Anterior thalamic syndrome

 

Ghika-Schmid F¹, Bogousslavsky J. Ann Neurol. 2000 Aug;48(2):220-7

The acute behavioral syndrome of anterior thalamic infarction: a prospective study of 12 cases.

 

Abstract

Using systematic investigations, including neurological and neuropsychological examinations and computed tomography and magnetic resonance imaging analyzed on anatomical maps, we prospectively studied 12 patients (age range, 63+/-19 years) with an isolated anterior thalamic infarct. They had acute, severe, perseverative behavior, which was apparent in thinking, speech, and all memory and executive tasks, combined with increased sensitivity to interference. They also showed superimposition of mental activities normally processed sequentially (e.g., giving biographical information while working on a calculation test), which we called palipsychism (from the Greek palin [again] and the Greek psyche [soul]). In addition, all 12 patients (8 with a left-sided infarct, 4 with a right-sided infarct) had word-finding difficulties, 7 of 12 with impaired naming, 8 of 12 with dysarthria, and 5 of 12 with hypophonia. Comprehension, repetition, written abilities, and reasoning were consistently preserved, but apathy was usual. All patients had anterograde memory impairment, with a delayed recall deficit, primarily verbal in left-sided infarcts and visuospatial in right-sided infarcts. Dysexecutive features such as difficulty in programming motor sequences were always present. Visual neglect or topographic disorientation was found in 3 patients. Magnetic resonance imaging emphasized involvement of the anterior group of thalamic nuclei, the mamillothalamic tract, and the anterior part of the internal medullary lamina, with structural sparing of the dorsomedial and ventrolateral nuclei. Sequential follow-up examinations showed spectacular improvement within a few months, with the only significant persisting abnormalities being memory dysfunction and apathy. The acute behavioral syndrome of anterior thalamic infarction is dominated by palipsychism, which corresponds to an overlap of sequential cognitive processes in two or more domains. Its association with severe perseverative behavior with increased sensitivity to interference, anterograde memory retrieval deficit, intrusions, naming difficulties with dysarthria and hypophonia, and apathy is suggestive of this type of infarct.

Koziol adjusted neuropsych exam

Need to adjust-- traditional tests lack tests of procedural learning, of reward systems.-

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Koziol notes the Tower tests, Card Sorting and others have convergent thinking; he advocates divergent thinking and creative ways to use existing tests.  For example readminister Trails A to get the best performance, the learning.  Trails B is harder, incorporates FPN but idea is same, speed should decrease with practice.  The cognitive control part diminishes as the test becomes routinized.  Similar for maze tests.  Don't norm it, use as individual self comparison (cites Reitan and Lezak).  Data would tell us about the individual's ability to automate. 

 

Prism Adaptation Task is very sensitive to the cerebellum. 

 

Programming motor sequences (Luria?) is the property of the frontal lobes.

 

Programming intention programs starting, perseverating, stopping, and lack of inhibition is basal ganglia governed.

 

Programming quality of movements, coordination, rate, rhythm,  and force of movements is under cerebellar control. 

 

Assessing reward paradigms:  Author pans the Iowa Gambling Test.  The "probabilistic category learning task" is utilized experimentally, successfully.  It measures whether people learn better before positive or negative outcomes.  The weather prediction task is another test that has been used experimentally.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

zs

Koziol: views of basl ganglia an cognitive control

1.  Basal ganglia are phylogenetically old and conserved for 560  millions of years. 

 

2.  There are  four cortical pathways that each contain a direct pathway D1 that releases behavior and an indirect pathway D2 that stops the behavior.  There is also a hyperdirect cortical path to the STN that generates global inhibition, and a fourth striosomal pathway from the paralimbic regions to the SN complex, that provides the basal ganglia with information about rewards of particular contexts.

 

3.  Basal ganglia subserve a variety of functions including category learning, motor learning, rule governed support of grammar systems, selection and gating of focused behaviors, cognitive control of working memory, and instrumental learning

 

4.  Through a series of excitatory and inhibitory processes, basal  ganglia gates behaviors based on reward based models.  How does it know what to gate?  D1  neurons stop GPi from inhibiting the thalamus.  However, it does so to release only a small specified behavior.  The behavior is amplified, the GO signal.  The decision is top down involving FPN and OF cortex, but once the behavior is represented in the premotor cortex, it can be gated outside cognitive conscious control.

 

5. Over time, a behavior shifts from cognitive loops to motor loops, and it also shifts from executive control to automatic control as it goes from limbic to DLPFC to OF to inf par to motor loops.  "Working memory" should be, but is not thought of as a dynamic, task dependent entity.  The "executive" can never be assessed except by task used to assess it. Hence EF tasks do not correlate with each other.  Towers tests, card sorting, and working memory tests do not predict each other.

 

 

Cerebrocerebellar circuitry

There are three systems in cerebellum:

1.Cortex to pons to deep cerebellar nuclei via mossy fiber projections

2. Neocortex to dentate nucleus to thalamus to cortex

3. Olive to cerebellum

 

What are they for? Cerebellum allows organism to predict or anticipate motor behaviors and produce rapi automatic predictive behaviors. These are called "internal models" and allow the cerebellum to copy the contents of the cortical "working memory"  or what the brain intends to do, which forms the basis of cerebellar cognitive control model.  The cerebellum can also adapt behavior across similar contexts, and become increasingly precise with practice.

 

Overlearned motor behaviors are represented in the anterior lobes of the cerebellum, whereas learning new sensorimotor information occurs in the posterior and inferior lobes of the cerebellum.

Koziol et al argue that it does for thought what it does for motor function and teaches the prefrontal cortex the anticipated rewards of an an action or thought.It underpins thinking and anticipatory cognitive control.

 

There are segregated modularities in the posterior lateral cerebellum for different tools.

 

 

Koziol Knowledge and anticipation

Knowledge about all behavior and rewards derives sensorimotor anticipation. Sensorimotor action is never random at any level of phylogeny. Hence impaired suck action as infant is associated with developmental anomalies.  The brain does not develop for thought, it develops to allow necessary interactions with environment, that cause knowledge.  Anticipatory actions include knowledge about reward values.  Anticipation drives all behavior. 

 

Corticobasal ganglia connections serve a binding function in the basla ganglia and procedural memories are stored in the supplementary motor and premotor cortices.  Learning new motor programs depends on posterior sensory elements as well.   However, this system is slow.

 

Fronto cerebellar systems are anticipatory systems, and allow motor responses that bypass the slower systems that incorpoate the sensory systems. The cerebellum learns to predict or anticipate motor behaviors after repeated practices or behaviors.  With the exception of the inferotemoral regions, every cortical system has segregated reciprocal connections with the cerebellum.

 

Humans have unique reciprocal connections, that are not present in animals, between the prefrontal cortices and the dentate nuclei of the cerebellum.These are important to attention, learning and memory and other aspects of cognitive control.

 

The basal ganglia is an instrumental learning  mechanism that operates on the basis of reward value.  It is a motor, cognitive and emotional gating center that operates on the basis of reward outcomes.  They select activities with positive rewards and avoid ones with negative rewards. 

Phylogeny of brain systems

These systems are superfluous and additive

 

1. System one-Automatic and somatic reflexes

2. Compound movements such as posture, breathing, saccadic eye movements and locomotion

3.  Functions such as nutrient, fight or flight reactions, sexual responses, feeding and drinking

4.  Motor activities involving cerebrum, basal ganglia and cerebellum eg. birds flying,

5.  Cerebral association functions in primates.

 

Notes expansion of cortex in mammals is proportional to expansion of striatum and cerebellum but in humans, cerebrum expands much more rapidly than the striatum.  The striatum receives projections from all cortical areas except the primary visual cortex.  The ratio of inputs is 20,000 cortical association neurons to 1 medium spiny neuron. It is estimated that 95 % of humans' activities are outside conscious cognitive control and are automatic.

 

Higher order systems of cognitive control coexist with primitive automatic systems. Vertically organized corticostriatal and corticocerebellar systems underlie cognitive control

Child development and attentional networks (from Koziol)

In children, FPN is less often activated and preferentially, caudate nucleus (CN) and insula are activated. In adolescents, wide rangig areas are activated.  Very young children cannot access CHC corticohippocampal cortical networks or FPN which are not developed as well, and typically "react"; by age 8 they may proactively access hippocampal contextual declarative (episodic and semantic) systems and FPN which is developing.  before that they do have working memory and can retrieve some information as it is needed for the moment.  Later, these systems in combination are part of the  working memory system.

 

As children develop, they increasingly develop capacity to react to contextual cues in their environment as their form of "cognitive control."  Later, they shift to recrutiing cognitive systems as they require it, and later proactively recruiting cognitive systems. 

 

Point is that over development, more brain systems are recruited into "cognitive control" but the systems remain dissociable, there is no cognitive control. 

Author notes that "composite score " of DS and letter number LN sequences are poor since they mask the findings of each.  Lexak says "composite scores have no place in neuopsychological assessment."  The correlation r between ds and LN is 0.49

 

Authors note that LN depends on procedurizing knowledge of letters and numbers as happens by middle childhood.  FPN is the flexible hub, and activates other brain areas as needed.

 

 

 

 

Digit Span PET san sctivation

digits forward  DF and digits backwards DB activate networks of FPN associated with working memory including right dorsolateralprefrontal cortex (DLPRC), bilateral inferior parietal lobue IPL, and ACC (anterior cingulate).  DB ALSO activates left DLPFC. ACC monitors effort  of performance, activates more with harder tasks.  Cerebellum also activates.  ACC to cerebellar peduncles support attention and working memory.

 

VN especially medial occipital play a role in orienting, maintaining and repressing attention.  It projects to both visual and auditory sensory processing areas. Both visual and auditory areas are activated with auditorily presented DS.

 

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Leonard Koziol Assumptions of brain organization

Traditional "domains" are artficial constructs:  language, visuospatial function, memory, attention, executive function, visuomotor integration. 

 

Frontal lobe construts such as working memory, inhibition, shifting and planning are not monolithic entitites.  All are multicomponent processes

 

Koziol says the functional arhitectural organization of the brain has other principal connections:

 

cerebrocortical,

cortical basal ganglia

cerebro cerebellar

basal ganglia cerebellar

 

Yeo and colleague J Neurophysiol 2011 described seven functional patterns of connnectivity:

 

FPN frontoparietal networks engages effortful cognitive tasks that require rules or information to be kept in mind for guiding behavior (cognitive control network)

 

VAN ventral attention network subserves object identification that includes contextual salience or reward value by identifying objects and what they are used for

 

DAN dorsal attention networks plays primary role in spatial attention, attentional shifting, object location and information about how objects are used.

 

VAN, DAN and FPN together form an "actional control network."

 

VN interacts with VAN and DAN to sustain attention and to suppress attention to irrelevant stimuli.

 

SMN sensorimotor network executes motor activity programmed by other networks.

 

LN limbic network interacts with the above to generate motivational and reward networks.

 

DMN default mode network is active at rest doing nothingbut thinking, imagining or dreaming

 

Castellanos et al. provides anatomy of above Trends  Cogn Neurosci 2012

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Wernicke area

Binder JR.  The Wernicke area; modern evidence and interpretation. Neurology; 2015;85:2170-75.

 

Blinder updates the concept of Wernicke area.  It currently is defined as pSTG and SMG, or posterior part of Brodman area 22 and area 40. 

 

Wernicke area is crucial for speech production, through its primary function of phonemic retrieval, but is not at all involved in speech comprehension, a reversal of the traditional notion.  Neuropsychologically, phonemic retrieval is demonstrated by visual rhyming judgment paradigms of testing.  This notion is supported by studies using fMRI, PET and MEEG studies as well as electrical stimulation studies.  Also in logopenic variant primary progressive aphasia, functional imaging shows involvement of the posterior STG and SMG.  

 

Re speech comprehension, lesions to Wernicke's area may cause conduction aphasia much more than comprehension disorders.  The latter are more likely to be related to lesions in medial temporal gyrus, angular gyrus, anterior STG,and areas in frontal lobes.  Comprehension is a two stage process, with the initial stage involving phonemic perception, which involves high level auditory areas in STG and superior temporal sulcus in both hemispheres.  These areas are anterior to Wernicke area. Bilateral lesions of these areas cause pure word deafness, which is rare. 

 

The second stage of speech comprehension,which involves a semantic network, includes a broader network of structures including AG, MTG, ventral temporal lobe, medial parietal, medial prefrontal,  and inferior lateral prefrontal. 

 

Lesions of Wernicke area would be expected to effect all aspects of speech production,including repetition, naming, reading aloud.  Speech repetition and reading aloud require input from the more anterior phoneme perception system (in the case of repetition) or letter/word perception system into the phoneme retrieval area (Wernicke area).  Spontaneous speech requires input from semantic areas into phoneme retrieval system.  A pure Wernicke area lesion would cause anomia or phonemic paraphasias.  This is seen, again, in lvppa and conduction aphasia,  although to a greater extent in lvppa.  A lesion of semantic areas would cause transcortical sensory aphasia.  Wernicke's aphasia would be caused by a lesion of phonologic retrieval (Wernicke area) plus semantic areas that are far larger. 

A systematic review of amnestic and non-amnestic mild cognitive impairment induc

Tannenbaum C, Paquette A, Hilmer S, Holroyd-Leduc J, Carnahan R; Drugs & Aging 29 (8), 639-58 (Aug 2012)A systematic review of amnestic and non-amnestic mild cognitive impairment induced by anticholinergic, antihistamine, GABAergic and opioid drugsCarnahan R; Drugs & Aging 29 (8), 639-58 (Aug 2012

 

Background: Mild cognitive deficits are experienced by 18% of community-dwelling older adults, many of whom do not progress to dementia. The effect of commonly used medication on subtle impairments in cognitive function may be under-recognized. Objective: The aim of the review was to examine the evidence attributing amnestic or non-amnestic cognitive impairment to the use of medication with anticholinergic, antihistamine, GABAergic or opioid effects. Methods: MEDLINE and EMBASE were searched for randomized, double-blind, placebo-controlled trials of adults without underlying central nervous system disorders who underwent detailed neuropsychological testing prior to and after oral administration of drugs affecting cholinergic, histaminergic, GABAergic or opioid receptor pathways. Seventy-eight studies were identified, reporting 162 trials testing medication from the four targeted drug classes. Two investigators independently appraised study quality and extracted relevant data on the occurrence of amnestic, non-amnestic or combined cognitive deficits induced by each drug class. Only trials using validated neuropsychological tests were included. Quality of the evidence for each drug class was assessed based on consistency of results across trials and the presence of a dose-response gradient. Results: In studies of short-, intermediate- and long-acting benzodiazepine drugs (n = 68 trials), these drugs consistently induced both amnestic and non-amnestic cognitive impairments, with evidence of a dose-response relationship. H(1)-antihistamine agents (n = 12) and tricyclic antidepressants (n = 15) induced non-amnestic deficits in attention and information processing. Non-benzodiazepine derivatives (n = 29) also produced combined deficits, but less consistently than benzodiazepine drugs. The evidence was inconclusive for the type of cognitive impairment induced by different bladder relaxant antimuscarinics (n = 9) as well as for narcotic agents (n = 5) and antipsychotics (n = 5). Among healthy volunteers>60 years of age, low doses of commonly used medications such as lorazepam 0.5 mg, oxybutynin immediate release 5 mg and oxycodone 10 mg produced combined deficits. Conclusion: Non-amnestic mild cognitive deficits are consistently induced by first-generation antihistamines and tricyclic antidepressants, while benzodiazepines provoke combined amnestic and non-amnestic impairments. Risk-benefit considerations should be discussed with patients in order to enable an informed choice about drug discontinuation or substitution to potentially reverse cognitive adverse effects.

60 Stars

cogweb

http://cogweb.ucla.edu/CogSci/

celebrities in cognitive neuroscience

http://carbon.ucdenver.edu/~mryder/itc_data/cogsci.html

evolutionary: brain size homo sapiens not largest

Brains of nonhuman hominids that had greater proportional brain size than homosapiens include

1. Boskops 1900 cc brains
2.  Fossils found in Shkul caves in Qafzeh, Israel; in Wadjak in Indonesia; Fish Hock of S Africa all were larger than humans' 1300 cc but not as large as the Boskops.

Counting-backward test for executive function in idiopathic normal pressure hydr

Kanno S, Saito M, Hayashi A, Uchiyama M, Hiraoka K, Nishio Y, Hisanaga K, Mori E; Acta Neurologica Scandinavica (Jan 2012)

OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.

Bedside testing of frontal lobes

Kramer JH, Quitania L in Miller BL, Cummings JL.  The Human Frontal Lobes functions and disorders.

Published tests:
D-Kefs
CANTAB
FAB
EXIT-  Executive Interview

bedside tests
fluency -- give F, A, S test and in alternate form give D only. Measure not only number of words produced, but also rule violations (giving responses with a different letter, and proper nouns) and repetitions.  Subjects who do worse on category fluency have more likelihood of temporal involvement, and those with letter fluency only are more likely to have frontal involvement.  Nonverbal analogue to letter fluency is design fluency. Show a box with five dots and ask them to create in one minute that have four lines that connect the dots. Several variations are used, one is d-kefs.

Mental flexibility-- on Trails B, Stuss et al. enhance the test by counting errors on Part B, which correlates best with DLPFC right sided injury. On DKEFS Trails, subjects alternate with letters and numbers.  Older patients maybe asked to shift between numbers and days of the week, with a record of time to complete task and how many sequencing errors are made.  Patients who cannot read may get Color Trails instead, connecting colored circles alternating between pink and yellow circles.  Alternate form of Trails:  Patients get one minute to create, from an array of dots (alternating half filled dots, half unfilled), as many designs as possible with four straight lines connecting dots.  In first form, they are asked only to use unfilled dots, in the second, to alternate between filled and unfilled dots. Design and rule violations (ie failure to shift) are recorded.

Abstract reasoning:    a) similarities between word pairs (dog/lion, table/chair. anger / joy)   and b) proverbs- eg. " An old ox plows a straight row" and "Shallow brooks are noise" and " A beard well lathered is half shaved."  Give credit for abstract and accurate answers.

Response inhibition:  a) Stroop-- tabulate correct responses in 60 seconds, and the number of inhibition errors.  b)  Salient responses :  Tell patient to to point to his chin while examiner touches nose, or tell patient to point to the ceiling while extending his hand   c) Opposite-- when I tap once, you tap twice, and vice versa.

Working memory-- backwards digit span, spelling "world" backwards, serial sevens, saying days of week backwards, months in reverse order.

primitive reflexes-- snout, suck and grasp and glabellar

Complex motor programs
1) fist palm edge task-- perform 10 times, record the number of trials to learn the task, the number of perseverations, and the fluency of the movements.
2)  Graphomotor sequences-- alternate m and n (cursive) elicit perseveration, micrographia.
3)  Rhythm test-- ask patient to imitate finger taps in complex patterns.

Behavior-- observe and record, use a modified Manchester Behavior Questionnaire to survery based on both information and report.  NPI and NPI-Q (short version) can be used (link to certification test: http://www.alz.washington.edu/cgi-bin/broker64)%20.%20May use the Dysexecutive Questionnaire (DEX) http://journals.lww.com/jonmd/Abstract/2008/01000/The_Dysexecutive_Questionnaire_Advanced__Item_and.13.aspx, Frontal Behavior Inventory (FBI) http://www.chumneurologie.org/conferences/FBI/FBI.pdf , and Frontal Systems Behavior Scale (FrSBE)

New Executive Brain VII Summary

Believes hippocampi is "center" for veridical decision making, DLPFC for adaptive decision making. 

Ventral tegmental lesions causing pseudofrontal syndrome

Goldberg et al. Cortex 1989  Reticulofrontal disconnection
update see Miller Nat Rev Neurosci 2000

DA depletion in midbrain caused frontal disconnection.
"Kevin" had retrograde without anterograde amnesia

Analogy- (partial) to schizophhrenia that also affects mesolimbic (temporal) and mesocortical (frontal) projections.  EG argues schizophrenia represents a top down organizing defect ie. a type of auditory agnosia.  Behav Brain Sci 1991.

New Executive Brain VI: Syndromes Orbitofrontal (OF) Pseudopsychopathy

Term is discarded.  However, OF lesions inject emotion into analytic decision making, prevent responding like an automaton. 

Social interactions:  ACC reins in amygdala.  In monkeys, ACC is more important than OF in socially appropriate behaviors (Ito et al.). 

EG argues, about moral reasoning and the frontal lobes, that understanding temporal relationships is key to understanding causation, and appreciation of consequences of behavior is necessary for moral reasoning.  Inferential reasoning of the if.then kind, is at basis both of language and of moral reasoning.  Counterfactuals, that is, if I had done this x then y would have happened, are impaired after OF damage.

New Executive Brain 3: Frontal lobe tests

Real life memory is not memorizing list given to us, but selecting task, and learning contextual information to task we chose.  Therefore the memory task is not "working memory" any longer. This may explain the disparity in frontal lobe role in memory in humans and animals.  Klingberg "The Overflowing Brain" (2008) gives a nice rendition of state of working memory.