Sunday, January 3, 2016

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. 

Saturday, October 31, 2015

From: Daniel Jacobs

Tuesday, September 11, 2012

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.


Sunday, February 19, 2012

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.

Tuesday, February 7, 2012

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.

Sunday, September 5, 2010

Bedside testing of frontal lobes

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

Published tests:
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: use the Dysexecutive Questionnaire (DEX), Frontal Behavior Inventory (FBI) , and Frontal Systems Behavior Scale (FrSBE)

Saturday, September 4, 2010

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.

The New Executive Brain V? Emotional brain, basal ganglia etc

Davidson et al. Left hemisphere lesions produce negative affect especially if they are closer to the frontal pole.  Right hemisphere lesions produce euphoria.  Left hemisphere activates to happy film, financial gain, right hemisphere to sad film and financial losses.  In the Ultimate Game, the right hemisphere activated to unfair offers.  Suppression of memories occurs via right or bilateral DLPFC affecting the right hippocampus.Meditation, deactivates left frontal.  Vicarious pain (watching others suffer) activates right frontal.  (Naomi Eisenberger,et al. Science 2003, study of social exclusion). 

Frontal lobes modify attenuate the amygdala (the "pre" prefrontal lobe actor); this done through orbitofrontal cortex.  The amygdala also show evidence of valence mirroring that of evolutionarily later frontal lobe, ie left positive valence, right negative.  Suppressing negative emotions is left DLPFC on left amygdala, fear engendering stimuli affect right amygdala, and lesion of right amygdala reduces the ability to experience fear.  Anxiety may be associated with a large or hyperactive right amygdala.  Emotionally charged crimes may be related to large right amygdala.  Removal of right amygdala may attenuate ability to appreciate emotion of fear in others' faces. 

In gambling experiment, both prefrontal and amygdalaoid lesions interfered with decision making, but only amygdaloid lesion was associated with a change in skin response.  Distant threats in a virtual reality environment were mediated by DFPFC, but immediate threats were mediated by amygdala. 

Author argues novelty/familiarization dichotomy can tie up loose ends of verbal/nonverbal debate. 

Parkinson patients avoid choices leading to bad outcomes (risk aversion) more than selecting ones leading to a good outcome.  (Frank et al., Science 2004). 

The New Executive Brain 3: Tests of Frontal Function

In real world, we choose a path and learn information we need; in memory tests we are given a list of words and told to memorize.  Difference is role of frontal lobes.  Hence, animal experiments show a more pronounced role for frontal memory than human experiments.  CVLT allows semantic clustering, which (postulated) may be due to frontal activity.  Most working memory tests lack a selection component.   Frontal role is to select information and hold it online and manipulate it as long as is needed.

Courtney et al. (Cereb Cortex 1996) showed faces on a grid then another set of faces with "what" question and "where" question, which respectively, activated ventral and dorsal visual stream representations within the frontal lobes (inferior and superior). 

"How does an organism decide what information is important enough to be kept online" is a question that has been ignored in almost all neuropsychological paradigms.  Goldberg divides decision making into veridical and ambiguous.  Veridical is "I spend 300 of 1000 dollars, how much is left?"  Ambiguous or adaptive is "Shall I wear gray, blue, or white?"  What is the answer?  Gertrude Stein asked "What is the question?"  Disambiguation may requires prioritizing (remember Buridano's donkey from Luria's books).  Individual must be able to disambiguate in multiple ways and switch set ( "White is for spring, but white is not allowed at school so I will wear gray").  Veridical decisions find the truth, adaptive ones find what is best for the organism. 

In Cognitive Bias Test, individual is given a card and asked to pick the one "they like the most."  Then they were asked to find the choice "most similar to the target" then the one "most different from the target."  Frontal lobe is required only for the first condition, the only one requiring disambiguation.  Frontal lesions did not affect the second and third conditions.  In Alz disease, the disambiguating test declined much faster.  Verdejo found same in individuals with substance abuse (altered adaptive but not veridical decision making).

Males made choices on CBT in a context dependent way, that is when the targets changed, so did their choices.  Females made context independent choices, that is their choices were stable regardless of target.  This is first account of gender differences in adaptive decision making.  Males with damaged right frontal lobe performed in an extremely context dependent manner, and males with damaged left frontal lobes performed in an extremely context independent manner. In females, damage to either frontal lobe caused context dependent choices.  The Wisconsin Card Sorting Test failed to differentiate laterality of the lesion. 

The effects of posterior lesions were less robust than those of frontal lesions, but were nonetheless dimorphic.  In males, posterior temporal lesions followed frontal lesions:  left sided lesions made males more context independent, and right sided lesions made males more context dependent.  In females, posterior lesions were opposite frontal lesions: on either side, they made decision making more context independent. 
Goldberg argues that in male laterality is more articulated, but in the female, front-back differences are more articulated. 

In functional imaging experiments, when asked to process verbal information, males coactivated front and back in same hemisphere, whereas females coactivated homologous regions across hemispheres.  Males have greater functional differentiation of the hemispheres, whereas females have greater functional integration of hemispheres-- note they also have bigger callosa.  However, males have larger longitudinal fasciculi within hemispheres (see book for citations). 

An overwhelming number favored similarity over novel among humans on the CBT (unlike other primates who picked the novel object).  However, that is only true among righthanders.  Among lefthanders, many picked the choice that differed from the target, not the one similar to it.  J Cogn Neurosci 1994. EG suspects that the 9:1 balance in favor of right handers represents evolutionary needs for stability versus innovation.  Functional roles of left handers may be reversed on CBT (Ibid.). 

The New Executive Brain 2: Novelty, subroutines, and hemispheres

1. Yakovlevian torque (see Lemay, Ann Ny Acad Sci 1976) shows the right frontal lobe is wider than and protrudes over the left, and the left occipital lobe is wider than and protrudes over the right.  This present in great apes to some degree, and there are gender differences.  Other assymetries include the planum temporale is larger in left side in human and this is also true in several other primates.  Spindle cells with long axons are more numerous in the right hemisphere.  White matter is more organized in the right than left frontal lobes in children and adults (Klingberg et al., 1999, Neuroreport).  Dopamine is more prevalent in the left hemisphere, norepinephrine on the right, and estrogen receptors are more prevalent on right (rats) Sandu et al, Exp Neurol 1985.  Goldberg argues that hemispheric assymetries exist in animal species and these cannot be based on language since animals lack language.  Is language a "special case" of some larger difference?

2.  Other right - left approaches (analytic/holistic, sequential/simultaneous processing) are difficult to operationalize and are rejected.

3. Bates E argued that in children, left hemisphere brain damage is inconsequential, but in right hemisphere patients it is devastating (in Bronan SH ed, Changing Nervous System:  neurobehavioral consequences of early brain disorders, Oxford University Press, 1999).

4. History of civilisation is right to left shift; translating Vygotsky cultural historical psychology in neuroanatomical terms would reach similar conclusion

5.  In neuropsych tests, averaging across six categories of WCST, the five trials of CVLT, and 30 trials of Benton Lines is not accurate anatomically.  Should rescore old tests with that in mind. 

6.  Agnosias:  leitmotif is left hemisphere is top down process, unable to recognize unique exemplars of generic categories "associative agnosias."  Right hemisphere lesion cannot recognize exemplars as their own selves or as different exemplars of same category ("apperceptive agnosias").  see Goldberg JCEN 1990.

7.  Animals may have paw prefence but its closer to 50-50 unlike humans. 

8.  Frontal function:  divide into perseverative (difficulty with cognitive flexibility) unable to transition from one activity to another; and field dependent behavior (echopraxia/echolalia).  Traditionally these are known as 2 aspects of executive control, ability to guide behavior by internal representations and ability to shift cognitive sets with exigencies.   These may be referred to as "stability" and "plasticity" as well.  Author postulates that D1 receptors maintain low level maintenance of current cognitive regime, and D2 receptors respond only to high levels of dopamine and cause destabilizing rapid updating of the cognitive regime, favoring the right hemisphere.  On Executive Control Battery,  perseveration was twice as common following left hemisphere injury.  Echopraxia was twice as severe after right hemisphere injury.  However, these differences were present only in men.

4. Authors Goldberg and Costa postulated the right hemisphere is important to cognitive novelty and the left to cognitive subroutines (Brain Lang 1981: 144-173).  Information is processed from novel to familiar.  .  The left hemisphere information is stored in better articulated neural networks and easier to access. The right hemisphere is modified at a slower rate than the let hemisphere.  It deals with novelty better due to it contains averaged default representation containing shared  poorly differentiated features of many prior situations.  The evidence that supports include Bever and Chiarello (Science 1974) who showed untrained musicians process with their right hemispheres, trained ones with their left hemispheres.  He discusses obscure / familiar faces as being processed with right and left, (Henson et al, Science 2000).   Alex Martin et al. (Hippocampus, 1997) used PET to show that with presentation of meaningful words, nonsense words, real objects and nonsense objects, the right mesiotemporal lobes were activated with first, novel presentation, decreasing with the second exposure. The left hemisphere activation was constant.  Learning a complex motor skill activated first the right MFG, then late in training left posterior parietal cortex, left dorsal premotor cortex,and right anterior cerebellar cortex (Shadmehr and Holcomb, Science 1997).

More studies:  learning grammar A and B:  initial activation occurred in right ventral striatum, left premotor and anterior cingulum, replaced gradually by activation of right DLF and right posterior parietal (Berns et al.  1997 Science).  Raichle (cereb Cortex 1994) found on  a task of finding appropriate verbs for nouns, in naive condition activated ACC, left prefrontal, left temporal, and right cerebellum, but after practice only left medial occipital was activated.  A task with longer processing has right hemisphere to a greater degree.

5.  Constructs that are analagous to the novelty/familiarity distinction:  Exploration/exploitation ( eg. gambling task, novel learning of task and exploiting task to make money) involved right frontopolar regions and left DLF regions respectively (Daw et al. Nature 2006 and Heekeren et al. Nature 2004).  Another distinction is critic and actor; critic learns to predict future awards and actor uses the rewards to guide behavior.  The "critic"  in an fMRI study is the bilateral putamen and right ventral striatum, and the actor is the left anterior caudate.  This resonates with an older idea that the OF lobes appraise value to person and prefrontal cortex navigates the external world. 

6. Pathologic augmentation of orientating reaction (PTSD) has ep activity mostly in right hemisphere (Metzger, 2005 in Vasterling and Brewin). 

The New Executive Brain by Elkhonon Goldberg I

Goldberg reviews much more information in this book than can be summarized here, but I would like to go over certain information that would be critical to Goldberg's overall "brain view."  I also include random references from the book that are less pertinent but interesting background nonetheless.

Goldberg is a protege of Alexander Luria's, but emigrated from the USSR in the early 1970s, establishing a career in New York, academic, eventually private practice.  He opens with a reference to The Creation of Adam, a painting in the Cistine Chapel that Goldberg presents as representing an allegory of the frontal lobes. 

1.  The left inferior prefrontal cortex becomes active when presented with statements with semantic violations (:"trains are sour").  Hagoort et al., Science 2004.  fMRI study.  Language and executive functions arose together.  Language builds models, executive functions manipulates them and conducts operations on them.

2.  Goal formation is action centered about "I need" not "It is."  Therefore, formation of goals relates to the emergence of the mental representation of the self, in turn related to the development of the frontal lobes.

3.  The dorsomedial thalamus nucelus is the highest point of integration in the thalamus and has many connections with the frontal lobes.  It also maintains connections with the hippocampus (memory), the cingulum (emotion and uncertainty), amygdala (relations among individuals in species) and hypothalamus (in charge of homeostatic functions). 

4.  Goldberg speaks of the "fallacies" of modularity (the high tech revival of 18th century phrenology").  For example, the planum temporale is critical for phonologic processing, but is not narrowly dedicated.  Rather, it is critical for auditory analysis in a categorical sense (is the sound a dog barking, a cat meowing , etc.).  It activates both when phonological discriminations are made and when environmental sounds are matched with their sources.  Fusiform gyrus is associated with facial recognition.  Goldberg differentiates between a prior, preordained modularity and a posteriori, resultant modularity.  A priori means the area is hard wired for the task.  A gradiential view of neocortical organization means that certain tightly  integrated neuronal groupings  emerge over time, due to cognitive history of individual.  This means is has less uniformity, more individual differences and will change over time.  The left hemisphere, which has more dedication to "subroutines" has more modularity and the right hemisphere has less.  Goldberg published his gradiential theory of modularity in 1989 in JCEN and republished as a book chapter in 1990 (Contemporary Neuropsychology and the Legacy of Luria, 1990).  "Modularity is best applied to an evolutionary old structure, the thalamus."  Goldberg discusses the "dynamic topology" of cortex and the evolving role of the thalamus in its new inferior position in the hierarchy, which is a reason its function has been elusive.

5.  Jordan Grafman et al. showed in an fMRI study that when a cognitive task is characterized by a hierarchy of goals, the regions around the frontal lobes are activated when subjects have to keep in mind the main goal while performing subordinate goals (Nature, 1999).  This was supported by D'espositio et al.who showed that increasingly abstract goals activate increasingly anterior portions of the frontal lobes.  Anterior prefrontal cortex  has a high number of dendritic spines per cell and high spine density, making it ideal for a variety of inputs.

6.  E Koechlin et al (Science 2003) introduced the notion of a "hierarchical cascade of executive processes."   The control operates in Brodman areas 6 (premotor), 44/45 (inferior frontal) and 46 (middle prefrontal) at level of stimuli, perceptual context, and temporal episode, respectively.  Goldberg analogizes to perseveration  of elements , features and activities, respectively. 

Tuesday, August 10, 2010

cognitive effects of androgen deprivation


Cognitive effects of androgen deprivation therapy in an older cohort of men with prostate cancer; Mohile SG, Lacy M, Rodin M, Bylow K, Dale W, Meager MR, Stadler WM; Critical Reviews in Oncology/Hematology 75 (2), 152-9 (Aug 2010)

OBJECTIVE: To determine the baseline prevalence of cognitive impairment in older men treated with ADT and to assess changes in cognitive performance over time. METHODS AND RESULTS: Thirty-two patients (median age of 71 years, range 51-87) were administrated an extensive neuropsychological testing battery prior to ADT initiation, with 21 (65%) completing post-treatment evaluations 6 months later. At baseline, 45% scored>1.5 standard deviations below the mean on>or = 2 neuropsychological measures. Using standardized inferential statistics, no change in cognition was documented following treatment. The Reliable Change Index revealed that, on a case-by-case basis, 38% demonstrated a decline in measures of executive functioning and 48% showed improvement on measures of visuospatial abilities. Within exploratory analyses, patients who scored below expectation at baseline displayed no change in cognition, while patients with average or better scores at baseline displayed improvements in visuospatial planning and timed tests of phonemic fluency. CONCLUSIONS: We found a high prevalence of lower than expected cognitive performance among a sample of patients just starting ADT for prostate cancer. Assessment of baseline cognitive function should be taken into account for future research and to inform clinical management.


Tuesday, July 27, 2010

Detestable or marvelous: Neuroanatomical correlates of character judgments

Croft KE, Duff MC, Kovach CK, Anderson SW, Adolphs R, Tranel D.

1. Neuropsychologia. 2010 May;48(6):1789-801. Epub 2010 Mar 6.
Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, University of Iowa College of Medicine, IA, USA.


As we learn new information about the social and moral behaviors of other people, we form and update character judgments of them, and this can profoundly influence how we regard and act towards others. In the study reported here, we capitalized on two interesting neurological patient populations where this process of complex "moral updating" may go awry: patients with bilateral damage to ventromedial prefrontal cortex (vmPFC) and patients with bilateral damage to hippocampus (HC). We predicted that vmPFC patients, who have impaired emotion processing, would exhibit reduced moral updating, and we also investigated how moral updating might be affected by severe declarative memory impairment in HC patients. The vmPFC, HC, and brain-damaged comparison (BDC) participants made moral judgments about unfamiliar persons before and after exposure to social scenarios depicting the persons engaged in morally good, bad, or neutral behaviors. In line with our prediction, the vmPFC group showed the least amount of change in moral judgments, and interestingly, the HC group showed the most amount of change. These results suggest that the vmPFC and hippocampus play critical but complementary roles in updating moral character judgments about others: the vmPFC may attribute emotional salience to moral information, whereas the hippocampus may provide necessary contextual information from which to make appropriate character judgments. 2010 Elsevier Ltd. All rights reserved.

PMCID: PMC2862792 [Available on 2011/5/1]

Damage to right ventromedial prefronal area abolishes judgment of harmful intent

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Neuron. 2010 Mar 25;65(6):845-51.


Moral judgments, whether delivered in ordinary experience or in the courtroom, depend on our ability to infer intentions. We forgive unintentional or accidental harms and condemn failed attempts to harm. Prior work demonstrates that patients with damage to the ventromedial prefrontal cortex (VMPC) deliver abnormal judgments in response to moral dilemmas and that these patients are especially impaired in triggering emotional responses to inferred or abstract events (e.g., intentions), as opposed to real or actual outcomes. We therefore predicted that VMPC patients would deliver abnormal moral judgments of harmful intentions in the absence of harmful outcomes, as in failed attempts to harm. This prediction was confirmed in the current study: VMPC patients judged attempted harms, including attempted murder, as more morally permissible relative to controls. These results highlight the critical role of the VMPC in processing harmful intent for moral judgment. (c) 2010 Elsevier Inc. All rights reserved.

Hippocampal damage abolishes stress response

Department of Psychology, Saint Louis University, St. Louis, MO 63103, USA.


The hippocampus (HC) is necessary for learning and memory, but it also plays a role in other behaviors such as those related to stress and anxiety. In support of the latter idea, we show here that bilateral HC damage abolishes the cortisol response to psychosocial stress. We collected salivary cortisol, heart rate, and affective responses to the Trier Social Stress Test (TSST) from 7 participants with bilateral HC lesions, 12 participants with damage outside the HC, and 28 healthy normal comparison participants matched to the HC participants on age and sex. HC participants showed elevated pre-stress cortisol, but no cortisol response to the TSST. Heart rate and affective responses in the HC group were similar to those of the comparison groups. Participants with brain damage outside the HC showed stress responses that were comparable to those of the healthy comparison group. These findings support the idea that the functions of the human HC extend beyond learning and memory, and suggest that the HC is necessary for producing the cortisol response to psychosocial stress.

PMCID: PMC2692817 [Available on 2010/6/1]

Localization of Benton Facial Recognition Test and J. Lo.

Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, University of Iowa College of Medicine, Iowa City, IA, USA.


Two of the most successful and widely used tests developed by Arthur Benton and colleagues are the Facial Recognition Test (FRT) and Judgment of Line Orientation Test (JLO), which probe visuoperceptual and visuospatial functions typically associated with right hemisphere structures, especially parietal, occipitoparietal, and occipitotemporal structures. Taking advantage of a large database of focal lesion patients (the Iowa Neurological Patient Registry), we used a new lesion-deficit mapping technique to investigate the neuroanatomical correlates of FRT and JLO performance. For the FRT, there were 201 patients with relevant data; of these, 38 were impaired on the FRT, and failure was most strongly associated with lesions in the right posterior-inferior parietal and right ventral occipitotemporal (fusiform gyrus) areas. For the JLO, there were 181 patients with relevant data; of these, 23 were impaired on the JLO, and failure was most strongly associated with lesions in the right posterior parietal region. These findings put new empirical teeth in the localizing value of the FRT and JLO tests, and they extend and sharpen previous work that had pointed to right posterior structures as being important for FRT and JLO performance

PMCID: PMC2853018 Free PMC Article

PMID: 19051129 [PubMed - indexed for MEDLINE]

Focality of clock drawing test determined by error type

Division of Behavioral Neurology and Cognitive Neuroscience, University of Iowa, IA, USA.


The Clock Drawing Test (CDT) is widely used in clinical neuropsychological practice. The CDT has been used traditionally as a "parietal lobe" test (e.g., Kaplan, 1988), but most empirical work has focused on its sensitivity and specificity for detecting and differentiating subtypes of dementia. There are surprisingly few studies of its neuroanatomical correlates. The authors investigated the neuroanatomical correlates of the CDT, using 133 patients whose lesions provided effective coverage of most of both hemispheric convexities and underlying white matter. On the CDT, 30 subjects were impaired and 87 were unimpaired (16 were "borderline"). Impairments on the CDT were associated with damage to right parietal cortices (supramarginal gyrus) and left inferior frontal-parietal opercular cortices. Visuospatial errors were predominant in patients with right hemisphere damage, whereas time setting errors were predominant in patients with left hemisphere lesions. These findings provide new empirical evidence regarding the neuroanatomical correlates of the CDT, and together with previous work, support the use of this quick and easily administered test not only as a screening measure but also as a good index of focal brain dysfunction. PsycINFO Database Record (c) 2008 APA, all rights reserved.

PMCID: PMC2834527 Free PMC Article

Sunday, July 25, 2010

Neurology of lying-- localizaion

Spence et al. Neuroreport 2001.  longer rt's and activation in VLPFC.
Langleben et al. Neuroimage 2002-- guilty knowledge test (GKT) and fMRI showed activation in SFG and ACC. 
Ganis et al. Cereb Cortex 2003.  right anterior prefrontal cortex was involved in well rehearsed more elaborate lies, whereas a network involving anterior prefrontal cortex involved in spontaneous lies.
Kozel et al J Neuropsychiatry and Clin Neurosci 2005- OF cortex and ACC involved in deceptio
Abe et al. (Brain 2009) noted PD patients are "honest" and have trouble lying, and that left DLPFC is dominant for inhibiting replies, esp truth telling, ie feigning ignorance. 
Karim et al. Cereb Cortex-- TMS of left cortex FACILITATES lying perhaps by relieving moral conflict.
Sellal JNNP 1993- reflex epilepsy, patient had seizures when he lied.  Had meningioma in right anterior clinoid.  Tumor pressed on amygdala. 
Hakun et al Neurocase 2008-- fMRI as lie detector-ventrolateral frontal activated even when lying was not demanded explicitly
Seth et al.  Neuroimage 2006- MEEG can be used for trial by trial detection of lies.
Modell et al.  J Neuropsychiatry and Clin Neurosci 1992-- pathological lying associated with decreased tracer uptake in right thalamus.
Yang et al. Br J Psych 2007.  Increased white matter among pathological liars especially OF, IFG, MFG.
Fenelon et al. BMJ 1991 and other cits.-- Munchhausen's s- associated with bilateral frontotemporal atrophy, hyperperfusion of right thalamus, cerebral palsy, high signal in PVWM bihemispheric. 
Grezes et al J Neurosci 2004.  detecting deception activates amygdala and rostral ACC.
Harada et al.  Neurosci Research 2009- moral and lie judgments activate VMPFC, lateral OF, left temporal, left temp-par junction, and right cerebellum.
Etcoff et al. Nature 2000- loss of language due to left MCA stroke was associated with increased ability to detect deception.
Stuss et al. Brain 2001-  bilateral esp right OF lesions impaired ability to detect deception.
Autistics have trouble lying.

Saturday, July 24, 2010

Go, no go task, parcellated and localized within the VLPFC and pre SMA

Chikazoe J.  Localizing performance of go/no-go tasks to prefrontal cortical subregions.  Curr Opin Psych 2010; 23: 267-272. 

Author divides go/no go tasks into components including working memory, stimulus-driven attention ( reorienting of attention), error monitoring, top down control processes, and response inhibition.  The literature suggests the VLPFC is key to response inhibition (see Buxbaum et al, Hum Brain Mapping 2005).  However, DLPFC and pre-SMA also are recruited for this task and for stop-signal and for antisaccade tasks.

Transcranial magnetic stimulation of right VLPFC disrupts response inhibition, but stimulation of left IFG, DLPFC, dorsal premotor cortex, and right angular gyrus does not.  Subregions of the VLPFC play different roles.  The subregions are posterior IFG, inferior frontal junction, and IFG/insula. 

pIFG usually activates with go/no go stimuli.  IFJ, located at border of inferior frontal sulcus and precentral sulcus, is associated with processing infrequent stimuli.  Thus pIFG is the "core region" for go/no go response inhibition. The same area is involved in reorienting attention (see Corbetta M, Neuron 2008).  The reorienting attention network involves pIFG, IFJ, IFG/insula, and temporal parietal junction.  This is segregated from a dorsal network involving the frontal eye fields (FEF), and intraparietal sulcus that employs a top down mechanism . pIFG may activate with both networks and provide the communication between the two. 

IFJ is involved in stimulus driven attention and is more involved in processing infrequent stimuli, such as infrequent go or infrequent no go on go/no go tasks.  By contrast pIFG is only activated on infrequent no go. 

IFG insula is activated, but is tough to differentiate from insula and IFG insula is also activated in many other tasks.  Its function is not specific and it may be more related to task awareness. 

Pre SMA on right is also core to response inhibition.  This is true on both lesion studies and TMR studies.  Pre SMA is robustly activated during go/no go whether the task is simple or complex or whether the test is oral or manual.  Pre SMA is thought to be important to conflict resolution of task.  The anteriror cingulate gyrus (ACC) activates for error processing.  DLPFC activation may be related to top down processes and working memory. 

Hemispheric asymmetry with right sided dominance is noted in most studies especially for pIFG.  However the left pre SMA and VLPFC may be important.  "Balance" may be disrupted with left sided lesions that can thus cause deficits on task also. 

Coin rotation test validation

Hill BD et al. The Neurologist. 2010; 16: 249-253
Authors validate a longstanding easy test for fine motor processing used for decades at LSU in 86 normals.  Task consists of counting number of 180 degree rotations of a quarter in ten seconds by the dominant and nondominant hands.  A correction for drops is used, but not that important.  Task is to rotate a quarter using thumb and fingers one and two in ten seconds with an examiner using a timer and counting.  If the coin is dropped, the subject gets another ten seconds.  The adjusted score is the number of rotations in ten seconds minus (0.1 x rotations x drops).  Traditionally, LSU has used a cut score of ten to indicate impairment.  Authors believe a cut score (for both hands) of 13 is better, with increased sensitivity and some loss of specificity.

Sunday, June 13, 2010

Hyperfamiliarity for faces (HFF) in epilepsy- left temporal localization?

Devinsky O  et al.  Neurology 2010;74: 970-974

Author reviews literature and attributes the first case to Kraepelin (1886).

Case one-- 46 yo policeman had a GTCS preceded by an aura of anxiety, deja vu and sulfuric smell. One month later the patient developed HFF (everyone seemed familiar), memory problems, distractibility and hyperemotionality for sadness.  FRT performance was low average but patient was impaired on Rey O delayed recall.

Case 2-  62 yo rh attorney developed CPS at age 31 with sense of doom, palpitations and nightmares.  Seizures involved HFF,

table has 2 more new cases and 5 old cases

Pertinent facts about HFF- specifically absent are delusions, hyperfamiliarity for nonface objects, or auditory hallucinations.  Lesions involved left hemisphere (5 cases), bilateral (2 cases) or unknown (2 cases). 

Authors cite that the hippocampus is important for recollection and the perirhinal cortex for feeling of familiarity.  Deja vu and deja vecu occur more often with right hemisphere lesions establishing "right sided dominance for familiarity."  The normal electrical response for familiarity is suppression v. activation for novelty stimulus.  Authors speculate the left (impaired) side is unable to recognize faces (nvelty signallig) whereas the right (unipaired) side is in overdrive and falsely signal familiarity. Patients quickly accept their familiarity is false, due to intact right hemisphere structures otherwise.   Contrtast to reduplication syndromes (Capgras) with right hemispheric and bifrontal abnormality. 

Tuesday, June 8, 2010

Emotional perception deficits in ALS

Zimmerman EK, Eslinger PJ, Simmons Z, Barrett AM.  Cog Behav Neurol 2007; 20: 79-82

Cognitive deficits occur in up to half of ALS patients, particularly bulbar ALS, including early bulbar ALS patients who are not demented. 

13 subjects with bulbar ALS  from teh Hershey ALS Center were given 2 tasks: the emotional faces task, in which they were required to point or say the word denoting the emotional facial expression (happy, sad, angry, afraid, disgusted).  Second, they were asked to respond to tape recording of emotionally intoned sentenced and identify the emotion conveyed. 

The ALS group did worse on the MMSE and GDS, control tasks for dementia and depression.  They also did worse on the facial task, especially for faces connoting sad, disgusted and surprised faces.  They did normally on the prosody task, but by emotion did worse on the surprised prosody recognition task. 

Sunday, June 6, 2010

Scales ADHD

* Conners parent-teacher rating scale
*ADHD Rating Scale
* SNAP IV Parent Teacher Rating (
* *** (best)Vanderbilt Assessment Scale (Parents and teachers) ( this is easy to get online and is free
In adults get
*adult ADHD report scale available at
*Conner's Adult ADHD Rating scales
*Adult ADHD rating scale IV
*Wender Utah Rating Scale
*Barfkley's Current Symptoms Scale

Thursday, June 3, 2010

Psychosis and EEG abnormalities as manifestations of Hashimoto' sencephalopathy

Sporis D, Habek M, Mubrin Z et al.  Cog Behav Neurol 2007: 20:138-140. 

Authors claim there are two forms:  a vasculitis type with strokelike manifestations  and seizures, and a diffuse progressive type with dementia and psychiatric manifestations.  Authors present a 38 year old woman (type 2) with a history of RA, and depression, and a history of hypothyroidism (not mandatory for HE), with acute psychosis with auditory hallucinations and bizarre behavior, a CSF pleocytosis (37 WBC, normal protein) normal memory, EEG showing slowing.  Behavioral exam abnormal calculations, constructional praxis, and attention.  CSF showed 12 cells. MRi showed punctuate lesions in left frontal gyrus. Treatment with methylprednisoline 1000 mg per day for three days followed by prednisone 50 mg per day for one month resulted in resolution of all symptoms and EEG, 

Authors discuss that half of patients have MRI abnormalities that can mimic tumor, granuloma, infection, stroke, degeneration, or leukodystrophy.  Several patients had other autoimmune abnormalities including RF, or p ANCA. Etiology of condition is not known.

Isolated inability to write cursively after transient ischemic attack (TIA)

Popescu I-M, Vaidya NA.  Cog Behav Neurol 2007; 131-135.  Case report

78 year old right handed truck driver whose TIA was bilateral upper extremity weakness that resolved the same day. Post TIA he could write block letters but not cursively.  On neurologic/behavioral examination, he complained of being unable to remember what he had read.  He was diagnosed with obstructive sleep apnea.  Elemental neurological examination was normal.  Behavioral examination showed a normal MMSE (29/30, minus one for recall) with perseverations noted  on an alternating programs test and Luria loops.  The patient had trouble with cursive copying and writing.  MRI could not be done (pacemaker); Spect showed bilateral hypoperfusion of the parietal and occipital lobes. Literature review of lesions suggests implied lesion of left superior parietal area (Alexander et al, Arch neurol 1992), parieto occipital white matter bilaterally (Baxter and Warrington, JNNP 1986).  Hanley JR, and Peters , S(Cortex, 1996) showed the opposite , in a patient who had a left hemisphere lesion, with impaired spelling of lower case letters  in block and had excellent cursive writing.  Ohno  et al. (Neurology, 2000) had a patient with pure apractic agraphia due to a thalamic lesion which blocked motor programming, and who could not write kana, kanji, Roman alphabet or Arabic numerals.  Otsuki et al. (JNNP, 1999) reported a patient with apractic agraphia due to a hemorrhage in the left superior parietal lobe. Authors believe cursive and block writing are represented differentially.

Finger agnosia in Alzheimer's disease

Shenal BV, Jackson MD, Crucian GP, Heilman KM.  Cog Behav Neurol 2006; 19:202-203.

Authors compared patients with Alzheimer's disease seen at Memory disorders clinic at University of Florida, comparing 38 AD patients and 10 normal age matched controls.  Subjects with Alzheimer's disease had trouble naming fingers, especially their index finger (correct answers allowed were index finger, forefinger, and "dog" finger."  All normal controls named all three fingers tested (including thumb, index finger, and pinky). AD patients 37 % could not name index finger, 5% could not name their thumb, 13 % could not name their pinky.   None could name index finger and not name thumb or pinky. 

Stratified by severity, with mild AD patients (mean MMSE of 23), moderate (mean MMSE of 19) and severe (mean MMSE of 11), 14 % of mild patients cold not name their index finger, 45 % of moderates could not, and 54 % of severe patients could not.

Friday, May 7, 2010

Ventromedial prefrontal cortex modulates fatigue after penetrating TBI

Pardini M, Krueger F, Raymont V, Grafman J.  Neurology 2010; 74:749-754.

97 PBI patients and 37 controls from Vietnam Head Injury Study were enrolled.  Fatigue was assessed via questionnaires (Krupp Fatigue Scale).  CT scan localization of lesions was made to nonfrontal, ventromedial prefrontal, and dorsolateral /lateral prefrontal.  All 3 areas were associated with fatigue, but only VM was associated with increasing fatigue with larger lesion volume.  Authors note this may allow linkage of fatigue to other ventromedial functions such as  effort and reward participation. 

Note one of references was a John Deluca functional MRI paper showing role for same area in MS related fatigue J Neurol Sci 2008; 270:28-39.

Cognitive effects of pregabalin in healthy volunteers

a double blind, placebo controlled trial  Salinsky M, Storzbach D, Munoz S.  Neurology 2010; 74: 755-761.

32 healthy volunteers were randomized to pregabalin (300 bid) or placebo for twelve weeks and underwent cognitive tests before and after.  Subjects on pregabalin showed worse performance on 3 of 6 target cognitive measures, including digit symbol test, Stroop, and Controlled Oral Word Association Test.  They were paralleled by changes on the Portland Neurotoxicity Scale.

Sunday, May 2, 2010

Parcelling frontal functions

Van Snellenberg JC, Wager TD.  Cognitive and motivational functions of the human prefrontal cortex.   from Christensen AL, Goldberg E, Bougakov D.  Luria's Legacy in the 21st Century. Oxford, University Press, 2009.  pp. 30-61.

Chapter summarized authors' (esp Wager's) meta-analyses of functional imaging studies.  These involve working memory, task switching, response inhibition, and emotion. cites Stuss and Alexander, 2007. See chapter.

Sunday, January 31, 2010

Luria-- Semantic fragments for repetition and recall

These stories have layers of meaning and complexity

1. Tolstoy's  The Hen and the Golden Eggs-  A man had a hen which laid golden eggs.  He wanted to get more of the eggs at once, and so he killed the hen.  But inside he found nothing; it was just a hen like any other.

2.  Tolstoy's The jackdaw and the Pigeons.  A jackdaw heard that some pigeons had plenty of food.  She painted herself white and flew into the pigeons house.  The pigeons thought she was a pigeon, and took her in.  However, she forgot herself and cried like a jackdaw.  The pigeons then realized she was a jackdaw and sent her away.  She went back to her family, but they did not recognize her, and would not have her either.

3.  Tolstoy's The Ant and the Pigeon.  An ant went down to the stream to drink.  A wave swamped him and he began to drown.  A pigeon flew past him and threw him a  twig.  He climbed on the twig and was saved.

The next day, a hunter set a net and caught the pigeon.  When he took it from the net, however, the ant crawled up stealthily and bit the hunter on his hand.  The hunter cried out and the pigeon flew away. 

4.  The Lion and the mouse.  A lion was asleep and a mouse ran over his body.  The lion awoke and caught the mouse.  The mouse begged him to let her go.  The lion laughed and let her go.  The next day, a hunter caught the lion and tied him with a rope to a tree.  The mouse came through stealthily, gnawed through the rope, and set the lion free.

5.  The Lion and the Fox.  The Lion grew old and  could no longer hunt animals.  So the lion had to learn how to live by cunning.  He lay in his den and pretended to be ill.   The animals came up to him and he ate them.  One day a fox came but would not go into his den.  The lion asked her "Why don't you come in?" The fox replied, " I can see tracks coming into your den but none coming out." 

6.  The Stupid Dog.  A dog was walking over a bridge at night and saw the reflection of the moon in the water. The dog decided it was cheese and jumped into the water.  But of course, she found nothing and only got wet.

Results  patients who had trouble recalling individual words sometimes had no trouble with semantic fragments, and normals had no trouble with 2 successive fragments.  Amnesics would present the semantic content of one part of the story but forget the second part (retroactive inhibition). 

Luria-- sentence repetition-- aphasia or amnesia??

AR Luria.  The Neuropsychology of Memory VH WInston and Sons, Washington , D.C. 1976 p. 103

Patients with vascular lesions could repeat one sentence, had trouble with the second one.  Patient either reverts to first sentence or contaminates elements, displaying "recency effect" but also simplifying the structure of the sentence while maintaining its elements.  However, patients with temporal lesions showed no "freezing or inert repetition" as in frontal lesions.

Sentence recall-- Luria

Although list learning requires multiple presentations, normals can easily recall one and then a second 7 or 8 word sentence (simplified if aphasic) and then repeat both sentences in order. 

first sentence:  "Apple trees grew in the garden  behind the high fence" or "The hunter killed a wolf on the edge of the forest.  "  Second sentence  :  " In Tashkent there was an earthquake and many houses were destroyed" or "In Tushino there was an air display and parachute jumps." 

Simpler versions "The boy is cold" or "the girl is asleep" or "the boy hit the dog" or "the girl drinks tea"

Results: Amnesics could repeat the sentences immediately, or after empty or filled pauses, with some trouble if the pause was filled with rapid speech.  However, when given a second sentence, they either lost the first or mixed up the elements. 

Disturbance of seriality due to left temporal lesions

Luria in Neuropsychology of memory states that left temporal lesions cause a disturbance of retroactive inhibition in which the last word of the list inhibits recall of predecessors on the list, especially with longer lists.  The effect only occurs with lists presented and reproduced verbally.  Luria gives original credit to Lashley

Lashley KS.  Functional determination of cerebral localization.  Arch Neurol Psych 38: 1937.

Learned motor responses.

Subject is asked to raise his left hand to one tap, and his right hand to 2 taps, or to raise his hand to one tap and to refrain from raising his hand to 2 taps. 

More complicated version: patient is asked to respond to a fist with a finger, or to a finger with a fist.  Or, he is asked to responnd to two taps with one tap, and to one tap with 2 taps. 

More complicated yet.  the subject is asked to respond to a weak tap with a powerful hand movement, and to a powerful tap with a weak hand movement.  Or, to respond to a short acoustic stimulus with a slow movement, and a long stimulus with a prolonged movement. (cf  Marushevskii M, Disturbance of the simplest forms of voluntary action in local lesions of the frontal lobes.  in Luria AR, Khomskaya ED (eds), The frontal lobes and the regulation of psychological processes. Moscow, MGU Press, 1966.

Luria's adaptation:  He would give one task, and when mastered give a second, then without repeating instructions, go back to the first, and then the second task.  Normals had little trouble either learning the task or switching.  Neither empty or filled paused had much effect, (except occipital lesions for visual tasks and temporal lesions for auditory tasks).  Massive tumors had problems with task. 

Patients with thalamic lesions could learn the task, but not do it verbally.  These patients learned the task, were not affected by interference, but could not talk about it. 

Unadze illusion fixed set test

From Luria's book Neuropsychology of  Memory

Unadze DN.  Experimental psychological investigations.  Moscow.  Nauka.  1966.

A subject is given 2 balls of different sizes to squeeze (one per hand) 10-15 times for several seconds per squeeze.  He compares their sizes and reports his finding.  Then, without visual inspection he is given 2 balls of equal size and asked to compare the sizes.  The result is that the hand that held the larger ball now reports it is holding a smaller ball, and is maintained even after 12-18 trials.

Luria's variation was to test normal, mildly and severely impaired subjects on the test.  He found that in severely amnesic subjects only, and only with interference, the fixed set effect was achieved but rapidly forgotten, underlying the importance in interference on somatic memory. Pauses less than 2 minutes had little effect on retention, as with other types of learning.

Saturday, January 30, 2010

Gerstmann's syndrome reader

Kombos T,  Picht t, Suess O.  Electrical Excitability of the Angular Gyrus. Journal of Clinical Neurophysiology 25(6) December 2008 .
Comment.  This is the first report of direct electrical stimulation of AG in humans. Stimulation resulted in responses in contralateral upper extremity in 3/5 patients.  No lower extremity stimulation was found.

Anema HA.a,  Kessels RPCcd, de Haan EHFe,  Kappelle L,  Leijten F, van Zandvoort Martine , Dijkerman,H.  Differences in finger localisation performance of patients with finger agnosia

 19(14) September 2008 . 
Comment : 3 patients with AG lesions were able to point with their finger effectively
to  a tactile stimulus (body schema intact) but unable to do so with a drawing  of hand or to name the finger. 
Other body parts did not have this dissociation between body schema and body image.

Tamura I, Kikuchi S, Otsuki M, Tashiro K. The writing of arabic numerals, kanji, and kana in brain-damaged patients. 14(6), 6 May 2003, pp 861-865.
Comment.  4 patients with Gerstmann's syndrome and 4 with Wernicke's aphasia were compared.  All patients could copy letters, and were righthanded.  Subjects were presented with coins, and then asked to write the respective number value in kana , Kanji and Arabic numerals. For GS patients, kanji writing was better than Arabic, that was better than kana writing.  For WA aphasia patients, Arabic numeral writing was better than kana and kanji. Discussion: "In the case of GS, there was a problem in the concept of number.  In the case of WA, the concept of number was relatively well preserved." GS subjects made substitution errors in Arabic number writing.  Authors postulate a deficiency processing recall of somesthetic graphemes linked to the  concept of number.

Wingard E, Barrett  A, Crucian G, Doty, L, Heilman, KM.  The Gerstmann syndrome in Alzheimer's disease. Journal of Neurology, Neurosurgery & Psychiatry  72(3) March 2002 .
Comment  :  among 38 patients with Alzheimer's disease, the four constituent components of Gerstmann's syndrome did not cluster together, leading the authors to speculate that their association is fortuitous due to contiguous networks, and that the four features of Gerstmann's syndrome do not share a common network.

Baciul M, Koenig O, Vernier M,  Bedoin N, Rubin C, Segebarth C. Categorical and coordinate spatial relations: fMRI evidence for hemispheric specialization. Neuroreport 10(6) April 1999.
Comment: 16 healthy males were examined on a coordinate and a category task using fMRI paradigm.  The category task was whether a dot was above or below a horizontal line. The coordinate task was whether the distance between the dot and the line was within a reference distance.  The coordinate task related to right AG activation which decreased over time.  The category task depended upon Left AG activation which did not decrease over time and in fact increased over time.  Results subserve the hypothesis that the left hemisphere subserves the development of new spatial categorization.

Thursday, January 7, 2010

Cognition and Fragile X syndrome

Fragile X problems persist into adulthood (even though it is considered a pediatric disease). Two separate conditions exist. Patients with the premutation (55-200 repeats of the FMR1 gene) have RNA toxicity but not full blown cognitive abnormalities. RNA toxicity can include primary ovarian insufficiency, fragile X associated tremor ataxia syndrome (FXTAS), fibromyalgia, hypothyroidism, and psychiatric issues such as anxiety and depression. Boys in this range can experience shyness, social anxiety disorders, ADHD and autism spectrum disorders. This is due to excess FMR1 gene.

Patients with the full mutation (greater than 200 repeats) have LACK of FMR1 and Fragile X syndrome (opposite of above in which there is excess RNA present). They present with severe cognitive abnormalities. In boys this manifests as autism, in girls as severe learning disabilities. They also have connective tissue disorders, agression, and psychiatric problems as above. Males with FXS usually have IQ below 70 (severe) but 15 % are "high functioning" with IQ above. High functioning is due to mosaicism within cells or within methylation and the degree of impairment is related to the amount of FMRP present. Among girls, 40 % have a normal IQ, 35 % are borderline, and 25 % have an IQ below 70. The activation percentage (pct of normal X that is active) correlates with disease and that and amount of FMRP available also affects functioning of offspring.

FXS is the most common cause of intellectual impairment and of autism spectrum disease. The full mutation occurs in 1:2500 in population, and the premutation occurs in 1:250 girls and 1:800 boys in the general population. Genetics: FXS patients always have their mother as a carrier. Fathers often pass the premutation on, to their daughters and it does not expand to a full mutation. Mothers with premutation often have expansion to full mutation in their offspring, especially if the number of repeats is greater than 100.

See also posts on FXS and FXTAS on

Sunday, January 3, 2010

Cognition and dystrophinopathy

Duchenne's muscular dystrophy has associated delayed milestones especially language, global cognitive impairment, and occassionally autism. Becker's muscular dystrophy has less common findings, but also, compared to general population, has more learning disabilities with normal intelligence, autism, attention and behavioral problems. Orofacial problems may occur.

Botteron S, Verdabout CM, Jeannet PY, Kiliardis S. Orofacial dysfunction in Duchenne Muscular Dystrophy. Arch Oral Biol 2009; 54(1): 26-31.

Cyrulnik SE, Fee RJ, De Vivo DC, et al. Delayed developmental language milestones in children with Duchenne's muscular dystrophy. J Pediatr 2007; 150 (5): 474-478.

Hinton VJ, Fee RJ, Goldstein EM, De Vivo DC. Verbal and memory skills in males with Duchenne muscular dystrophy. Dev Med Child Neurology 2007; 49 (2): 123-128.

Young HK, Barton BA, Waisbren S, et al. Cognitive and psychological profile of males with Becker muscular dystrophy. J Child Neurol 2008; 23 (2): 155-162.

Sunday, December 6, 2009

Luria audiomotor integrative tasks

Pitch tests should be kept simple, give 2 sounds ask which is higher or lower.

reproduction of tones

reproduction of rhythmic taps first by imitation, then by verbal instruction, then by reproduction with verbal enforcement

Tactile functions p. 444

discriminative sensation "epicritic" (Head, 1920).
Ideas test with head and point of pin, patient must discriminate which, or use 3 items and ask patient to discriminate. Localize touch by asking patient to point to spot, and make it harder by asking him to point to same spot on the opposite limb. Use Weber's touch compass to discriminate 2 point differentiation threshold in millimeters. Also use it to differentiate Double simultaenous stimulation which is difficult in patients with right parietal injury. Finally measure up and down movements and ability to trace numbers and letters in the hand. Cites Teuber, 1959. Notes that lesions is left hemisphere for are tightly organized in postcentral area, but right hemisphere lesions are more distributed and even left hemisphere lesions occassionally cause left arm abnormalities.

Kinesthetic function (position sense)
simple move a finger, toe, arm and ask whether its up or down (or mimic with other side)
More complicated-- mimic posture in the other hand.

differentiates from amorphosythesis (denny brown 1952, 1958).

More Luria tests

from "Higher Cortical Functions in Man" p. 428

Complex motor functions

1. Reaction tests-- basic format is for subject to raise his hand in response to a tap or another stimulus. This then can be the basis of more complex tests.
Abnormalities are rarely seen with simple reaction tests, exceptions being "freezing" in position in htn, motor impersistence in frontal lesions, or premature responses in frontal lesions.
Next step is to respond alternately, eg. raise the left hand to one tap, and the right to two taps, or raise the hand with one tap and refrain from moving the hand with two. Start with strict alternating pattern, eg a-b-a-b-a-b- then suddenly break the stereotype and go out of order eg b-b and see what the patient does. Alternately, can ask for an oral answer to a stimulus eg. to one tap, say "I must" or "left" and to 2 taps "I must not" or "right." The third stage is to tell the subject to respond orally and perform appropriate motor action at same time (cites Kohomskaya, 1956, 1958). Then give a complex response, eg to one stimulus give a weak response, and to another a strong response of same hand.

2. " Raise finger if I raise fist, and fist if I raise my finger"
3. Ask patient to copy a series of figure eg. circle, triangle, square and cross, then a second series eg square square triangle, cross and see if they perseverate. May use five elements. May see forget last response, perseverate, not remember etc. Temporal lobe lesions may make it difficult to copy to verbal instruction but OK to copy from sight. Differentiate the two by asking patient to repeat the command before performing it.


Apathy with subthalamic stimulation (and face recognition)

apathy evaluation scale

Le Jeune et al. Neurology 2009; 73:1746-1751.

Studied STN stimulation in PET study. All had bilateral STN implantation. 12 patients showed worse apathy 3 months after STN stimulation. Motor function was used. The AES was used. PET showed positive correlation with right Brodmann's areas 10 (r frontal middle gyrus) and area 46 (R IFG) and negative correlation with right posterior cingulum (are 31) and left media frontal lobe ( area 9).

Postop neuropsych differed on WCST perseverative errors and Stroop.

Wednesday, December 2, 2009

raloxifene improves verbal memory in postmenopausal women

Raloxifene improves verbal memory in late postmenopausal women: a randomized, double-blind, placebo-controlled trial; Jacobsen DE, Samson MM, Emmelot-Vonk MH, Verhaar HJ; Menopause (Nov 2009)

    OBJECTIVE:: The aim of this study was to examine the effects of raloxifene compared with those of placebo on verbal memory, mental processing speed, depression, anxiety, and quality of life. METHODS:: A randomized, double-blind, placebo-controlled trial of 213 healthy women 70 years or older was conducted between July 2003 and January 2008 at the University Medical Centre Utrecht, the Netherlands. Participants were randomly assigned to receive raloxifene (60 mg) or placebo daily for 12 months. Measurements were taken at baseline and after 3, 6, and 12 months. The change in scores from baseline was calculated. The main outcome measures were direct and delayed verbal memory (Groningen 15 Words test), mental processing speed (Trails B test), mood/depression (Geriatric Depression Scale), anxiety (State-Trait Anxiety Inventory 1 and 2), and quality of life (Women's Health Questionnaire and EuroQol-5 dimensional questionnaire). RESULTS:: Direct verbal memory improved significantly with raloxifene compared with placebo: the women receiving raloxifene repeated more words in the words A + B test than did the women receiving placebo (P = 0.025). At 12 months, the change from baseline was 16 words in the raloxifene group and 10 words in the placebo group. In the words A test, direct repetition was also significantly better among women receiving raloxifene than among women receiving placebo (P = 0.023), with the change from baseline in the number of words repeated being nine words in the raloxifene group and six words in the placebo group at 12 months. CONCLUSIONS:: In postmenopausal women, raloxifene gave significantly improved verbal memory when compared with placebo.

Sunday, November 29, 2009

WHIMS MRI study brain atrophy and estrogen

NEUROLOGY 2009;72:135-142
1403 women aged 71-89, a subset of WHI trial, were scanned on average four years apart.  Frontal lobe volume was less at followup in women in estrogen or estrogen plus progesterone arms.  Temporal lobe and total brain volume were not affected as markedly. The adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

The cognitive measure used was the modified MMSE 3M

  1. Teng EL, Chui H. The Modified Mini-Mental State (3MS) Exam. J Clin Psychiatry 1987;48:314–318.

Confabulation and other delusional syndromes

Confabulation is usually associated with memory (medial temporal or diencephalic) and executive (bifrontal) dysfunction.7-9
  1. Benson DF, Djenderedjian A, Miller BL, et al. Neural basis of confabulation. Neurology 1996;46:1239–1243.[Abstract/Free Full Text]
  2. Moscovitch M, Melo B. Strategic recall and the frontal lobes: evidence from confabulation and amnesia. Neuropsychologia 1997;35:1017–1034.[Medline]
  3. Johnson MK, Hayes SM, D'Esposito M, Raye CL. Confabulation. In: Grafman J, Boller F. Handbook of Neuropsychology,

The anterior parahippocampal cortex (perirhinal cortex, Brodmann areas 35 and 36) is activated by familiarity, while the hippocampus and posterior parahippocampal cortex mediate recollection.49 Perirhinal cortex stimulation evokes déjà vu and déjà vécu (already experienced).50 Further, the right hemisphere dominates in familiarity decisions14,48; déjà vu is more common with right than left temporal lobe seizures or stimulation.48,51 Lesions that destroy or isolate stimuli from right perirhinal cortex may lead to loss of familiarity (e.g., Capgras syndrome) while hyperfamiliarity (i.e., misidentifying strange people as familiar [Fregoli syndrome]) may result from overactivity in right perirhinal cortex from stimulation or disinhibition. Two cases of nondelusional hyperfamiliarity for faces resulted from left-sided lesions (lateral temporal-occipital and anterior cingulate),52,53 possibly disinhibiting right hemisphere areas that imbue faces or places with familiarity.

  1. Gainotti G. Face familiarity feelings, the right temporal lobe and the possible underlying neural mechanisms. Brain Res Rev 2007;56:214–235.[Medline]
  2. Bowles B, Crupi C, Mirsattari SM, et al. Impaired familiarity with preserved recollection after anterior temporal-lobe resection that spares the hippocampus. Proc Natl Acad Sci 2007;104:16382–16387.[Abstract/Free Full Text]
  3. Vignal J-P, Maillard L, McGonigal A, Chauvel P. The dreamy state: hallucinations of autobiographic memory evoked by temporal lobe stimulations and seizures. Brain 2007;130:88–89.[Abstract/Free Full Text]
  4. Mullan S, Penfield W. Illusions of comparative interpretation and emotion. Arch Neurol Psychiatry 1959;81:269–284.[Abstract/Free Full Text]
  5. Vuilleumier P, Mohr C, Valenza N, Wetzel C, Landis T. Hyperfamiliarity for unknown faces after left lateral temporo-occipital venous infarction: a double dissociation with prosopagnosia. Brain 2003;126:889–907.[Abstract/Free Full Text]
  6. Nente F, Carrillo-Mezo R, Mendez MF, Ramirez-Bermudez J. Pathological hyperfamiliarity for others from a left anterior cingulate lesion. J Neuropsychiatry Clin Neurosci 2007;19:345–346.[Free Full Text]
Hughlings Jackson and right hemisphere expression, and callosal syndromes
  1. Jackson JH. Evolution and dissolution of the nervous system. In: Taylor J, ed. Selected Writings of John Hughlings Jackson, Volume 2. New York: Basic Books; 1884/1958:45–75.
  2. Sperry RW, Zaidel E, Zaidel D. Self recognition and social awareness in the deconnected minor hemisphere. Neuropsychologia 1979;17:153–166.[Medline]
  3. Gazzaniga MS. Cerebral specialization and interhemispheric communication. Brain 2000;123:1296–1326.
  4. Gazzaniga MS. The split brain revisited. Sci Am 1998;279:50–55.[Medline]
ego boundaries response to next patient syndrome
  1. Bogousslavsky J, Regli F. Response-to-next-patient-stimulation: a right hemisphere syndrome. Neurology 1988;38:1225–1227.[Abstract/Free Full Text]

Saturday, November 28, 2009

Neuropsych and carotid stenosis

M. Silvestrini, MD, I. Paolino, MD, F. Vernieri, MD, C. Pedone, MD, R. Baruffaldi, MD, B. Gobbi, MD, C. Cagnetti, MD, L. Provinciali, MD and M. Bartolini, MD . Cerebral hemodynamics and cognitive performance in patients with asymptomatic carotid stenosis. NEUROLOGY 2009;72:1062-1068
Objective: The aim of this study was to investigate whether the presence of severe internal carotid artery stenosis may be associated with different cognitive performance in relation to the side of the stenosis and its hemodynamic consequences.

Methods: Eighty-three patients with asymptomatic severe unilateral internal carotid stenosis were included. A neuropsychological investigation including Verbal Fluency using phonemic and category access, Coloured Progressive Matrices, and Complex Figure Test Copy was performed. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler ultrasonography using the breath-holding index (BHI). Thirty healthy subjects comparable for demographic characteristics and vascular risk profile served as controls. Subjects with carotid stenosis were classified into two groups: preserved CVR (BHI 0.69), 48 patients (25 with left and 23 with right stenosis); and impaired CVR (BHI <0.69), 35 patients (19 with left and 16 with right stenosis).

Results: Subjects with left stenosis and reduced CVR had significantly lower performances at phonemic verbal fluency with respect to controls and the other groups of stenosis. In subjects with right stenosis and reduced CVR, scores obtained in Coloured Progressive Matrices and in Complex Figure Test Copy were significantly lower with respect to the other groups.

Conclusions: These results suggest that an alteration of cerebrovascular reactivity may be responsible for reduction in some cognitive abilities involving the function of the hemisphere ipsilateral to carotid stenosis. Such findings may be of interest for providing a more comprehensive indication to surgical treatment in subgroups of subjects with asymptomatic carotid stenosis.