Daniel L. Drane

The memory assessment scales and lateralized temporal lobe epilepsy

We report Memory Assessment Scales (MAS) performance in 101 patients with unilateral temporal lobe epilepsy (TLE; left, n = 51; right, n = 50) with left cerebral language dominance. A significant multivariate group effect was present for the major summary indices (Verbal Memory, Visual Memory, and Global Memory, p < .04). Univariate analyses revealed no significant differences for either the Global Memory or Verbal Memory summary scores, although a significant group difference was present for Visual Memory (p < .04). The Verbal Memory-Visual Memory discrepancy score was significantly different between right and left TLE groups (p < .004). Verbal Memory scores were at least 14 points lower than Visual Memory scores in 34 patients (left = 20, 59%; right = 14, 41%). Visual Memory scores were at least 14 points lower than Verbal Memory performance in 20 patients (left = 5, 25%; right = 15, 75%). Diagnostic efficiency statistics show higher sensitivity but lower specificity in group classification for left TLE patients. These data suggest that the MAS is sensitive to material-specific memory deficits associated with a unilateral temporal lobe seizure focus. However, over one-third of the patients (19/54) with at least a 14-point Verbal Memory-Visual Memory discrepancy were classified incorrectly. The MAS, like other material-specific memory measures, should be interpreted within the context of other clinical findings.

False-Positive Error Rates for Reliable Digit Span and Auditory Verbal Learning Test Performance Validity Measures in Amnestic Mild Cognitive Impairment and Early Alzheimer Disease.

OBJECTIVE The objective is to examine failure on three embedded performance validity tests [Reliable Digit Span (RDS), Auditory Verbal Learning Test (AVLT) logistic regression, and AVLT recognition memory] in early Alzheimer disease (AD; n = 178), amnestic mild cognitive impairment (MCI; n = 365), and cognitively intact age-matched controls (n = 206). METHOD Neuropsychological tests scores were obtained from subjects participating in the Alzheimers Disease Neuroimaging Initiative (ADNI). RESULTS RDS failure using a ≤7 RDS threshold was 60/178 (34%) for early AD, 52/365 (14%) for MCI, and 17/206 (8%) for controls. A ≤6 RDS criterion reduced this rate to 24/178 (13%) for early AD, 15/365 (4%) for MCI, and 7/206 (3%) for controls. AVLT logistic regression probability of ≥.76 yielded unacceptably high false-positive rates in both clinical groups [early AD = 149/178 (79%); MCI = 159/365 (44%)] but not cognitively intact controls (13/206, 6%). AVLT recognition criterion of ≤9/15 classified 125/178 (70%) of early AD, 155/365 (42%) of MCI, and 18/206 (9%) of control scores as invalid, which decreased to 66/178 (37%) for early AD, 46/365 (13%) for MCI, and 10/206 (5%) for controls when applying a ≤5/15 criterion. Despite high false-positive rates across individual measures and thresholds, combining RDS ≤ 6 and AVLT recognition ≤9/15 classified only 9/178 (5%) of early AD and 4/365 (1%) of MCI patients as invalid performers. CONCLUSIONS Embedded validity cutoffs derived from mixed clinical groups produce unacceptably high false-positive rates in MCI and early AD. Combining embedded PVT indicators lowers the false-positive rate.

Word Memory Test Profiles in Two Cases with Surgical Removal of the Left Anterior Hippocampus and Parahippocampal Gyrus

One principle underlying the use of the Word Memory Test (WMT) as an effort test is that with good effort, recognition scores above the cutoffs will be observed. However, to understand the limits of effort testing, it is necessary to study people known to have severe impairment and significant neuropathology involving memory structures. Goodrich-Hunsaker and Hopkins (2009) reported that three amnesic patients with bilateral hippocampal damage had severely impaired free recall of the WMT word list but passed the recognition subtests of the WMT, which are often called effort subtests. We tested two patients with surgical resections in the left anterior temporal region to treat chronic intractable epilepsy; both patients had suffered postoperative strokes. Patient A was a 15-year-old boy and Patient B was a 58-year-old woman. Despite destruction of the left anterior hippocampus and the parahippocampal gyrus and despite impairment of free recall, both cases passed the easy WMT effort subtests. These data reinforce previous findings that people with severe impairment of free recall will score much higher on the verbal recognition memory subtests than on the more difficult memory subtests. Even severe memory impairment and/or removal of hippocampal areas do not necessarily lead to failure on the easy WMT recognition subtests.

Lorazepam effects on Word Memory Test performance: a randomized, double-blind, placebo-controlled, crossover trial.

The Word Memory Test (WMT) is a common measure of symptom validity. To investigate the effects of acute benzodiazepines on WMT scores, oral lorazepam 2 mg (LOR) and placebo were administered 1 week apart in a randomized, double-blind, placebo-controlled, crossover study. A total of 28 participants completed the study and were administered the WMT during each drug condition. Within-participant comparisons of LOR vs placebo revealed significant LOR effects for Immediate Recognition (p = .007) and Consistency (p = .019), but not Delayed Recognition (p = .085). Significant LOR effects were present for Reaction Time Measures (Immediate Recognition RT, p = .013; Delayed Recognition RT, p = .001; Multiple Choice RT, p = .011) and Delayed Memory scores (Multiple Choice, p = .007; Paired Associates, p = .029; Free Recall, p = .001). A pattern similar to crossover results was detected for LOR vs placebo between-group differences for initial test assessment scores. When examined using publisher recommended cut scores for the principal WMT measures, there were six participants failing the WMT during initial LOR testing; all six subsequently performed in the normal range upon retesting with placebo. One participant failed WMT during placebo and obtained passing scores during LOR. These data indicate that multiple WMT measures may be affected by acute LOR dosing, and provide additional evidence that potential latent variables and their effects on both SVT performance and cognitive function should be part of the clinical decision-making process.

Direct electrical stimulation of the amygdala enhances declarative memory in humans

Significance Memories for emotional events tend to persist, raising a fundamental question about how the brain prioritizes significant memories. Past studies have pointed to a central role for the amygdala in mediating this endogenous memory enhancement. However, the premise that the amygdala can causally enhance declarative memory has not been directly tested in humans. Here we show that brief electrical stimulation to the human amygdala can enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response, likely by engaging other memory-related brain regions. The results show the human amygdala has a general capacity to initiate enhancement of specific declarative memories rather than a narrower role limited to indirectly mediating emotional effects on memory. Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala’s interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies.

Epilepsy and Seizures

Epilepsy represents an important area of clinical neuropsychological practice and research. Historically, clinical neuropsychology studies primarily involved patients with seizures that were not adequately controlled by anti-epileptic drugs, termed medically refractory or intractable epilepsy. However, the role of the neuropsychological evaluation and the clinical neuropsychologist has expanded well beyond a narrow focus on patients with medically intractable epilepsy. This chapter will provide an overview of the application of neuropsychology, psychology, and quality of life to patients with epilepsy, including a special section for the clinical neuropsychologist in the surgery team (see section “Neuropsychological (Cognitive and Behavioral) Comorbidity in Epilepsy”). Section “Neuropsychological Assessment Guide” provides an overview of assessment practices.

The Impact of Interictal Discharges on Performance

Purpose of ReviewOur purpose is to review evidence relating to the concept that interictal epileptiform discharges (IEDs) impair brain performance.Recent FindingsSophisticated measures of motor and cognitive performance have clarified older observations, confirming that in both animals and humans, IEDs affect aspects of performance, IED morphology, frequency, anatomical distribution, and duration matter. However, we now know that it is difficult to draw a line between IEDs and seizures, not only by electrical criteria but even by metabolic and molecular measures.SummaryIEDs impair performance acutely and probably chronically. Thus, there are good theoretical reasons for suppressing them, but no consensus has been reached on how much effort this deserves. Many antiepileptic medications effective for control of clinical seizures have little effect on IEDs. Better methods of measuring outcomes may allow selection of individual patients for whom treatment aimed at IEDs is worthwhile.

NIH Toolbox Picture Sequence Memory Test for Assessing Clinical Memory Function: Diagnostic Relationship to the Rey Auditory Verbal Learning Test

Background The NIH Cognitive Toolbox Picture Sequence Memory Test (PSMT) was developed as a measure of learning ability. PSMT use in clinical populations is only beginning to be investigated. Method PSMT performance was analyzed in a retrospective series of 221 patients referred to either the Deep Brain Stimulation Clinic (n = 128) for presurgical evaluation, or to the Cognitive Screening Clinic (n = 93). Patients were also administered the Rey Verbal Auditory Verbal Learning test (AVLT). In addition to correlation between measures, classification agreement was examined based upon performance ratings of normal (>16th percentile), borderline (5-16th percentile), or impaired (<5th percentile). Results Correlation between measures was significant (r = 0.48, p < .0001), with classification agreement of 62% (weighted Kappa = 0.43). For patients with valid PVT scores (n = 147), correlation between tests was 0.67 (p < .0001) with a classification agreement of 72% (weighted Kappa = 0.44). Multiple level likelihood ratios (LRs) relating PSMT to various dichotomous AVLT learning classifications were modest, with the largest group LR obtained for impaired PSMT increasing the likelihood of obtaining impaired AVLT by 7.62 (95% CI = 3.54-16.42). Conclusion Despite significant correlations between measures, the NIH Toolbox PSMT and AVLT learning score often generate different interpretive results. Impaired PSMT appears better at predicting impaired AVLT performance rather than predicting combined borderline/impaired AVLT performance. Ultimately, individual clinicians will need to determine whether the PSMT can be used independently without other memory tests in the clinical environment in which they practice while further validation studies are performed.