The frontal lobe role in memory: a review of convergent evidence and implications for the Wada memory test

doi:10.1016/S1525-5050(02)00039-2

Epilepsy & Behavior

Volume 3, Issue 4, August 2002, Pages 309-315

https://doi.org/10.1016/S1525-5050(02)00039-2 Get rights and content

Abstract

Functional imaging studies have implicated the frontal lobe in many of the memory processes often thought to be the domain of medial temporal structures. Results from fMRI studies of normal subjects have suggested that some components of memory formation, including those components tested during the Wada memory test, may involve frontal lobe regions. Specific behavioral disruptions during carotid amytal injections support a model for frontal lobe anesthesia in explaining results of the Wada memory test. Cortical stimulation data suggest that frontal lobe disruption is sufficient to cause memory disturbances. The convergence of evidence suggests frontal lobe memory may limit the predictive value of the Wada memory test in defining the risk of memory loss following temporal lobectomy.

Introduction

Recent advances in functional imaging, especially functional magnetic resonance imaging (fMRI), have refocused attention on the role of the frontal lobes in memory processes [1]. Additional evidence from lesion studies, and from cortical stimulation mapping, supports such roles for the frontal lobe. Results from material-by-hemisphere interactions when different stimuli are presented during the Wada memory test are also reviewed. The collective data and anatomic basis for the Wada test leave open the possibility that the results of the Wada memory test may be driven by impairment of frontal lobe function. Portions of this review have been presented in abstract form [2].

Section snippets

Functional imaging of frontal and medial temporal regions

Attempts to localize anatomical substrates for memory processes have historically focused on the role of the medial temporal lobe (MTL). This broad anatomical term incorporates the hippocampus, parahippocampal gyrus, entorhinal cortex, and, in some uses, the amygdala. The severe amnesia observed following bilateral MTL injury, as in the famous case of H.M., who underwent surgical removal of both MTLs [3], has left no doubt as to the importance of this area in memory. Injury to other cortical

Preoperative prediction of memory loss: the cerebral amytal (Wada) test

Memory loss following neurosurgical procedures involving resection of the medial temporal lobes remains a feared complication. A common cause of medically intractable seizure disorders is mesial temporal sclerosis. Patients who suffer from epilepsy due to mesial temporal sclerosis may be candidates for surgical treatment if seizures can be demonstrated to arise from one temporal lobe. Surgery for intractable seizures requires extensive resection of medial temporal lobe structures, including

The Wada memory test

Two major methods exist for testing memory preoperatively with the Wada test [14]. Both methods involve the presentation of items following intracarotid injection of sodium amytal. After injection, the hemisphere injected becomes anesthetized. In the first method (the “Seattle” test), visually presented, namable objects are presented. Testing begins prior to injection of amytal. Patients are presented visual line drawings of objects and instructed to name them. A written sentence is then

Limitations of the Wada test

In addition to anatomical questions about the validity of the Wada test to assess medial temporal lobe function, the documented predictive value of the Wada test is suboptimal. When postoperative neuropsychological tests are performed, the cerebral amytal test is found to be only partially predictive of postoperative verbal memory deficits [14]. Although severe global amnesia can be avoided if patients pass the cerebral amytal test prior to resection of medial temporal structures, significant

Areas of the brain anesthetized by the Wada test

Not only does the Wada test not accurately predict the effects of MTL removal, additional studies suggest the metabolic changes from amytal injection may not primarily involve MTL structures [15]. Medial temporal lobe structures receive perfusion from both the anterior (carotid) and posterior (vertebrobasilar) circulation [16]. Branches of the middle cerebral and anterior choroidal artery perfuse anterior medial temporal lobe structures, with posterior regions arising from branches of the

The frontal lobe affects memory when injured

Although many regions of cortex, including lateral temporal and parietal cortex, may also contribute to effects of an intracarotid amytal injection, the frontal lobe is, for reasons mentioned, especially of interest in considering effects of memory disruption. Lesion data, although classically focusing on frontal lobe functions such as speech production, response selection, and executive functions [1], also supports a role for frontal lobe in memory. Impairment of source memory [26],

Lateralization of memory functions: the Wada test and the frontal lobes

Thus, if disruption of frontal lobe function is a plausible source for memory changes seen during the Wada test, the lateralization of memory disruption should follow changes seen in frontal lobe activation for different tests. One paradigm used in the neuroimaging literature, encoding of words or faces during fMRI tasks, reveals very strong lateralization of frontal lobe activation in normal subjects [9], with poor lateralization of activation seen for medial temporal regions. If memory

Is disruption of the frontal lobe sufficient?

Although the results of lateralization of memory formation during the Wada test are suggestive of frontal lobe involvement, and lesion literature suggests a role for the frontal lobe and memory, it is not clear that an acute “lesion” of the frontal lobe should cause the disruption in memory seen during the Wada testing. Another model of frontal lobe disruption, which provides anatomic specificity, is cortical stimulation. If focal frontal lobe disruption is sufficient to cause memory

Correlating fMRI and Wada test

In a separate patient, with left frontal seizures by surface recordings, Wada testing lateralized language to the left and verbal memory to the right (based on Montreal testing of verbal encoding). In the setting of this unusual dissociation, a fMRI was obtained (below) during tasks that activate both speech areas (e.g., classic Broca’s area, inferior frontal gyrus) and the more dorsolateral frontal area discussed above as a region involved in memory. In this patient, inferior frontal

Acknowledgements

This work was supported by NIH grant K23 NS41272.

References (34)

J.G. Ojemann et al.
Imaging studies of memory and attention
Neurosurg. Clin. North Am.
(1997)
W.M. Kelley et al.
Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding
Neuron.
(1998)
C.B. Dodrill et al.
An exploratory comparison of three methods of memory assessment with the intracarotid amobarbital procedure
Brain and Cognition
(1997)
T. Curran et al.
False recognition after a right frontal lobe infarction: memory for general and specific information
Neuropsychologia
(1997)
D.L. Schacter et al.
False recognition and the right frontal lobe: a case study
Neuropsychologia
(1996)
J. Ojemann et al.
Frontal lobe memory: evidence from fMRI, Wada, and cortical stimulation
Epilepsia
(2001)
S. Corkin
Lasting consequences of bilateral medial temporal lobe lobectomy: clinical course and experimental finding in H.M
Semin. Neurol.
(1984)
R.G. Ojemann
Correlations between specific human brain lesions and memory changes: a critical survey of the literature
Neurosci. Res. Program Bull Suppl.
(1966)
R.L. Buckner et al.
Frontal cortex contributes to human memory formation
Nat. Neurosci.
(1999)
L.R. Squire et al.
Activation of the hippocampus in normal humans: a functional anatomical study of memory
Proc. Natl. Acad. Sci. USA
(1992)

R.L. Buckner et al.

Functional anatomical studies of explicit and implicit memory retrieval tasks

J. Neurosci.

(1995)

K.B. McDermott et al.

Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study

Memory

(1999)

J. Brewer et al.

Making memories: activity that predicts how well visual experience will be remembered

Science

(1998)

A.D. Wagner et al.

Material specific lateralization of prefrontal activation during episodic encoding and retrieval

NeuroReport

(1998)

A.D. Wagner et al.

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity

Science

(1998)

C. Branch et al.

Intracarotid sodium amytal for the lateralization of cerebral speech dominance

J. Neurosurg.

(1964)

B.G. Kim et al.

Interpretation of Wada memory test for lateralization of seizure focus by use of 99Tc-HMPAO SPECT

Epilepsia

(2000)

Cited by (20)

Sex and gender differences in neuropsychological symptoms for clinical diagnosis of Alzheimer’s disease
2021, Sex and Gender Differences in Alzheimer’s Disease
Cognitive impairment remains a primary measure to diagnose Alzheimer’s disease, but new profiles incorporating sex/gender-related cognitive differences are needed. This chapter characterizes profiles of the classical cognitive domains of language, memory, and executive dysfunction, and reviews why sex/gender-dependent cognition is needed to measure disease detection and progression. Differences in sex/gender-specific cognitive profiles are lifelong, and disparate trajectories toward late life also require new cut points to detect disease. The chapter reviews why qualitative measures are sensitive either to underlying disease or to the harbingers of the disease cascade. Linguistic semantic organization, memory functions of learning, encoding, and retrieval mechanisms, as well as executive organizational functions are vulnerable. Profiles of these cognitive domains may also reflect availability of cognitive compensation, which should also be sex/gender-specific. As reported by Sundermann, Biegon, et al. (2016, Neurology, 86, 1368–1376), women’s “better” compensatory verbal skills may mask underlying early disease-related impairment. The consequence is that greater neurodegeneration is required for clinical impairment to be detected in women compared to men. This chapter advocates that cognitive and biological mechanisms are inseparable, and that sex-specific “cognitive biomarkers” are essential measures to detect and capture progression of impending Alzheimer’s disease.
Female verbal memory advantage in temporal, but not frontal lobe epilepsy
2018, Epilepsy Research
Citation Excerpt :
The temporal lobe and the hippocampus are crucial for episodic memory (Squire and Zola-Morgan, 1997). In addition, frontal lobe structures may support memory encoding and retrieval through organizational and controlling processes (Fletcher and Henson, 2001; Ojemann and Kelley, 2002). For instance, semantic clustering during word list recall is related to frontal lobe functioning (Long et al., 2010; Manning et al., 2012; Savage et al., 2001).
Women show better performance than men on a range of episodic memory tasks. Evidence regarding a neuroanatomical localization of this effect remains ambiguous. It has been suggested that anterior temporal lobe structures are responsible for sex differences in verbal memory, yet temporal lobe epilepsy (TLE) and TLE surgery do not affect women’s verbal memory advantage. Instead, frontal lobe regions may be relevant for female verbal memory superiority, i.e. by enabling more efficient encoding and retrieval strategies in women. The aim of the present study was to investigate whether women’s verbal memory advantage can be found in patients with frontal lobe epilepsy (FLE), and how patients with FLE and those with TLE differ with regard to sex differences in verbal memory. Fifty patients with unilateral FLE (26 women, 24 men) were compared with 183 patients with unilateral TLE (90 women, 93 men) on both verbal learning and delayed memory. We found that women showed better verbal memory than men in the TLE group, but not in the FLE group. In addition, we found that patients with TLE showed worse verbal learning than those with FLE. Our findings support the idea that women’s advantage in verbal memory may be related to frontal lobe function.
Age-related differences in prefrontal control of heart rate in humans: A pharmacological blockade study
2009, International Journal of Psychophysiology
The Neurovisceral Integration Model is based on the premise of significant central nervous system–peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1–10 of inactivation) [Roy's Root (10,59) = 0.378, p = 0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system–peripheral nervous system relationships.
Claude Bernard and the heart-brain connection: Further elaboration of a model of neurovisceral integration
2009, Neuroscience and Biobehavioral Reviews
The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model. Specifically we review recent neuroanatomical studies that implicate inhibitory GABAergic pathways from the prefrontal cortex to the amygdala and additional inhibitory pathways between the amygdala and the sympathetic and parasympathetic medullary output neurons that modulate heart rate and thus heart rate variability. We propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. We next review the evidence on the role of vagally mediated heart rate variability (HRV) in the regulation of physiological, affective, and cognitive processes. Low HRV is a risk factor for pathophysiology and psychopathology. Finally we review recent work on the genetics of HRV and suggest that low HRV may be an endophenotype for a broad range of dysfunctions.
Lessons for neuropsychology from functional MRI in patients with epilepsy
2004, Epilepsy and Behavior
This contribution aims to review the major findings of pre- and postsurgical functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy from a neuropsychological perspective. We compared the contribution of fMRI with the intracarotid amytal procedure (IAP) with respect to functional mapping of language and memory in patients with therapy-resistant epilepsy. We conclude that using comprehensive language paradigms, fMRI has been able (1) to provide estimates of the degree of language lateralization including the degree of involvement of the nondominant hemisphere, (2) to provide information on the location of its activated network during expressive and receptive language, and (3) to help delineate eloquent language regions in the vicinity of the surgical target, thus preventing postoperative complications. The contribution of the frequently observed nondominant hemisphere activation to language should be explored and its clinical relevance determined. Evidence from fMRI studies is accumulating that reorganization of cognitive and motor function favors the activation of contralateral homotopic areas, although this process is far from understood. The exact functional contribution of atypical areas of activation should be investigated critically. In the presurgical evaluation process, detailed and reliable localization of language and memory functions of the individual patient is mandatory and should be the ultimate goal in the development of comprehensive clinical fMRI protocols.
Validity of the WADA test [3]
2002, Epilepsy and Behavior

View all citing articles on Scopus

View full text

ReviewThe frontal lobe role in memory: a review of convergent evidence and implications for the Wada memory test

Abstract

Introduction

Section snippets

Functional imaging of frontal and medial temporal regions

Preoperative prediction of memory loss: the cerebral amytal (Wada) test

The Wada memory test

Limitations of the Wada test

Areas of the brain anesthetized by the Wada test

The frontal lobe affects memory when injured

Lateralization of memory functions: the Wada test and the frontal lobes

Is disruption of the frontal lobe sufficient?

Correlating fMRI and Wada test

Acknowledgements

Neurosurg. Clin. North Am.

Neuron.

Brain and Cognition

Neuropsychologia

Neuropsychologia

Frontal lobe memory: evidence from fMRI, Wada, and cortical stimulation

Epilepsia

Lasting consequences of bilateral medial temporal lobe lobectomy: clinical course and experimental finding in H.M

Semin. Neurol.

Correlations between specific human brain lesions and memory changes: a critical survey of the literature

Neurosci. Res. Program Bull Suppl.

Frontal cortex contributes to human memory formation

Nat. Neurosci.

Activation of the hippocampus in normal humans: a functional anatomical study of memory

Proc. Natl. Acad. Sci. USA

Functional anatomical studies of explicit and implicit memory retrieval tasks

J. Neurosci.

Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study

Memory

Making memories: activity that predicts how well visual experience will be remembered

Science

Material specific lateralization of prefrontal activation during episodic encoding and retrieval

NeuroReport

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity

Science

Intracarotid sodium amytal for the lateralization of cerebral speech dominance

J. Neurosurg.

Interpretation of Wada memory test for lateralization of seizure focus by use of 99Tc-HMPAO SPECT

Epilepsia

Review
The frontal lobe role in memory: a review of convergent evidence and implications for the Wada memory test