has a neg­a­tive expe­ri­ence in school, like being ter­ri­bly embar­rassed when asked to read in front of the class, the hip­pocam­pus just won’ t let go of this mem­o­ry, and it shouts it out to the amyg­dala. Since the amyg­dala has signed a no con­fi­den­tial­i­ty agree­ment, it sends a warn­ing to the rest of the brain to go into pro­tec­tion mode. A rather amaz­ing arrange­ment, don’t you think?

What’s real­ly inter­est­ing about this is that the hip­pocam­pus spe­cial­izes in pro­cess­ing the con­text of a sit­u­a­tion. As a result, the child under stress gen­er­al­izes the entire sit­u­a­tion and uses it as jus­ti­fi cation for anx­i­ety or stress: “ Hey, they’re telling me to go to social stud­ies class. ”Even though not every­thing about social stud­ies may be a threat — per­haps just the fact that they read out loud in there — the hip­pocam­pus sends out a gen­er­al alert. So the stu­dent responds by protest­ing the whole enchi­la­da: “No way I’m going there.”

The amyg­dala is also wired to the medi­al pre­frontal cor­tex. Want to know why this is impor­tant? This is the area of the brain that seems to be involved in plan­ning a spe­cif­ic response to a threat to safe­ty. Here ’ s how it works: the child is hit with the gigan­tic Titan­ic news (which may be just “social stud­ies com­ing up next” to the rest of the group, but it’s “Sub­merged ice­berg ahead!” to the kid wor­ried about per­ceived hor­rors there). This two — way  com­mu­ni­ca­tion between the pre­frontal cor­tex and the lim­bic sys­tem (par­tic­u­lar­ly the amyg­dala) enables us to exer­cise con­scious con­trol over our anx­i­ety. The emo­tion — cog­ni­tion con­nec­tion allows us to feel that we can do some­thing about the dan­ger that lies ahead. The child is then faced with the neces­si­ty of choos­ing a course of action that looks best for get­ting out of dan­ger. This seems very pro­tec­tive but tends to be coun­ter­pro­duc­tive, because the very mech­a­nism that allows us to cre­ate an escape plan can actu­al­ly cre­ate anx­i­ety. “ Oh crud — now we have to do some­thing! ” The brain not only allows us to imag­ine a neg­a­tive out­come, which can help us avoid dan­ger, it makes it pos­si­ble for us to imag­ine dan­gers that do not actu­al­ly exist. This is a prob­lem for chil­dren who have ADHD, and a huge prob­lem for stu­dents who have both anx­i­ety dis­or­ders and ADHD. If you do a brain scan of a per­son with ADHD while putting on pres­sure to per­form in a cer­tain way, you see that this “to do” order results in a decrease in activ­i­ty in the pre­frontal cor­tex (instead of increas­ing it, as it does in most peo­ple). This helps explain why kids with ADHD don ’ t respond well to lists. These are read as “thou shalt” mes­sages. What helps some of us stay orga­nized sends some kids with ADHD up the wall.

The Thal­a­mus Bone’s Con­nect­ed to the …

Of course, it’s not real­ly a bone; it’s a plum — shaped mass of gray
mat­ter that’s mul­ti­lay­ered and mul­ti­fac­eted. The thal­a­mus, anoth­er part of the lim­bic sys­tem, sits on top of the hypo­thal­a­mus which, in turn, sits on top of the brain stem, which is in the cen­ter of the base of the brain. This is a great loca­tion for the thal­a­mus because it acts as a relay sys­tem that sends nerve fi bers upstairs to all parts of the cere­bral cor­tex as well as many sub-cor­ti­cal (under­neath the cor­tex) parts of the brain. The thal­a­mus receives infor­ma­tion from every sen­so­ry organ and its asso­ci­at­ed neu­rons except the olfac­to­ry (smell) sys­tem. The hypo­thal­a­mus gets infor­ma­tion from the eyes, the ears, the skin, and the tongue, and it for­wards these mes­sages to the cor­re­spond­ing areas of the cor­tex where they are processed. In terms of stress, this relay sys­tem is how the brain knows that it’s in a dan­ger­ous envi­ron­ment.

That Stinks!

There’s a bulb — shaped brain struc­ture (called, as you might guess, the olfac­to­ry bulb ) that has the spe­cial­ized task of mak­ing sense of scents. Think about this: you can’t see when you are sleep­ing, but you can smell. This is awful­ly help­ful at night, espe­cial­ly when there’s a fire. And when you get hold of a bad piece of fish. That’s prob­a­bly why the nose gets its own spe­cial recep­tor. It’s anoth­er exam­ple of how sen­si­tive the brain is to changes in the envi­ron­ment, and how it’s always on alert!

To Be Con­tin­ued…

  • Octo­ber 31st: The Lit­tle Brain Down Under
  • Novem­ber 7th:Stress Response Explained
  • Novem­ber 14th: The Human Brain Likes Bal­ance
  • Novem­ber 21st: To Fight, Flee or Freeze –That is the Ques­tion

Jerome Schultz Jerome J. Schultz, Ph.D., the Author of Nowhere to Hide: Why Kids with ADHD and LD Hate School and What We Can Do About It (Jossey-Bass; August 2011), is a clin­i­cal neu­ropsy­chol­o­gist and is on the fac­ulty of Har­vard Med­ical School in the Depart­ment of Psy­chi­a­try. He served until recent­ly as the Co-Direc­tor of the Cen­ter for Child and Ado­les­cent Devel­op­ment, CCAD, a mul­ti-dis­ci­pli­nary diag­nos­tic and treat­ment clin­ic which is a ser­vice of the Cam­bridge Health Alliance, a Har­vard Teach­ing Hos­pi­tal.

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