# Presentation: 351032

## Cognitive Effects in Adolescents Exposed Prenatally to  Marihuana or Cigarettes

- American Psychiatric Association
- New York, 2004

## Prenatal Marihuana Exposure and Its Putative Impact Upon Executive Functioning in Offspring – 
A 25 Year Prospective Study

- Prenatal Marihuana Exposure and Its Putative Impact Upon Executive Functioning in Offspring –
- A 25 Year Prospective Study

## The Ottawa Prenatal Prospective Study

## Slide 4

## Two General Areas

- General Cognition and Executive Function
- Visuoperception

## Summary of Cigarette Findings0-4 years of age

- _Newborn_ -     auditory responsiveness & habituation;            tremors & motoric reflexes
- _1 year _-    MDI (96 vrs 110) & verbal cluster.
- _2 years _-  MDI (106 vrs 119) & Reynell Expressive &     Comprehensive. Significance lost when confounds controlled.
- _3 years _-  GCI & language after confounds controlled.
- _4 years _-  GCI & language after confounds controlled

## 	   Prenatal Marihuana      Summary Up To Preschool 

- Course of pregnancy, fetal and postnatal growth and behavior are relatively unaffected during neonatal and toddler  stages
- Starting at approximately 3 years of age converging findings suggest that overall IQ is not affected but abstract/visual reasoning subscales on IQ tests are negatively impacted  as are facets of attention.
- Together, this suggests an impact on aspects of Executive Function - this will be elaborated in a moment.

##   Effects of Prenatal Exposure to Marihuana (and Cigarettes) on Cognitive Tasks in 9 to 12 Year-Old Offspring

## Differential Consequences of the Drugs

*General Intelligence versus Aspects of Executive Function*

## Executive Functioning which is largely under the control of Prefrontal LobesInvolves

- Planning for the future/decision making
- Self monitoring/error correction/flexibility/budgeting of time
- Working Memory- Integration of past and new information
- Control over dominant responses
- Attention allowing control of interference
- The Prefrontal lobes allow us to respond           			-not simply react

## Paradox of Executive System Assessment

- Trying to assess ability to set goals, plan & organize behavior in pursuit of those goals,  and flexibly solve problems in the context of an unstructured real world
- YET
- using a test situation in which
- highly structured tasks are presented in a highly controlled environment

## The evaluator and evaluation context can become the prosthetic frontal lobes for the subject.

##   Poor Executive Function

- A dysregulation of goal directed behaviour
- not attributable to a more basic deficit in perception, memory, or language comprehension
- Occurs across tasks varying in content & surface characteristics
- Despite understanding goal of task, prefrontal dysfunction results in impaired performance (intrusions of task irrelevant behaviour, perseveration, lack of initiative etc.)

## Tasks Used To AssessGeneral Intellectual Abilities

- WISC-III -all 13 Subtests & Composite Scores :
-  Information; Similarities; Arithmetic; Vocabulary; Comprehension; Digit Span
-  Picture Completion; Coding; Block Design; Object Assembly; Symbol Search; Mazes
-  Verbal IQ; Performance IQ; Full Scale IQ
-  Verbal Comprehension; Perceptual Organization; Freedom from Distractibility; Processing Speed

## Executive Function Tasks

- _Working memory_
-       Fluency Test                                          	Auditory Working Memory
- _Motor Sequencing & Speeded Response_
-      Tactual Performance Task
- _Visual Analysis & Hypothesis Testing_
-      Category Test

## Executive Function Tasks (continued)

- _Inhibition of Prepotent Response_
-       Gordon Delay Task  (DRL schedule)
- _Sustained Attention_
-       Gordon Vigilance Task

## Discriminant Function Analysis

_*Cigarettes*_
**Primary predictors**
- 1/ WISC full-scale IQ
-  2/ Verbal IQ
-  3/ Freedom from   Distractibility Index
-  4/ Verbal Comprehension. Index

_*Marihuana*_
**Primary Predictors**
- 1/ Category Test
- 2/ Responses on Delay Task
- 3/ WISC Block Design
- 4/ WISC Picture Completion
- 5/ Efficiency Ratio on Delay Task

## Overview of Cognitive Outcomes in 9-12 Year-Olds

_*Cigarettes*_
- IQ impacted
- Many individual WISC tests significant dose response effects
- Verbal domain particularly impacted
- No effect on non-verbal Executive Function tasks

_*Marihuana*_
- IQ not impacted
- No individual WISC tests significantly impacted
- DFA Composite score suggests aspect of E. F. impacted - Visual Analysis (Block Design, Picture Completion & Category Test) + Impulsivity

## Welsh (1991) E.F. factors identified in normative sample  

- Hypothesis (Visual) Testing & Impulse Control;
- Fluid & Speeded Response;
- Planning

## Two Types of Intelligence

_**Fluid Intelligence **_**may be highly related to Prefrontal lobe Function**

## Conclusions

- There is a disassociation between consequences of in utero exposure to cigarettes and marihuana.
- Cigarettes impact on overall IQ and auditory/verbal domain.
- Marihuana impacts upon a more subtle, ‘top-down’, integrative process that involves aspects of Executive Functioning.

## Facets of Attention are Affected 13-16 year old Offspring Prenatally Exposed to Marihuana

## Attention Measures Used in Present Report(part of a large OPPS battery given to the 13-16 year olds)

- Continuous Performance Task (CPT) - omissions, commission, reaction time, change in reaction time as test proceeds.
- Wisconsin Card Sort (WCST)- errors, number of stimuli.
- Stroop - interference score.
- Arithmetic subtest from WISC.
- Sentence Memory Test.
- Seashore Rhythm Test.
- Knox Cube Test.

## Mirsky’s 1996 Five Factor Model of Attention Based on 14 Test Scores

_*Focus/execute*_*: *allocation of attentional resources while screening out irrelevant stimuli.
_*Shift/flexibility*_: ability to move attention across stimuli
_*Arouse/exert: *_maintenance of attention over time
_*Encode/retain (working memory)*_: mentally holding information while utilizing or manipulating it.
_*Stability*_: consistency of attention over time

## Restricted Five Factor Solution Conducted on OPPS Sample Based on 11 Attention VariablesCompared to Mirsky’s model -Extracted Variance & Individual Factors are very similar

_*Shift/flexibility*_: (like Mirsky - & similar tests loaded -        	e.g. Wisconsin Card Sort)
_*Encode/Retain:*_ (like Mirsky -similar test-WISC Arithmetic plus, in present work, Seashore, Knox and Sentence Memory loaded)
_*Impulsivity*_: (similar to Mirsky’s ‘arouse/exert’ - CPT variables loaded in both)
_*Stability: *_(like Mirsky -CPT variables loaded in both)
_*Focus/Execute*_: (like Mirsky - Stroop variable loaded in both)

## Association of Maternal Smoking & Components of Attention

_*Encode/Retain *_   p<.05 after control for confounds.
_*Impulsivity*_   associated only in the youngest ten percent of the sample (13 yrs. 1 month or less) at p<.05 after control for confounds.

## Interpretation of Cigarette Findings(Impulsivity)

- Developmentally, inhibitory control (_*impulsivity*_) stabilizes at approximately 12 yrs of age.
- Consistent with extant literature with younger children prenatally exposed to cigarettes, tobacco impacts on this domain but, is only seen among the youngest children in the present work.
- Beyond 13 yrs, the developmental delay associated with in utero exposure has been overcome.

## Interpretation of Cigarette FindingsEncode/Retain

- Developmentally, unlike impulsivity, working memory  (_*encode/retain*_) continues to undergo developmental changes until at least 15 years of age.
- Thus the impact of prenatal tobacco exposure manifests itself across all ages in the present work.

## Association of Maternal Marihuana Use & Components of Attention

_*Stability*_: has loadings both from CPT reaction times that became less consistent as test proceeded and increased omission errors. p<.01 after control of confounds.

## Interpretation of Marihuana FindingsStability

- Findings with respect to omission errors are consistent with earlier reports from the OPPS (at 6 years of age)
- Combination of response variability & omission errors are a sensitive indicant of performance on sustained attention that continues to develop throughout adolescence.
- The OPPS marihuana/stability association did not interact with age

## Summary

- Results obtained from the 13-16 year old OPPS sample are strikingly similar to the five factor model proposed by Mirsky.
- Prenatal exposure to cigarettes or marihuana have differential consequences upon some of these components of attention
-       _cigarettes_ impact upon the ability to temporarily hold information while processing incoming data and, among the younger children, is negatively associated with impulse control
-       _marihuana_ is associated with sustained attentional focus over time

## Visuoperceptual Performance of 9-12 Year Olds Prenatally Exposed to Marihuana

## Visuoperceptual Tasks

- _Fundamental skills _(based on the Test of Visual Perceptual Skills - [TVPS] with 7 subtests)
-     e.g. visual discrimination
-      It has a Summary Score - **Perceptual ****	****	****	****	****Quotient**

## Visuoperceptual Tasks

- Visuoperceptual Problem Solving ( based on 4 tests of the WISC)
-  These tests involve the fundamental   		visuoperceptual skills coupled with 		integrative & analytical abilities
-      e.g. block design
-     It has a summary score - **Perceptual Index**

##    Non-perceptual Control Tasks

- I.Q. (WISC)
- Visuomotor (Beery)
- Memory ( digit span)
- Attention (Freedom form Distractibility -   			WISC)

##     Results in Cigarette Offspring

_*TVPS (fundamental*_*)*
-  **Perceptual Quotient****    	(Summary Score)
-  V. Discrimination**
-  V. Memory*
-  V. Spatial Relations**
-  V. Form Constancy**
-  V. Sequential Memory**
-  V. Figure-ground
-  V. Closure*

_*Complex Visual-Perceptual*_
-  **Perceptual Index       **		Summary  Score*
-  Picture Completion
-  Picture Arrangement*
-  Block Design*
-   Object Assembly*			                                       * sig. before control	         ** sig. after prenatal  & P.Q. 		controls

##     Results in Marihuana Offspring

_*TVPS (fundamental*_*)*
-  **Perceptual Quotient    **	(Summary Score)
-  V. Discrimination
-  V. Memory
-  V. Spatial Relations
-  V. Form Constancy
-  V. Sequential Memory
-  V. Figure-ground
-  V. Closure

_*Complex Visual-Perceptual*_
-  **Perceptual Index       **		Summary  Score**
-  Picture Completion
-  Picture Arrangement
-  Block Design*
-   Object Assembly**					       * sig. before control	       ** sig. after prenatal & P.Q.       		controls

## The significant association between prenatal marihuana use and the Perceptual Index (summary score representing complex visuoperceptual performance) remainswhen the Perceptual Quotient (the summary score representing fundamental visuoperceptual skills) is used as a covariate 

## This would suggest that (unlike prenatal cigarettes)prenatal marihuana affects a ‘top-down’, integrative & analytical visuoperceptual functions as opposed to a basic visuoperceptual function. 

## “Patients with frontal lesions do not analyse the (block design) diagram and they make no attempt to convert ‘units of impression’ into ‘units of construction.’ They manipulate the cubes impulsively in accordance with direct impressions. They do not actively work in order to complete the test and they do not evaluate their mistakes.”

- 				Luria - The Working Brain, 1973

## These marihuana results are consistent with
1/ Earlier cognitive observations in which the Category Test was the best discriminator of prenatal marihuana exposure - it has a high factor loading with Picture Completion & Block Design
2/Frontal Lobe patients
3/Aspects of Executive Function being impacted by prenatal marihuana exposure

- These marihuana results are consistent with
- 1/ Earlier cognitive observations in which the Category Test was the best discriminator of prenatal marihuana exposure - it has a high factor loading with Picture Completion & Block Design
- 2/Frontal Lobe patients
- 3/Aspects of Executive Function being impacted by prenatal marihuana exposure

## Cognitive Functioning in 13-16 year olds prenatally exposed to Cigarettes or Marihuana- Differential Effects

## 		Background	  Prenatal Cigarettes

- Lower general cognitive performance in preschool & school age -dose dependent
- Verbal/auditory processing in a wide range of tasks impacted from infancy onward

**Notes:**
Infants-habituation,IQ verbal subscales, phon-reading, auditory processing, verbal memory

## 		    		   Background	    Prenatal Marihuana

- Not associated with poorer overall cognitive performance
- Poorer abstract/visual reasoning first noted at 3 and 4 yrs of age
- Sustained attention negatively impacted and longer latencies on visual search paradigms
- ‘top-down’ impact- facets of executive function

**Notes:**
Marihuana age of onset, IQ effects, frontal lobe damage, CBF and EEG studies and behaviors in users.

## Tasks

- _	__General Cognition_
- 		WISC _	_
- _	__Achievement_							WRAT (reading, spelling [orally presented], arithmetic)
- 		Peabody Spelling [visual recognition]
- _	_
- _	__Memory_
- 		Auditory (sentence memory)
- 		Visual (Knox cube)

## Tasks  (continued)

- _Aspects of Executive Function_
- 		Working Memory & Latencies
- 			Missing numbers (auditory)
- 			Abstract Designs (visual)
- 		Perseveration
- 			WCST
- 		Response Inhibition
- 			Stroop

##   Significant Cigarette Results

- _Before Adjustment_
- WRAT Reading
- WRAT Arithmetic
- WISC IQ
- Sentence Memory
- Knox Cube

- _After Adjustment_
- WISC IQ
- Sentence Memory

**Notes:**
WISC IQ 113, 109, 105
Sentence memory 57, 49, 38  Adjusted scores
Parental education primary variable that was adjusted

##      Significant Marihuana Results

- _Before Adjustment_
- Peabody Spelling
- Abstract Design Latency

- _After Adjustment_
- Peabody Spelling
- Abstract Design Latency

## Interpretation of Cigarette Findings

- IQ deficits consistent with earlier findings
- Vulnerability of verbal memory also consistent with findings at younger ages
- Why achievement tests not significantly related while IQ is after statistical adjustment?
- Possibly reflecting formal learning versus application of learning in new and different situations. Parental Education was major confounder

## Interpretation of Marihuana Findings

- Like in this & other cohorts at younger ages, IQ not related - contrast to prenatal cigarettes.
- Consistent with other reports, complex visual behaviour impacted (Peabody spelling versus WRAT spelling; longer latency [but not increased errors] on abstract design)
- Longer latencies (but not increased errors) also noted in visual search tasks in other cohorts. Possibly, the longer latencies reflect slower processing speed.

**Notes:**
No impact on WCST latencies - these latencies highly correlated with IQ, abstract design latency not correlated with IQ.

## Summary

- Present findings are consistent with and extend observations made in this cohort when 9-12 years of age and earlier.
- Differential impact of prenatal cigarettes versus prenatal marihuana
- Cigarettes impact on overall intelligence and verbal aspect of memory
- Marihuana does not impact upon overall intelligence but does on tasks requiring visual analysis.

## Slide 52

## QUESTIONS