Frontal lobe syndrome- impairments of attention, temporal integration (preceptumotor) motility, affect

Frontaltemporal lobar atrophy-45-65 year disinhibited-overactive, restless, dynamic aphasia-

restricted repertoire of speech Orbito-medial frontal lobe, temporal cortical atrophy

inert-apathetic, unresponsive lack of abstracton, planning, self-regulation

Dorsolateral frontalcortex. striatum, thalamus, amygdala

Progression-akinesia rigidity Imaging- 133-xenon inhalation and SPECT1: spongiform degeneration - Loss of cortical nerve sells 2: gliosis Pick's - microvaculation of neuropil Amytrophic (motor neuron disease) widespread vasculation, muscular weakness, bulbar palsyAlchoholism-corpus callosum interhemispheric discontinuation Marchiafava-Bignami

Sensory modality dissociation Spatial working memory-sulcus principalis Walker's 46/Brodmann's 46

mid-dorsolateral PFCPattern form working memory –Inferior dorsolateral PFC Walker's 12 Processing dissociation Self ordered nonspatial monitoring-

Dorsolateral PFC Walker's 9/Brodmann's 9,46Supra-modal working memory - Lateral PFC cross-modal

visual/tactile

Globus pallidus interna → substantia nigra → anterolateral thalamus medialdorsal Thalamus →

Striatum → globus pallidus externa → subthalamic nucleus ←

Orbitofrontal Cortex → caudate nucleus → dorsolateral thalamus Anterior cingulate cortex →

→ nucleus accumbens → globus pallidus ← Putamen longitudinal fasciculus

Procedural knowledge-measured by tasks expressed by prior changes in performance (habits/skills)

Explicit knowledge 100 ms responseIncrease in cortical motor output and decreased motor threshold

Progressive supranuclear palsy in basal ganglia-greater number of repetitions to achieve explicit response

Cerebello-cortical interaction – lateralized time index to events

Dorsolateral prefrontal cortex procedural learning not response execution

Baddeley's model-Dorsolateral-Prefrontal subcortical circuit -

retrevial, verbal fluency, calculation Supervisory controlling system Central Executive

Articulatory,Visuospatial- ability to hold memories for short periods while updatingOrbitofrontal subcortical circut-

socially modulated behaviorMedial Frontal Subcortical- motivation

Afferent EfferentOrbitofrontal(multiple sclerosis, head trauma, prions, herpes encephalitis)

Dorsolateral prefrontaltemporalamygdala

Dorsolateral prefrontaltemporal poleamygdala

Ventral caudate(mania) (dopamine)

AmygdalaVentral tegmentalSubstantia nigraMidbrain rapheMD thalamusSuperior temporal

Medial Globus Pallidus/Substantia negra(obsessive compulsive)

Ventral Tegmental

VA/MD thalamus (GABA) Prefrontal Cortex Amygdala

Orbitofrontal subcortical circut-socially modulated behavior

Afferent Efferent

Dorsolateral prefrontal cortex(depression)

OrbitofrintalParietal/Auditory associationCingulate gyrusRetrosplenial cortexParahippocampal gyrusPresubiculum

Orbitofrontal cortexCingulate gyrusRetrosplenial cortexParahippocampal gyrusPresubiculum

Dorsal Caudate(huntington's, neuroanthocytosis)

Substantia nigraParietalTemporalOccipitalMd thalamus

Subthalamic nucleus (glutamate)

Frontal association

VD/MD thalamus (GABA) Frontal cortexCaudate Nucleus

Dorsolateral-Prefrontal subcortical circuit Executive behavior-retrevial, verbal fluency, calculation

Afferent Efferent

Anterior cingulate Dorsolateral prefrontalVentral tegmental

Dorsolateral prefrontal

Nucleus accumbens Medial orbitofrontalPosterior insulaHippocampal subiculumLateral hypothalamusPerirhinal and enterorhinal

SeptumNucleus stria terminalisPeriaqueductal gray mattterMedial hypothalamusVentral tegmental

Ventral GP/SN Anteroir insularAnteroventral temporalCingulate cortex

Lateral habennulaCingulate cortexLateral hypothalamus

Medialdorsal thalamus Nucleus acumbens Amygdala

Medial Frontal Subcortical-motivation

“Mnemonic Processing” – PetridesMultisensory information is processed in the posterior association cortexRelating new info with stored representations leads to integration of new materialTransient storage multimodal posterior cortical association area → Ventrolateral frontal cortical connection → inferior frontal gyrusActive selection, comparison, judgement requiring conscious effortLinguistics– Left supramarginal gyrus → parietal post temporal (transient matinence)ventrolateral frontal (Executive functions) (45 Pars triangularis+47/12 Pars orbitalis) Mid-dorsolateral frontal Mnemonic memory manipulation - Medial temporal lobe

“dorsal dynamic ability disrupt automatic response” - Dubois EVR bilateral ablation venteromedial frontal - Social adaptive deficit sociopathyUnfitness to forecast future consequences of choicesPlanning problem solving conceptualizationWorking memory – ability to hold internal representations in short ter and manipulate mnemonic connections to provide behavior based on ideas rather than immediate stimuliBetween perception and action elaborating future action schemesDorsolateral PFC – delayed response tasks

Goldman-Rakic – Same function differentiated specific sense domainSpatial working – sulcus principalis 46 spatial response delayedPattern - inferior lateral PFC delayed object alternationHigh monitoring – Walkers 9 middorsolateral self ordered tasksCrossmodal working memory lateral prefrontalcortex

1 Encoding visiospatial information STM2, Matinence in short term storage3 Executive phase planning self generated responseProcessing spatial component within workingProcessing temporal ordering component of visual

Increased deficit response programming necicities manipulation complex repitioionsInability to supress involuntary inert emerging stereotypesInhibiton repeated behavior allow elaboration of goal related activitiesIncreased tendancy to alternate – lesion contention schedDifficulty modifing response after negative reinforcementMatinence of mental representations → excution self-programmedSpatial delayed response 2 squares 1 arrow dissapearsControl 10 correct sucessive response dorsolateral PFC ischemia 2.8 errors beforeSupramodal attentional deficit effect temoral processing sucessive stimuliDifficulty inhibiting nonpertient internal cuesDeficit judging recency Supervisory attentional systemTemporospatial recall test Square sucessive blue to redDL PFC lesions 4 → 9 test delayed # inncorect sequences to none

Goldman-Rakic at Yale“Architecture Prefrontal cortex and central executive”Baddely’s working memory modelCentral executive – articulatory loop and visuospatial scratch padWorking memory cardinal specialiazation of Prefrontal cortexCentral executive multiple segregated specialized domainsEach domain networks with sensor mnemonic motor motivationalSpecialized prefrontal cortex replicated in cortical subdivisions interactions causing cognitionPrincipal sulcus surrounded by 46 in monkeys – visuospatial sketch padRegistering sensory cues, holding it in line, releasing motor responseRemoval of target from view delay (50a0 ms) trigger maximal neuronal firing remaining till endMemory fieNeuron Location related to spatial location (out of sight, out of mind)Obeys distinction between working (PFC) and associative memory (hippocampus)Oculomotor delayed response paradigm visuospatial order

Guidance for subsequent saddic eye movementsRegistering sensory cue, holding, releasing response

Modular and columnar units, common spatial selectivities“Memory fields” removal of target, increase in firingContent specific neuronal firing accurate recallCompartmentalized architecture for processing mirror anatomyMatinence of representational information in absence of stimulusAnti saccade Paradigm suppress automatic tendancy to respond,

choosing oppositeStroop test – read word discordant ink colorEnhanced activity ODR delay presented to be remembered on rightSame neuron commanding oculomotor response engaged when suppressedPropositional thinking primate PFC mental processingInferior convexity specialized recalling stimuli attributes including color and form44/47 open ended verbal generationDifferent cells different time pointsPassive storage and processing

Stimuli in center of visual field enjoy faster perceptual processing called retinal acuity effectSpatial selective attention enhancing processing of eraly perceptual shystems in location specific manner. Spatial rehersal in which interaction of attentional perception mediates on line matinence of spatial information. Rehersal of spatial info corresponds to spatial selective attention, creating location specific change in visual provessing mechanismsAnalogus principal sulcus mediates visuospatial fieldRecognition of objects, patterns 12 inferior convexity of PFCSpatial/pattern delayed response either 39/40 spatial or 12/45 feature

Pascal-Leone valenceia SpainProcedural knowledge measured by tasksExpressed as changes in performance as a result of prior experiencesDeclaritive - aquizition of facts and information for reconciliationExplicit – awareness exposure to task results in improved performanceSerial reacion time test procedural

4 buttons 1 each finger 500 ms new number, # stays if incorrectRrepeated implicit → explicit reaction → anticipationNew motor skill adaptation cortical motor outputsSerial cortical mapping with transcranial magnetic stimulationPiano decrease motor threshold, increase output of flexor/extensorMultihand – switch increase reactiontime intermanual transfer only

mirroredSpatial coordinates of movememnts or motor output patternsMotor output coded implitic → explicit perceptually codedParkinsons – procedural uses declarative, increased repititionCerebrocortical interaction required for SRTT procedural

Self-ordered matching or conditional mid-dorsolateral frontal cortex 46/9 rightVerbal self-ordered/externally ordered bilateral mid dorsolateral fcOrbitofrontal cortex strong connection with medial temporal limbic region Medial (cingulate and subcallosal) frontal cortex damage cause recognition memory disorderFailed habituation to repeated presentation of stimuliCBf familiarity subtracted from novelty condition hypothesis activation in orbitofrontal cortex and adjacent limbic cingulate region as a result of novel inspection of stimuli and subsequent

encodingRecognition condition two stimuli, pick familiar activation of the

ventrolateral frontal cortex in recognition condition peak located between horizontal ramus and lateral orbital sulcus

47/12Extensive monitoring requirements mid-dorsolateral frontal cortexExplicit judgments held in short term memory ventrolateral frontal cortex

“Human rehearsal processes” PET- Awh, Smith, Jonides UMichWorking memory passive storage buffer and active rehearsal maintenance Word length effect- list recalled in order greater accuracy in shorter

pronunciation, Faster rehearsal, less likely word decaysArticulatory suppression effect-Veral working memory require to

articulate a familiar item, memory accuracy declines. Concurrant articulation disrupts implicit rehersal, declining recall

Positron emission – Intravenous catheter in right arm for radioactive tracer, band attatched to forehead, bolus injection 66 mCi of 15O

labeled water. PET acquision using Siemens CTI-931 08-12 5 s after count rate intervals at 14 min Transformed to sterotactic coordinate then linearly scaled to dimensions of standard atlas brain, normalizing pixel values for global flow-rate differences with data averages obtaining variances for two conditions of interest. Analyzed by performing post-hoc t tests and voxel-by-voxel basis then corrected showing stereotaxic coordinate Z-scoreMost areas of activation in left including 7/40 in parietal cortex 44 Broca’s- responsible for specifying the articulatory features of utterance to be internally generatedinferior 6 (premotor) and superior aspect of area 6 (supplementary motor area) high-level preparation and planning of movement

Shimamura “Memory and the Prefrontal cortex”Prefrontal lesions less likely to engage in useful organizational streategues such as subjective organization or category clusteringCategory cues and structure information of word list are semantic organization of new information not Retrieval of general semantic knowledge shows preponderance of left prefrontalRetrieval of episodic or aurobiographical preponderance of right prefrontalAB AC paired associate learning impairment in ignoring earlier associationsPrefrontal regions imparment in free recal over recognition memory producing greater susceptibility to interferenceMilner was first to observe frontal lesions impaired temporal order

Metamemory- “feeling of knowing” assessing what one knows and doesn’t know. Difficulty making estimates or inferences from everyday experiencesPrefrontal cortex dynamic filtering mechanism for irrelevant or extraneous processingAmplitude of middle latency auditory evoked potentials potentiated in prefrontal lesions disinhibition of posterior cortical activity.Normal individuals increase in dorsolateral prefrontal cortex related to decreases in activity in posterior cortical regions as a result of extensive reciprocal connections there is inhibitory control of response