COGNITION AND ECT Iannis M. Zervas, M.D. Athens University Medical School

COGNITION AND ECTCOGNITION AND ECT

Iannis M. Zervas, M.D.Iannis M. Zervas, M.D.

Athens University Medical SchoolAthens University Medical School

ECT effects on cognitionECT effects on cognition

MemoryMemory

OtherOther

ECT effects on memoryECT effects on memory

Apparent Apparent

RealReal

Apparent effectsApparent effects-positive-positive

Memory iMemory improvement (!)mprovement (!)

Inaccurate psychologically but Inaccurate psychologically but

crucial from a psychiatric crucial from a psychiatric viewpointviewpoint

Apparent effectsApparent effects-negative-negative

Residual psychopathology Residual psychopathology (depression)(depression)

Drug effects Drug effects (psych, anesthesia, other)(psych, anesthesia, other)

New psychosis New psychosis (young, new onset)(young, new onset)

Unmasking of dementia Unmasking of dementia (old)(old)

Subjective complaints Subjective complaints (various motives)(various motives)

Real effectsReal effects

DisorientationDisorientation

Anterograde amnesiaAnterograde amnesia

Retrograde amnesiaRetrograde amnesia

ECT AnterogradeRetrograde

recentremote

Time course Time course of memory disturbanceof memory disturbance

AcuteAcute

SubacuteSubacute

Long-termLong-term

ECT effects on non-memory ECT effects on non-memory cognitioncognition

Acute phase ( 0-7 hours)Acute phase ( 0-7 hours)

General intelligenceGeneral intelligence no change*no change* Perceptual functionPerceptual function no change*no change*

AttentionAttention -left side inattention-left side inattention-reduced -reduced

speed in speed in vigilance vigilance taskstasks

*No change can be attributed to ECT*No change can be attributed to ECT

ECT effects on non-memory ECT effects on non-memory cognitioncognition

Subacute phase (7-72 hours)

IntelligenceIntelligence no change or improvedno change or improved Language Language verbal fluency verbal fluency

may be affectedmay be affected

Perceptual/Visuospatial Perceptual/Visuospatial no change Motor function no change Motor function no changeno change

Higher cognitive/ frontal Higher cognitive/ frontal no changeno change

ECT effects on non-memory cognitionECT effects on non-memory cognitionMiddle subacute period (72 hrs -1 Middle subacute period (72 hrs -1

wk)wk)

IntelligenceIntelligence improvement MMSE improvement MMSE LanguageLanguage improvement improvement (rel. to (rel. to

depression)depression)

Perceptual Perceptual improvement improvement Attention/frontal no change Attention/frontal no change (better in (better in

reaction time)reaction time)

ECT effects on non-memory ECT effects on non-memory cognitioncognition

Late subacute phase (1 wk -7 mo)Late subacute phase (1 wk -7 mo)

IntelligenceIntelligence improved improved (or no change due to ECT)(or no change due to ECT)

LanguageLanguage no change no change (due to ECT)(due to ECT)

PerceptualPerceptual improved improved (normalized depr. changes)(normalized depr. changes)

MotorMotor improved improved ( trend)( trend)

Attention/frontalAttention/frontal improved mental shiftsimproved mental shifts no change in vigilance

Memory disturbance Memory disturbance Acute phaseAcute phase

PostictalPostictal

InterictalInterictal

Acute memory disturbanceAcute memory disturbance

PostictalPostictal

Acute memory disturbanceAcute memory disturbance

InterictalInterictal

Subacute memory Subacute memory disturbancedisturbance

MemoryMemory effects effects

Large inter-individual variability in:Large inter-individual variability in:

SeveritySeverity

Persistence (Persistence (ReversibilityReversibility))

Subjective tolerance / discomfort Subjective tolerance / discomfort

Factors affecting severity Factors affecting severity

Number of treatmentsNumber of treatments FrequencyFrequency Stimulus intensityStimulus intensity

Electrode placementElectrode placement

WaveformWaveform OxygenationOxygenation MedicationsMedications

Factors affecting Factors affecting persistencepersistence

Prolonged post-ictal disorientationProlonged post-ictal disorientation Pre-ECT cognitive impairmentPre-ECT cognitive impairment

Probably ageProbably age, , neurological illness neurological illness (e.g. Parkinson’s dis(e.g. Parkinson’s diseaseease) )

other obvious factors never studied other obvious factors never studied ( i.e. substance abuse, medications, ( i.e. substance abuse, medications,

cardiac output status, etc) cardiac output status, etc)

Attempts to ameliorateAttempts to ameliorate

Non-pharmacologicNon-pharmacologicalal methods methods ( schedule, oxygen, ( schedule, oxygen, electrode electrode placement, placement, etc)etc)

Various pharmacological methodsVarious pharmacological methods

ECT memory disturbanceECT memory disturbancePharmacological attemptsPharmacological attempts

ACTHACTH dexamethasonedexamethasone naloxonenaloxone vasopressinvasopressin T4T4 TRHTRH physostigminephysostigmine

caffeinecaffeine CaCa++ ++ channel channel

blockersblockers piracetampiracetam pramiracetampramiracetam inositolinositol ergoloid mesylates ergoloid mesylates herbal preparationsherbal preparations

Memory systems involved in ECT with related brain

structures

Short-term memory or immediate

Verbal Visual

Neocortex

Long-term memory

Declarative

Learning Retrieval

Medial temporal Lobe Diencephalon

Non-Declarative

Priming Procedural

Striatum/cerebellum Neocortex

Immediate / short-term memory (working memory)

Prefrontal cortex involved; Medial temporal lobe lesions spare this subtype

Dysfunctions after course of ECT (patients learn OK but forget fast)

Returns to baseline after a few weeks Old patients more sensitive plus difficulty

to learn new material. In 6 months no difference with younger.

Declarative memory* New learning (anterograde amnesia)

Transitory difficulties in retaining new information and in recognizing or retrieving information learned some time previously

Increases with increasing number of treatments

Not associated with global cognitive dysfunction

Recovers within a few weeks after ECT

*conscious recollection of facts and events, autobiographical or public

Declarative memoryRemote memory (Retrograde amnesia)

Deficits in recall of autobiographical facts and events learned before ECT

Temporal gradient ( more so for events within the year prior to ECT)

Worse with bilateral Worse with sinewave treatments Reversible by 3 -6 months

Non-declarative memory*No change

includes

• procedural learning ( neostriatum)

• classical conditioning ( amygdala, cerebellum)

• perceptual priming (cortical areas)

Implicit memory**

No change

*non-conscious recollection of performance

**non-conscious ability to learn spatial and temporal data

Neurobiological correlates

Transient disruption of mechanisms for consolidation, retention, maintenance

Disruption of LTP related to persistence of stimuli, specificity /plasticity, associative organization

Possibly causes massive long-term induction of potentiation and saturates synaptic strengths obstructing formation of new memories

Time course of memory disturbance coincides with LTP disruption

Related to mesial temporal lobe; less affected by bifrontal treatments

Neurochemical correlates

ECT inhibits activity of central cholinergic system= decrease in cholinergic transmission

Excessive release of excitatory amino acids and activation of their receptors

Ketamine ( NMDA antagonist) may be better alternative for anesthesia

In support ofMedial Temporal Lobe (MTL)Dysfunction in ECT memory disturbance

role of MTL in memory low seizure threshold in hippocampus LTP disruption (ECS) is a

hippocampal process theta activity in left frontal and

temporal sites associated with greater retrograde amnesia for autobiographical information

In support of involvement of Prefrontal Cortex (PFC)in ECT memory dysfunction

Most profound physiological effects of ECT found in PFC -reductions in CB,

-reductions in metabolic rate, -EEG slow wave activity

Retrograde amnesia greater for public events ( PFC) not autobiographical (hippocampus)

Tests of frontal lobe function can co-vary with tests of retrograde amnesia

SUMMARYSUMMARY

ECT affects selectively memory ECT affects selectively memory parametersparameters

There is large inter-individual There is large inter-individual variabilityvariability

Memory disturbance is not related to Memory disturbance is not related to clinical effects on depressionclinical effects on depression

SUMMARYSUMMARY Memory disturbance is in general Memory disturbance is in general

reversiblereversible

In some cases some retrograde In some cases some retrograde amnesia for sporadic events (public amnesia for sporadic events (public mainly) may persistmainly) may persist

Both mesial temporal lobe and Both mesial temporal lobe and prefrontal cortex (lowest seizure prefrontal cortex (lowest seizure threshold in brain) have been threshold in brain) have been implicated in memory troubleimplicated in memory trouble

CONCLUSIONCONCLUSION One should keep in mind that for most One should keep in mind that for most

patients memory improves patients memory improves

Cost-benefit analysis for the patient Cost-benefit analysis for the patient

Simple measures can contain Simple measures can contain disturbancedisturbance

Memory parameters should be Memory parameters should be monitored systematically - best to monitored systematically - best to acknowledge and support / educate acknowledge and support / educate patient and family patient and family