Using ADHD as a model for understanding neural networks

Dr. Laura Jansons02/22/2014

ADHD

• Diagnosis made by behavior observation: DSM-V – 18 symptoms of ADHD, need to meet a percentage

of them to be diagnosed– Diagnosed using behavioral checklists– Problem for neuropsychologists:• DSM-V is not based on NP test data• DSM-V not based on Neuroanatomy• DSM-V is based on “lesion” or disease model.

– Old: ADHD is dysfunction of frontal lobe– New: abnormally functioning brain circuitry – New: Several etiological influences, “common disease-

common variant model”– New: ADHD is not one thing, there is not one place on

the brain we can map.

• Based on what we’ve learned from neuroimaging, we should be thinking in terms of loops and connections, and not land marks.

• Those loops recruited in ADHD: –Cerebro-cortical–Cortical-basal ganglia–Cerebo-cerebellar–Basal ganglia-cerebellar

7 brain networks involved in ADHDYeo and colleagues (2011)

• Frontal Parietal network: effortful cognitive tasks, esp. novel.

• Ventral attentional network : directs attn. to salient objects. “What” you are seeing or “what” an object is used for.

• Dorsal attentional network : Where and How of spatial attn. “Where” is object located and “how” do I use it.

• Visual Network: interacts with dorsal and ventral route

• Limbic network: anticipation of rewards, monitors errors and conflict resolution.

• Sensory-motor network: motor skills

• Default mode network: What you are imagining at rest.

• What this means for neuropsychologists is that it is no longer appropriate to think of ADHD as a simple ‘‘frontal-lobe disorder’’

• Need to replace the localizationist view, ADHD is not just one thing from one place in the brain with one trajectory.

• This is why there is no NP test available, ADHD is heterogeneous, the symptoms are heterogeneous.

Functionally mapping ONE symptom of ADHD using one type of test

• Stevens and colleagues, 2007, provided the first description of how multiple neural network dynamics are associated with response inhibition in normal control adolescent and adult subjects in the performance of a “Go-No-Go” task.

• There is not one region in the brain responsible for inhibiting response.

• There are “loops” of communication that leads to disinhibition, in fact there are three.

• We are always “idling” and anticipating. When the light is red, the car is not “off”.

• There is a lot going on when you inhibit a response.

Withholding response

These loops can be mapped on the brain via fMRI.The following is the “blue”, “yellow” and “red” circuit.Correctly rejected No-Go stimuli involved with successful response inhibition:

13Stevens, et al, 2007

Blue: pay attention there’s something unique going on here, what do I do?

Yellow: transforming senses into actions. Object recognition, salience/reward value

Red: Executive Control and Working Memory

Fig. 1. Brain regions in each component associated with successful response inhibition. (A) Fronto-striatal-thalamic indirect pathway engagement consistent withmodulation of motor function (Blue); (B) precentral gyri deactivation concurrent with prefrontal and inferotemporal activation (Yellow); (C) frontoparietal circuitactivity consistent with higher-order presentations of No-Go’ response contingencies (Red). Statistical results are thresholded at a low of p < .001, corrected forsearching the whole brain.

Summary Stevens 2007

• Causal relationships among ensembles of different brain regions.

• May help understand that there is no one linear cause for disinhibition, alterations in specific connections or brain region could impact psychopathological conditions.

Stevens 2009

• Network dynamics supporting correct responses and errors of commission

• NCs between 11 and 37• Go/No-Go task

Stevens 2009

• The analysis found five distinct functional networks related to correct hits and errors.

Go

XRapidly presented(1000 ms intervals)

85% Go stimuliright index finger taps

Go

X

Go

X

No Go

K

Correct Button Pushes

A: a motor-execution neural circuit integrated with frontal, parietal, and striatal regions (Orange), B: the ‘default mode’ neural network (imagining a task as if you were doing it)

Errors A

A: a motor-execution neural circuit showing absent or decreased activity in brain regions engaged for higher-order control

(things are going on implicitly—without thought)

“whoops”

Car’s going down the road without a driver, disturbance in intention program, start, stay stop. Connection between working memory and Impulsivity—environment , stimulus, triggers behavior not thought

Errors B

B: a low-probability stimulus processing functional circuit that has a greater response amplitude to errors

Errors C

C: the pregenual cingulate-temporal lobe network possibly reflecting an affective response to errors (bilateral amygdala activation)

• Why are NP task so inadequate? Behaviorally defined criteria in ADHD do not easily ‘‘map’’ on to functional brain networks.

• With the advent of functional neuroimaging, it was seen conclusively that these sorting and planning tasks should not fairly be considered ‘‘frontal’’ tests.

• assessment instruments were never designed to evaluate the networks and interactions in question.

• CPT’S are not ADHD tests: they measure a range of impulses and don’t correlate with one another.

• Current: widely accepted belief of causal heterogeneity in ADHD. ADHD is not one thing with one cause.

• the challenge to functional neuroimaging is to find a way to effectively ‘‘diagnose’’ ADHD.

• Neuropsychology can establish itself at the ‘‘ground floor’’ in developing methodologies to explore these different dimensions of behavior.

• Challenge in the field today seems to need a way to bring these two worlds together.