Medial temporal lobe roles in human path integration.

Path integration is a process in which observers derive their location by integrating self-motion signals along their locomotion trajectory. Although the medial temporal lobe (MTL) is thought to take part in path integration, the scope of its role for path integration remains unclear. To address this issue, we administered a variety of tasks involving path integration and other related processes to a group of neurosurgical patients whose MTL was unilaterally resected as therapy for epilepsy. These patients were unimpaired relative to neurologically intact controls in many tasks that required integration of various kinds of sensory self-motion information. However, the same patients (especially those who had lesions in the right hemisphere) walked farther than the controls when attempting to walk without vision to a previewed target. Importantly, this task was unique in our test battery in that it allowed participants to form a mental representation of the target location and anticipate their upcoming walking trajectory before they began moving. Thus, these results put forth a new idea that the role of MTL structures for human path integration may stem from their participation in predicting the consequences of one's locomotor actions. The strengths of this new theoretical viewpoint are discussed.

Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia.

Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups.

The correlation between vagus nerve stimulation efficacy and partial onset epilepsies.

PURPOSE: To evaluate the correlation between vagus nerve stimulation (VNS) efficacy and partial seizures originating from different brain regions. MATERIALS AND METHODS: The authors retrospectively analyzed the data of 46 subjects with medically intractable epilepsy who had insertion of VNS between April 1999 and July 2005. The clinical outcome was assessed with Engel classification. Subjects were divided into group A (Engel I, II, and III) and group B (Engel IV) for statistical analysis. Group A was referred as a satisfactory outcome. The statistical analysis of the data was assessed whether these parameters such as age, type of seizure, age at insertion of VNS, and lengths of follow-up affect the outcome. RESULTS: Nineteen patients (41.3%) had a satisfactory outcome (Engel II, III). The analysis of VNS efficacy demonstrated that 65% of the patients with frontal lobe epilepsy and only 15% of the patients with temporal lobe epilepsy (TLE) had a satisfactory outcome. There was a statistically significant difference between these types of epilepsyand VNS outcomes (Fisher exact test, P = 0.004). CONCLUSION: VNS is more effective in frontal lobe epilepsy than in temporal lobe epilepsy. Further studies are warranted to verify our findings and the correlation between types of epilepsy and VNS outcome.

Improvement in smell and taste dysfunction after repetitive transcranial magnetic stimulation.

BACKGROUND: Olfactory and gustatory distortions in the absence of odors or tastants (phantosmia and phantageusia, respectively) with accompanying loss of smell and taste acuity are relatively common symptoms that can occur without other otolaryngologic symptoms. Although treatment of these symptoms has been elusive, repetitive transcranial magnetic stimulation (rTMS) has been suggested as an effective corrective therapy. OBJECTIVE: The objective of the study was to assess the efficacy of rTMS treatment in patients with phantosmia and phantageusia. METHODS: Seventeen patients with symptoms of persistent phantosmia and phantageusia with accompanying loss of smell and taste acuity were studied. Before and after treatment, patients were monitored by subjective responses and with psychophysical tests of smell function (olfactometry) and taste function (gustometry). Each patient was treated with rTMS that consisted of 2 sham procedures followed by a real rTMS procedure. RESULTS: After sham rTMS, no change in measurements of distortions or acuity occurred in any patient; after initial real rTMS, 2 patients received no benefit; but in the other 15, distortions decreased and acuity increased. Two of these 15 exhibited total inhibition of distortions and return of normal sensory acuity that persisted for over 5 years of follow-up. In the other 13, inhibition of distortions and improvement in sensory acuity gradually decreased; but repeated rTMS again inhibited their distortions and improved their acuity. Eighty-eight percent of patients responded to this therapeutic method, although repeated rTMS was necessary to induce these positive changes. INTERPRETATION: These results suggest that rTMS is a potential future therapeutic option to treat patients with the relatively common problems of persistent phantosmia and phantageusia with accompanying loss of taste and smell acuity. Additional systematic studies are necessary to confirm these results.

Carbonic anhydrase I, II, and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. METHODS: Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. RESULTS: After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. CONCLUSIONS: rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities.

Bilateral and independent Broca areas confirmed by Wada test and functional magnetic resonance imaging.

Accurate preoperative evaluation of language dominance is critical when evaluating potential patients for temporal lobe epilepsy surgery. Although most people have left-sided language dominance, a minority of patients have been described with either bilateral or right hemispheric dominance. We present a patient with right temporal lobe epilepsy who presented with bilateral and functionally independent Broca areas, as confirmed by Wada testing and functional magnetic resonance imaging.

Tailored anteromedial lobectomy in the treatment of refractory epilepsy of the temporal lobe: long term surgical outcome and predictive factors.

OBJECTIVE: To analyze long-term results and to determine prognostic factors on seizure outcome in a series of patients with temporal lobe epilepsy (TLE) who underwent anteromedial temporal lobectomy (AMTL). MATERIALS AND METHODS: From 1995 to 1998 forty-two patients suffering from non-lesional TLE underwent tailored AMTL at our Institution. We retrospectively reviewed surgical results and calculated predictive factors of good outcome in the long term. RESULTS: Sixty-four percent of patients were rendered seizure free (median follow up 60 months). Eleven cases (26.2%) had a significant reduction of disabling epileptic episodes. Poor seizure control was observed in four patients (9.5%). Overall surgical morbidity was 4.7%. Medial temporal sclerosis (MTS) was the most common histopathological finding (69% of cases). The presence of unilateral hippocampal abnormalities on qualitative MRI was significantly associated with excellent postoperative outcome (p<0.011). Qualitative preoperative MRI had a positive predictive value of 83% in detecting both MTS at pathological examination and excellent outcome. CONCLUSIONS: Tailored AMTL is a safe and effective procedure in the treatment of selected patients with medically refractory TLE. Data from preoperative qualitative MRI well correlated with histopathological findings. The presence of unilateral hippocampal atrophy on qualitative MRI was predictive of excellent outcome in the long-term follow up.

Spatial memory following temporal lobe resection.

The present study sought a clearer understanding of spatial memory function consequent to temporal lobe resection, and, in particular, of spatial memory function with respect to two- as well as three-dimensional frames of reference. Relative to a group of 15 control participants, a group of 15 epilepsy patients with right temporal resections demonstrated deficits of memory for locations in a two-dimensional display. A group of 13 epilepsy patients with left temporal resections did not demonstrate such deficits. The right and the left resection groups both demonstrated deficits of memory for item-location relationships in a two-dimensional display. The right but not the left resection group demonstrated deficits of memory for item-location relationships in a three-dimensional display. The differing results that were observed for item-location relationships in two- and three-dimensional displays were attributed to differences in the way item information is bound with location information concerning two- and three-dimensional domains.

Path integration deficits during linear locomotion after human medial temporal lobectomy.

Animal navigation studies have implicated structures in and around the hippocampal formation as crucial in performing path integration (a method of determining one's position by monitoring internally generated self-motion signals). Less is known about the role of these structures for human path integration. We tested path integration in patients who had undergone left or right medial temporal lobectomy as therapy for epilepsy. This procedure removed approximately 50% of the anterior portion of the hippocampus, as well as the amygdala and lateral temporal lobe. Participants attempted to walk without vision to a previously viewed target 2-6 m distant. Patients with right, but not left, hemisphere lesions exhibited both a decrease in the consistency of path integration and a systematic underregistration of linear displacement (and/or velocity) during walking. Moreover, the deficits were observable even when there were virtually no angular acceleration vestibular signals. The results suggest that structures in the medial temporal lobe participate in human path integration when individuals walk along linear paths and that this is so to a greater extent in right hemisphere structures than left. This information is relevant for future research investigating the neural substrates of navigation, not only in humans (e.g., functional neuroimaging and neuropsychological studies), but also in rodents and other animals.